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Abstract Long-distance transport and associated fasting of unweaned calves have the potential to compromise the animals’ welfare. This observational study aimed to determine how transport and fasting durations impacted the physiology and health of 115 transported calves in three transport groups; IRE (n = 20, mean age 29.8d; short road transport (~ 29 h incl. resting time) and short feed deprivation (~ 11 h)), INT (n = 65, mean age 24.9d; long road/ferry transport (~ 79 h incl. resting times) and long feed deprivation (~ 28 h and 25 h)), and NLD (n = 30, mean age 17.7d; short road transport (~ 28 h incl. resting time) and long feed deprivation (> 18 h)). All calves travelled through an assembly centre. Each calf was blood sampled (arrival at destination farm, 1-week and 3-weeks post-arrival), health scored (arrival, 1, 3, 7, 8, 20d post-arrival) and weighed (farm/mart of origin [IRE and INT only], arrival, and 3-weeks post-arrival). (Generalised) linear mixed models were used to analyse differences in blood variables, weight, and health scores on arrival and during recovery (all other timepoints). Despite differing transport durations, both INT and NLD calves exhibited glucose, beta-hydroxy-butyrate, non-esterified-fatty-acids and sodium levels outside reference limits upon arrival, which were different from values observed in IRE calves (p

Abstract The ongoing circulation of influenza A H5N1 in the United States has raised concerns of a pandemic caused by highly pathogenic avian influenza. Although the United States has stockpiled and is prepared to produce millions of vaccine doses to address an H5N1 pandemic, currently circulating H5N1 viruses contain multiple mutations within the immunodominant head domain of hemagglutinin (HA) compared to the antigens used in stockpiled vaccines. It is unclear if these stockpiled vaccines will need to be updated to match the contemporary H5N1 strains. Here we show that a replicating RNA vaccine expressing the HA of an H5N1 isolated from a US dairy cow confers complete protection against homologous lethal challenge in mice. A repRNA encoding the HA of a clade 1 H5 from 2004 (A/Vietnam/1203/2004) as utilized by some stockpiled vaccines, confers only partial protection. Our data highlight the utility of nucleic acid vaccines to be rapidly updated to match emergent viruses of concern while demonstrating that contemporary bovine H5N1 viruses can evade immunity elicited by historical HA antigens.

Background: Partial-thickness rotator cuff tears (PTRCTs), often considered less severe than full-thickness rotator cuff tears (FTRCTs), can be equally symptomatic. Despite the prevalence of PTRCTs, scholarly attention has predominantly focused on FTRCTs, resulting in a relative neglect of PTRCTs. This study aimed to assess the incidence of surgical repairs for PTRCTs in the United States (U.S.) using the Nationwide Ambulatory Surgery Sample (NASS) database and delineate practice patterns among a group of American Shoulder and Elbow Surgeons (ASES) members. Methods: The NASS database, representing approximately 67% of U.S. ambulatory surgical encounters, was queried to obtain the incidence of PTRCT and FTRCT repairs for the year 2019. Data on patient sex, hospital location, setting, teaching affiliation and size, and primary payor were also obtained. Separately, a retrospective chart review was conducted by 13 ASES research group members, collecting data on rotator cuff repairs performed from July 2021 to June 2022 at their individual institutions. Collected data included age, sex, extent and type of rotator cuff tears, duration of symptoms prior to surgical repair, and type and duration of nonoperative treatment. Results: The NASS database showed that PTRCT repairs accounted for at least 23% of the 187,787 rotator cuff repairs performed in 2019, with potential underestimation due to unspecified tear categorization. The retrospective chart review of the ASES research group revealed that PTRCT repairs constituted 27.8% of all rotator cuff repairs with substantial variability among institutions (8.6%-67.1%), that nonoperative measures were commonly employed, with a mean 12-month duration before surgical repair, and that the most common type of nonoperative treatment was supervised physical therapy combined with corticosteroid injection (37.7%). Discussion: This study revealed approximately one-fourth of all rotator cuff repairs conducted in the U.S. were attributed to PTRCTs with substantial variability in proportion of PTRCT repairs across individual orthopedic practices. The overall duration of nonoperative treatment was consistent with the existing literature. This study provides insights into the landscape of PTRCT repairs and associated practice patterns. Further investigation into factors influencing treatment decisions is warranted.

Background and aims – Cinchona (Rubiaceae) tree bark is the key source of quinine alkaloids used as malaria treatment. Cinchona trees were introduced to Democratic Republic of the Congo (DRC) in the early 20th century. Currently, the eastern DRC accounts for an estimated 55% of the global supply of quinine. The aim of this study is to obtain more insights into what context Cinchona is cultivated, what the scale of the farming and its management is, and how specific risks are being dealt with. Material and methods – Data was collected on Cinchona tree distribution, socio-economic variables, farm characteristics, and cultivation techniques based on interviews with 185 smallholder farmers in five regions (groupements) across the eastern DRC. Key results – Most Cinchona trees are grown at elevations between 1588 and 1627 m a.s.l. and most farmers preferred growing C. calisaya in a monoculture cultivation system, with in vivo propagation, and their own seed sources. Cassava was the dominant crop as previous cultivation and as a crop grown together with Cinchona. Eucalyptus was the dominant tree species grown together with Cinchona. Furthermore, most of the farmers apply a 1 × 1 m spacing and most do not use any additional fertilizer input. The most reported plant disease is linear canker. Conclusion – To sustainably increase the productivity of Cinchona in the DRC, smallholder farmers should be given appropriate training to empower them to carry out their own in vitro propagation and apply integrated soil fertility management and integrated pest management. Our results provide information on current cultivation of Cinchona in the DRC, which may become more important given the rising resistance of the malaria parasite against other medicines.

Abstract Background Diagnostic tests and knowledge of their diagnostic accuracies are important for animal trypanosomosis surveillance and treatment. Methodology : A cross-sectional study was conducted in November 2021 to compare the performance of rapid diagnostic test (RDT) and PCR-based assay for the detection of trypanosome infections. Random sampling and probability proportional to size sampling were used to sample study households and animals from the sampled household respectively. Animals were screened for the presence of trypanosomes using both tests. A total of 100 cattle (52 from Apac and 48 from Kiryandongo districts) were included in the study. The percentage of positive tests, sensitivity, and specificity of the tests using mini PCR as a reference were computed. Cohen’s kappa statistics was computed to assess how well the rapid diagnostic test agrees with the mini PCR. McNemar’s statistic assessed if the proportion of positive tests identified by mini PCR significantly differed from that identified by the rapid diagnostic test. Results The mini PCR test detected 31.2% Trypanosome spp positive samples in Kiryandongo while it detected only 5.7% positive samples in Apac district. The rapid diagnostic test (RDT) analysis detected 91.6% Trypanosome spp positive samples in Kiryandongo district and only 46.1% in Apac district. T. congolense was the most common Trypanosoma species identified in Apac (36.5%) and Kiryandongo (47.9%) by the RDT. The percentage of each of the Trypanosome species (T.vivax, T.congolense, and mixed infection of T.vivax and T. congolense) detected by RDT differed significantly (p

Abstract Stress is a key factor in psychotic relapse, and mindfulness offers stress resilience and well-being benefits. This study examined the effects of mindfulness-based intervention for psychosis (MBI-p) in preventing relapse at 1 year among patients with remitted psychosis in Hong Kong. MBI-p is a newly developed manual-based mindfulness protocol and was tested to have improved well-being and clinical outcomes in a pilot study with remitted psychosis patients. In this multisite, single-blind, 1-year randomized controlled trial (RCT), 152 fully remitted patients diagnosed with schizophrenia or non-affective psychosis were randomized to receive either a 7-week MBI-p or a 7-week psychoeducation program. Outcomes were assessed before and after the intervention, and then monthly for one year. Relapse rate and severity at one year were the primary outcomes. Secondary outcomes included psychopathology, functioning, mindfulness, and psychosocial factors such as stress and expressed emotions. No significant differences were found in the rate and severity of relapse between the MBI-p and psychoeducation groups in either intention-to-treat or per-protocol analyses. While MBI-p improved observation and non-reactivity to the inner experience of mindfulness, psychoeducation was found to benefit functioning and psychosocial functioning more than MBI-p. This is the first RCT to test MBI-p’s effectiveness in preventing relapse among patients with remitted psychosis in Hong Kong. We postulate that the lack of significance is due to the heightened effectiveness of psychoeducation in coping with stress during the pandemic and the multifactorial causes leading to relapse. This suggests the possibility of combining these two interventions to improve their efficacy. Trial registration: NCT04060498.

Abstract Background Dementia poses a significant burden on healthcare systems. Early identification of individuals at risk for cognitive decline is crucial. The retina, an extension of the central nervous system, reflects neurodegenerative changes. Optical coherence tomography (OCT) is a non-invasive tool for assessing retinal health and has shown promise in predicting cognitive decline. However, prior studies produced mixed results. Methods This study investigated a large cohort (n = 490) of Asian individuals attending memory clinics. Participants underwent comprehensive neuropsychological testing annually for five years. Retinal thickness was measured by OCT at baseline. We assessed the association between baseline retinal thickness and subsequent cognitive decline. Results Participants with a significantly thinner macular ganglion cell-inner plexiform layer (GCIPL) at baseline (≤ 79 μm) had a 38% greater risk of cognitive decline compared to those who did not (≥ 88 μm; p = 0.037). In a multivariable model accounting for age, education, cerebrovascular disease status, hypertension, hyperlipidemia, diabetes and smoking, thinner GCIPL was associated with an increased risk of cognitive decline (hazard ratio = 1.14, 95% CI = 1.01–1.30, p = 0.035). Retinal nerve fiber layer (RNFL) thickness was not associated with cognitive decline. Conclusions This study suggests that OCT-derived macular GCIPL thickness may be a valuable biomarker for identifying individuals at risk of cognitive decline. Our findings highlight GCIPL as a potentially more sensitive marker compared to RNFL thickness for detecting early neurodegenerative changes. Trial registration number and name of the trial registry National Healthcare Group Domain-Specific Review Board (NHG DSRB) reference numbers DSRB Ref: 2018/01368. Name of the trial: Harmonisation project.

Abstract There is uncertainty about how best to diagnose asthma, especially in primary care where mis-diagnosis is common. To address this, we developed a clinical decision support system (CDSS) for asthma diagnosis in children and young people (aged 5-25 years). This study explored the feasibility and acceptability of the CDSS in UK primary care. We recruited general practices from England and Scotland. The CDSS was available for use during routine consultations for six months. We analysed CDSS usage and, toward the end of the study, undertook qualitative interviews with clinicians who had used the CDSS. Within the 10 practices who completed the study, the CDSS was used by 75 out of 94 clinicians. 11 clinicians from 8 practices were interviewed. The CDSS was acceptable to participants who particularly commented on the ease of use and auto-population of information from the patient record. Barriers to use included the inability to record findings directly into the patient notes and a sense that, whilst possibly useful for trainees and junior colleagues, the CDSS would not necessarily lead to a change in their own practice. The CDSS was generally well received by primary care clinicians, though participants felt it would be most useful for trainees and less experienced colleagues.

Bacterial biocontrol agents that antagonize soilborne pathogens are increasingly considered alternatives to chemical pesticides, but their in vivo efficacy is often inconsistent, restricting commercial use. The efficacy of a biocontrol agent can depend on rhizosphere competence and its interaction with native microbiomes, which can affect ecosystem functioning. This study investigated the capacity of a Bacillus cereus sensu lato biocontrol strain (S-25) to persist on roots and in the rhizosphere of cucumber and evaluated its impact on bacterial and fungal community composition in the rhizosphere in the absence and presence of Rhizoctonia solani, the causative agent of damping-off disease in young seedlings. Following amendment, S-25 abundance in the cucumber rhizosphere decreased by two orders of magnitude but remained relatively high for the duration of the experiment, in contrast to the root surface, where it was not detected. Amendment with S-25 significantly reduced the incidence of disease caused by R. solani without reducing the relative abundance of the fungal pathogen. Interestingly, R. solani did not substantially alter the rhizosphere microbial community, whereas S-25 reduced bacterial diversity and facilitated a shift in community composition, with increased relative abundance of Acidobacteriota and Actinomycetota, and reduced abundance of Pseudomonadota, Bacteroidota, and Verrucomicrobiota. Collectively, this study provides important insights into the mode of persistence of biocontrol agents and their effect on native microbiomes in the rhizosphere of pathogen-inoculated plants. It demonstrates that amendment can significantly alter local microbiomes and suggests that optimizing amendment regimes or selecting strains with higher rhizosphere competence can enhance future biocontrol agents.

Abstract Background Over the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer. Methods The RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac. The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI. Conclusion The RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808 .

Aims and method The aim was to evaluate an innovative pathway in police custody suites that aimed to specifically address alcohol-related health needs through screening and brief interventions by police custody staff. This paper presents a qualitative investigation of challenges involved in implementing the pathway. Qualitative interviews were carried out with 22 staff involved with commissioning and delivering the pathway; thematic analysis of interview data was then undertaken. Results An overarching theme highlights the challenges and uncertainties of delivering brief alcohol interventions in the custody suite. These include challenges related to the setting, the confidence and competence of the staff, identifying for whom a brief intervention would be of benefit and the nature of the brief intervention. Clinical implications Our findings show that there is a lack of clarity over how alcohol-related offending can be identified in police custody, whose role it is to do that and how to intervene.

Abstract Background Cognitive impairment is an increasingly recognized comorbidity of diabetes, yet the mechanisms underlying this association remain poorly understood. This knowledge gap has contributed to conflicting findings regarding the impact of diabetes on long-term cognitive outcomes in older adults. The presence of cerebrovascular disease (CeVD) may potentially modify this relationship. However, interactive effect between diabetes and subclinical MRI markers of CeVD on cognitive trajectories and incident dementia remains unexplored. Methods A total of 654 participants underwent brain MRI at baseline, from whom 614 with at least one follow-up were selected for longitudinal analysis. Cognitive tests were performed annually up to 5 years. CeVD markers of interest were lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), cortical microinfarcts (CMIs), intracranial stenosis (ICS), and cortical infarcts. Blood-based Alzheimer biomarkers, including p-tau181 and p-tau181/Aβ42 ratio, were used as indicators of Alzheimer pathology. Results At baseline, diabetes was associated with lower cognitive performance and higher burden of CeVD, but not p-tau181 or p-tau181/Aβ42 ratio. Longitudinally, we found an interactive effect of diabetes and WMHs, rather than an independent effect of diabetes, on cognitive decline and dementia risk. Subgroup analyses showed association of diabetes with cognitive outcomes was stronger in participants with high WMHs load but non-significant in those with low WMHs load. Moreover, these associations remained unchanged after adjusting for blood-based Alzheimer biomarkers. Conclusions The effect of diabetes on cognitive decline is contingent upon the presence of WMHs and independent of Alzheimer’s pathology. This finding raises the possibility of utilizing WMHs as an imaging biomarker to identify diabetic subgroup at greater risk of developing cognitive impairment. Furthermore, therapeutic interventions targeting WMHs may prevent cognitive deterioration in older adults with diabetes.

Abstract Approximately a quarter of the human genome consists of gene deserts, large regions devoid of genes often located adjacent to developmental genes and thought to contribute to their regulation. However, defining the regulatory functions embedded within these deserts is challenging due to their large size. Here, we explore the cis-regulatory architecture of a gene desert flanking the Shox2 gene, which encodes a transcription factor indispensable for proximal limb, craniofacial, and cardiac pacemaker development. We identify the gene desert as a regulatory hub containing more than 15 distinct enhancers recapitulating anatomical subdomains of Shox2 expression. Ablation of the gene desert leads to embryonic lethality due to Shox2 depletion in the cardiac sinus venosus, caused in part by the loss of a specific distal enhancer. The gene desert is also required for stylopod morphogenesis, mediated via distributed proximal limb enhancers. In summary, our study establishes a multi-layered role of the Shox2 gene desert in orchestrating pleiotropic developmental expression through modular arrangement and coordinated dynamics of tissue-specific enhancers.

In the software product line (SPL), configuration management (CM) is a multidimensional problem that is taking great attention in software development. Although much research has been developed on this topic, there is no clear view of the current state of it. In this study, we used a systematic method to develop a map of configuration management across product lines to classify relevant literature. The resulting map provides an overview of this research through the identification of the main activities of the CM, the types and trends of research as well as the maturity of existing contributions. Because the CM in SPL is still in its formative stage, we believe that this work will contribute to the process of providing a more common and coherent conceptual basis for its understanding. In addition, it can help to detect important research problems and gaps.

When calves are reared by cows, separation can be stressful, and it is often advised to use gradual weaning to minimize this stress. In foster cow systems, one gradual weaning method is to remove the foster cows, one by one, from the cow-calf group. The response to one-by-one removal of foster cows of 32 calves housed in 5 groups was studied. Calves were fostered to a designated foster cow individually, in pairs, or in trios, at the age of 1 to 2 wk and then housed in groups of 4 to 6 foster cows and 6 to 11 calves until gradual weaning started at 3 mo of age. Calf behavior and aggression received by calves from cows were recorded using video during 18 h before any foster cow was removed, as well as 18 h before and 18 h after the designated foster cow was removed from the group. Before any foster cow was removed, the calves spent a similar amount of time sucking the designated foster cow and other cows (in total 43 ± 5 min/18 h). The total duration of sucking was similar before and after the designated foster was removed, as the duration of sucking other cows increased. The number of aggressive events received from other cows also increased. The results indicate that milk availability for the group of calves decreases as foster cows are gradually removed and that the older and heavier calves increasingly compete with the younger and lighter calves for the available milk. This weaning method may also compromise the welfare of the foster cows that are left to wean off an increasing number of calves, and this warrants further research.

Wastewater surveillance (WWS) can leverage its wide coverage, population-based sampling, and high monitoring frequency to capture citywide pandemic trends independent of clinical surveillance. Here we conducted a nine months daily WWS for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 12 wastewater treatment plants (WWTPs), covering approximately 80% of the population, to monitor infection dynamics in Hong Kong, China. We found that the SARS-CoV-2 virus concentration in wastewater was correlated with the daily number of reported cases and reached two pandemic peaks three days earlier during the study period. In addition, two different methods were established to estimate the prevalence/incidence rates from wastewater measurements. The estimated results from wastewater were consistent with findings from two independent citywide clinical surveillance programmes (rapid antigen test (RAT) surveillance and serology surveillance), but higher than the cases number reported by the Centre for Health Protection (CHP) of Hong Kong, China. Moreover, the effective reproductive number (Rt) was estimated from wastewater measurements to reflect both citywide and regional transmission dynamics. Our findings demonstrate that large-scale intensive WWS from WWTPs provides cost-effective and timely public health information, especially when the clinical surveillance is inadequate and costly. This approach also provides insights into pandemic dynamics at higher spatiotemporal resolutions, facilitating the formulation of effective control policies and targeted resource allocation.

As the COVID-19 pandemic began spreading worldwide in late 2019 and early 2020, many vaccine candidates were developed to combat the disease. However, new COVID-19 variants such as Omicron and Delta continue to emerge globally despite advancements in vaccine technology, leaving certain countries and variants more vulnerable than others to future outbreaks of these variants. This research aims to analyze the susceptibility of different countries to a COVID-19 outbreak, present the first visualization of the spread of COVID-19, and predict which countries are at greater risk for future outbreaks of new variants based on various factors. We created interactive maps to understand the pandemic’s spread and identify high-risk countries based on their vaccination percentages. Then we employed binary classification, K-nearest neighbors (KNN), and neural network machine learning models to predict each country’s risk factor. The risk factor determines whether a country is safe from a new COVID-19 variant based on vaccine percentage and government stringency. The neural network achieved the highest accuracy, classifying countries as high risk or low risk with 94% accuracy. Inspired by the Albert Barabasi model, we graphed connections between countries based on vaccination percentages. These graphs illustrate the correlation between the two countries and better demonstrate how their vaccination rates relate to the probability of a new COVID-19 outbreak.

IntroductionGesture-based interactions provide control over a system without the need for physical contact. Mid-air haptic technology allows a user to not visually engage with the interface while receiving system information and is readily manipulable, which has positive implications for automotive environments. It is important, however, that the user still feels a sense of agency, which here refers to perceiving system changes as caused by their gesture.MethodsIn the current study, 36 participants engaged in an experimental time perception task with an automotive-themed infotainment menu, serving as an implicit quantitative measure of agency. This was supplemented with additional self-reported measures. They selected different icons via gesture poses, with sensory feedback either visually or haptically. In addition, (sensory) feedback was also the same for each icon, arbitrarily different or carried semantic information.ResultsMid-air haptics increased agency compared to visual, and this did not vary as a function of feedback meaning. Agency was also associated with general measures of trust and usability.DiscussionOur findings demonstrate positive implications for mid-air haptics in automotive contexts and highlight the general importance of user agency.

Summary: The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and the emergence of recurrence. Here, we build a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass and the SVZ of 15 patients and two histologically normal SVZ samples as controls. We identify a ZEB1-centered mesenchymal signature in the tumor cells of the SVZ. Moreover, the SVZ microenvironment is characterized by tumor-supportive microglia, which spatially coexist and establish crosstalks with tumor cells. Last, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays reveal that the interleukin (IL)-1β/IL-1RAcP and Wnt-5a/Frizzled-3 pathways represent potential therapeutic targets in the SVZ. Our data provide insights into the biology of the SVZ in patients with GBM and identify potential targets of this microenvironment.

Climate change is a significant threat to public health, exacerbating existing challenges in healthcare systems. The anticipated impacts encompassing increased global surface temperatures, rising sea levels, water and food insecurity, geopolitical instability and the heightened frequency, duration, and intensity of natural disasters coupled with the healthcare sector's contribution to carbon emissions, necessitate urgent action from healthcare professionals. However, while healthcare professionals are called to engage in climate action, defined as an action to combat climate change and its impacts, the healthcare workforce also faces unprecedented challenges exacerbated by the public health emergencies (e.g.: COVID-19 pandemic) such as fatigue, burnout, and workforce shortages. Dealing with these challenges leaves little opportunity or time for healthcare professionals to engage in climate change mitigation and adaptation. In this perspective paper, we outline the fundamental aspects of change fatigue and suggest solutions to engage healthcare professionals in climate action.

Summary: Background: Infections and sepsis are leading causes of morbidity and mortality in women during pregnancy and the post-pregnancy period. Using data from the 2017 WHO Global Maternal Sepsis Study, we explored the use of early warning systems (EWS) in women at risk of sepsis-related severe maternal outcomes. Methods: On April 27, 2023, we searched the literature for EWS in clinical use or research in obstetric populations. We calculated the proportion of women for whom each existing EWS identified them as at risk for developing severe maternal outcomes by infection severity (complications and severe maternal outcomes). Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios, and J statistics were calculated to assess EWS performance. Machine learning was used to test the diagnostic potential of routine maternal sepsis markers. Findings: 21 EWS were assessed in 2560 women from 46 countries with suspected or confirmed infections. The NICE Risk Stratification tool, Modified Shock Index, maternity Systemic Inflammatory Response Syndrome, and Early Maternal Infection Prompts scores had high sensitivity (88.1–97.5%) for identifying sepsis-related severe maternal outcomes. The quick Sequential Organ Failure Assessment (SOFA) in Pregnancy score and Obstetrically modified SOFA had high specificity (90.4–100%) for identifying women with sepsis-related severe maternal outcomes. Furthermore, combinations of sepsis markers had very low sensitivity and high specificity using machine learning. Interpretation: No score demonstrated enough diagnostic accuracy to be used alone to identify sepsis. However, obstetric—and sepsis-specific EWS performed better for early identification of maternal sepsis than non-obstetric and non-sepsis-specific scoring systems. There are limitations to applying EWS to real-world data, mainly due to the incompleteness of medical data that hinders EWS effectiveness. There is a need to continue developing and testing criteria for early identification of maternal sepsis. Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), WHO, Merck for Mothers, U.S. Agency for International Development, Wellcome Trust, and National Institute for Health and Care Research.

Category: Ankle Arthritis; Ankle Introduction/Purpose: Osteoarthritis (OA) of the tibiotalar joint is associated with a high degree of morbidity, comparable to the final stages of renal and heart failure. The incidence of OA in the tibiotalar joint is as high as 47.7 per 100,000 inhabitants, most of whom will require surgical intervention to improve their quality of life. To date, there is scarce literature on the alignment in Total Ankle Arthroplasty (TAA) and its implications for patient-reported outcome measures (PROMs). Furthermore, no evidence has yet analyzed the association between alignment assessed with weight-bearing CT (WB-CT) and PROMs. Methods: A prospective cohort study was conducted, including all TAAs performed between 2015 and 2023, with a minimum follow-up of 12 months and a WB-CT taken within the first 12 months postoperatively. Revision TAAs, those lost to follow-up, and cases lacking WB-CT in the first 12 months were excluded. The anterior distal tibial angle (ADTA) and medial distal tibial angle (MDTA) were assessed with WB-CT, along with the internal rotational angle of the talar component. TAAs exhibiting an ADTA or MDTA with angles outside the range of normality were considered to have misaligned prostheses. The PROMs were assessed in the preoperative scenario and again at 2 months, 6 months, 1-year and 2-year post-surgery. The association between alignment and PROMs was evaluated using the Mann-Whitney test, while the association between the internal rotation of the talar component and PROMs was analyzed with the Spearman test. Statistical significance was set at p=0.05. Results: 74 TAAs were included. No statistically significant difference was found between correctly aligned and misaligned prostheses in the ADTA or MDTA and PROMs. However, the internal rotation angle of the talar component showed a statistically significant association with both the vitality component (p = 0.01, rho = -0.52) and the physical function component (p < 0.01, rho = 0.60) of the SF-36 score. Meanwhile, the VAS, AOFAS, FAAM, FAOS, and SMFA showed no statistical association. Conclusion: In our cohort of patients with TAA, coronal or sagittal misalignment, as assessed with WB-CT, shows no association with PROMs. It's worth mentioning that PROMs are subjective, multifactorial measures that should be interpreted with caution, and the importance of achieving correct alignment should not be minimized. Although internal rotation of the talar component is associated with better PROMs, to date, no cutoff value has been described, and further efforts should be made to elucidate the optimum internal rotation of the talar component.

This research involves the development of a thermoplastic polymer biocomposite in a matrix of recycled expanded polystyrene reinforced with banana pseudostem fiber and crushed peanut shells. Six models were produced with different doses, of which the one that obtained the best result was the last one, with a content of 63% EPS, 25% banana fiber (40 mm), and 12% crushed peanut shells (1 to 3 mm). In the bending test, it achieved an MOR of 12 N/mm2 and an MOE of 55 N/mm2; the compressive strength was 8.60 N/mm2; moisture absorption was 10%; and in the thermal conductivity test, it had a value of 0.095 W/m‧k, which means it has an adequate insulating capacity. The values obtained comply with the Ecuadorian standard INEN 3110 for particleboards. This work shows the capacity of the materials used to produce different light, resistant, insulating components that can be used in buildings.

Category: Sports Introduction/Purpose: Achilles tenorrhaphy is one of the most common procedures performed in foot and ankle surgery, and percutaneous techniques are safe and achieve good outcomes. Over the past 20 years, the WALANT technique (Wide-awake local anesthesia no-tourniquet) has gained popularity due to its advantages: it does not depend on the availability of complex operating rooms or anesthetists, allows for intraoperative functional evaluation, presents lower costs, and few complications have been reported. However, there is scarce literature regarding the complications associated with the WALANT technique in foot and ankle surgery, especially in percutaneous Achilles tenorrhaphy. Methods: A retrospective cohort study included patients over 18 who underwent percutaneous Achilles tenorrhaphy using the Dresden technique, with a minimum follow-up of 6 months. The WALANT group was treated on an outpatient basis in a minor surgery theater, while the standard treatment (ST) group underwent surgery in the main theater with spinal anesthesia. Categorical data were analyzed using the Chi-square test, with statistical significance set at p = 0.05. Results: A total of 51 patients were included (19 WALANT and 32 ST), all male, with an average age of 43.1 years. There was one case of surgical wound infection (SWI) in the WALANT group (5.26%); there were no cases of SWI in the ST group, with no statistically significant differences (p=0.18). In the WALANT group, there were no cases of re-rupture, and in the ST group, there was 1 (6.3%) re-rupture that did not require reintervention; no statistically significant difference was found (p=0.19). Additionally, 15.79% of the WALANT group presented with transient hypoesthesia (up to 6 months) of the sural nerve, compared to 3.13% in the ST group, with no statistically significant differences (p=0.10). No cases of deep venous thrombosis were found in either group. Conclusion: The WALANT technique demonstrates no differences in complications between the two groups, indicating it is considered a safe technique regarding associated complications. It's worth mentioning that the WALANT technique is considered a more cost-effective option due to the lower use of resources.

There is a growing interest in understanding the factors that influence a user's perception and preferences for video quality. This study specifically focuses on how various factors, including video content, display settings, viewer characteristics, and the ambient environment, affect the subjective video quality assessment (VQA) of TV displays. To investigate these factors, two psychophysical experiments were conducted, and the results indicate that all four factors have a significant impact on video quality perception in different ways. This study is beneficial for researchers and developers who aim to improve display and environmental settings to provide viewers with the best possible viewing experience.

Indonesia, known for its high biodiversity, is threatened due to alien plants that invade local plant species in forest areas. West Bali National Park is overgrown with invasive exotic plants, such as Lantana camara L., known locally as the kembang telek. The research aims to predict the distribution of L. camara using species distribution models (SDMs) and analysis variable contribution in the model featured in the biodiversity climate change virtual laboratory (BCCVL) application. L. camara distribution prediction model in Bali used the Bioclim data input by identifying areas of low, medium, and high habitat suitability. Central mountainous regions, including parts of Buleleng, Jembrana, Bangli, Karangasem, and Tabanan, show the highest suitability. Response curves demonstrated the correlation between climate variables and occurrence probability, highlighting the specific condition of rainfall and temperature ranges favoring Lantana's growth. The model showed a reliable AUC value of 0.89, indicating realibility. Potential improvements through additional environmental parameters were suggested. While L. camara has some potential benefits as a medicinal plant in Balinese culture, its invasive nature poses significant threats to native ecosystems. The predictive map offers valuable insights for authorities to implement initiative-taking strategies for preventing and controlling Lantanas spread in vulnerable areas of Bali.

This study is the first to optimize the use of return air, along with other supply conditions, in underfloor air distribution (UFAD) systems to achieve acceptable indoor air quality (IAQ) and thermal comfort while minimizing energy consumption. A comprehensive 3D computational fluid dynamics (CFD) model has been developed to simulate airflow patterns, thermal fields, and CO2 distribution in a standard office environment. The CFD approach used in this research has been validated against experimental data found in the literature. A parametric study was conducted, varying supply diffuser size, supply air velocity and temperature, and the return air ratio to identify the optimal UFAD system settings. These settings aim to minimize energy use while keeping CO2 levels within the recommended 1100 ppm in the breathing zone and ensuring that the percentage of people dissatisfied (PPD) remains at 10%. The findings indicate that using a 20 cm × 20 cm supply diffuser, setting the supply air temperature to 17°C, supply velocity to 1.2 m/s, and recirculating 29% of the return air will result in optimal performance.

Heart failure, a leading driver of global mortality, remains a topic of intense contemporary research interest due to the prevailing unmet need in cardiometabolic therapeutics. Numerous mechanisms with the potential to influence the onset and development of heart failure remain incompletely understood. Firstly, myocardial autophagy, which involves lysosomal degradation of damaged cellular components, confers context-dependent beneficial and detrimental effects. Secondly, sterile inflammation may arise following cardiac stress and exacerbate the progression of heart failure. Inflammation changes in a temporal manner and its onset must be adequately resolved to limit progression of heart failure. Mitochondria are an important factor in contributing to sterile inflammation by releasing damage associated molecular patterns (DAMPs) including mitochondrial DNA (mtDNA). Accordingly, this is one reason why the selective autophagy of mitochondria to maintain optimal function is important in determining cardiac function. In this review, we examine the increasing evidence suggesting crosstalk between autophagy and sterile inflammation together with their role in the development of heart failure. In particular, this is exemplified in the preclinical models of ischaemia/reperfusion injury and pressure overload induced heart failure. We also highlight potential therapeutic approaches focusing on autophagy and addressing sterile inflammation, aiming to enhance outcomes in heart failure.

Earthquake magnitude prediction is critical in seismology, with significant implications for disaster risk management and mitigation. This study presents a novel earthquake magnitude prediction model by integrating regression analysis with Convolutional Recurrent Neural Networks (CRNNs). It utilises Convolutional Neural Networks (CNNs) for spatial feature extraction from 2-dimensional seismic signal images and Long Short-Term Memory (LSTM) networks to capture temporal dependencies. The innovative model architecture incorporates residual connections and specialised regression techniques for sequential data. Validated against a comprehensive seismic dataset, the model achieves a Mean Squared Error (MSE) of 0.1909 and a Root Mean Squared Error (RMSE) of 0.4369, with a coefficient of determination of 0.79772. These metrics, alongside a correlation coefficient of 0.8980, demonstrate the model's accuracy and consistency in predicting earthquake magnitudes, establishing its potential for enhancing seismic risk assessment and informing early warning systems.

Background: Shoulder arthroplasty (SA) has been shown to improve quality of life, though outcomes may vary between individuals. Multiple factors may affect outcomes, including preoperative mental health conditions (MHCs). The goal of this systematic review was to evaluate the clinical and functional outcomes after SA in patients with MHC compared to patients without MHC. Methods: This systematic review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines outlined by Cochrane Collaboration. A search of PubMed, the Medline Library, and EMBASE was conducted from inception until September 2023 to obtain studies reporting outcomes after total shoulder arthroplasty and reverse total shoulder arthroplasty in patients with and without MHC. Study characteristics and information on clinical and functional outcomes were collected. All included studies were case-control studies. The methodological quality of the included primary studies was appraised using the methodological index for nonrandomized studies scoring. Results: Eleven articles published between 2016 and 2023 met inclusion criteria. In total, 49,187 patients, 49,289 shoulders, and five different MHC were included. 8134 patients in the cohort had a diagnosed MHC. The mean patient age was 67.8 years (range, 63.5-71.6 years), and 52.6% of the patients were female. The mean follow-up time was 35.5 months (range, 16.2-58.3 months). Reverse total shoulder arthroplasty was the most common type of procedure (25,543 shoulders, 51.8%). Depression and anxiety were the most reported psychiatric diagnoses (7990 patients, 98.2%). Patients with versus without MHC reported mean improvements of 38 and 42 in American Shoulder and Elbow Surgeons shoulder score and mean Visual Analog Scale pain improvements of 4.7 and 4.9, respectively. Mean complication rates of 31.4% and 14.2% were observed in patients with versus without MHC, respectively. The most prevalent surgical complication in patients with MHC was infection (1.8%), followed by prosthetic complication (1.7%), and adhesive capsulitis (1.6%). Conclusions: Patients with MHC may have lower preoperative range of motion, worse postoperative shoulder function, and higher postoperative pain levels than patients without MHC. Patients with MHC demonstrated improvements in range of motion and functional outcomes after SA but had higher reported complication and revision rates when compared to patients without MHC. Depression and anxiety were the leading conditions correlated with lower outcomes in patients with MHC after SA. Preoperative physical therapy, mental health counseling, and expectation setting may help these patients reach the maximal achievable benefit from SA.

Abstract Background Several diagnostic environments in Uganda lack real-time, robust and high-throughput technologies for comprehensive typing of microbes, which is a setback to infectious disease surveillance. This study combined various wet laboratory diagnostics to understand the epidemiology of pathogenic staphylococci isolated from animals in Uganda and the implications for global health security priorities. Methods A retrospective study was conducted employing records and pathogenic staphylococci (from animals) archived at the Central Diagnostic Laboratory (CDL), Makerere University, Uganda, between January 2012 and December 2019. The bacteria were speciated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and tested for virulence factors [beta lactamases, lecithinase, deoxyribonuclease (DNase), haemolysins] and resistance to ten antimicrobials of clinical and veterinary relevance. Tetracycline and methicillin resistance genes were also tested. Results The prevalent diseases were mastitis in cattle and skin infections in dogs. Of the 111 staphylococci tested by MALDI-TOF MS, 79 (71.2%) were Staphylococcus aureus, 27 (24.3%) were Staphylococcus pseudintermedius and 5 (4.5%) were Staphylococcus schleiferi. All these strains expressed haemolysins. The prevalence of strains with lecithinase, penicillinase, cephalosporinase and DNase was 35.9% (14/39), 89.7% (35/39), 0.0% (0/39) and 87.2% (34/39), respectively. Staphylococci were primarily resistant to early penicillins (over 80%), tetracycline (57.7%), and chloramphenicol (46.2%). Minimal resistance was noted with cloxacillin (0.0%), ciprofloxacin (9.6%), and cefoxitin (3.8%). The prevalence of multidrug resistance (MDR) was 78.8% for general staphylococci, 82.2% for S. aureus, 73.1% for S. pseudintermedius, and 60.0% for S. schleiferi. Multidrug resistant staphylococci were significantly more prevalent in the cattle isolates than in the dog isolates (P

A new species of rock-dwelling Leiolepis is described from the Khorat Plateau in northeastern Thailand. Leiolepis glaurung sp. nov. can be differentiated from all other sexual species of Leiolepis by a combination of having a black gular region with a wide medial yellow stripe, a yellow ventrum with black mottling, bright red to orange subcaudal coloration, having reduced to no expandable flanks, and having only one black transverse bar on the flanks. This is the first rocky habitat-adapted Leiolepis. Leiolepis glaurung sp. nov. demonstrates numerous ecological adaptations to survive in these rocky habitats. Leiolepis are known for their expandable flanks with bright display colors, however Leiolepis glaurung sp. nov. has reduced or no ability to expand its flanks. We hypothesize this is an adaptation to reduce their body diameter to better fit into smaller rocky burrows unlike the larger and deeper burrows constructed in looser soils by other Leiolepis species. This discovery increases the number of Leiolepis species in Thailand to six, and worldwide to 11.

Abstract Background Honey bees are the principal commercial pollinators. Along with other arthropods, they are increasingly under threat from anthropogenic factors such as the incursion of invasive honey bee subspecies, pathogens and parasites. Better tools are needed to identify bee subspecies. Genomic data for economic and ecologically important organisms is increasing, but in its basic form its practical application to address ecological problems is limited. Results We introduce HBeeID a means to identify honey bees. The tool utilizes a knowledge-based network and diagnostic SNPs identified by discriminant analysis of principle components and hierarchical agglomerative clustering. Tests of HBeeID showed that it identifies African, Americas-Africanized, Asian, and European honey bees with a high degree of certainty even when samples lack the full 272 SNPs of HBeeID. Its prediction capacity decreases with highly admixed samples. Conclusion HBeeID is a high-resolution genomic, SNP based tool, that can be used to identify honey bees and screen species that are invasive. Its flexible design allows for future improvements via sample data additions from other localities.

Abstract Background Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson’s Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. Methods In a case–control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer’s disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. Results The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. Conclusions and Relevance Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.

Abstract Multiple sclerosis (MS) is uncommon in China and the standard of care is underdeveloped, with limited utilization of disease-modifying treatment (DMT). An understanding of real-world disease burden (including direct medical, non-medical, and indirect costs, such as loss of productivity), is currently lacking in this population. To investigate the overall burden of managing patients with MS in China, a cross-sectional survey of physicians and their consulting patients with MS was conducted in 2021. Physicians provided information on healthcare resource utilization (HCRU; consultations, hospitalizations, tests, medication) and associated costs. Patients provided data on changes in their life, productivity, and impairment of daily activities due to MS. Results were stratified by disease severity using generalized linear models, with a p value

Abstract Background Aboriginal and Torres Strait Islander communities in remote Australia have initiated bold policies for health-enabling stores. Benchmarking, a data-driven and facilitated ‘audit and feedback’ with action planning process, provides a potential strategy to strengthen and scale health-enabling best-practice adoption by remote community store directors/owners. We aim to co-design a benchmarking model with five partner organisations and test its effectiveness with Aboriginal and Torres Strait Islander community stores in remote Australia. Methods Study design is a pragmatic randomised controlled trial with consenting eligible stores (located in very remote Northern Territory (NT) of Australia, primary grocery store for an Aboriginal community, and serviced by a Nutrition Practitioner with a study partner organisation). The Benchmarking model is informed by research evidence, purpose-built best-practice audit and feedback tools, and co-designed with partner organisation and community representatives. The intervention comprises two full benchmarking cycles (one per year, 2022/23 and 2023/24) of assessment, feedback, action planning and action implementation. Assessment of stores includes i adoption status of 21 evidence-and industry-informed health-enabling policies for remote stores, ii implementation of health-enabling best-practice using a purpose-built Store Scout App, iii price of a standardised healthy diet using the Aboriginal and Torres Strait Islander Healthy Diets ASAP protocol; and, iv healthiness of food purchasing using sales data indicators. Partner organisations feedback reports and co-design action plans with stores. Control stores receive assessments and continue with usual retail practice. All stores provide weekly electronic sales data to assess the primary outcome, change in free sugars (g) to energy (MJ) from all food and drinks purchased, baseline (July-December 2021) vs July-December 2023. Discussion We hypothesise that the benchmarking intervention can improve the adoption of health-enabling store policy and practice and reduce sales of unhealthy foods and drinks in remote community stores of Australia. This innovative research with remote Aboriginal and Torres Strait Islander communities can inform effective implementation strategies for healthy food retail more broadly. Trial registration ACTRN12622000596707, Protocol version 1.

Achievement inequality has been on the rise. Globally, students from disadvantaged backgrounds perform worse academically than their peers, even with equal ability. This represents a significant loss of potential and perpetuates inequality. We organized this interdisciplinary Special Collection to uncover experiences that contribute to achievement inequality, identify interventions that reduce it, and sketch a research agenda. We hope it inspires scholars committed to addressing social problems through basic research.

Abstract Predicting the blood–brain barrier (BBB) permeability of small-molecule compounds using a novel artificial intelligence platform is necessary for drug discovery. Machine learning and a large language model on artificial intelligence (AI) tools improve the accuracy and shorten the time for new drug development. The primary goal of this research is to develop artificial intelligence (AI) computing models and novel deep learning architectures capable of predicting whether molecules can permeate the human blood–brain barrier (BBB). The in silico (computational) and in vitro (experimental) results were validated by the Natural Products Research Laboratories (NPRL) at China Medical University Hospital (CMUH). The transformer-based MegaMolBART was used as the simplified molecular input line entry system (SMILES) encoder with an XGBoost classifier as an in silico method to check if a molecule could cross through the BBB. We used Morgan or Circular fingerprints to apply the Morgan algorithm to a set of atomic invariants as a baseline encoder also with an XGBoost classifier to compare the results. BBB permeability was assessed in vitro using three-dimensional (3D) human BBB spheroids (human brain microvascular endothelial cells, brain vascular pericytes, and astrocytes). Using multiple BBB databases, the results of the final in silico transformer and XGBoost model achieved an area under the receiver operating characteristic curve of 0.88 on the held-out test dataset. Temozolomide (TMZ) and 21 randomly selected BBB permeable compounds (Pred scores = 1, indicating BBB-permeable) from the NPRL penetrated human BBB spheroid cells. No evidence suggests that ferulic acid or five BBB-impermeable compounds (Pred scores

Introduction: Ovarian cancer has an unknown pathogenesis, and cytokines may play an important role in the aetiology and prognosis. Tumour Necrosis Factor-alpha (TNF-α) and its receptors (TNFR1 and TNFR2) are involved in the biology of ovarian cancer, tumour pathogenesis, and their relationship with prognostic factors. They are involved in biological processes such as immunoregulation, growth modulation, and cell differentiation. Aim: To evaluate stromal immunostaining of TNF-α and its receptors (TNFR1 and TNFR2) in malignant ovarian neoplasms, comparing it with benign ovarian neoplasms and non neoplastic ovarian lesions. Materials and Methods: A cross-sectional study was carried out at the Department of Gynaecology and Obstetrics, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil, from January 1997 to December 2020. Patients with ovarian lesions who underwent surgical treatment according to pre-established criteria (n=95) were included in the study. Patients with benign (n=37) and malignant (n=43) ovarian epithelial neoplasms, and non neoplastic ovarian lesions (n=15) were included. Data evaluated included age, parity, hormonal status (menarche or menopause), histological grade, and staging. Immunohistochemical study was performed to evaluate stromal TNF-α, TNFR1, and TNFR2. Data were analysed by GraphPad Prism 6 and IBM Statistical Package for the Social Sciences (SPSS) Statistics 20.0 software. The comparison between non neoplastic tumours, benign and malignant neoplasms was performed by the Fisher’s exact test with a significance level below 0.05. Results: Considering staining intensity 0 and 1 as “weak immunostaining” and 2 and 3 as “strong immunostaining,” TNF-α stromal immunostaining was stronger (2/3) in benign ovarian neoplasms compared to non neoplastic tumours (p-value=0.0016) and in malignant neoplasms compared to non neoplastic tumours (p-value

Abstract Tiled amplicon sequencing has served as an essential tool for tracking the spread and evolution of pathogens. Over 15 million complete SARS-CoV-2 genomes are now publicly available, most sequenced and assembled via tiled amplicon sequencing. While computational tools for tiled amplicon design exist, they require downstream manual optimization both computationally and experimentally, which is slow and costly. Here we present Olivar, a first step towards a fully automated, variant-aware design of tiled amplicons for pathogen genomes. Olivar converts each nucleotide of the target genome into a numeric risk score, capturing undesired sequence features that should be avoided. In a direct comparison with PrimalScheme, we show that Olivar has fewer mismatches overlapping with primers and predicted PCR byproducts. We also compare Olivar head-to-head with ARTIC v4.1, the most widely used primer set for SARS-CoV-2 sequencing, and show Olivar yields similar read mapping rates (~90%) and better coverage to the manually designed ARTIC v4.1 amplicons. We also evaluate Olivar on real wastewater samples and found that Olivar has up to 3-fold higher mapping rates while retaining similar coverage. In summary, Olivar automates and accelerates the generation of tiled amplicons, even in situations of high mutation frequency and/or density. Olivar is available online as a web application at https://olivar.rice.edu and can be installed locally as a command line tool with Bioconda. Source code, installation guide, and usage are available at https://github.com/treangenlab/Olivar .

Antimicrobial resistance presents a substantial threat to global public health, demanding urgent attention and action. This study focuses on lanthipeptides, ribosomally encoded peptides that display significant structural diversity and hold promising potential as antibiotics. Genome mining was employed to locate biosynthetic gene clusters (BGCs) containing class II lanthipeptide synthetases encoded by lanM genes. A phylogenetic study analyzing homologous sequences of functional LanM sequences revealed a unique evolutionary clade of 17 LanM proteins associated with 12 Clostridium bacterial genomes. In silico exploration identified nine complete BGCs, including one super-cluster containing two co-localized operons from Clostridium cellulovorans 743B, that encode for two new peptides named clostrisin and cellulosin. Each operon was heterologously expressed in Escherichia coli. Molecular weights associated with the expected post-translational modifications of the purified lanthipeptide were confirmed by MS–MS/MS analysis for cellulosin, while clostrisin was not post-translationally modified. Both peptides demonstrated antimicrobial activity against multidrug-resistant bacteria, such as a clinical strain of Staphylococcus epidermidis MIQ43 and Pseudomonas aeruginosa PA14. This is the first report of lanthipeptides from the Clostridium genus produced with its native biosynthetic machinery, as well as chemically and biologically characterized. This study showcases the immense potential of genome mining in identifying new RiPP synthetases and associated bioactive peptides.

This paper presents a method for learning world models for wheel loaders performing automatic loading actions on a pile of soil. Data-driven models were learned to output the resulting pile state, loaded mass, time, and work for a single loading cycle given inputs that include a heightmap of the initial pile shape and action parameters for an automatic bucket-filling controller. Long-horizon planning of sequential loading in a dynamically changing environment is thus enabled as repeated model inference. The models, consisting of deep neural networks, were trained on data from a 3D multibody dynamics simulation of over 10,000 random loading actions in gravel piles of different shapes. The accuracy and inference time for predicting the loading performance and the resulting pile state were, on average, 95% in 1.2 ms and 97% in 4.5 ms, respectively. Long-horizon predictions were found feasible over 40 sequential loading actions.

Mastomys natalensis and M. coucha are commensal rodent species endemic to Africa. A recent taxonomic revision within Mastomys leaves the parasite–host list of M. natalensis questionable and that of M. coucha incomplete. The current study aimed to develop a better understanding of the ectoparasite diversity associated with the 2 distinct but closely related rodent species and to explore the influence of host and habitat type on ectoparasite infestations. Between 2014 and 2020, 590 rodents were trapped in 3 habitat types (village, agriculture and natural) across a wildlife-human/domestic animal interface. In total 48 epifaunistic species (45 ectoparasitic and 3 predatory) represented by 29 genera from 4 taxonomic groups (fleas, lice, mites and ticks) were recorded. Only 50% of the epifauna were shared between the 2 rodent species, with mites the most speciose taxon in both host species. The abundance of epifaunistic individuals, and also those of mites and fleas, were significantly higher on male M. natalensis, while ticks were significantly higher on reproductively active M. natalensis. For both rodent species, infestations by most epifaunistic taxa (on M. natalensis) and some taxa (on M. coucha) were significantly lower in the village as opposed to the less disturbed agricultural and natural habitat types. The study highlights the importance of host life history, even in closely related rodent species, in shaping parasite profiles and a loss of parasite diversity in more extreme anthropogenic habitats.

Genetic diversity enhancement to select Bambara groundnut (Vigna subterranea [L.] Verdc. 2x = 2n = 22) breeding lines with economic traits is imperative to improve the crop's utilization in Sub-Saharan Africa. Gamma radiation is a vital mutagenic agent to create novel allelic combinations required for developing climate-smart Bambara groundnut varieties to contribute to food production and nutrition security in drier regions, including Namibia. Therefore, the objective of the present study was to identify optimal gamma radiation doses to enhance genetic diversity in Bambara groundnut genotypes. The present study was conducted in root boxes under a custom-made shade-net house at Mannheim Crop Research Station, Tsumeb, Namibia. Three Bambara groundnut genotypes (Uniswa Red, Dip C and KFBN 9709) were gamma irradiated at six doses (0, 50, 100, 150, 200, and 250 Gy) were laid out in a randomized complete block design (RCBD) with three replications. Data were collected on days to emergence (DTE), emergence percentage (%EM), seedling survival percentage (%SS), seedling length (SLT), and shoot weight (STW). A non-significant interaction of genotype × gamma radiation dose was detected, showing stable responses indicating that genotypes require varying gamma radiation doses for mutagenesis. A significant (p

Abstract. Objectives:. To describe operative results after humerus nonunion surgery in patients whose initial humerus shaft fracture (OTA/AO code 12) was treated nonoperatively and to identify risk factors of nonunion surgery failure in the same population. Design:. Case series. Setting:. Nine academic level 1 trauma centers. Patients/Participants:. One hundred twenty patients with humerus nonunion whose initial fracture was treated nonoperatively. Intervention:. Operative treatment of humerus nonunions. Main Outcome Measurements:. Rate of recalcitrant nonunion after humerus nonunion surgery. Results:. Of 108 humerus nonunions, 26 (24.07%) failed to unite after nonunion surgery. Moreover, 34 patients (31.48%) experienced 1 or more postoperative complications. Multivariate analysis found that the use of bone graft or bone graft substitute was not associated with successful nonunion surgery (95% odds ratio confidence interval [CI] [0.67–5.3], P = 0.23). Tobacco use was associated with an increased risk of persistent nonunion (P = 0.0041). Postoperative complications (P = 0.0001) were also associated with an increased risk of persistent nonunion. Diabetes and open fracture were not associated with differences in the nonunion repair success rate. Conclusions:. As the largest and most generalizable to date, this multicenter study found that nearly 1 in 4 patients with a humeral nonunion after initial nonoperative management failed their nonunion surgical treatment. While postoperative complications were associated with recalcitrant nonunion, surgical adjuncts such as bone grafting and type did not seem to influence the success rate of nonunion surgery. Smoking is a modifiable risk factor suggesting that smoking cessation should be part of the intervention. These findings can be used to give patients and surgeons a realistic expectation of results and complications after humerus nonunion surgery. Level of Evidence:. Therapeutic level III.

Introduction In Australia, kidney failure treatment disparities exist between Aboriginal and/or Torres Strait Islander (First Nations) and non-First Nations people. Despite persistent calls from First Nations patients with kidney failure, they are less likely to have treatment that allows them to live at home.Methods and analysis This is a prospective, multicentre study based in Australia. The aim of the study is to characterise the socioeconomic, environmental, health service and biomedical factors driving the health outcomes and patterns of health service utilisation experienced by First Nations patients and investigate whether health service changes to address these identified barriers can achieve higher rates of renal replacement therapy at home on country. This will be achieved by mixed-methods data collection at health service (audit and process data), staff (surveys and qualitative interviews) and patient (survey testing, feedback sessions, health outcomes) levels. A process evaluation will identify barriers and enablers to health services changes in relation to cultural safety. Baseline and follow-up data will be compared to assess the extent to which health services change their service delivery and the impact on health outcomes for First Nations patients with kidney failure. Qualitative and quantitative data will be integrated to provide an in-depth understanding of project outcomes and impacts.Ethics and dissemination This study is funded by the National Health and Medical Research Council of Australia (GNT1158075). Ethics approval has been obtained so far from the Human Research Ethics Committee (HREC) of the Northern Territory Department of Health and Menzies School of Health Research (2019-3530), Far North Queensland HREC (2023/QCH/99606 (Nov ver 4)-1732), the Central Adelaide Local Health Network HREC (2023/HRE00209), the Aboriginal Health Council of South Australia (AHREC Protocol #: 04-23-1078), the Aboriginal Health and Medical Research Council of New South Wales (AH&MRC HREC reference: 2230/24) and the Far North Queensland Human Research Ethics Committee (FNQ HREC reference: HREC/2023/QCH/99606 (Nov ver 4)-1732). Study participants, policy makers and community organisations will be provided with updates of study findings. Dissemination of study findings will be through peer-reviewed publications and conference presentations.Trial registration number ACTRN12623001241628.

Background The association between platelet endothelial cell adhesion molecule‐1 (PECAM‐1) with cerebral small‐vessel disease and cognition in dementia‐free subjects remains uninvestigated. Methods and Results A prospective cohort of dementia‐free subjects was recruited from memory clinics and followed up for 5 years. Annual neurocognitive assessments and twice‐yearly brain magnetic resonance imaging scans were performed. Associations of baseline plasma PECAM‐1 levels with cerebral small‐vessel disease, cognitive decline (Montreal Cognitive Assessment scores and executive function Z scores), and incident dementia were evaluated. Of 213 subjects (aged 70.2±7.7 years, 51.2% men), median PECAM‐1 levels were 0.790 (interquartile range, 0.645–0.955 ng/mL). Compared with the highest tertile, subjects within the lowest PECAM‐1 tertile had greater cross‐sectional white matter hyperintensity volume (β=4.84 [95% CI, 0.67–9.01]; P=0.023), age‐related white matter change scores (β=1.39 [95% CI, 0.12–2.67]; P=0.033), and cerebral microbleeds (Adjusted risk ratio, 2.59 [95% CI, 1.19–5.62]; P=0.016). Of the 204 participants with follow‐up data (median, 60.0 [interquartile range, 60.0–60.0] months), 24 (11.8%) developed incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM‐1 had a higher risk of incident dementia (first tertile: adjusted hazard ratio [AHR], 4.52 [95% CI, 1.35–15.13]; P=0.024; second tertile: AHR, 3.28 [95% CI, 1.02–10.60]; P=0.047). The lowest PECAM‐1 tertile was associated with greater progression of white matter hyperintensity volume (β=4.15 [95% CI, 0.06–8.24]; P=0.047), cerebral microbleeds (incident relative risk [IRR], 2.21 [95% CI, 1.05–4.65]; P=0.036), and decline in executive function (β=−0.45 [95% CI, −0.76 to −0.14]; P=0.004), and Montreal Cognitive Assessment (β=−1.32 [95% CI, −2.30 to −0.35]; P=0.008) scores. Conclusions In dementia‐free subjects, lower circulating PECAM‐1 levels are associated with greater cerebral small‐vessel disease progression and cognitive decline, thus warranting future study as a potential therapeutic target.

Renal calculi weighing over 200 g are relative rare in modern urological practice since most stones might cause renal dysfunction before reaching such size. We here reported an extremely rare case of giant stones in single kidney of a 72-year-old Chinese male patient who had 30 years long-term history of lithiasis in the right kidney. These huge kidney stones, total weight 832.6 g were successfully removed with multiple sessions of surgery. Kidney function was relatively stable after long-term medical care in primary care centers. Timely treatment of kidney stones early should arouse more attention worldwide.