76,729 results on '"D'Have, K."'
Search Results
2. Determining application rates of FYM and pressmud to improve soil health properties in salt degraded soils.
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M L Dotaniya, M D Meena, R L Choudhary, M K Meena, V D Meena, H V Singh, R S Jat, R K Doutaniya, Kuldeep Kumar, Harpreet Singh, and P K Rai
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Medicine ,Science - Abstract
Improving food grain production by enhancing plant nutrient availability is critical for meeting future production. In this line, degraded soils may have the potential to meet the food demand of future population. However, the key challenge is excessive concentration of salts. It adversely mediates the soil fertility parameters, physical properties and soil enzymatic activities. Addition of organic substances, such as farm yard manure (FYM) and pressmud (PM), may improve soil health parameters. An incubation experiment was conducted with graded application of FYM (0, 2.5, 5 and 10 t/ha) and PM (0, 2.5, 5 and 10 t/ha) to monitor the nutrient release pattern of FYM and PM; and its effect on soil physico-chemical properties and soil enzymatic activities. The results showed that soil pH and EC were reduced after the one year incubation period. It was also observed that available plant nutrients like N, P, K, S and soil enzymatic activities reported highest in treatment FYM and PM (each applied 10 t/ha) over control. The findings of this study suggested that organic amendments can improve soil fertility, mitigate salt ion toxicity, and enhance food production potential, particularly in arid and semi-arid soils.
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- 2025
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3. Protocol for evaluating the effects of integrating music with taekwondo training in children with autism spectrum disorder: A randomized controlled trial.
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Clare C W Yu, Kam M Mok, Emma Mak, Chun T Au, Dorothy F Y Chan, Stanley Wu, Raymond C K Chung, Matthew C K Ip, and Simpson W L Wong
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Medicine ,Science - Abstract
BackgroundChildren with autism spectrum disorder (ASD) are known to experience difficulties in coordinating fine- and gross-motor movement. Previous interventional studies have reported significant effect of exercise-based intervention programs on improving motor skills and alleviating symptoms in ASD; however, researchers are yet to know why some participants experienced less improvement than others. One plausible explanation for suboptimal treatment outcomes is insufficient engagement in the exercise programs due to the children's difficulties in following instructions and performing the correct movements. In the proposed research, we will test the above speculation by manipulating the amount of music-therapy elements into a 10-week Taekwondo training program designed specifically for children with autism.MethodsThis is a randomized controlled trial. Seventy-two children aged 7 to 9 years who meet the diagnostic criteria of ASD will be recruited and randomized into either the "Taekwondo training with elements of music therapy" group or the "Taekwondo training alone" group. In both groups, the participating children will attend Taekwondo training sessions twice a week over 10 consecutive weeks. In the "Taekwondo training with elements of music therapy" group, elements of music therapy will be incorporated into the Taekwondo training. Assessment will be conducted before the program commences, immediately after the completion of the 10-week program, and 2 months after the post-test. The outcome domains to be evaluated include the immediate effects during the exercise sessions. These effects include the level of engagement in the exercise sessions (primary outcome), enjoyment, physical activity level, and rate of perceived exertion. Furthermore, the evaluation will also cover the overall effects of the training program on gross motor skills, Taekwondo skills performance, executive function, psychosocial functioning, and behavioral problems.Discussion/findingsThe findings of this study will inform strategies for the promotion of physical activity and engagement among children with ASD when participating in exercise training classes. The study will also suggest the importance of regular physical activity for the physical and mental well-being of children with ASD.Trial registrationClinical trial registration: URL: http://www.clinicaltrials.gov. ClinicalTrials.gov Identifier: NCT06277778. Registered on 15 February 2024.
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- 2025
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4. Prevalence and genetic diversity of tick-borne encephalitis virus in ixodid ticks from specific regions of northwestern Russia.
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Alena A Sharova, Nikolay K Tokarevich, Regina R Baimova, Olga A Freylikhman, Islam A Karmokov, Ekaterina G Riabiko, Gelena A Lunina, Roman V Buzinov, Olga V Sokolova, Lidia V Buts, Lubov A Bespyatova, Liliya A Bubnova, Olga S Safonova, Elena L Kalinina, Andrey I Stankevich, Rose Vikse, Ashild K Andreassen, Anna S Gladkikh, Majid Forghani, Anastasia S Gritseva, Margarita R Popova, Edward S Ramsay, and Vladimir G Dedkov
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Medicine ,Science - Abstract
Russia is a country with a high incidence of tick-borne encephalitis (TBE). In northwestern regions of Russia, 110 TBE cases were registered in 2021. The largest numbers of TBE cases were registered in the Arkhangelsk region and St. Petersburg. TBEV seropositivity among healthy individuals, including the unvaccinated population in northwestern Russia, was found in 12.2% of studied samples, indicating active TBEV circulation. The prevalence of TBEV is 2.4% in the two tick species most common in northwestern regions of Russia, Ixodes ricinus and Ixodes persulcatus. However, there is still no comprehensive data on the molecular characterization and phylogenetic analysis of the circulating TBEV strains. The purpose of the study was to determine the prevalence of TBEV and to identify its subtypes in ixodid ticks collected in specific areas of northwestern Russian regions. Phylogenetic analysis of E protein sequences of ten obtained strains showed that they all belong to the Siberian subtype, which were clustered into two groups: the most numerous Baltic group, clusteron 3D; and the Vasilchenko group. However, some unique isolates may form new clusterons.
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- 2025
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5. Study protocol for a hybrid implementation-effectiveness trial of Game Changers for Cervical Cancer Prevention in Uganda.
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Glenn J Wagner, Laura M Bogart, Joseph K B Matovu, Violet Gwokyalya, Jolly Beyeza-Kashesya, Allison Ober, Harold D Green, Sylvia Nakami, Margrethe Juncker, Eve Namisango, Emmanuel Luyirika, Ryan K McBain, Kathryn Bouskill, and Rhoda K Wanyenze
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Medicine ,Science - Abstract
IntroductionCervical cancer (CC) is the leading cause of cancer-related deaths among Uganda women, yet rates of CC screening are very low. Training women who have recently screened to engage in advocacy for screening among women in their social network is a network-based strategy for promoting information dissemination and CC screening uptake.MethodsDrawing on the Exploration, Preparation, Implementation and Sustainment (EPIS) framework for implementation science, this hybrid type 1 randomized controlled trial (RCT) of a peer-led, group advocacy training intervention, Game Changers for Cervical Cancer Prevention (GC-CCP), will examine efficacy for increasing CC screening uptake as well as how it can be implemented and sustained in diverse clinic settings. In the Preparation phase we will prepare the four study clinics for implementation of GC-CCP and the expected increase in demand for CC screening, by using qualitative methods (stakeholder interviews and client focus groups) to identify and address structural barriers to easy access to CC screening. In the Implementation phase, GC-CCP will be implemented over 36 months at each clinic, with screened women (index participants) enrolled as research participants receiving the intervention in the first 6 months as part of a parallel group RCT overseen by the research study team to evaluate efficacy for CC screening uptake among their enrolled social network members. All research participants will be assessed at baseline and months 6 and 12. Intervention implementation and supervision will then be transitioned to clinic staff and offered as part of usual care in the subsequent 30 months as part of the Sustainability phase. Using the RE-AIM framework, we will evaluate engagement in GC-CCP and CC advocacy (reach), alter CC screening (effectiveness), adoption into clinic operations, implementation outcomes (acceptability, feasibility, fidelity, cost-effectiveness) and maintenance.DiscussionThis is one of the first studies to use a network-driven approach and empowerment of CC screened peers as change agents to increase CC screening. If shown to be an effective and sustainable implementation strategy for promoting CC screening, this peer advocacy model could be applied to other preventative health behaviors and disease contexts.Trial registrationNIH Clinical Trial Registry NCT06010160 (clinicaltrials.gov; date: 8/17/2023).
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- 2025
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6. Correction: Developing climate-resilient rice varieties (BRRI dhan97 and BRRI dhan99) suitable for salt-stress environments in Bangladesh.
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Sanjoy K Debsharma, M Akhlasur Rahman, Mahmuda Khatun, Ribed F Disha, Nusrat Jahan, Md Ruhul Quddus, Hasina Khatun, Sharifa S Dipti, Md Ibrahim, K M Iftekharuddaula, and Md Shahjahan Kabir
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0294573.].
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- 2025
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7. Association between early life second-hand smoke exposure on child sleep and psychoactive substance use on adult sleep patterns in an urban informal settlement in Uganda.
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Solomon T Wafula, Lydia N Namakula, John B Isunju, Richard K Mugambe, Tonny Ssekamatte, David Musoke, and Rhoda K Wanyenze
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Medicine ,Science - Abstract
BackgroundPsychoactive substance use in adults and second-hand smoke (SHS) exposure among children are leading contributors to sleeping problems. Despite this, there is limited data on how these exposures influence sleep patterns in informal settings. Our study assessed the associations between substance use, SHS exposure and sleep disturbances among adults and children in an urban informal settlement in Uganda.MethodsWe conducted a cross-sectional study in an urban informal settlement in Kampala, Uganda. Data was collected on self-reported sleep problems among adults including sleep duration, insomnia and sleep dissatisfaction, as well, as sleep-disordered breathing (SDB) in children. We evaluated children's early-life SHS exposure and psychoactive substance use in adults using questionnaires. We modelled the associations between the exposures and sleep problems in adults and children using modified Poisson regression.ResultsData were collected from 284 adults, who also reported on their children's sleep experience. Among adults, 59.2% reported insufficient sleep (less than 7 hours), 34.9% experienced insomnia, and 28.3% were dissatisfied with their sleep patterns. Active smoking was associated with insomnia (Prevalence Ratio (PR) = 2.74, 95% Confidence Interval (CI): 1.14-6.59), and alcohol use was associated with sleep dissatisfaction (PR = 1.81, 95% CI 1.23-2.69). In children, 40.0% (88/220) exhibited SDB problems. Those exposed to SHS either during pregnancy or within six months post-birth had a higher risk of SDB than unexposed children (PR = 1.78, 95% CI 1.21-2.61). The risk was also elevated for children exposed to SHS during both periods (PR = 1.48, 95% CI 1.02-2.13).ConclusionsOur findings suggest that smoking was associated with insomnia and alcohol with sleep dissatisfaction among adults. Early-life SHS exposure was associated with an increased risk of SDB in children. These results emphasize the need to support ongoing public health initiatives and maintain a smoke-free environment, particularly for children in their early life.
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- 2025
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8. Characterization of two affinity matured Anti-Yersinia pestis F1 human antibodies with medical countermeasure potential
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Velappan, Nileena, Biryukov, Sergei S, Rill, Nathaniel O, Klimko, Christopher P, Rosario-Acevedo, Raysa, Shoe, Jennifer L, Hunter, Melissa, Dankmeyer, Jennifer L, Fetterer, David P, Bedinger, Daniel, Phipps, Mary E, Watt, Austin J, Abergel, Rebecca J, Dichosa, Armand, Kozimor, Stosh A, Cote, Christopher K, and Lillo, Antonietta M
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunization ,Vector-Borne Diseases ,Emerging Infectious Diseases ,Infectious Diseases ,Biodefense ,Animals ,Humans ,Mice ,Yersinia pestis ,Plague ,Antibodies ,Bacterial ,Bacterial Proteins ,Female ,Antibody Affinity ,Medical Countermeasures ,Antigens ,Bacterial ,Disease Models ,Animal ,General Science & Technology - Abstract
Yersinia pestis, the causative agent of plague and a biological threat agent, presents an urgent need for novel medical countermeasures due to documented cases of naturally acquired antibiotic resistance and potential person-to-person spread during a pneumonic infection. Immunotherapy has been proposed as a way to circumvent current and future antibiotic resistance. Here, we describe the development and characterization of two affinity matured human antibodies (αF1Ig AM2 and αF1Ig AM8) that promote survival of mice after exposure to aerosolized Y. pestis. We share details of the error prone PCR and yeast display technology-based affinity maturation process that we used. The resultant matured antibodies have nanomolar affinity for Y. pestis F1 antigen, are produced in high yield, and are resilient to 37°C stress for up to 6 months. Importantly, in vitro assays using a murine macrophage cell line demonstrated that αF1Ig AM2 and αF1Ig AM8 are opsonic. Even more importantly, in vivo studies using pneumonic plague mouse models showed that 100% of the mice receiving 500 μg of IgGs αF1Ig AM2 and αF1Ig AM8 survived lethal challenge with aerosolized Y. pestis CO92. Combined, these results provide evidence of the quality and robustness of αF1Ig AM2 and αF1Ig AM8 and support their development as potential medical countermeasures against plague.
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- 2024
9. Effect of multiple micronutrient-fortified bouillon on micronutrient status among women and children in the Northern Region of Ghana: Protocol for the Condiment Micronutrient Innovation Trial (CoMIT), a community-based randomized controlled trial.
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Wessells, K, Haskell, Marjorie, Kumordzie, Sika, Arnold, Charles, Davis, Jennie, Becher, Emily, Fuseini, Ahmed, Nyaaba, Kania, Tan, Xiuping, Lietz, Georg, Vosti, Stephen, Adu-Afarwuah, Seth, Engle-Stone, Reina, and Adams, Katherine
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Humans ,Female ,Ghana ,Micronutrients ,Food ,Fortified ,Adult ,Adolescent ,Child ,Preschool ,Middle Aged ,Nutritional Status ,Young Adult ,Lactation ,Male ,Hemoglobins ,Iodine - Abstract
INTRODUCTION: Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana. METHODS: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participants household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development. DISCUSSION: Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022).
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- 2024
10. Isolation and characterization of 24 phages infecting the plant growth-promoting rhizobacterium Klebsiella sp. M5al.
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Marissa R Gittrich, Courtney M Sanderson, James M Wainaina, Cara M Noel, Jonathan E Leopold, Erica Babusci, Sumeyra C Selbes, Olivia R Farinas, Jack Caine, Joshua Davis Ii, Vivek K Mutalik, Paul Hyman, and Matthew B Sullivan
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Medicine ,Science - Abstract
Bacteriophages largely impact bacterial communities via lysis, gene transfer, and metabolic reprogramming and thus are increasingly thought to alter nutrient and energy cycling across many of Earth's ecosystems. However, there are few model systems to mechanistically and quantitatively study phage-bacteria interactions, especially in soil systems. Here, we isolated, sequenced, and genomically characterized 24 novel phages infecting Klebsiella sp. M5al, a plant growth-promoting, nonencapsulated rhizosphere-associated bacterium, and compared many of their features against all 565 sequenced, dsDNA Klebsiella phage genomes. Taxonomic analyses revealed that these Klebsiella phages belong to three known phage families (Autographiviridae, Drexlerviridae, and Straboviridae) and two newly proposed phage families (Candidatus Mavericviridae and Ca. Rivulusviridae). At the phage family level, we found that core genes were often phage-centric proteins, such as structural proteins for the phage head and tail and DNA packaging proteins. In contrast, genes involved in transcription, translation, or hypothetical proteins were commonly not shared or flexible genes. Ecologically, we assessed the phages' ubiquity in recent large-scale metagenomic datasets, which revealed they were not widespread, as well as a possible direct role in reprogramming specific metabolisms during infection by screening their genomes for phage-encoded auxiliary metabolic genes (AMGs). Even though AMGs are common in the environmental literature, only one of our phage families, Straboviridae, contained AMGs, and the types of AMGs were correlated at the genus level. Host range phenotyping revealed the phages had a wide range of infectivity, infecting between 1-14 of our 22 bacterial strain panel that included pathogenic Klebsiella and Raoultella strains. This indicates that not all capsule-independent Klebsiella phages have broad host ranges. Together, these isolates, with corresponding genome, AMG, and host range analyses, help build the Klebsiella model system for studying phage-host interactions of rhizosphere-associated bacteria.
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- 2025
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11. Seroprevalence and associated factors for hepatitis B and hepatitis C viral infection among patients with diabetes mellitus in Northern Tanzania.
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Doreen T Eliah, Nyasatu G Chamba, Abid M Sadiq, Amos O Mwasamwaja, Faustini C Kimondo, Cuthbert D Matay, Eliada B Nziku, Tumaini E Mirai, Ibrahim Ali Ibrahim Muhina, Fuad H Said, Sarah K Gharib, Furaha S Lyamuya, Elifuraha W Mkwizu, Kajiru G Kilonzo, Venance P Maro, and Elichilia R Shao
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Medicine ,Science - Abstract
BackgroundThe coexistence of viral hepatitis with diabetes mellitus (DM) significantly escalates the risk of severe outcomes. This study aimed to determine the seroprevalence and associated factors of hepatitis B (HBV) and hepatitis C (HCV) viral infections among DM patients in northern Tanzania.Materials and methodsConducted between February 2023 and May 2023, this hospital-based cross-sectional study enrolled 189 patients with DM from the Diabetic Clinic of Kilimanjaro Christian Medical Centre. A structured questionnaire captured relevant clinical information, and plasma blood sample was assessed for hepatitis B surface antigen and anti-hepatitis C antibody seropositivity. Data analysis employed SPSS v26, and a chi-square test was used to determine the statistical difference of HBV and HCV among patients with DM. Logistic regression was performed to determine factors associated with HBV and HCV.ResultsAmong the 189 patients with DM, the seroprevalence of HBV and HCV infections stood at 2.1% and 0.5%, respectively. Males constituted a significant majority (80%) of those affected by viral hepatitis. Furthermore, 60% of affected patients were in non-union relationships (single, widowed, or divorced), and 40% reported multiple sexual partners. However, the study found no significant association between traditional associated factors and viral infection acquisition.ConclusionThe study's findings reveal a relatively low prevalence of HBV and HCV infections among patients with DM compared to the general population, with no significant association among factors. Nonetheless, the results underscore the importance of early screening and vaccination for HBV and HCV in patients with DM. Such efforts are crucial for curbing infection spread and reducing the risk of hepatocellular carcinoma development in this vulnerable population.
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- 2025
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12. Evaluating the structure-based virtual screening performance of SARS-CoV-2 main protease: A benchmarking approach and a multistage screening example against the wild-type and Omicron variants.
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Noha Galal, Botros Y Beshay, Omar Soliman, Muhammad I Ismail, Mohamed Abdelfadil, Mohamed El-Hadidi, Reem K Arafa, and Tamer M Ibrahim
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Medicine ,Science - Abstract
COVID-19 still poses a worldwide health threat due to continuous viral mutations and potential resistance to vaccination. SARS-CoV-2 viral multiplication hindrance by inhibiting the viral main protease (Mpro) deemed propitious. Structure-based virtual screening (SBVS) is a conventional strategy for discovering new inhibitors. Nonetheless, the SBVS efforts against Mpro variants needed to be benchmarked. Herein, in the first stage of the study, we evaluated four docking tools (FRED, PLANTS, AutoDock Vina and CDOCKER) via an in-depth benchmarking approach against SARS-CoV2 Mpro of both the wild type (WTMpro) and the deadly Omicron P132H variant (OMpro). We started by compiling an active dataset of non-covalent small molecule inhibitors of the WTMpro from literature and the COVID-Moonshot database along with generating a high-quality benchmark set via DEKOIS 2.0. pROC-Chemotype plots revealed superior performance for AutoDock Vina against WTMpro, while both FRED and AutoDock Vina demonstrated excellent performance for OMPro. In the second stage, VS was performed on a focused library of 636 compounds transformed from the early-enriched cluster related to perampanel via a scaffold hopping approach. Subsequently, molecular dynamics (MD) simulation and MM GBSA calculations validated the binding potential of the recommended hits against both explored targets. This study provides an example of how to conduct an in-depth benchmarking approach for both WTMPro and OMPro variants and offering an evaluated SBVS protocol for them both.
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- 2025
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13. Differential impact of divalent metals on native elongating transcript sequencing (NET-seq) protocols for RNA polymerases I and II.
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Abigail K Huffines and David A Schneider
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Medicine ,Science - Abstract
Throughout all domains of life, RNA polymerases (Pols) synthesize RNA from DNA templates, a process called transcription. During transcription, Pols require divalent metal cations for nucleotide addition and cleavage of the nascent RNA after misincorporation or polymerase stalling. Recently, several next-generation sequencing techniques have emerged to study transcription at single-nucleotide resolution in vivo. One such technique, native elongating transcript sequencing (NET-seq), allows for isolation of transcription elongation complexes associated with a specific Pol, defining polymerase occupancy on the DNA template. Originally developed to study RNA polymerase II (Pol II), NET-seq has been adapted for RNA polymerase I (Pol I) and bacterial RNA polymerase. We recently optimized Pol I NET-seq in Saccharomyces cerevisiae, however, we omitted nucleases and their metal cofactors, which are commonly used in Pol II NET-seq. Here, we investigated the effect of CaCl2 ± MNase and MnCl2 ± DNase I on Pol I occupancy. We found that exposure of Pol I to CaCl2 and MnCl2 during NET-seq caused a significant reduction in immunoprecipitation of nascent rRNA compared to the untreated control samples, with a more severe effect when incubated with MnCl2 vs. CaCl2. Surprisingly, in contrast to the Pol I results, we found that metal treatment during Pol II NET-seq did not have a significant effect on nascent transcript capture. Taken together, these observations reinforce the conclusion that transcription elongation complexes formed by Pols I and II have unique characteristics and emphasize the need to carefully consider experimental conditions deployed in all stages of nucleic acid library generation.
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- 2025
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14. Composition, determinants, and risk factors of low birth weight in Sri Lanka.
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Sachith Mettananda, Himali Herath, Ayesha Thewage, Kumudu Nanayakkara, Indeewari Liyanage, K S Udani, Rajika Savanadasa, Sampatha Goonewardena, Nimesha Gamhewage, Asiri Hewamalage, Dhammica Rowel, Abner Elkan Daniel, Chithramalee de Silva, and Susie Perera
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Medicine ,Science - Abstract
IntroductionLow birth weight continues to pose significant challenges to healthcare systems worldwide. Despite substantial improvement in various public health indicators, many developing countries have failed to achieve a significant reduction in low birth weight rates. One major obstacle is the sparsity of data on the determinants of low birth weight. Here, we aim to determine the composition and risk factors for low birth weight in Sri Lanka, a prototype developing nation.MethodologyWe conducted a countrywide multicentre cross-sectional study in August and September 2023 in 13 purposively selected hospitals representing all nine provinces and different tiers of specialist hospitals in Sri Lanka. All live-born neonates were recruited prospectively, and their mothers were interviewed by trained data collectors to gather information on socio-demographic background, medical and obstetric history, and delivery details. Birth weight was measured immediately after the birth by trained healthcare personnel attending the delivery.ResultsA total of 9130 live-born neonates were recruited, of which 52% were males. The mean birth weight was 2827g (95%CI 2817-2838g), and 1865 (20.4%) newborns were low birth weight. The prevalence of prematurity was 10.9% (n = 998), and 1819 (20.0%) neonates were born small for gestational age. Of the low birth weight neonates, 64% were small for gestational age, and 37% were preterm; 11% were both small for gestational age and preterm. Teenage pregnancy (p = 0.022), low maternal pre-pregnancy body mass index (pConclusionThis study presents the results of one of the most extensive country-wide studies evaluating the composition and determinants of low birth weight. The study highlights the importance of considering small for gestational age and prematurity as separate categories of low birth weight. Small for gestational age contributes to approximately two-thirds of the low birth weight burden. Therefore, targeting modifiable risk factors for small for gestational age while mitigating the burden of prematurity is the most feasible approach to reduce the prevalence of low birth weight in developing countries, including Sri Lanka.
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- 2025
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15. A catechol-O-methyltransferase genetic variant impacts functional movement in tactical athletes.
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Marcus K Taylor, Lisa M Hernández, Richard C Allsopp, and John J Fraser
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Medicine ,Science - Abstract
Functional movement is a valuable indicator of physical performance, injury risk, and/or musculoskeletal impairment following injury. However, genetic variation and gene-environment interactions that may affect functional movement are largely unexplored. We recently reported a linkage between trauma exposure and functional movement in male tactical athletes. Here, we examined the effect of a common genetic variant, rs737865, within the catechol-O-methyltransferase gene on functional movement in specialized military personnel (N = 134). We also explored whether rs737865 modulated the influence of trauma exposure. Genotyping was determined from saliva, trauma exposure was self-reported using the Brief Trauma Questionnaire, and functional movement was evaluated using the Functional Movement Screen™. The effect of rs737865 on functional movement was evaluated using general linear models, while associations between trauma and functional movement were determined with regression models. An alpha level of 0.05 was set as the threshold for significance. In the standard three-genotype model (GG, AG, AA), rs737865 predicted functional movement (p = 0.03, η2p = 0.05). Specifically, GG (n = 9) exhibited the highest functional movement scores (mean [M] ± standard deviation [SD] = 17.2±1.9), followed by AG (n = 45; M±SD = 15.9±2.5), and then AA (n = 80; M±SD = 15.2±2.3). The connection between rs737865 and functional movement was preserved in both the dominant G model (G vs AA; p = 0.03, η2p = 0.04) and the dominant A model (A vs GG; p = 0.03, η2p = 0.03). The rs737865 variant also modulated the influence of trauma on functional movement. To our knowledge, this is the first discovery linking rs737865 to functional movement, which may lead to greater precision in musculoskeletal injury risk stratification and increased efficacy of strength and conditioning programs in tactical athletes. In resource constrained settings, genomic modeling may help to direct limited assets to at-risk subgroups (for screening purposes). It may also help to individualize, and enhance, strength and conditioning programs based on the genomic signature of a person's training response.
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- 2025
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16. A qualitative exploration of the educational needs of people living with heart failure: BANDAIDD-Explore study.
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Caleb Ferguson, Scott William, Sabine Allida, Peter S Macdonald, Gary Kilov, Clara K Chow, Anthony Keech, and BANDAIDD Study Investigator team
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Medicine ,Science - Abstract
This is an exploratory qualitative study of cardiovascular clinicians, people living with heart failure (HF), and their caregivers. The aim was to understand the unmet educational needs in self-management for adults living with HF. Four focus groups were conducted face-to-face or via videoconference, recorded, and transcribed verbatim for thematic analysis. A total of 23 participants were recruited and included in analyses (clinicians n = 13; adults with HF n = 7; caregivers n = 3). The focus groups were on average 81 (range 73 to 91) minutes in duration. Seven key themes were identified which were: (i) Understanding and reinforcing the signs and symptoms, self-management, medications, and prognosis and severity of HF; (ii) Providing concise and timely education; (iii) Building trust and relationships; (iv) Accessibility of education to support patient needs; (v) Engaging family members and informal caregivers; (vi) Tailoring education to patients diverse needs; and (vii) Navigating the health system and dealing with continuity of care. There were several unmet educational needs for people living with heart failure and their caregivers. Providing patient-centred education is critical to developing understanding and reinforcing the signs and symptoms, prognosis, and severity of heart failure, to underpin self-management and optimise medication adherence. Clinicians, patients, and their caregivers provided several suggestions for improvement, such as the importance of providing concise and timely education and building trust and relationships between clinicians and patients. Priorities for education improvement were also provided, including regional and rural considerations; engaging informal family caregivers; tailoring to culturally and linguistically diverse and indigenous peoples, navigating the health system and ensuring continuity of care.
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- 2025
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17. Impact of human body shape on free convection heat transfer.
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Shri H Viswanathan, Ankit Joshi, Lyle Bartels, Kambiz Sadeghi, Jennifer K Vanos, and Konrad Rykaczewski
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Medicine ,Science - Abstract
Understanding the thermal comfort and safety of diverse populations within indoor settings requires a quantitative understanding of the primary heat exchange pathways between occupants and their surroundings: radiation and free convection. Thus far, however, free convective heat transfer coefficients have only been determined for the average Western adult. To this end, we investigated how variation in body shape impacts free convection heat transfer using an experimentally validated numerical model. The multiphysics model was compared against experiments conducted using the thermal manikin ANDI ("Advanced Newton Dynamic Instrument") in a climate-controlled enclosure across five air-to-skin temperature differences ranging from 4.9 to 13.9°C. The difference between measured and simulated heat fluxes for the whole body, and per anatomical region, was typically
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- 2025
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18. Death and disappearance: Measuring racial disparities in mortality and life expectancy among people in state prisons, United States 2000-2014.
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Bryan L Sykes, Ernest K Chavez, and Justin D Strong
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Medicine ,Science - Abstract
BackgroundResearch on carceral institutions and mortality finds that people in prisons and jails have a high risk of death immediately following release from custody and that while incarcerated, racial disparities in prisoner mortality counter observed death patterns among similarly situated non-incarcerated, demographic groups. Yet, many of these studies rely on data prior to the millennium, during the COVID-19 pandemic, or are relegated to a small number or select group of states. In this paper, we explore changes in mortality and life-expectancy among different demographic groups, before and after the Great Recession, across forty-four states that reported deaths in custody to the federal government between 2000 and 2014.MethodsDrawing on a novel dataset created and curated, we calculate standard, age- specific quantities (death rates and life-expectancy) using period lifetable methods, disaggregated by race and sex, across three different periods (2000-2004, 2005-2009, and 2010-2014) for each state. Ordinary least squares regression models with state and year fixed-effects are included to examine state-level factors that may explain differences in prisoner mortality rates between 2000 and 2014. We also benchmark death counts reported to federal agencies with official state reports to cross-validate general mortality patterns.ResultsAmong imprisoned men, age-specific trends in mortality have shifted across the three periods. Following the Great Recession and the push for criminal justice reforms, prisoner mortality dropped significantly and is concentrated at older ages among men during 2010-2014; the shifting pattern of mortality means that men age 30 in 2010-2014 had similar death rates as men in their early 20s during 2000-2004, representing a 7.5 year shift in age-specific mortality rates. Gains in the mortality decline were disproportionately experienced by Non-Hispanic White and Non-Hispanic Black men, with the latter experiencing the greatest gains in life-expectancy of any demographic group. State-level violent crime rates are strongly and positively associated with prison mortality rates across states, net of socioeconomic and political factors. The large and significant disappearance of deaths in prisons from official data reported to federal agencies calls into question the narrowing gap in racial disparities among people in carceral facilities.ConclusionsLegal decisions and social policies aimed at reducing mortality may be most effective in the short-run; however, the effects of these policy changes may fadeout over time. Research should clearly discern whether changes in mortality rates across states are due to diminished gains in social policies or increases in the disappearance (or underreporting) of deaths in custody. Understanding how and why gains in survivorship may stall is important for aligning health initiatives with social policy to facilitate maximal and consistent mortality declines for all demographic groups.
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- 2025
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19. Respiratory pathology in the mdx/utrn -/- mouse: A murine model for Duchenne Muscular Dystrophy (DMD).
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Marán Y Hernández Rodríguez, Debolina D Biswas, Aoife D Slyne, Jane Lee, Evelyn Scarrow, Sarra M Abdelbarr, Heather Daniels, Ken D O'Halloran, Leonardo F Ferreira, Charles A Gersbach, and Mai K ElMallah
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Medicine ,Science - Abstract
Duchenne muscular dystrophy (DMD) is an X-linked devastating disease caused by a lack of dystrophin which results in progressive muscle weakness. As muscle weakness progresses, respiratory insufficiency and hypoventilation result in significant morbidity and mortality. The most studied DMD mouse model- the mdx mouse- has a milder respiratory phenotype compared to humans, likely due to compensatory overexpression of utrophin. mdx/utrn-/- mice lack both dystrophin and utrophin proteins. These mice have an early onset of muscular dystrophy, severe muscle weakness, and premature death, but the respiratory pathophysiology is unclear. The objective of this study is to characterize the respiratory pathophysiology and histopathology using whole body plethysmography to measure breathing and metabolism, diaphragm muscle functional analysis, histology, and immunohistochemistry. The mdx/utrn-/- mice have significant respiratory and metabolic deficits with respiratory insufficiency and hypoventilation when exposed to hypoxia and hypercarbia as early as 6 weeks of age. They also have significant diaphragmatic weakness and disrupted diaphragmatic structural pathology. The mdx/utrn-/- mice display respiratory dysfunction that mimics the DMD phenotype and therefore can provide a useful model to study the impact of novel therapies on respiratory function for DMD.
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- 2025
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20. Navigating uncertainty in environmental DNA detection of a nuisance marine macroalga.
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Patrick K Nichols, Kaʻuaʻoa M S Fraiola, Alison R Sherwood, Brian B Hauk, Keolohilani H Lopes, Colt A Davis, James T Fumo, Chelsie W W Counsell, Taylor M Williams, Heather L Spalding, and Peter B Marko
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Medicine ,Science - Abstract
Early detection of nuisance species is crucial for managing threatened ecosystems and preventing widespread establishment. Environmental DNA (eDNA) data can increase the sensitivity of biomonitoring programs, often at minimal cost and effort. However, eDNA analyses are prone to errors that can complicate their use in management frameworks. To address this, eDNA studies must consider imperfect detections and estimate error rates. Detecting nuisance species at low abundances with minimal uncertainty is vital for successful containment and eradication. We developed a novel eDNA assay to detect a nuisance marine macroalga across its colonization front using surface seawater samples from Papahānaumokuākea Marine National Monument (PMNM), one of the world's largest marine reserves. Chondria tumulosa is a cryptogenic red alga with invasive traits, forming dense mats that overgrow coral reefs and smother native flora and fauna in PMNM. We verified the eDNA assay using site-occupancy detection modeling from quantitative polymerase chain reaction (qPCR) data, calibrated with visual estimates of benthic cover of C. tumulosa that ranged from < 1% to 95%. Results were subsequently validated with high-throughput sequencing of amplified eDNA and negative control samples. Overall, the probability of detecting C. tumulosa at occupied sites was at least 92% when multiple qPCR replicates were positive. False-positive rates were 3% or less and false-negative errors were 11% or less. The assay proved effective for routine monitoring at shallow sites (less than 10 m), even when C. tumulosa abundance was below 1%. Successful implementation of eDNA tools in conservation decision-making requires balancing uncertainties in both visual and molecular detection methods. Our results and modeling demonstrated the assay's high sensitivity to C. tumulosa, and we outline steps to infer ecological presence-absence from molecular data. This reliable, cost-effective tool enhances the detection of low-abundance species, and supports timely management interventions.
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- 2025
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21. Spatio-temporal variation in pollen collected by honey bees (Apis mellifera) in rural-urban mosaic landscapes in Northern Europe.
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Yoko L Dupont, Thorsten J S Balsby, Mette B Greve, Luna K Marcussen, and Per Kryger
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Medicine ,Science - Abstract
Pollen is a source of protein, lipids, vitamins and minerals for bees and other flower-visiting insects. The composition of macro- and micronutrients of pollen vary among different plant species. Honey bees are long-distance foragers, collecting nectar and pollen from plants within several kilometers of their hive. Availability of pollen within the foraging range of honey bees is highly dynamic, changing seasonally, and across different landscapes. In the present study, the aim was to investigate the composition of pollen collected by honey bees in rural-urban landscape mosaics typical of Northern Europe. Samples of corbiculate pollen were collected 3-9 times during the growing season by citizen scientist bee keepers from a total of 25 observation apiaries across Denmark in 2014-2015. Palynological analysis was conducted identifying 500 pollen grains per sample to pollen type (mostly plant genus). Pollen diversity denoted the number of different pollen types in a sample, while relative abundance was calculated as the proportional representation of a pollen type, if found in >1% of the sample. The quantity of pollen types across study years and sites was measured as the occurrence of each pollen type (number of samples with the pollen type present) and abundance (total number of pollen grains). Pollen diversity was highly variable, with effects of season, year, and area of green urban spaces. In terms of quantity, a few key pollen types occurred repeatedly and abundantly in the samples. Only 17 pollen types were present in >15 samples. These pollen types were consistent across study years and different landscapes. Pollen diversity may impact colony health, and hence foraging decisions by honey bees, especially in late summer. However, the bulk of the pollen collected by colonies came from a limited number of pollen sources, regardless of year and landscape context in the rural-urban landscape mosaics of Denmark.
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- 2025
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22. Higher education students' perceptions of ChatGPT: A global study of early reactions.
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Dejan Ravšelj, Damijana Keržič, Nina Tomaževič, Lan Umek, Nejc Brezovar, Noorminshah A Iahad, Ali Abdulla Abdulla, Anait Akopyan, Magdalena Waleska Aldana Segura, Jehan AlHumaid, Mohamed Farouk Allam, Maria Alló, Raphael Papa Kweku Andoh, Octavian Andronic, Yarhands Dissou Arthur, Fatih Aydın, Amira Badran, Roxana Balbontín-Alvarado, Helmi Ben Saad, Andrea Bencsik, Isaac Benning, Adrian Besimi, Denilson da Silva Bezerra, Chiara Buizza, Roberto Burro, Anthony Bwalya, Cristina Cachero, Patricia Castillo-Briceno, Harold Castro, Ching Sing Chai, Constadina Charalambous, Thomas K F Chiu, Otilia Clipa, Ruggero Colombari, Luis José H Corral Escobedo, Elísio Costa, Radu George Crețulescu, Marta Crispino, Nicola Cucari, Fergus Dalton, Meva Demir Kaya, Ivo Dumić-Čule, Diena Dwidienawati, Ryan Ebardo, Daniel Lawer Egbenya, MoezAlIslam Ezzat Faris, Miroslav Fečko, Paulo Ferrinho, Adrian Florea, Chun Yuen Fong, Zoë Francis, Alberto Ghilardi, Belinka González-Fernández, Daniela Hau, Md Shamim Hossain, Theo Hug, Fany Inasius, Maryam Jaffar Ismail, Hatidža Jahić, Morrison Omokiniovo Jessa, Marika Kapanadze, Sujita Kumar Kar, Elham Talib Kateeb, Feridun Kaya, Hanaa Ouda Khadri, Masao Kikuchi, Vitaliy Mykolayovych Kobets, Katerina Metodieva Kostova, Evita Krasmane, Jesus Lau, Wai Him Crystal Law, Florin Lazăr, Lejla Lazović-Pita, Vivian Wing Yan Lee, Jingtai Li, Diego Vinicio López-Aguilar, Adrian Luca, Ruth Garcia Luciano, Juan D Machin-Mastromatteo, Marwa Madi, Alexandre Lourenço Manguele, Rubén Francisco Manrique, Thumah Mapulanga, Frederic Marimon, Galia Ilieva Marinova, Marta Mas-Machuca, Oliva Mejía-Rodríguez, Maria Meletiou-Mavrotheris, Silvia Mariela Méndez-Prado, José Manuel Meza-Cano, Evija Mirķe, Alpana Mishra, Ondrej Mital, Cristina Mollica, Daniel Ionel Morariu, Natalia Mospan, Angel Mukuka, Silvana Guadalupe Navarro Jiménez, Irena Nikaj, Maria Mihaylova Nisheva, Efi Nisiforou, Joseph Njiku, Singhanat Nomnian, Lulzime Nuredini-Mehmedi, Ernest Nyamekye, Alka Obadić, Abdelmohsen Hamed Okela, Dorit Olenik-Shemesh, Izabela Ostoj, Kevin Javier Peralta-Rizzo, Almir Peštek, Amila Pilav-Velić, Dilma Rosanda Miranda Pires, Eyal Rabin, Daniela Raccanello, Agustine Ramie, Md Mamun Ur Rashid, Robert A P Reuter, Valentina Reyes, Ana Sofia Rodrigues, Paul Rodway, Silvia Ručinská, Shorena Sadzaglishvili, Ashraf Atta M S Salem, Gordana Savić, Astrid Schepman, Samia Mokhtar Shahpo, Abdelmajid Snouber, Emma Soler, Bengi Sonyel, Eliza Stefanova, Anna Stone, Artur Strzelecki, Tetsuji Tanaka, Carolina Tapia Cortes, Andrea Teira-Fachado, Henri Tilga, Jelena Titko, Maryna Tolmach, Dedi Turmudi, Laura Varela-Candamio, Ioanna Vekiri, Giada Vicentini, Erisher Woyo, Özlem Yorulmaz, Said A S Yunus, Ana-Maria Zamfir, Munyaradzi Zhou, and Aleksander Aristovnik
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Medicine ,Science - Abstract
The paper presents the most comprehensive and large-scale global study to date on how higher education students perceived the use of ChatGPT in early 2024. With a sample of 23,218 students from 109 countries and territories, the study reveals that students primarily used ChatGPT for brainstorming, summarizing texts, and finding research articles, with a few using it for professional and creative writing. They found it useful for simplifying complex information and summarizing content, but less reliable for providing information and supporting classroom learning, though some considered its information clearer than that from peers and teachers. Moreover, students agreed on the need for AI regulations at all levels due to concerns about ChatGPT promoting cheating, plagiarism, and social isolation. However, they believed ChatGPT could potentially enhance their access to knowledge and improve their learning experience, study efficiency, and chances of achieving good grades. While ChatGPT was perceived as effective in potentially improving AI literacy, digital communication, and content creation skills, it was less useful for interpersonal communication, decision-making, numeracy, native language proficiency, and the development of critical thinking skills. Students also felt that ChatGPT would boost demand for AI-related skills and facilitate remote work without significantly impacting unemployment. Emotionally, students mostly felt positive using ChatGPT, with curiosity and calmness being the most common emotions. Further examinations reveal variations in students' perceptions across different socio-demographic and geographic factors, with key factors influencing students' use of ChatGPT also being identified. Higher education institutions' managers and teachers may benefit from these findings while formulating the curricula and instructions/regulations for ChatGPT use, as well as when designing the teaching methods and assessment tools. Moreover, policymakers may also consider the findings when formulating strategies for secondary and higher education system development, especially in light of changing labor market needs and related digital skills development.
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- 2025
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23. Evaluation of comorbidity burden on disease progression and mortality in patients with interstitial pneumonia with autoimmune features: A retrospective cohort study.
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Elena K Joerns, Michelle A Ghebranious, Traci N Adams, and Una E Makris
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Medicine ,Science - Abstract
BackgroundInterstitial pneumonia with autoimmune features (IPAF) is a subset of interstitial lung disease that manifests with features of autoimmunity while not meeting classification criteria for a defined rheumatic disease. Comorbidity burden is an important prognostic indicator in various rheumatic and interstitial lung diseases, but few studies have commented on comorbidities in this population. This study was conducted to evaluate the association of individual comorbidities, the Charlson Comorbidity Index (CCI), and the Rheumatic Disease Comorbidity Index (RDCI) with lung disease progression and transplant/mortality outcomes in patients with IPAF.MethodsIn a retrospective study, we evaluated the prevalence and severity of comorbidities in an institutional cohort of patients with IPAF. Using Cox regression, we correlated the association of individual comorbidities and comorbidity indices with time to lung disease progression (relative forced vital capacity decline of 10% or more) and with time to lung transplant/death. We compared the performance of CCI and RDCI in predicting outcomes.ResultsHistory of cerebrovascular accident (CVA) or cardiovascular disease (CVD), moderate-severe chronic kidney disease, and fracture was associated with a faster onset of lung disease progression, while a history of gastroesophageal reflux was protective. History of CVA/CVD, diabetes mellitus, and lymphoma were associated with a faster onset of lung transplant/death. Both CCI and RDCI were associated with shorter time to lung disease progression and lung transplant/death in unadjusted analyses. However, only CCI was associated with shorter time to lung transplant/death in analyses adjusted for age, sex, pulmonary function, and radiographic pattern of lung lesion.ConclusionsCCI and RDCI may be useful tools in assessing prognosis in patients with IPAF in terms of both lung disease progression and mortality. Prospective studies are needed to further evaluate the performance of CCI and RDCI and the impact of optimizing comorbid conditions that may mitigate poor outcomes among patients with IPAF.
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- 2025
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24. Structure in transition: The role of structure in facilitating workplace efficacy and belonging for military veterans and civilians.
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W Connor Gibbs, Lauren Ortosky, Alair MacLean, Aaron C Kay, and David K Sherman
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Medicine ,Science - Abstract
Employment transitions necessitate a degree of uncertainty and lack of control, which may present a challenge to succeeding and belonging at a new organization. The present research tests ideas derived from compensatory control theory which posits that people may seek external structure to help exert control over their lives when they experience a lack of control in an important life domain - and that this can aid in their goal pursuit. Across three studies, we explore whether the perception of a higher degree of organizational structure can help employees compensate for uncertainty and lack of control and facilitate transitioning employees' occupation self-efficacy and sense of belonging in a new work environment. This research focuses on military veterans, who face significant challenges during their separation from military service and transition to civilian employment, as an exemplar of the people experiencing employment transitions more generally, and compares them (in two studies) with civilian participants. Across three studies, two using simple correlational methods, one using an experimental methodology with veterans and civilians, we find consistent evidence that when transitioning employees perceive greater structure at their organization, this facilitates increased feelings of occupational self-efficacy which, in turn, promotes greater feelings of belonging at work. When people perceive greater structure in their environment, people feel more efficacious and a greater sense that they belong at work. The results are discussed in the context of compensatory control theory, addressing the challenges of transitioning employees, and in particular, transitioning military veterans.
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- 2025
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25. Impact of pharmacist-led intervention for reducing drug-related problems and improving quality of life among chronic kidney disease patients: A randomized controlled trial.
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Roheena Zafar, Inayat Ur Rehman, Yasar Shah, Long Chiau Ming, Khang Wen Goh, Amal K Suleiman, and Tahir Mehmood Khan
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Medicine ,Science - Abstract
IntroductionChronic kidney disease (CKD) patients suffer from different comorbid conditions and are prone toward drug-related problems (DRPs) which affect their clinical parameters as well as quality of life (QoL). This study was aimed to evaluate the impact of clinical pharmacist-led interventions on the mean number of DRPs and the mean QoL score difference per patient DRPs in CKD patients.MethodAn open-labeled, randomized control trial performed from April 2023 to July 2023 in the nephrology unit of a tertiary care setting in Peshawar Pakistan. Those patients who met the inclusion criteria were randomized into two groups 1:1, i.e., control and intervention group. Clinical pharmacists identified the DRPs at baseline using Pharmaceutical Care Network Europe (PCNE) 9.1 guidelines. The QoL of patients were assessed at baseline and endpoint by using the Functional Assessment of Non-Life-Threatening Conditions (FANLTC) questionnaire.ResultsA total of 100 patients were recruited having 50 in each group. The pharmacist identified a total of n = 230 DRPs in the intervention group, majority of the DRPs were attributed to inappropriate drug selection according to guidelines/formulary"; "inappropriate combinations of drugs or with herbal medications or dietary supplements"; and situations where "too many different drugs or active ingredients were prescribed". There was 46.52% reduction in the DRPs while comparing baseline and endpoint interventions suggested by pharmacist in the intervention group. The clinical pharmacist provided interventions in order to resolve the DRPs, and 37.40% interventions were accepted and fully implemented; 31.30% of the interventions were accepted and partially implemented. The clinical pharmacist identification and proposed intervention for DRPs contributed to a statistically significant improvement in QoL, from mean ± SD scored 58.64 ± 9.10 at the baseline to 74.48 ± 10.11 at the endpoint, with a p-value of ConclusionA significant improvement in the QoL and laboratory parameters for patients with CKD following clinical pharmacist-led interventions having proposed interventions were implemented successfully from baseline to endpoint; however, a considerable number of proposed interventions were not accepted and implemented.
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- 2025
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26. Investigation of customized total knee implant with articular cartilage under loading conditions using finite element analysis.
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Shady A Alshewaier, Mohamed Yacin Sikkandar, Ali Ahmed Ali Almakrami, S Sabarunisha Begum, Ahmad Alassaf, Ibrahim AlMohimeed, S Meenatchi Sundaram, Dheeraj Poojary, Natteri M Sudharsan, and Eddie Y K Ng
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Medicine ,Science - Abstract
Knee osteoarthritis (KOA) is a degenerative joint disease predominantly affecting the elderly and is often managed through knee replacement surgeries. West Asians, who frequently engage in activities involving bending and kneeling during their prayers, tend to exhibit distinct bone anatomy compared to the Caucasian population. This research posits that patient-specific, customized knee implants with articular cartilages may lead to reduced post-surgical discomfort and a better implant fit compared to conventional standard implants. This study presents a novel concept and approach for the development of a customized total knee implant with articular cartilages, specifically tailored to simulate loading conditions using finite element analysis (FEA) for the Saudi Arabian population. The research analyses patient-specific customized knee implants with articular cartilages under both pre- and post-implant conditions using a finite element model (FEM). Computed tomography (CT) images of patients were utilized to create a solid model, which was then analysed under various constraints and conditions. The meshing process employed tetrahedral elements, converging with 76,197 nodes and 43,009 elements. The analysis was conducted under different body weights, specifically 75-80 kg and 100-105 kg. Two sets of force and moment were applied: the first with a force of 1000 N and a moment of 1.5 N-m, and the second with a force of 750 N and a moment of 0.8 N-m. The results indicated a 5% reduction in stress with implants designed for a 100 kg body weight, along with a significant reduction in ligament strain when compared to conventional knee joint stresses. This study offers a promising pathway toward reducing post-surgical discomfort. The proposed innovative solution has the potential to revolutionize total knee implant technology, offering enhanced functionality and improved patient outcomes for the Saudi Arabian population.
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- 2025
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27. Factors associated with knowledge and practice regarding oxygen administration: A cross-sectional study among registered nurses working in wards and ICUs at Muhimbili National Hospital in Dar es Salaam, Tanzania.
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Magdalena S Kimario, Joel Seme Ambikile, and Masunga K Iseselo
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Medicine ,Science - Abstract
BackgroundOxygen is a vital therapy approved by WHO, crucial for critically ill patients as a supplemental treatment. Nurses' pivotal role in oxygen administration is poorly understood. This study aimed to assess factors associated with oxygen administration to critically ill patients among nurses at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania.MethodsA descriptive cross-sectional study was conducted among 208 nurses using a simple random technique to recruit respondents. Data were collected in May 2022 via a self-administered questionnaire, designed and tested by the authors. Mean knowledge and practice scores were used to categorize knowledge and practice as high or low respectively. The Chi-square test and multiple logistic regression analyses were performed to evaluate factors associated with knowledge and practice regarding oxygen administration. Statistical significance was determined at a p-value less than 0.05.ResultsOf the 208 respondents, 96(46.2%) and 78(37.5%) had low knowledge and low practices regarding oxygen administration, respectively. Receiving in-service training on oxygen administration (AOR: 3.515; pConclusionA substantial proportion of nurses had inadequate knowledge and practices regarding oxygen administration. While none of the assessed factors were found to have a statistical association with practice on oxygen administration, it is important to note their clinical significance. Healthcare institutions can benefit from implementing regular in-service training programs to address these knowledge and skills gaps and ensure that nurses are well-prepared for proper oxygen administration. Additionally, ongoing monitoring and support are essential to help translate improved knowledge into effective clinical practices.
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- 2025
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28. First-line glaucoma monotherapy medication patterns in Finland during 1995-2019 based on a population-based study.
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Petri K M Purola, Seppo V P Koskinen, and Hannu M T Uusitalo
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Medicine ,Science - Abstract
BackgroundThe long-term patterns in first-line glaucoma medication are not well established. Exploring these in longitudinal and population-based settings would provide information for the healthcare systems to plan glaucoma care accordingly.ObjectiveTo evaluate patterns in first-line glaucoma monotherapy in Finland during 1995-2019 based on nationwide survey and register data.MethodsA population-based cohort study with 25 years of total follow-up. The cohort (n = 9288) is a random sample drawn from the nationwide health examination survey FinHealth 2017 which represents the Finnish population aged 30 years or older in 2017. Glaucoma patients were selected from the survey participants based on linked register data that included prescriptions and special reimbursements for glaucoma medication. The patterns, length of use, age at initiation, and persistence of first-line glaucoma drug monotherapies were observed during 1995-2019.ResultsA total of 141 glaucoma patients with glaucoma drug monotherapy as a first-line glaucoma therapy were identified from the sample. The proportion of patients continuing with their first-line monotherapy was 64% after 1 year, 37% after 3 years, and 21% after 5 years of follow-up. During the 25 years there was a shift from beta-blockers to prostaglandin analogues as the prominent first-line glaucoma drug class. The length of use was longer for prostaglandin analogues compared with beta-blockers among patients continuing with their first-line monotherapy after 5 years of follow-up. The non-persistence rate was 38% of all patients during their first-line monotherapy. Timolol fixed-combinations were the most common second-line glaucoma therapy with a share of 39% after 5 years of follow-up.ConclusionsDuring the 25-year follow-up a shift from beta-blockers to prostaglandin analogues had occurred and long initial therapies of over 5 years had become more common. However, the decline in the continuation of the initial therapy still occurred early with 1 out of 3 patients continuing after 3 years. This decline together with the consistent problem of non-persistence remain clinical challenges in topical drug therapy of glaucoma.
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- 2025
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29. Obesity phenotypes and dyslipidemia in adults from four African countries: An H3Africa AWI-Gen study.
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Engelbert A Nonterah, Godfred Agongo, Nigel J Crowther, Shukri F Mohamed, Lisa K Micklesfield, Palwendé Romuald Boua, Alisha N Wade, Solomon S R Choma, Hermann Sorgho, Isaac Kissiangani, Gershim Asiki, Patrick Ansah, Abraham R Oduro, Shane A Norris, Stephen M Tollman, Frederick J Raal, Marianne Alberts, Michele Ramsay, and as members of AWI-Gen and the H3Africa Consortium
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Medicine ,Science - Abstract
IntroductionThe contribution of obesity phenotypes to dyslipidaemia in middle-aged adults from four sub-Saharan African (SSA) countries at different stages of the epidemiological transition has not been reported. We characterized lipid levels and investigated their relation with the growing burden of obesity in SSA countries.MethodsA cross-sectional study was conducted in Burkina Faso, Ghana, Kenya and South Africa. Participants were middle aged adults, 40-60 years old residing in the study sites for the past 10 years. Age-standardized prevalence and adjusted mean cholesterol, LDL-C, HDL-C, triglycerides and non-HDL-C were estimated using Poisson regression analyses and association of body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WTHR) with abnormal lipid fractions modeled using a random effects meta-analysis. Obesity phenotypes are defined as BMI ≥ 30 kg/m2, increased WC and increased waist-to-hip ratio.ResultsA sample of 10,700 participants, with 54.7% being women was studied. Southern and Eastern African sites recorded higher age-standardized prevalence of five lipid fractions then West African sites. Men had higher LDL-C (19% vs 8%) and lower HDL-C (35% vs 24%) while women had higher total cholesterol (15% vs 19%), triglycerides (9% vs 10%) and non-HDL-cholesterol (20% vs 26%). All lipid fractions were significantly associated with three obesity phenotypes. Approximately 72% of participants in the sample needed screening for dyslipidaemia with more men than women requiring screening.ConclusionObesity in all forms may drive a dyslipidaemia epidemic in SSA with men and transitioned societies at a higher risk. Targeted interventions to control the epidemic should focus on health promoting and improved access to screening services.
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- 2025
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30. Correction: Price tag of glaucoma care is minor compared with the total direct and indirect costs of glaucoma: Results from nationwide survey and register data.
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Petri K M Purola, Joonas Taipale, Saku Väätäinen, Mika Harju, Seppo V P Koskinen, and Hannu M T Uusitalo
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0295523.].
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31. Neonatal outcomes and resuscitation practices following the addition of heart rate-guidance to basic resuscitation.
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Jackie K Patterson, Daniel Ishoso, Adrien Lokangaka, Pooja Iyer, Casey Lowman, Joar Eilevstjønn, Ingunn Haug, Beena D Kamath-Rayne, Eric Mafuta, Helge Myklebust, Tracy Nolen, Antoinette Tshefu, Carl Bose, and Sara Berkelhamer
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Medicine ,Science - Abstract
AimTo evaluate the impact of heart rate-guided basic resuscitation compared to Helping Babies Breathe on neonatal outcomes and resuscitation practices in the Democratic Republic of the Congo.MethodsWe conducted a pre-post clinical trial comparing heart rate-guided basic resuscitation to Helping Babies Breathe in three facilities, enrolling in-born neonates ≥28 weeks gestation. We collected observational data during a convenience sample of resuscitations and extracted clinical data from the medical record for all participants. We evaluated our primary outcome of effective breathing at three minutes after birth among newborns not breathing well at 30 seconds after birth employing generalized linear models using maximum likelihood estimation.ResultsAmong 1,284 newborns with observational data, there was no difference in the proportion effectively breathing at three minutes (adjusted relative risk 1.08 [95% CI 0.81, 1.45]). Among 145 receiving bag mask ventilation, time to bag mask ventilation decreased 64.3 seconds during heart rate-guided resuscitation (pConclusionDuring heart rate-guided basic resuscitation, time to bag mask ventilation was reduced by greater than one minute. The increase in death before discharge and unchanged perinatal mortality may be due to resuscitation of newborns with a higher risk of mortality who were previously presumed stillborn. A cluster-randomized trial of heart rate-guided basic resuscitation is needed to evaluate its impact on neonatal mortality in low-resource settings.
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- 2025
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32. Associations of heavy metals and urinary sodium excretion with obesity in adults: A cross-sectional study from Korean Health Examination and Nutritional Survey.
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Juyeon Lee and Sue K Park
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Medicine ,Science - Abstract
BackgroundsSodium and heavy metals are among the key elements to which humans are exposed due to environmental pollution and food consumption. Investigating the association between heavy metals, urinary sodium excretion, and obesity is of significant importance, given potential implications for public health. Therefore, this study aims to explore the relationship between heavy metals, urinary sodium excretion, and overweight and obesity in the Korean population.MethodsData from 6,609 participants in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2012 were analyzed. Associations between heavy metals (cadmium, mercury), urinary arsenic, sodium excretion levels, and overweight/obesity were assessed using polytomous logistic regression models, adjusting for confounders.ResultsHigher mercury (OR = 1.57, 95% CI = 1.31-1.88) and urinary sodium (OR = 2.21, 95% CI = 1.84-2.66) levels are associated with an increased risk of overweight and obesity. Notably, participants with elevated levels of both mercury and urinary sodium had the highest odds of being overweight and obesity (OR = 3.61, 95% CI = 2.61-5.00). In contrast, other heavy metals, such as serum cadmium and urinary arsenic, were not statistically significantly associated with the risk of overweight and obesity.ConclusionsThis finding highlights the intricate multiplicative effect between mercury and sodium on obesity, necessitating further research to validate and understand the connections. Heavy metals, particularly mercury, exert an influence on obesity, and the possibility of an enhanced impact on obesity, especially when acting in conjunction with salt, is indicated.
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- 2025
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33. Urine tenofovir adherence testing: Perspectives of recently diagnosed South African adolescents and young adults with HIV accessing care via mobile HIV clinics.
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Michalina A Montaño, Siyaxolisa Sindelo, Amanda Fata, Elzette Rousseau, Linda-Gail Bekker, Ingrid T Katz, and Paul K Drain
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Medicine ,Science - Abstract
BackgroundAdolescents and young adults (AYA) living with HIV face several challenges to engaging in HIV care, which can impact adherence to antiretroviral therapy (ART). Point-of-care (POC) diagnostics that detect tenofovir in urine may be a useful tool to support ART adherence, but perspectives from AYA in South Africa have not been explored.MethodsWe conducted in-depth interviews (IDIs) among young people (age 18-24) newly diagnosed with HIV in Cape Town, and a focus group discussion (FGD) with HIV care providers to understand their perspectives regarding the use of POC urine tenofovir testing to support ART adherence. Transcripts were analyzed using Dedoose, with an iterative thematic approach.ResultsTranscripts from 8 IDI participants and 8 FGD participants were included in the analysis. Major themes identified during analysis related to beliefs about POC urine adherence testing and recommendations for future clinical implementation. Most IDI participants indicated they would want to use the tests if clinically available, and both IDI and FGD participants believed the tests would be helpful to clinicians. Participants believed the tests could motivate people to take their ART regularly, either by reassuring them ART was present in their bodies, or to avoid the negative consequences of being found to be non-adherent. Drawbacks of POC adherence testing identified by respondents included not wanting to be caught skipping ART doses, concerns about privacy, how the test results would be explained, and adding to the amount of testing required for HIV clinical care.ConclusionsAYA living with HIV in South Africa had favorable views toward POC tenofovir adherence testing and felt utilizing these tests in HIV clinical care would motivate people to remain adherent to ART.
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- 2025
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34. A prospective model of the potential clinical and economic impact of cervical cancer screening supported by a mobile phone app.
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Fredrick Chite Asirwa, Brian W Bresnahan, Faith Yego, Dana Duncan, James K Karichu, and Louis P Garrison
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Medicine ,Science - Abstract
IntroductionCervical cancer is a preventable and highly curable disease when detected early and adequately treated, yet it remains the leading cause of cancer-related death in women in Kenya due to low screening coverage and treatment. Implementing World Health Organization screening guidelines for human papillomavirus (HPV) is challenging due to the complex logistics of result return and follow-up requiring multiple clinic visits. Increasing the use of mobile technology can support follow-up care in cervical cancer screening programs.MethodsWe developed a prospective clinico-economic model to assess the potential impact of a mobile phone-based application ("app") communicating laboratory results and recommendations to improve follow-up care for cervical cancer screening in Kenya. The model is structured to simulate a three-visit pathway for HPV-based screening used in a clinical trial of the app and based on epidemiological data, clinical guideline-based workflow, and patient-based behavioral pathways. Published literature, expert elicitation, and time-and-motion observations were used to estimate clinical data, care pathways, and visit-related costs. This analysis was conducted from a base-case healthcare system perspective with a scenario from a "limited" societal perspective.ResultsIn a simulated cohort of women using the app-based intervention compared to conventional care, with 10,000 women in each arm, use of the app is projected to increase healthcare costs by $12.53 per enrolled woman during the trial period and to detect and treat an additional 247 women-229 with precancerous cervical lesions and 18 with cervical cancer. The incremental cost-effectiveness ratio of the app versus conventional care was $174 per case detected and treated. This would be cost-saving given the average lifetime cost per cervical cancer case of $1,000-$3,000.ConclusionUse of a mobile phone-based app is costlier than conventional screening but by improving visit compliance, it can be a cost-effective and cost-saving strategy to enhance detection and treatment in cervical cancer screening programs.
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- 2025
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35. Comparative performance of disability measures.
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Scott D Landes, Jean P Hall, Bonnielin K Swenor, and Nastassia Vaitsiakhovich
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Medicine ,Science - Abstract
Researchers and federal agencies are currently discussing the best way to measure disability in US federal surveys. One idea being discussed is expanding/supplementing the question sets commonly used to capture disability status in order to better capture a broader segment of the disabled population. We used data from the 2010-2018 National Health Interview Survey to examine the performance of questions commonly used to measure disability in the US-the ACS-6 and Washington Group Short Set questions-in capturing intellectual and developmental disabilities, mental health disabilities, and physical health disabilities. We found that neither set of disability questions was sufficient to fully capture these disability statuses. We contend that current disability questions used in US population surveys must be expanded/supplemented in order to increase the inclusiveness of disability measurement, and thereby, improve efforts to reduce disparities experienced by the disabled population.
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- 2025
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36. 3D ophthalmic ultrasonography at the slit lamp using existing ultrasound systems.
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Jack O Thomas, Josiah K To, Parsa Riazi Esfahani, Frithjof Kruggel, William C Tang, and Andrew W Browne
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Medicine ,Science - Abstract
PurposeThis study aims to explore the feasibility and performance of three-dimensional ultrasound (3DUS) imaging in ophthalmology using commercially available ultrasound probes adapted to a slit lamp.SignificanceDespite ultrasound's long-standing application in eye care for visualizing ocular components, the evolution of 3DUS technology has remained inactive, with limited development and commercial availability. This study introduces a novel method that could potentially enhance ophthalmic diagnostics and treatment planning by providing comprehensive 3D views of ocular structures using existing ultrasound probes adapted to the conventional slit lamp.MethodsA custom system was designed for mounting a linear actuator to a slit lamp and enabling the horizontal actuation of any ultrasound probe. Ophthalmic and non-ophthalmic ultrasound probes were tested for their ability to reconstruct 3DUS images of the posterior pole. The study involved designing and evaluating three US phantoms ex vivo and performing in vivo imaging on human subjects to assess the system's applicability.ResultsThe system successfully acquired 3D volume scans of phantoms and live human eyes, demonstrating the system's potential for detailed ocular imaging. The adaptability of the device allowed for compatibility with various ultrasound probes. In vivo imaging revealed the system's capability to produce high-resolution 3D reconstructions of ocular structures, including eyes with pathological conditions.ConclusionsThe introduction of a slit lamp-mounted 3DUS system represents a significant advancement in ophthalmic ultrasonography, offering a practical and accessible solution for comprehensive 3D ocular assessments. The device's modularity and compatibility with existing ultrasound probes make it a versatile tool for a wide range of ophthalmic applications. Further research and clinical trials are needed to optimize the system's performance and validate its clinical utility.
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- 2025
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37. Identity as a resource or a demand.
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Karishma K Singh, Andrew J Elliot, Elizabeth D Handley, and Jeremy P Jamieson
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Medicine ,Science - Abstract
Individuals embody various social identities that can impact how they interface with the social environment. Stigma theories suggest that members of low-status or marginalized groups possess devalued social identities, and therefore, experience more stress. While social identities can lead to increased stress, individuals' appraisals of their identities are not necessarily perceived as harmful/demanding. Rather, social identities can also be appraised as resources or sources of strength bringing opportunities and facilitating goal attainment. Using the biopsychosocial (BPS) model of challenge and threat as a conceptual foundation, this research developed a novel measure to assess individuals' appraisals of their social identities. In Study 1 (N = 575), confirmatory factor analysis (CFA) evaluated the theorized factor structure (i.e., resource and demand appraisals) and assessed the overall fit of the model. Structural equation modeling (SEM) tested for associations between the resource and demand latent factors. Individuals appraising their ethnic-racial identity as a resource exhibited improved self and intergroup outcomes, while those perceiving it as a demand reported worse self-based and intergroup outcomes, as well as more distress. Study 2 (N = 743 Black and White Americans), which was preregistered, examined group differences in appraisals of ethnic-racial identity. SEM revealed that Black participants were more likely than White participants to appraise their ethnic-racial identity as demanding, leading to worse social and intergroup outcomes. Even when Black participants perceived their ethnic-racial identity as a resource, they still reported higher levels of discrimination, intergroup anxiety, and behavioral avoidance compared to their White counterparts. Implications for theory development and application to the stress literature are discussed.
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- 2025
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38. Comparison of inductively coupled plasma mass spectrometry and molybdenum blue colorimetry for total phosphorus determination in freshwater invertebrates.
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Molly S Costanza-Robinson, Baker J Angstman, Qiting Cai, Charles Forbes, Julia S Keon, Shuyi Lin, Emma D Neill, Elizabeth G Peebles, Ella Roelofs, and Eric K Moody
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Medicine ,Science - Abstract
Molybdenum blue colorimetry (MBC) is the dominant, well-established method used for determining total P in environmental media, including in organismal tissues. However, other elemental methods for P determination are available, including inductively coupled plasma mass spectrometry (ICP-MS). Given the extensive literature using MBC to determine P in organismal samples, it is important to assess P analyses by ICP-MS and MBC to ensure that the two methods produce comparable data. In this work, we compared ICP-MS and MBC for total P determination in freshwater invertebrates, including the potential for analytical interferences, by applying both methods to three standard reference materials (SRMs) and 106 freshwater invertebrate samples. Average total P recoveries for SRMs were slightly higher for ICP-MS (99.8 ± 5.2%) than MBC (96.5 ± 5.4%), but both methods indicated good accuracy. Total P in invertebrates determined using the two methods was strongly linearly correlated (r = 0.96) with a slope of 1.01. On the whole, total P measured using ICP-MS exceeded that measured by MBC, but average pair-wise differences in %P were biologically negligible (0.044 ± 0.054). %P for SRMs and invertebrate samples run on ICP-MS in kinetic energy discrimination and standard modes compared favorably (e.g., SRM P recovery of 102% by both methods), indicating negligible influence of polyatomic ions on ICP-MS analysis. Similarly, analysis of P spike recoveries by ICP-MS (100.2 ± 3.4%) and MBC (107.0 ± 2.8%) were both considered acceptable. We conclude that ICP-MS represents a reliable and comparable alternative to MBC for determining total P in freshwater invertebrates while also offering the opportunity to measure additional biologically relevant elements in a single analysis.
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- 2025
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39. The liminal space between hope and grief: The phenomenon of uncertainty as experienced by people living with relapsing-remitting multiple sclerosis.
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Eva C van Reenen, Inge A M van Nistelrooij, Leo H Visser, Janet W K de Beukelaar, Stephan T F M Frequin, and Alistair R Niemeijer
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Medicine ,Science - Abstract
BackgroundPeople with the chronic disease Multiple Sclerosis are subjected to different degrees of profound uncertainty. Uncertainty has been linked to adverse psychological effects such as feelings of heightened vulnerability, avoidance of decision-making, fear, worry, anxiety disorders, and even depression. Research into Multiple Sclerosis has a predominant focus on the scientific, practical, and psychosocial issues of uncertainty. In comparison, existential uncertainty has been under-researched, even though it might pose a greater burden to those experiencing it.ObjectiveTo understand the lived experience of uncertainty for people living with relapsing-remitting Multiple Sclerosis.MethodsThis study followed a phenomenological research design, employing elements of both the Reflective Lifeworld Approach and Phenomenology of Practice. Seventeen people with a recent (ResultsThe lived experience of uncertainty can be described as a stumbling motion across the liminal space between hope and grief while dealing with oscillating feelings of unrest concerning the body, self, and others. The following four constituents further illuminate the meaning of the phenomenon: Having to constantly (re)define unfamiliar and intangible bodily changes on one's own; Unsteady navigating amidst a destabilization of the imagined life; Relating to others as a source of, mirror or buffer for uncertainty; Going through overwhelming fears and worries while clinging to one's own logic.ConclusionAdding to existing qualitative and phenomenological research into MS and theories on uncertainty, this study portrays uncertainty as a multifaceted experience. The findings imply the need for a continuous attunement of healthcare practitioners to the expectations, fears, avoidance techniques, and other uniquely personal circumstances of people with Multiple Sclerosis.
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- 2025
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40. Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells.
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Vivian Y Tat, Aleksandra K Drelich, Pinghan Huang, Kamil Khanipov, Jason C Hsu, Steven G Widen, Chien-Te Kent Tseng, and George Golovko
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Medicine ,Science - Abstract
Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3/2B4 cells). Total RNA extracted at 12, 24, and 48 hours after β-CoVs or mock infection of Calu-3/2B4 cells were subjected to RNA sequencing and functional enrichment analysis to select genes whose expressions were significantly modulated post-infection. The results demonstrate that SARS-CoV-1 and -2 stimulate similar yet distinct innate antiviral signaling pathways in pathologically relevant human lung epithelial cells. Furthermore, we found that many genes related to the viral life cycle, interferons, and interferon-stimulated genes (ISGs) were upregulated at multiple time points. Based on their profound modulation upon infection by SARS-CoV-1, SARS-CoV-2, and Omicron BA.1, four ISGs, i.e., bone marrow stromal cell antigen 2 (BST2), Z-DNA Binding Protein 1 (ZBP1), C-X-C Motif Chemokine Ligand 11 (CXCL11), and Interferon Induced Transmembrane Protein 1 (IFITM1), were identified as potential drug targets against β-CoVs. Our findings suggest that these genes affect both pathogens directly and indirectly through the innate immune response, making them potential targets for host-directed antivirals. Altogether, our results demonstrate that SARS-CoV-1 and SARS-CoV-2 infection induce differential effects on host innate immune responses.
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- 2025
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41. Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells.
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Rachana Pandey, Purushothaman Natarajan, Umesh K Reddy, Wei Du, Cristian Sirbu, Moussa Sissoko, and Gerald R Hankins
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Medicine ,Science - Abstract
Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella sativa, has been extensively researched for its anticancer properties across various human cancers. However, its specific anti-cancer mechanisms and pathways in glioblastoma remain to be completely elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-Seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 μM and 5 μM TQ concentrations. However, at 25 μM and 50 μM, TQ significantly reduced cell viability dose-dependently. We identified 1548 DEGs at 25 μM TQ (684 up-regulated, 864 down-regulated) and 2797 DEGs at 50 μM TQ (1528 up-regulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5) while modulating Wnt signaling and up-regulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anti-cancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies.
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- 2025
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42. Mental health challenges and perceptions of stigma among youth living with HIV in Tanzania.
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Laura S Mkumba, Fortunata Nasuwa, Blandina T Mmbaga, Aisa M Shayo, Coleen K Cunningham, Karen E O'Donnell, and Dorothy E Dow
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Medicine ,Science - Abstract
Youth living with HIV (YLWH) face psychosocial challenges and HIV-related stigma, which impact adherence to antiretroviral therapy (ART). This study was designed to understand better the change in mental health symptoms and experiences with stigma among YLWH in Tanzania who completed the original pilot Sauti ya Vijana (SYV), a mental health and life skills group intervention. YLWH who completed SYV and demonstrated a change of ≥2 points in either direction on their Patient Health Questionnaire PHQ-9 (depression screener) from baseline to 18 months were purposively sampled. HIV Stigma was measured using 10-questions from the Berger HIV Stigma Scale, and findings ranged from 4-16 for internal stigma and 6-24 for external stigma. In-depth interviews (IDI) were conducted in Kiswahili and included topics such as history of mental health challenges, perceptions of stigma, and experiences with the SYV intervention. Interviews were transcribed, translated to English, and analyzed for emergent themes. Ten youth, 18-25 years of age, were interviewed; 70% were male. Mean (SD) PHQ-9 scores were 7.3 (SD = 3.5) at baseline and 5.6 (SD = 5.0) at 18 months. All participants reported experiencing intermittent episodes of mental health challenges due to difficult interpersonal relationships and fear of stigma. Youth relied on peer support and skills from the SYV intervention to cope with mental health challenges and stigma. Participants reported fear of being stigmatized by others, which led to behaviors such as skipping medication or avoiding situations for worry about unintentional disclosure. All participants endorsed experiencing external stigma on the HIV stigma scale; however, only 3 of 10 participants reported experiencing enacted stigma when directly asked to describe an experience during in-depth interviews. Participants described how SYV helped them have "more confidence", accept themselves, and incorporate positive coping skills such as relaxation (deep breathing) when they felt stressed. The findings suggest SYV helped YLWH accept themselves, develop positive coping methods, and identify and form peer social support; but stigma remains common. Descriptions of stigma were not recognized as such; experiences of enacted stigma were acknowledged by some participants. More research is needed to understand and measure mental distress and wellness as well as stigma in this population so that interventions may more accurately detect change in key outcomes.
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- 2025
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43. Effect of intra- and inter-specific plant interactions on the rhizosphere microbiome of a single target plant at different densities.
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Derek R Newberger, Heather L Deel, Daniel K Manter, and Jorge M Vivanco
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Medicine ,Science - Abstract
Root and rhizosphere studies often focus on analyzing single-plant microbiomes, with the literature containing minimum empirical information about the shared rhizosphere microbiome of multiple plants. Here, the rhizosphere of individual plants was analyzed in a microcosm study containing different combinations and densities (1-3 plants, 24 plants, and 48 plants) of cover crops: Medicago sativa, Brassica sp., and Fescue sp. Rhizobacterial beta diversity was reduced by increasing plant density for all plant mixtures. Interestingly, plant density had a significant influence over beta diversity while plant diversity was found to be a less important factor since it did not have a significant change. Regardless of plant neighbor identity or density, a low number of rhizobacteria were strongly associated with each target species. Nonetheless, a few bacterial taxa were shown to have conditional associations such as being enriched within only high plant densities, which may alleviate plant competition between these species. Also, we found evidence of bacterial sharing of nitrogen fixers from alfalfa to fescue. Although rhizosphere bacterial networks had overlapping bacterial modules, the modules showing the largest percentage of the network changed depending on plant neighbor. In summary, this study found that for the most part plants maintained their rhizosphere microbiome despite escalating plant-plant competition.
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- 2025
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44. Childhood trauma and subclinical PTSD symptoms predict adverse effects and worse outcomes across two mindfulness-based programs for active depression.
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Nicholas K Canby, Elizabeth A Cosby, Roman Palitsky, Deanna M Kaplan, Josie Lee, Golnoosh Mahdavi, Adrian A Lopez, Roberta E Goldman, Kristina Eichel, Jared R Lindahl, and Willoughby B Britton
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Medicine ,Science - Abstract
Within mindfulness-based programs (MBPs), mixed results have been found for the role of childhood trauma as a moderator of depression outcomes. Furthermore, childhood trauma and PTSD symptoms have been identified as possible risk factors for the occurrence of meditation-related adverse effects (MRAE). The present research examined multiple forms of childhood trauma and PTSD symptoms as predictors of depression treatment outcomes and MRAEs. Various forms of childhood trauma (e.g., abuse and neglect) were examined as predictors of depression treatment outcomes and participant attrition using secondary analyses of two MBP clinical trials (N = 52 and 104, respectively). Study 2 also examined meditation-related side effects (MRSE) and MRAE as outcomes and current subclinical and past PTSD symptoms as predictors. Childhood trauma led to worse depression outcomes across both study 1 and study 2, such that total childhood trauma and childhood sexual abuse were significant predictors across both studies. Childhood sexual abuse predicted attrition in study 2. Finally, multiple forms of childhood trauma and PTSD symptoms predicted MRSE, while total childhood trauma, childhood emotional abuse, and subclinical PTSD symptoms predicted lasting MRAE. Childhood trauma and PTSD symptoms may lead to worse outcomes and a greater occurrence of adverse effects within MBPs for active depression. These results call for further trauma-sensitive modifications, safety monitoring, participant screening, and provider education when implementing these programs.
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- 2025
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45. Site-selective photo-crosslinking for the characterisation of transient ubiquitin-like protein-protein interactions.
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Zac Sandy, Zijuan Wang, Deepak Behera, Benjamin M Foster, Finlay A Martin, Kira Brüninghoff, Kathleen M Cain, Wolfgang Dörner, Maria Jose Cabello-Lobato, Josep V Forment, Matthew J Cliff, Igor Larrosa, Perdita Barran, Duncan L Smith, Henning D Mootz, and Christine K Schmidt
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Medicine ,Science - Abstract
Non-covalent protein-protein interactions are one of the most fundamental building blocks in cellular signalling pathways. Despite this, they have been historically hard to identify using conventional methods due to their often weak and transient nature. Using genetic code expansion and incorporation of commercially available unnatural amino acids, we have developed a highly accessible method whereby interactions between biotinylated ubiquitin-like protein (UBL) probes and their binding partners can be stabilised using ultraviolet (UV) light-induced crosslinks. The stabilised protein complexes can be purified using affinity purification and identified by mass spectrometry. The resultant covalent bonds can withstand even the harshest washing conditions, allowing for the removal of indirect binders whilst retaining and capturing weak and transient interactors that are commonly lost during wash steps. This technique is widely applicable and highly effective for identifying site-selective non-covalent interactors. Members of our team have previously demonstrated the benefit of this method using the small ubiquitin-like modifier (SUMO). Here, we provide further proof-of-principle validation of the method and highlight its generality by applying an optimised workflow to a lesser studied UBL, interferon stimulated gene 15 (ISG15). We show that this method is able to capture known ISG15 interactors from a complex protein mixture in a site-selective manner, only capturing proteins that specifically interact with the region of ISG15 where the unnatural amino acid was incorporated. This exquisite degree of sensitivity and specificity greatly improves upon previous screens aimed at identifying downstream non-covalent binders, or readers, of ISG15. Taken together, the approach opens the possibility of characterising previously undetected protein-protein interactions, with the potential of elucidating molecular mechanisms behind the most complex and poorly understood processes in the cell.
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- 2025
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46. Correction: Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: Study protocol for a double-blind single dummy randomized controlled trial.
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Laurie Zawertailo, Helena Zhang, Noreen Rahmani, Tarek K Rajji, and Peter Selby
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0277408.].
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- 2025
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47. First report of MDR virulent Pseudomonas aeruginosa in apparently healthy Japanese quail (Coturnix japonica) in Bangladesh.
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Alamgir Hasan, Md Tanjir Ahmmed, Bushra Benta Rahman Prapti, Aminur Rahman, Tasnim Islam, Chandra Shaker Chouhan, A K M Anisur Rahman, and Mahbubul Pratik Siddique
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Medicine ,Science - Abstract
Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen associated conditions like septicaemia, respiratory disorders, and diarrhoea in poultry, particularly in Japanese quail (Coturnix japonica). The infection causes huge economical losses due to its high transmissibility, mortality and zoonotic potential. This study aimed to isolate, identify, detect virulence genes, and profile multidrug resistance (MDR) of P. aeruginosa from Japanese quail. Oral and rectal swabs were collected from 110 apparently healthy quail birds across various districts in Bangladesh. Bacterial isolation and identification were performed using cultural, morphological, biochemical, and polymerase chain reaction (PCR) methods. Antibiotic susceptibility was assessed using the disc diffusion method, and virulence genes were detected through PCR. Multivariable logistic regression was used to identify risk factors for P. aeruginosa infection. Both conventional and PCR methods revealed that 25 (22.73%) of the quail birds were positive for P. aeruginosa. The results showed that quail birds in Narsingdi were five times more likely to harbor Pseudomonas species (OR: 5.02; 95% CI: 1.34-18.84) compared to those in Mymensingh Sadar. Additionally, quail birds younger than eight weeks had nearly six times higher odds (OR: 5.93; 95% CI: 1.96-17.91) of carrying Pseudomonas compared to older birds. Female quail birds had almost four times higher odds (OR: 3.77; 95% CI: 1.30-10.93) of harboring Pseudomonas species than males. All 25 P. aeruginosa isolates exhibited multi drug-resistance (MDR) patterns. Virulence gene analysis revealed the consistent presence of exoA and rhlR in all isolates, while exoS, exoY, rhlI, and rhlAB showed variable distribution. The high prevalence of MDR and virulent P. aeruginosa in apparently healthy quail birds particularly in Mymensingh and Dhaka divisions, highlights the urgent need for a comprehensive 'One Health' approach to proactively address and mitigate the potential risk this organism poses to both quail and human populations.
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- 2025
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48. Effect of bar jump height on kinetics and kinematics of take-off in agility dogs.
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Leena Inkilä, Anna Boström, Pedro Valadão, Janne Avela, Simon Walker, Johanna Mäkitaipale, Anna Bergh, and Heli K Hyytiäinen
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Medicine ,Science - Abstract
Sport-related injuries have been reported to occur in around one-third of agility dogs. Higher bar height in competitions has been shown to increase odds of an injury. This study evaluated the effect of bar height on the kinetics and kinematics at take-off to a bar jump. Forces from fore- and hindlimb pairs were measured with force plates. A three-dimensional motion capture system was used to measure sagittal joint kinematics of the shoulder, elbow, carpus, hip, stifle, and tarsal joints, as well as limb coordination, trunk horizontal velocity, take-off distance, and take-off angle. Data were collected for 17 Border Collies at three different bar heights: 80%, 100%, and 120% of wither height. A linear mixed model was used for statistical analysis. At higher bar height, decelerative impulses were greater and accelerative impulses decreased along with greater vertical impulses from forelimb and hindlimb pairs (p
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- 2025
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49. Assessing a bundle of peer counseling, mobile phone messages, and mama kits in promoting timely initiation of and exclusive breastfeeding in Uganda: A cluster randomized controlled study.
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David Mukunya, James K Tumwine, Grace Ndeezi, Milton W Musaba, Justin Bruno Tongun, Josephine Tumuhamye, Agnes Napyo, Faith Oguttu, Daphine Amanya, Beatrice Odongkara, Vincentina Achora, Thorkild Tylleskar, and Victoria Nankabirwa
- Subjects
Medicine ,Science - Abstract
BackgroundTimely initiation of and exclusive breastfeeding have been recommended as key interventions to enable countries to attain the sustainable development target of reducing neonatal mortality to no more than 12 deaths per 1000 live births and to reduce mortality of children under 5 years to no more than 25 deaths per 1000 live births.MethodsWe conducted a cluster randomized controlled trial with the main objective to assess the effect of an integrated package consisting of: peer counseling, mobile phone messages, and mama kits on promoting health facility births between January 2018 and February 2019, in Lira district, Northern Uganda. In this article, we assessed the effect of the intervention on our two secondary objectives: timely initiation of and exclusivity of breastfeeding. We used a generalized estimation equation of the Poisson family, with a log or identity link, taking clustering into account to estimate prevalence ratios and prevalence differences.ResultsA total of 64% (594/926) of participants in the intervention arm initiated breastfeeding within the first hour after birth compared to 60% (493/829) in the control arm. The proportion of participants in the intervention arm that initiated breastfeeding within the first hour of life did not significantly differ from that in the control arm [Prevalence Ratio (PR) 1.08 (0.97 to 1.21)] and [Prevalence Difference (PD) 0.05 (-0.02 to 0.12)]. When we restricted the analysis to only mothers who decided on when to breastfeed, there was some evidence of intervention effectiveness [PR 1.20, 95% CI (0.99-1.5)]. In the intervention arm, 89% (804/904) of participants exclusively breastfed their infants in the first month of life compared to 81% (656/813) in the control arm. Participants in the intervention arm were 10% more likely to have exclusively breastfed in the preceding 24 hours compared to mothers in the control arm [PR 1.10 (1.04 to 1.17)] and [PD 0.08 (0.04 to 0.13)], and 16% more likely to have exclusively breastfed since birth compared to mothers in the control arm [PR 1.16 (1.03 to 1.30)] and [PD 0.12 (0.03 to 0.20].ConclusionThe intervention improved the proportion of mothers who practiced exclusive breastfeeding in the first month of life, but did not increase the proportion of mothers who initiated breastfeeding in the first hour of life. Future breastfeeding promotion interventions should consider including a health facility component and improving maternal autonomy to promote timely initiation of breastfeeding.
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- 2025
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50. Utilizing a novel fecal sampling method to examine resistance of the honey bee (Apis mellifera) gut microbiome to a low dose of tetracycline.
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Casey L Gregory, Emma L Bradford, Richard D Fell, David C Haak, and Lisa K Belden
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Medicine ,Science - Abstract
Disruption of host-associated microbial communities can have detrimental impacts on host health. However, the capacity of individual host-associated microbial communities to resist disturbance has not been well defined. Using a novel fecal sampling method for honey bees (Apis mellifera), we examined the resistance of the honey bee gut microbiome to disruption from a low dose of the antibiotic, tetracycline (4.5 μg). Prior to the experiment, bacterial communities from fecal samples were compared to communities from dissected whole guts of the same individuals to ensure fecal samples accurately represented the gut microbiome. Fecal samples were collected from lab-caged honey bees prior to, and five days after, tetracycline exposure to assess how antibiotic disturbance affected the communities of individuals. We used metrics of alpha and beta diversity calculated from 16S rRNA gene amplicon sequences to compare gut community structure. Low dose tetracycline exposure did not consistently change honey bee gut microbiome structure, but there was individual variation in response to exposure and specific taxa (one ASV assigned to Lactobacillus kunkeei and one ASV in the genus Bombella) were differentially abundant following tetracycline treatment. To assess whether individual variation could be influenced by the presence of tetracycline resistance genes, we quantified the abundance of tet(B) and tet(M) with qPCR. The abundance of tet(M) prior to tetracycline treatment was negatively correlated with change in community membership, assessed by difference in Jaccard dissimilarity over the five-day experiment. Our results suggest that the honey bee gut microbiome has some ability to resist or recover from antibiotic-induced change, specific taxa may vary in their susceptibility to tetracycline exposure, and antibiotic resistance genes may contribute to gut microbiome resistance.
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- 2025
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