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There are currently no clinical strategies utilizing tumor gene expression to inform therapeutic selection for patients with head and neck squamous cell carcinoma (HNSCC). One of the challenges in developing predictive biomarkers is the limited characterization of preclinical HNSCC models. Patient-derived xenografts (PDXs) are increasingly recognized as translationally relevant preclinical avatars for human tumors; however, the overall transcriptomic concordance of HNSCC PDXs with primary human HNSCC is understudied, especially in human papillomavirus-associated (HPV+) disease. Here, we characterized 64 HNSCC PDXs (16 HPV+ and 48 HPV-) at the transcriptomic level using RNA-sequencing. The range of human-specific reads per PDX varied from 64.6%-96.5%, with a comparison of the most differentially expressed genes before and after removal of mouse transcripts revealing no significant benefit to filtering out mouse mRNA reads in this cohort. We demonstrate that four previously established HNSCC molecular subtypes found in The Cancer Genome Atlas (TCGA) are also clearly recapitulated in HNSCC PDXs. Unsupervised hierarchical clustering yielded a striking natural division of HNSCC PDXs by HPV status, with C19orf57 (BRME1), a gene previously correlated with positive response to cisplatin in cervical cancer, among the most significantly differentially expressed genes between HPV+ and HPV- PDXs. In vivo experiments demonstrated a possible relationship between increased C19orf57 expression and superior anti-tumor responses of PDXs to cisplatin, which should be investigated further. These findings highlight the value of PDXs as models for HPV+ and HPV- HNSCC, providing a resource for future discovery of predictive biomarkers to guide treatment selection in HNSCC.

Numerous studies have examined substance use and smoking behavior among adolescents and university students. However, little is known about these behaviors among students undergoing university entrance tests, a critical transition period from adolescence to adulthood. The entrance test can significantly affect students' mental health, potentially leading to substance use. This study aims to investigate the prevalence of cigarette smoking and substance use among students taking these exams and the associated factors. A cross-sectional survey was carried out on September 4th and 11th, 2022 to collect data from 1,480 university entrance test-taking students using a convenience sampling technique. Chi-square tests and logistic regression were conducted using SPSS software. Besides, GIS mapping was used to visualize the distribution of substance use and smoking behavior across districts via ArcGIS. The study found a 10% prevalence of current tobacco smoking and 4% substance use. Females (OR = 1.98; 95% CI: 1.38-2.85), urban residence (OR = 2.03; 95% CI: 1.42-2.88), repeater (OR = 1.45; 95% CI: 1.02-2.06), anxiety (OR = 1.55, 95% CI: 1.10-2.19), burnout (OR = 1.51, 95% CI: 1.00-2.12), and suicidal behavior (OR = 1.57; 95% CI: 1.03-2.40) were the significant factors for cigarette use. Whereas the urban residence (OR = 1.91; 95% CI: 1.11-3.31), anxiety (OR = 2.47, 95% CI: 1.45-4.20), and suicidal behavior (OR = 2.76; 95% CI: 1.55-4.92) significantly increased the risk of substance use. GIS analysis revealed males varied in substance use and females in tobacco smoking by district. Repeat test-takers were associated with district variations in both smoking and substance use. Educational institutions, public health authorities, and policymakers must implement mental health support and substance use prevention programs for students. Integrating mental health education, providing resources, and enforcing regulations can promote healthier coping strategies and reduce substance use risks among students.

There is a lack of community-based rehabilitation for stroke in the Philippines, and research on this topic is limited. Different challenges may be encountered in urban and rural settings. The aim of the Tulong, Ugnayan ng Lingap At gabaY (TULAY) project is to develop a context-appropriate, community-based stroke support programme, consisting of self-management and training resources to augment the rehabilitation and recovery process. An important stage in the development of this programme is to qualitatively explore the experiences and needs of all stakeholders. Using co-designed and evidence-based topic guides, in-depth semi-structured interviews will be conducted with people living with stroke, household carers and care providers. We will aim to gain a representation of different regions (within Luzon, Visayas, and Northern Mindanao), socioeconomic levels, and urban and rural locations. For people with stroke and household carers, interviews will be supplemented by auto-photography and visual elicitation to widen access for those that prefer to share their experiences visually or have communication problems. An interpretivist paradigm will be applied across all interview data and the consolidated criteria for reporting qualitative research (COREQ) will be followed. Thematic analysis will be undertaken using guidance by Braun and Clarke. To our knowledge, this study is the first of its kind in the Philippines. It has several methodological strengths, including the capture of perspectives from multiple stakeholders in diverse settings, the inclusion of people with communication difficulties, use of visual methods, and analysis in the native language. The findings will have various applications, including the potential to influence policy, practice and guidelines, and to inform the development of the TULAY stroke support programme.

[This corrects the article DOI: 10.1371/journal.pone.0306071.].

IntroductionDepression is a prevalent and debilitating mental illness affecting young women worldwide. This study aimed to identify psychosocial determinants of major depressive disorder (MDD) among young women in Bihar and Uttar Pradesh, India.MethodsData from "Understanding the Lives of Adolescents and Young Adults" (UDAYA) study (2018-19) for young women aged 12-23 years, both married and unmarried was used for this paper. MDD was evaluated using the Patient Health Questionnaire PHQ-9 with a cut-off score of ≤10. The determinants of MDD were identified through multilevel binary logistic regression analysis.ResultsThe prevalence of MDD was 13.6% (95% CL 12.2-15.2) and 5.1% (95% CL 4.2-6.1) for young married women and unmarried girls, respectively. Among the young married women, community-level variables like dowry-related humiliation (1.74, 95% CI 1.15-2.64), and sexual assaults (2.15, 95% CI 1.24-3.73) were significantly associated with MDD. For unmarried girls, reporting of family violence 25% of participants) (0.42; 95% CI 0.23-0.74) remain significant predictors of MDD. At individual level, for both the groups, age, participation in decision making (on education), social capital (currently attending school/educational course and number of friends), self-efficacy, telephonic harassment, and physical activity were associated with MDD. Wealth index, job seeking, participation in decision making (on health-seeking), parental interactions and physical abuse (for unmarried girls only) and education, reported last sexual intercourse, pressure from the in-laws' to conceive (for young married women only) were associated with MDD.ConclusionsFor young married women, community level targeted interventions should focus on the social ecology to foster a sense of safe community environment. For unmarried girls, additionally, interventions should aim to optimize their family environment for effective mental health outcomes.

BackgroundARDS is a heterogeneous syndrome with distinct clinical phenotypes. Here we investigate whether the presence or absence of large pulmonary ultrasonographic consolidations can categorize COVID-19 ARDS patients requiring mechanical ventilation into distinct clinical phenotypes.MethodsThis is a retrospective study performed in a tertiary-level intensive care unit in Israel between April and September 2020. Data collected included lung ultrasound (LUS) findings, respiratory parameters, and treatment interventions. The primary outcome was a composite of three ARDS interventions: prone positioning, high PEEP, or a high dose of inhaled nitric oxide.ResultsA total of 128 LUS scans were conducted among 23 patients. The mean age was 65 and about two-thirds were males. 81 scans identified large consolidation and were classified as "C-type", and 47 scans showed multiple B-lines with no or small consolidation and were classified as "B-type". The presence of a "C-type" study had 2.5 times increased chance of receiving the composite primary outcome of advanced ARDS interventions despite similar SOFA scores, Pao2/FiO2 ratio, and markers of disease severity (OR = 2.49, %95CI 1.40-4.44).ConclusionThe presence of a "C-type" profile with LUS consolidation potentially represents a distinct COVID-19 ARDS subphenotype that is more likely to require aggressive ARDS interventions. Further studies are required to validate this phenotype in a larger cohort and determine causality, diagnostic, and treatment responses.

IntroductionUnderstanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia.MethodsWe performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures.ResultsData from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, pConclusionIn men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

Roads negatively impact wildlife through habitat fragmentation, loss of habitat connectivity, and wildlife-vehicle collisions, thus road mitigation structures, such as wildlife crossing structures (WCS), wildlife guards (WG), and fencing are commonly used to address this issue all over the world, including in the United States. In South Texas, such structures were built or modified along a State Highway in an effort to address road mortality for the endangered ocelot (Leopardus pardalis) and non-target wildlife species. The goal of this study was to examine temporal changes in wildlife interactions with WCS and WG during and after their construction and modification along a South Texas highway and to determine whether environmental factors influenced use of WCS. Using camera traps deployed to monitor the road mitigation structures, we compared crossing rates, repel rates, and species richness of all species that interacted with the structures, and we examined whether differential wildlife use of WCS and WG was affected by one or more structural dimensions, distance to nearby vegetation, and water presence. Crossings through WCS by wildlife decreased following the completion of construction of mitigation structures; however, repel interactions at WG increased. Overall, crossings decreased at WCS that had higher openness ratios and during periods of precipitation and higher daily temperatures, but distance to vegetation had minimal influence. These factors were shown to influence crossings of each of the five most frequently observed species differently. Lastly, the presence of pooled water at one WCS caused a decrease in crossings when the water level was highest but was not a barrier at lower water levels. By examining influences on wildlife interaction with road mitigation structures, we conclude that a variety of structures, including different WCS configurations, can be beneficial in facilitating movement and restricting entry into the right-of-way for a diversity of wildlife species beyond the target species.

With the overall objective of providing implication for clinical and research practices regarding the identification and measurement of modifiable predicting factors for return to work (RTW) in people with musculoskeletal disorders (MSDs) and common mental disorders (CMDs), this study 1) systematically examined and synthetized the research evidence available in the literature on the topic, and 2) critically evaluated the tools used to measure each identified factor. A systematic search of prognostic studies was conducted, considering four groups of keywords: 1) population (i.e., MSDs or CMDs), 2) study design (prospective), 3) modifiable factors, 4) outcomes of interest (i.e., RTW). Studies showing high risk of bias were eliminated. Tools used to measure prognostic factors were assessed using psychometric and usability criteria. From the 78 studies that met inclusion criteria, 19 (for MSDs) and 5 (for CMDs) factors reaching moderate or strong evidence were extracted. These factors included work accommodations, RTW expectations, job demands (physical), job demands (psychological), job strain, work ability, RTW self-efficacy, expectations of recovery, locus of control, referred pain (back pain), activities as assessed with disability questionnaires, pain catastrophizing, coping strategies, fears, illness behaviours, mental vitality, a positive health change, sleep quality, and participation. Measurement tools ranged from single-item tools to multi-item standardized questionnaires or subscales. The former generally showed low psychometric properties but excellent usability, whereas the later showed good to excellent psychometric properties and variable usability. The rigorous approach to the selection of eligible studies allowed the identification of a relatively small set of prognostic factors, but with a higher level of certainty. For each factor, the present tool assessment allows an informed choice to balance psychometric and usability criteria.

BackgroundThe Women's Health Needs Study (WHNS) collected information on the health characteristics, needs, and experiences, including female genital mutilation (FGM) experiences, attitudes, and beliefs, of women aged 18 to 49 years who were born, or whose mothers were born, in a country where FGM is prevalent living in the US. The purpose of this paper is to describe the WHNS design, methods, strengths and limitations, as well as select demographic and health-related characteristics of participants.MethodsWe conducted a cross-sectional survey from November 2020 -June 2021 in four US metropolitan areas, using a hybrid venue-based sampling (VBS) and respondent-driven sampling (RDS) approach to identify women for recruitment.ResultsOf 1,132 participants, 395 were recruited via VBS and 737 RDS. Most were born, or their mothers were born, in either a West African country (Burkina Faso, Guinea, Mali, Mauritania, Sierra Leone, The Gambia) (39.0%) or Ethiopia (30.7%). More than a third were aged 30-39 years (37.5%) with a majority who immigrated at ages ≥13 years (86.6%) and had lived in the United States for ≥5 years (68.9%). Medicaid was the top health insurer (52.5%), followed by private health insurance (30.5%); 17% of participants had no insurance. Nearly half of women reported 1-2 healthcare visits within the past 12 months (47.7%). One in seven did not get needed health care due to cost (14.8%). Over half have ever used contraception (52.1%) to delay or avoid pregnancy and 76.9% had their last pelvic and/or Papanicolaou (pap) exam within the past 3 years. More than half experienced FGM (55.0%). Nearly all women believed that FGM should be stopped (92.0%).ConclusionThe VBS/RDS approach enabled recruitment of a diverse study population. WHNS advances research related to the health characteristics, needs, and experiences of women living in the US from countries where FGM is prevalent.

Histone variants are paralogs that replace canonical histones in nucleosomes, often imparting novel functions. However, how histone variants arise and evolve is poorly understood. Reconstruction of histone protein evolution is challenging due to large differences in evolutionary rates across gene lineages and sites. Here we used intron position data from 108 nematode genomes in combination with amino acid sequence data to find disparate evolutionary histories of the three H2A variants found in Caenorhabditis elegans: the ancient H2A.ZHTZ-1, the sperm-specific HTAS-1, and HIS-35, which differs from the canonical S-phase H2A by a single glycine-to-alanine C-terminal change. Although the H2A.ZHTZ-1 protein sequence is highly conserved, its gene exhibits recurrent intron gain and loss. This pattern suggests that specific intron sequences or positions may not be important to H2A.Z functionality. For HTAS-1 and HIS-35, we find variant-specific intron positions that are conserved across species. Patterns of intron position conservation indicate that the sperm-specific variant HTAS-1 arose more recently in the ancestor of a subset of Caenorhabditis species, while HIS-35 arose in the ancestor of Caenorhabditis and its sister group, including the genus Diploscapter. HIS-35 exhibits gene retention in some descendent lineages but gene loss in others, suggesting that histone variant use or functionality can be highly flexible. Surprisingly, we find the single amino acid differentiating HIS-35 from core H2A is ancestral and common across canonical Caenorhabditis H2A sequences. Thus, we speculate that the role of HIS-35 lies not in encoding a functionally distinct protein, but instead in enabling H2A expression across the cell cycle or in distinct tissues. This work illustrates how genes encoding such partially-redundant functions may be advantageous yet relatively replaceable over evolutionary timescales, consistent with the patchwork pattern of retention and loss of both genes. Our study shows the utility of intron positions for reconstructing evolutionary histories of gene families, particularly those undergoing idiosyncratic sequence evolution.

Breast cancer remains a critical global concern, underscoring the urgent need for early detection and accurate diagnosis to improve survival rates among women. Recent developments in deep learning have shown promising potential for computer-aided detection (CAD) systems to address this challenge. In this study, a novel segmentation method based on deep learning is designed to detect tumors in breast ultrasound images. Our proposed approach combines two powerful attention mechanisms: the novel Positional Convolutional Block Attention Module (PCBAM) and Shifted Window Attention (SWA), integrated into a Residual U-Net model. The PCBAM enhances the Convolutional Block Attention Module (CBAM) by incorporating the Positional Attention Module (PAM), thereby improving the contextual information captured by CBAM and enhancing the model's ability to capture spatial relationships within local features. Additionally, we employ SWA within the bottleneck layer of the Residual U-Net to further enhance the model's performance. To evaluate our approach, we perform experiments using two widely used datasets of breast ultrasound images and the obtained results demonstrate its capability in accurately detecting tumors. Our approach achieves state-of-the-art performance with dice score of 74.23% and 78.58% on BUSI and UDIAT datasets, respectively in segmenting the breast tumor region, showcasing its potential to help with precise tumor detection. By leveraging the power of deep learning and integrating innovative attention mechanisms, our study contributes to the ongoing efforts to improve breast cancer detection and ultimately enhance women's survival rates. The source code of our work can be found here: https://github.com/AyushRoy2001/DAUNet.

BackgroundLimited research addressed links between nutritional status, dietary habits, and cognitive functions in young children. This study assessed the status of cognitive functions and their association with nutritional status and dietary habits of school age children of Bangladesh.MethodsThis cross-sectional multi-centre study was conducted on 776 participants in 11 conveniently selected educational institutions. A printed questionnaire with three sections (Section 1: background information, section 2: PedsQL™ Cognitive Functioning Scale, and section 3: semi-quantitative food-frequency questionnaire) was utilized for the data collection purpose. Sections 1 and 3 were self-reported by parents, and trained volunteers completed section 2 in-person along with the anthropometric measurements. Statistical analyses were done in Stata (v.16). Mean with standard deviation and frequencies with percentages were used to summarize quantitative and qualitative variables, respectively. Pearson's chi-square test and Spearman's rank correlation coefficient were used to explore bivariate relationships.ResultsThe mean age of the participants was 12.02±1.88 years, and the majority (67%) were females. The prevalence of poor cognitive function was 46.52%, and among them, 66.02% were females. In terms of body mass index (BMI), 22.44% possessed normal weight, 17.51% were overweight, and 5.19% were obese. This study found a statistically significant relationship between BMI and cognitive functions. Furthermore, different dietary components (e.g., protein, carbohydrate, fat, fiber, iron, magnesium) showed a significant (pConclusionBMI and dietary habits were associated with the cognitive function of young children in Bangladesh. Although the cross-sectional design of the study precludes causal relationships from being determined, the study finding deserves further examination via longitudinal research.

IntroductionWhile a number of studies have examined the nutritional impacts of agroecological interventions, few have examined impacts on child development, maternal and child anemia, and men's dietary diversity. Moreover, there have been few such evaluations at scale. We evaluated the impact of a large-scale, multi-component food-based nutrition intervention involving homestead food production, nutrition counselling, cooking demonstrations, and crop planning exercises.MethodsA cross-sectional assessment was conducted in 2021-2022 of 50 intervention villages where the nutrition-sensitive agroecology program had been implemented since 2018 and 79 control villages where only the agroecology program had been implemented. Data on self-reported dietary intake, caregiver-reported early child development, anthropometric measurements, and hemoglobin concentrations were collected using standardized procedures by trained Nutrition Farming Fellows, who were also responsible for implementing the program.ResultsA sample of 3,511 households (1,121 intervention and 2,390 control) participated in the survey. Dietary diversity scores (DDS) among women and men were mean (SD) 6.53 (±1.62) and 6.16 (±1.65), respectively, in intervention villages and 5.81 (±1.58) and 5.39 (±1.61), respectively, in control villages (pConclusionNutrition-sensitive agroecological programs may be effective in improving diets, nutrition, and child development in rural India.

IntroductionDuring the COVID-19 pandemic, ventilator shortages necessitated the development of new, low-cost ventilator designs. The fundamental requirements of a ventilator include precise gas delivery, rapid adjustments, durability, and user-friendliness, often achieved through solenoid valves. However, few solenoid-valve assisted low-cost ventilator (LCV) designs have been published, and gas exchange evaluation during LCV testing is lacking. This study describes the development and performance evaluation of a solenoid-valve assisted low-cost ventilator (SV-LCV) in vitro and in vivo, focusing on gas exchange and respiratory mechanics.MethodsThe SV-LCV, a fully open ventilator device, was developed with comprehensive hardware and design documentation, utilizing solenoid valves for gas delivery regulation. Lung simulator testing calibrated tidal volumes at specified inspiratory and expiratory times, followed by in vivo testing in a porcine model to compare SV-LCV performance with a conventional ventilator.ResultsThe SV-LCV closely matched the control ventilator's respiratory profile and gas exchange across all test cycles. Lung simulator testing revealed direct effects of compliance and resistance changes on peak pressures and tidal volumes, with no significant changes in respiratory rate. In vivo testing demonstrated comparable gas exchange parameters between SV-LCV and conventional ventilator across all cycles. Specifically, in cycle 1, the SV-LCV showed arterial blood gas (ABG) results of pH 7.54, PCO2 34.5 mmHg, and PO2 91.7 mmHg, compared to the control ventilator's ABG of pH 7.53, PCO2 37.1 mmHg, and PO2 134 mmHg. Cycle 2 exhibited ABG results of pH 7.53, PCO2 33.6 mmHg, and PO2 84.3 mmHg for SV-LCV, and pH 7.5, PCO2 34.2 mmHg, and PO2 93.5 mmHg for the control ventilator. Similarly, cycle 3 showed ABG results of pH 7.53, PCO2 32.1 mmHg, and PO2 127 mmHg for SV-LCV, and pH 7.5, PCO2 35.5 mmHg, and PO2 91.3 mmHg for the control ventilator.ConclusionThe SV-LCV provides similar gas exchange and respiratory mechanic profiles compared to a conventional ventilator. With a streamlined design and performance akin to commercially available ventilators, the SV-LCV presents a viable, readily available, and reliable short-term solution for overcoming ventilator supply shortages during crises.

IntroductionThere have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening.MethodsBetween August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma.ResultsOf the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants.ConclusionUse of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)

BackgroundParticipation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear.ObjectiveThis cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks.MethodsWe assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds.ResultsOlder participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks.ConclusionWe show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity.Trial registrationGerman Clinical Trials Register (DRKS00007966, 04/05/2015).

The analysis of the DNA entrapped in ancient shells of molluscs has the potential to shed light on the evolution and ecology of this very diverse phylum. Ancient genomics could help reconstruct the responses of molluscs to past climate change, pollution, and human subsistence practices at unprecedented temporal resolutions. Applications are however still in their infancy, partly due to our limited knowledge of DNA preservation in calcium carbonate shells and the need for optimized methods for responsible genomic data generation. To improve ancient shell genomic analyses, we applied high-throughput DNA sequencing to 27 Mytilus mussel shells dated to ~111-6500 years Before Present, and investigated the impact, on DNA recovery, of shell imaging, DNA extraction protocols and shell sub-sampling strategies. First, we detected no quantitative or qualitative deleterious effect of micro-computed tomography for recording shell 3D morphological information prior to sub-sampling. Then, we showed that double-digestion and bleach treatment of shell powder prior to silica-based DNA extraction improves shell DNA recovery, also suggesting that DNA is protected in preservation niches within ancient shells. Finally, all layers that compose Mytilus shells, i.e., the nacreous (aragonite) and prismatic (calcite) carbonate layers, with or without the outer organic layer (periostracum) proved to be valuable DNA reservoirs, with aragonite appearing as the best substrate for genomic analyses. Our work contributes to the understanding of long-term molecular preservation in biominerals and we anticipate that resulting recommendations will be helpful for future efficient and responsible genomic analyses of ancient mollusc shells.

In Nepal, visceral leishmaniasis (VL) has been targeted for elimination as a public health problem by 2026. Recently, increasing numbers of VL cases have been reported from districts of doubtful endemicity including hills and mountains, threatening the ongoing VL elimination program in Nepal. We conducted a multi-disciplinary, descriptive cross-sectional survey to assess the local transmission of Leishmania donovani in seven such districts situated at altitudes of up to 1,764 meters in western Nepal from March to December 2019. House-to-house surveys were performed for socio-demographic data and data on past and current VL cases. Venous blood was collected from all consenting individuals aged ≥2 years and tested with the rK39 RDT. Blood samples were also tested with direct agglutination test, and a titer of ≥1:1600 was taken as a marker of infection. A Leishmania donovani species-specific PCR (SSU-rDNA) was performed for parasite species confirmation. We also captured sand flies using CDC light traps and mouth aspirators. The house-to-house surveys documented 28 past and six new VL cases of which 82% (28/34) were without travel exposure. Overall, 4.1% (54/1320) of healthy participants tested positive for L. donovani on at least one serological or molecular test. Among asymptomatic individuals, 17% (9/54) were household contacts of past VL cases, compared to 0.5% (6/1266) among non-infected individuals. Phlebotomus argentipes, the vector of L. donovani, was found in all districts except in Bajura. L. donovani was confirmed in two asymptomatic individuals and one pool of sand flies of Phlebotomus (Adlerius) sp. We found epidemiological and entomological evidence for local transmission of L. donovani in areas previously considered as non-endemic for VL. The national VL elimination program should revise the endemicity status of these districts and extend surveillance and control activities to curb further transmission of the disease.

ObjectivesThe response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India.MethodsIn part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design.Expected outcomeThe study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia.Trial registrationThe study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

In recent decades, minimally invasive surgery has become the favoured surgical technique, with increasing utilisation of robotic surgery to enhance patient outcomes. However, the design complexity of surgical robotic instruments can pose challenges in maintaining adequate cleaning, disinfection and sterilisation-particularly of the device's interior. In our hospital, robotic instruments are reused for a maximum of ten successive patients, following the manufacturer's guidelines. To the best of our knowledge, neither the manufacturer nor ISO standards have specified any methods to determine the sterility of robotic instruments after cleaning, disinfection and sterilisation procedures. In a small pilot study, we used a locally developed protocol to evaluate the sterility of 20 da Vinci SI robotic instruments, with the aim of determining whether the recommended cleaning, disinfection and sterilisation process is adequate to achieve safe usage in subsequent patients. None of the 20 instruments showed viable micro-organisms, therefore the robotic instruments were considered sterile, and suitable for re-use. We recommend our protocol to other hospitals, to be used as an essential control element in the assessment of their unique reprocessing technique for robotic instruments.

BackgroundThe Oncotype DX® Breast Recurrence Score assay can guide recommendations made to patients with oestrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer regarding post-surgery adjuvant therapy. Standard practice is to order the test in the post-operative setting on a specimen from the excised invasive carcinoma. However, it has been shown to be technically possible to perform the test on the diagnostic core biopsy. By testing the diagnostic core biopsy in the pre-operative setting, the wait for excised invasive carcinoma Recurrence Score results could be reduced allowing patients to be more accurately counselled regarding their treatment pathway sooner with any adjuvant treatment recommendations expedited. This would allow for more efficient streaming of follow up appointments. The aim of this study is to compare the impact on the patient treatment pathway of performing the Oncotype DX® test on the diagnostic core biopsy pre-operatively (intervention) as opposed to the excised invasive carcinoma (control).Methods and analysisThis parallel group randomised controlled trial aims to recruit 330 newly diagnosed patients with grade 2 or grade 3, ER+, HER2-, invasive intermediate risk early-stage breast cancer. Participants will be randomised 2:1 to the preoperative testing of the diagnostic core biopsy compared to the post-operative testing of the excision specimen. The primary endpoint is number of clinical touchpoints between treating team and patient from initial approach until offer and prescription of the first adjuvant treatment. Secondary endpoints include time from diagnosis to offer and prescription of the first adjuvant treatment, patient-reported anxiety scores and health cost impact analysis collected at baseline, following the post-operative clinic and following the offer of adjuvant treatment, and number of alterations in treatment sequence from original planned surgical treatment to neoadjuvant therapy.Trial registrationThe study was registered on ISRCTN (ISRCTN14337451) on the 16th August 2022.

Mitosis is the process by which eukaryotic cells divide to produce two similar daughter cells with identical genetic material. Research into the process of mitosis is therefore of critical importance both for the basic understanding of cell biology and for the clinical approach to manifold pathologies resulting from its malfunctioning, including cancer. In this paper, we propose an approach to study mitotic progression automatically using deep learning. We used neural networks to predict different mitosis stages. We extracted video sequences of cells undergoing division and trained a Recurrent Neural Network (RNN) to extract image features. The use of RNN enabled better extraction of features. The RNN-based approach gave better performance compared to classifier based feature extraction methods which do not use time information. Evaluation of precision, recall, and F-score indicates the superiority of the proposed model compared to the baseline. To study the loss in performance due to confusion between adjacent classes, we plotted the confusion matrix as well. In addition, we visualized the feature space to understand why RNNs are better at classifying the mitosis stages than other classifier models, which indicated the formation of strong clusters for the different classes, clearly confirming the advantage of the proposed RNN-based approach.

This study's aim is to describe the imaging findings in pregnant patients undergoing emergent MRI for suspected acute appendicitis, and the various alternative diagnoses seen on those MRI scans. This is a single center retrospective analysis in which we assessed the imaging, clinical and pathological data for all consecutive pregnant patients who underwent emergent MRI for suspected acute appendicitis between April 2013 and June 2021. Out of 167 patients, 35 patients (20.9%) were diagnosed with acute appendicitis on MRI. Thirty patients (18%) were diagnosed with an alternative diagnosis on MRI: 17/30 (56.7%) patients had a gynecological source of abdominal pain (e.g. ectopic pregnancy, red degeneration of a leiomyoma); 8 patients (26.7%) had urological findings such as pyelonephritis; and 6 patients (20%) had gastrointestinal diagnoses (e.g. abdominal wall hernia or inflammatory bowel disease). Our conclusions are that MRI is a good diagnostic tool in the pregnant patient, not only in diagnosing acute appendicitis, but also in providing information on alternative diagnoses to acute abdominal pain. Our findings show the various differential diagnoses on emergent MRI in pregnant patients with suspected acute appendicitis, which may assist clinicians and radiologists is patient assessment and imaging utilization.

Since 1997 Tanzania has undertaken a process to identify and declare a network of Nature Forest Reserves (NFRs) with high biodiversity values, from within its existing portfolio of national Forest Reserves, with 16 new NFRs declared since 2015. The current network of 22 gazetted NFRs covered 948,871 hectares in 2023. NFRs now cover a range of Tanzanian habitat types, including all main forest types-wet, seasonal, and dry-as well as wetlands and grasslands. NFRs contain at least 178 of Tanzania's 242 endemic vertebrate species, of which at least 50% are threatened with extinction, and 553 Tanzanian endemic plant taxa (species, subspecies, and varieties), of which at least 50% are threatened. NFRs also support 41 single-site endemic vertebrate species and 76 single-site endemic plant taxa. Time series analysis of management effectiveness tracking tool (METT) data shows that NFR management effectiveness is increasing, especially where donor funds have been available. Improved management and investment have resulted in measurable reductions of some critical threats in NFRs. Still, ongoing challenges remain to fully contain issues of illegal logging, charcoal production, firewood, pole-cutting, illegal hunting and snaring of birds and mammals, fire, wildlife trade, and the unpredictable impacts of climate change. Increased tourism, diversified revenue generation and investment schemes, involving communities in management, and stepping up control measures for remaining threats are all required to create a network of economically self-sustaining NFRs able to conserve critical biodiversity values.

Turmeric, a globally cultivated spice, holds significance in medicine, and cosmetics, and is also a very popular ingredient in South Asian cuisine. A study involving 53 turmeric genotypes evaluated for rhizome yield and related traits at Spices Research Center, Bogura, Bangladesh over three years (2019-22). A randomized complete block design was followed with two replications. ANOVA revealed significant trait variations among genotypes. Genotype T0015 emerged as the highest yielder at 28.04 t/ha. High heritability (0.58-0.99) and genetic advance characterized plant height (PH), mother rhizome weight (WMR), primary and secondary finger weights (WPF and WSF), and yield per plant (YPP) across seasons. Genetic gain (GG) was prominent in these traits. Genotypic and phenotypic coefficient variations (GCV and PCV) (6.24-89.46 and 8.18-90.88, respectively) across three years highlighted mother rhizome weight's importance followed by numbers of primary finger (NPF), and WPF. Positive and significant correlations, especially with PH, WMR, WPF, and YPP, emphasized their relevance to fresh yield (FY). Multiple linear regression identified PH, number of mother rhizome (NMR) and WMR as key contributors, explaining 37-79% of FY variability. Cluster analysis grouped genotypes into five clusters with maximum distance observed between clusters II and III. The geometric adaptability index (GAI) assessed adaptability and superiority, revealing nine genotypes outperforming the best existing cultivar. Genotype T0117 as the top performer based on GAI, followed by T0103 and T0094. Mean rank analysis favoured T0121 as the best performer, succeeded by T0117, T0082 and T0106. The top ten genotypes (T0015, T0061, T0082, T0085, T0094, T0103, T0106, T0117, T0121 and T0129) were identified as superior based on yield and overall ranking, warranting further evaluation. These findings may induce a window for improving turmeric research and ultimately play a role in enhancing its cultivation and productivity.

Most environments favor defection over cooperation due to natural selection. Nonetheless, the emergence of cooperation is omnipresent in many biological, social, and economic systems, quite contrary to the well-celebrated Darwinian theory of evolution. Much research has been devoted to better understanding how and why cooperation persists among self-interested individuals despite their competition for limited resources. Here we go beyond a single social dilemma since individuals usually encounter various social challenges. In particular, we propose and study a mathematical model incorporating both the prisoner's dilemma and the snowdrift game. We further extend this model by considering ecological signatures like mutation and selfless one-sided contribution of altruist free space. The nonlinear evolutionary dynamics that results from these upgrades offer a broader range of equilibrium outcomes, and it also often favors cooperation over defection. With the help of analytical and numerical calculations, our theoretical model sheds light on the mechanisms that maintain biodiversity, and it helps to explain the evolution of social order in human societies.

Patients with epilepsy, who later succumb to sudden unexpected death, show altered brain tissue volumes in selected regions. It is unclear whether the alterations in brain tissue volume represent changes in neurons or glial properties, since volumetric procedures have limited sensitivity to assess the source of volume changes (e.g., neuronal loss or glial cell swelling). We assessed a measure, entropy, which can determine tissue homogeneity by evaluating tissue randomness, and thus, shows tissue integrity; the measure is easily calculated from T1-weighted images. T1-weighted images were collected with a 3.0-Tesla MRI from 53 patients with tonic-clonic (TC) seizures and 53 healthy controls; images were bias-corrected, entropy maps calculated, normalized to a common space, smoothed, and compared between groups (TC patients and controls using ANCOVA; covariates, age and sex; SPM12, family-wise error correction for multiple comparisons, p

BACKGROUND:Studies estimate that the number of cancer survivors will double by 2050 due to improvements in diagnostic accuracy and treatment efficacy. Despite the growing population of cancer survivors, there is a paucity of research regarding how these individuals experience the transition from active treatment to long-term surveillance. While research has explored this transition from more organized venues, such as support groups for cancer survivors, this paper explores the discourses surrounding cancer survivorship on social media, paying particular attention to how individuals who identify as cancer survivors represent their experience. METHODS:We identified social media posts relating to cancer survivorship on Twitter and Instagram in early June 2018, in order to coincide with National Cancer Survivorship Day on June 3, 2018. We used nine pre-selected hashtags to identify content. For each hashtag, we manually collected the 150 most recent posts from Twitter and the 100 most recent plus the top 9 posts from Instagram. Our preliminary sample included 1172 posts; after eliminating posts from one hashtag due to irrelevance, we were left with 1063 posts. We randomly sampled 200 of these to create a subset for analysis; after review for irrelevant posts, 193 posts remained for analysis (118 from Instagram and 75 from Twitter). We utilized a grounded theory approach to analyze the posts, first open-coding a subset to develop a codebook, then applying the codebook to the rest of the sample and finally memo writing to develop themes. RESULTS:Overall, there is substantial difference in the tone and thematic content between Instagram and Twitter posts, Instagram takes on a more narrative form that represents journeys through cancer treatment and subsequent survivorship, whereas Twitter is more factual, leaning towards advocacy, awareness and fundraising. In terms of content type, 120 posts (62%) of the sample were images, of which 42 (35%) were images of the individual posting and 28 (23%) were images of patients posted by family or friends. Of the remaining images, 14 (12%) were of support groups and 7 (6%) were of family or friends. We identified four salient themes through analysis of the social media posts from Twitter and Instagram: social support, celebrating milestones and honoring survivors, expressing identity, and renewal vs. rebirth. DISCUSSION:We observed a marked relationship between physical appearance, functional status and survivorship. Additionally, our findings suggest the importance of social support for cancer patients and survivors as well as the role social media can pay in identity formation. CONCLUSION:Our findings suggest that individuals who identify as survivors on social media define their identity fluidly, incorporating elements of physical, emotional and psychological health as well as autonomy.

The critically endangered Amargosa vole (Microtus californicus scirpensis) is found only in rare marsh habitat near Tecopa, California in a plant community dominated by three-square bulrush (Schoenoplectus americanus). Since the earliest research on the Amargosa vole, the existing paradigm has been that these voles are obligatorily dependent on bulrush as their only food source and for the three-dimensional canopy and litter structure it provides for predator avoidance. However, no prior research has confirmed the diet of the Amargosa vole. In this study we characterized the Amargosa vole' nutritional needs, analyzed the quality of bulrush by forage analysis, and performed microhistological and metabarcoding analyses of vole feces to determine what foods were consumed in the wild. All bulrush plant tissues analyzed were low in fat (from 0.9% of dry matter in roots to 3.6% in seeds), high in neutral detergent fiber (from 5.9% in rhizomes to 33.6% in seeds), and low in protein (7.3-8.4%). These findings support the conclusion that bulrush alone is unlikely to support vole survival and reproduction. Fecal microhistology and DNA metabarcoding revealed relatively diverse diets including plants in 14 families, with rushes (Juncaceae), bulrushes (Cyperaceae), and grasses (Poaceae) being the most common diet items. On microhistology, all analyzed samples contained bulrush, sedges (Carex sp.), rushes (Juncus sp.), and beaked spikerush (Eleocharis rostrellata) even from marshes where non-bulrush plants were uncommon. There was evidence of insects at

Objective measures of adherence for antiretrovirals used as pre-exposure prophylaxis (PrEP) are critical for improving preventative efficacy in both clinical trials and real-world application. Current objective adherence measures either reflect only recent behavior (eg days for plasma or urine) or cumulative behavior (eg months for dried blood spots). Here, we measured the accumulation of the antiretroviral drug maraviroc (MVC) in hair strands by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) to evaluate adherence behavior longitudinally at high temporal resolution. An MSI threshold for classifying daily adherence was established using clinical samples from healthy volunteers following directly observed dosing of 1 to 7 doses MVC/week. We then used the benchmarked MSI assay to classify adherence to MVC-based PrEP regimens in hair samples collected throughout the 48-week HPTN069/ACTGA5305 study. We found that only ~32% of investigated hair samples collected during the study's active dosing period showed consistent daily PrEP adherence throughout a retrospective period of 30 days, and also found that profiles of daily individual adherence from MSI hair analysis could identify when patients were and were not taking study drug. The assessment of adherence from MSI hair strand analysis was 62% lower than adherence classified using paired plasma samples, the latter of which may be influenced by white-coat adherence. These findings demonstrate the ability of MSI hair analysis to examine daily variability of adherence behavior over a longer-term measurement and offer the potential for longitudinal comparison with risk behavior to target patient-specific adherence interventions and improve outcomes.

Intensive management may be necessary to protect some highly vulnerable endangered species, particularly those dependent on water availability regimes that might be disrupted by ongoing climate change. The Amargosa vole (Microtus californicus scirpensis) is an increasingly imperiled rodent constrained to rare wetland habitat in the Mojave Desert. In 2014 and 2016, we trapped and radio-collared 30 voles, 24 were translocated and six remained at donor and recipient marshes as resident control voles. Soft-release was performed followed by remote camera and radio-telemetry monitoring. Although comparative metrics were not statistically significant, the mean maximum known distance moved (MDM) was longer for translocated (82.3 ± 14.6 m) vs. resident-control voles (74.9 ± 17.5 m) and for female (98.4 ± 19.9 m) vs. male (57.8 ± 9.1 m) voles. The mean area occupied (AO) tended to be greater in female (0.15 ± 0.04 ha) vs. male (0.12 ± 0.03 ha) voles, and control voles (0.15 ± 0.05 ha) compared with translocated voles (0.13 ± 0.03 ha). The mean minimum known time alive (MTA) was 38.2 ± 19.4 days for resident-control voles and 47.0 ± 10.6 days for translocated voles. Female survival (55.7 ± 14.3 days) exceeded that of males (31.5 ± 9.4 days) regardless of study group. Activity in bulrush/rushes mix and bulrush vegetation types was strongly and significantly overrepresented compared with salt grass and rushes alone, and habitat selection did not differ between resident and translocated voles. Our results provide ecological and methodological insights for future translocations as part of a strategy of promoting long-term survival of an extremely endangered small mammal in a wild desert environment.

Providing brief interventions by certified peer recovery support specialists (CPRSS) in the emergency department (ED) following a drug related visit is a promising method of service engagement and has garnered national attention. This study examines CPRSS's perceptions of the qualities that enable them to deliver interventions in the ED. We conducted qualitative interviews with 14 CPRSSs working in EDs. Interview topics included how the participants became involved with CPRSS work, experiences working in the ED, how the ED differs from other settings, and what interactions with patients look like. Interviews were digitally recorded, transcribed, and analyzed for emerging categories. Three categories were identified relating to CPRSS work: (1) how they approach peer work, (2) inherent qualities required to do the work, regardless of the setting, and (3) context-specific skills required to do the work in the ED. When describing their approach to this work, participants talked about CPRSS work as their life calling and their passion. Participants also identified certain qualities that all CPRSS workers possess, regardless of the setting, including the ability to build rapport, strong listening skills, and a shared lived experience. Lastly, participants identified how specific hard and soft skills help them to navigate organizational and structural challenges in the ED. The unique conditions of the ED and the required qualities of a CPRSS should be considered when implementing an ED-based intervention.

We developed and tested the Indian Autism Screening Questionnaire (IASQ), which was reported to be reliable and valid as compared to the Indian Scale for Assessment of Autism (ISAA) and the Childhood Autism Rating Scale -2 (CARS2). The present study describes the feasibility, acceptability, sociodemographic and developmental details of IASQ study participants in 5 settings- a psychiatry outpatients' clinic (n = 145), a specialised paediatric clinic (n = 24), a speciality disability centre (n = 174), a primary school (n = 41) and a government housing colony (n = 255). The IASQ could be easily administered and understood. Consistent with prior reports, the male-female ratio of participants with autism was 3.8:1. Developmental complications were reported more frequently in clinical settings, while delivery by Caesarean section was commoner among community-dwelling higher socioeconomic status mothers (53% of the officers' sample). Mothers of participants with autism more frequently reported Caesarean section birth for the proband (χ2 = 41.61, p < .0001) and prenatal and postnatal complications. Binary logistic regression confirmed that perinatal complications in the mother and father's (older) age at birth of the participant were associated with autism. The IASQ is a reliable, practical tool for screening for autism in clinical and non-clinical settings in India.