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Pain is a highly complex and individualized experience with biopsychosocial components. Neuroimaging research has shown evidence of the involvement of the central nervous system in the development and maintenance of chronic pain conditions, including urological chronic pelvic pain syndrome (UCPPS). Furthermore, a history of early adverse life events (EALs) has been shown to adversely impact symptoms throughout childhood and into adulthood. However, to date, the role of EAL's in the central processes of chronic pain have not been adequately investigated. We studied 85 patients (56 females) with UCPPS along with 86 healthy controls (HCs) who had resting-state magnetic resonance imaging scans (59 females), and data on EALs as a part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Study. We used graph theory methods in order to investigate the impact of EALs on measures of centrality, which characterize information flow, communication, influence, and integration in a priori selected regions of interest. Patients with UCPPS exhibited lower centrality in the right anterior insula compared to HCs, a key node in the salience network. Males with UCPPS exhibited lower centrality in the right anterior insula compared the HC males. Females with UCPPS exhibited greater centrality in the right caudate nucleus and left angular gyrus compared to HC females. Males with UCPPS exhibited lower centrality in the left posterior cingulate, angular gyrus, middle temporal gyrus, and superior temporal sulcus, but greater centrality in the precuneus and anterior mid-cingulate cortex (aMCC) compared to females with UCPPS. Higher reports of EALs was associated with greater centrality in the left precuneus and left aMCC in females with UCPPS. This study provides evidence for disease and sex-related alterations in the default mode, salience, and basal ganglia networks in patients with UCPPS, which are moderated by EALs, and associated with clinical symptoms and quality of life (QoL).

The controversy over the existence or the need for G-protein coupled receptors (GPCRs) in plant G-protein signalling has overshadowed a more fundamental quest for the role of AtGCR1, the most studied and often considered the best candidate for GPCR in plants. Our whole transcriptome microarray analysis of the GCR1-knock-out mutant (gcr1-5) in Arabidopsis thaliana revealed 350 differentially expressed genes spanning all chromosomes. Many of them were hitherto unknown in the context of GCR1 or G-protein signalling, such as in phosphate starvation, storage compound and fatty acid biosynthesis, cell fate, etc. We also found some GCR1-responsive genes/processes that are reported to be regulated by heterotrimeric G-proteins, such as biotic and abiotic stress, hormone response and secondary metabolism. Thus, GCR1 could have G-protein-mediated as well as independent roles and regardless of whether it works as a GPCR, further analysis of the organism-wide role of GCR1 has a significance of its own.

The aim of this study was to determine specific distribution of metals in the termite Tumulitermes tumuli (Froggatt) and identify specific organs within the termite that host elevated metals and therefore play an important role in the regulation and transfer of these back into the environment. Like other insects, termites bio-accumulate essential metals to reinforce cuticular structures and utilize storage detoxification for other metals including Ca, P, Mg and K. Previously, Mn and Zn have been found concentrated in mandible tips and are associated with increased hardness whereas Ca, P, Mg and K are accumulated in Malpighian tubules. Using high resolution Particle Induced X-Ray Emission (PIXE) mapping of whole termites and Scanning Electron Microscope (SEM) Energy Dispersive X-ray (EDX) spot analysis, localised accumulations of metals in the termite T. tumuli were identified. Tumulitermes tumuli was found to have proportionally high Mn concentrations in mandible tips. Malpighian tubules had significant enrichment of Zn (1.6%), Mg (4.9%), P (6.8%), Ca (2.7%) and K (2.4%). Synchrotron scanning X-ray Fluorescence Microprobe (XFM) mapping demonstrated two different concretion types defined by the mutually exclusive presence of Ca and Zn. In-situ SEM EDX realisation of these concretions is problematic due to the excitation volume caused by operating conditions required to detect minor amounts of Zn in the presence of significant amounts of Na. For this reason, previous researchers have not demonstrated this surprising finding.

Pain is a highly complex and individualized experience with biopsychosocial components. Neuroimaging research has shown evidence of the involvement of the central nervous system in the development and maintenance of chronic pain conditions, including urological chronic pelvic pain syndrome (UCPPS). Furthermore, a history of early adverse life events (EALs) has been shown to adversely impact symptoms throughout childhood and into adulthood. However, to date, the role of EAL’s in the central processes of chronic pain have not been adequately investigated. We studied 85 patients (56 females) with UCPPS along with 86 healthy controls (HCs) who had resting-state magnetic resonance imaging scans (59 females), and data on EALs as a part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Study. We used graph theory methods in order to investigate the impact of EALs on measures of centrality, which characterize information flow, communication, influence, and integration in a priori selected regions of interest. Patients with UCPPS exhibited lower centrality in the right anterior insula compared to HCs, a key node in the salience network. Males with UCPPS exhibited lower centrality in the right anterior insula compared the HC males. Females with UCPPS exhibited greater centrality in the right caudate nucleus and left angular gyrus compared to HC females. Males with UCPPS exhibited lower centrality in the left posterior cingulate, angular gyrus, middle temporal gyrus, and superior temporal sulcus, but greater centrality in the precuneus and anterior mid-cingulate cortex (aMCC) compared to females with UCPPS. Higher reports of EALs was associated with greater centrality in the left precuneus and left aMCC in females with UCPPS. This study provides evidence for disease and sex-related alterations in the default mode, salience, and basal ganglia networks in patients with UCPPS, which are moderated by EALs, and associated with clinical symptoms and quality of life (QoL). [ABSTRACT FROM AUTHOR]

Objective: To determine the rate of Medicare opt-out among optometrists and ophthalmologists and to contrast the differences in the characteristics and geographic distribution of these populations., Design: A retrospective cross-sectional study., Setting: Using a publicly available Centers for Medicare & Medicaid Services (CMS) data set, we collated data for ophthalmologists and optometrists who opted out in each year between 2005 and 2023. We calculated the rate of opt-out annually in each year window and cumulatively from 2005 to 2023. Comparative analysis was used to identify clinician characteristics associated with opt-out., Main Outcomes and Measures: Both annual and cumulative rate of ophthalmologist and optometrist opt-out from Medicare., Results: The estimated prevalence of Medicare opt-outs was 0.52% (77/14,807) for ophthalmologists and 0.38% (154/40,526) for optometrists. Ophthalmologists opting out were predominantly male (67.5%), had a longer practice duration (average 31.8 years), and were more often located in urban areas (83.1%), compared to optometrists (53.2% male, average 19.6 years in practice, 59.1% in urban areas, p = 0.04, p<0.001, p<0.001 respectively). Approximately 83% of ophthalmologists were either anterior segment or oculoplastics specialties, while the majority (52.1%) of optometrists were in optometry-only practices; >75% of identified clinicians were in private practice. Geographical distribution across the US showed variable opt-out rates, with the top 3 states including Oklahoma (3.4%), Arizona (2.1%), and Kansas (1.6%) for ophthalmology and Idaho (4.3%), Montana (3.1%), and Wyoming (1.4%) for optometry., Conclusions and Relevance: Few ophthalmologists and optometrists opt-out of Medicare but this trend has significantly increased since 2012. Of those who disenrolled from Medicare, 83% of ophthalmologists were in urbanized areas while 41% of optometrists were in non-urbanized areas. Because reasons for Medicare opt-out cannot be solely determined by administrative data, further investigation is warranted given the potential impact on healthcare accessibility., Competing Interests: We have read the journal’s policy regarding competing interests and the authors of the manuscript have no financial support for this work that could have influenced its outcome. The following general competing interests are as follows: Michael Maywood: none Harris Ahmed none Ravi Parikh: Financial disclosures: Consultant fees from GLG, Health and Wellness Partners, Axon Advisors LLV; Funding from AAO for AAO-related work with Relative Value Update Committee Tedi Begaj: Financial disclosures: Consultant fees from Regenxbio, Eyepoint, (Copyright: © 2024 Maywood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Data annotation in NLP is a costly and time-consuming task, traditionally handled by human experts who require extensive training to enhance the task-related background knowledge. Besides, labeling social media texts is particularly challenging due to their brevity, informality, creativity, and varying human perceptions regarding the sociocultural context of the world. With the emergence of GPT models and their proficiency in various NLP tasks, this study aims to establish a performance baseline for GPT-4 as a social media text annotator. To achieve this, we employ our own dataset of tweets, expertly labeled for stance detection with full inter-rater agreement among three annotators. We experiment with three techniques: Zero-shot, Few-shot, and Zero-shot with Chain-of-Thoughts to create prompts for the labeling task. We utilize four training sets constructed with different label sets, including human labels, to fine-tune transformer-based large language models and various combinations of traditional machine learning models with embeddings for stance classification. Finally, all fine-tuned models undergo evaluation using a common testing set with human-generated labels. We use the results from models trained on human labels as the benchmark to assess GPT-4's potential as an annotator across the three prompting techniques. Based on the experimental findings, GPT-4 achieves comparable results through the Few-shot and Zero-shot Chain-of-Thoughts prompting methods. However, none of these labeling techniques surpass the top three models fine-tuned on human labels. Moreover, we introduce the Zero-shot Chain-of-Thoughts as an effective strategy for aspect-based social media text labeling, which performs better than the standard Zero-shot and yields results similar to the high-performing yet expensive Few-shot approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liyanage et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As people age, their ability to maintain homeostasis in response to stressors diminishes. Physical frailty, a syndrome characterized by loss of resilience to stressors, is thought to emerge due to dysregulation of and breakdowns in communication among key physiological systems. Dynamical systems modeling of these physiological systems aims to model the underlying processes that govern response to stressors. We hypothesize that dynamical systems model summaries are predictive of age-related declines in health and function. In this study, we analyze data obtained during 75-gram oral-glucose tolerance tests (OGTT) on 1,120 adults older than 50 years of age from the Baltimore Longitudinal Study on Aging. We adopt a two-stage modeling approach. First, we fit OGTT curves with the Ackerman model-a nonlinear, parametric model of the glucose-insulin system-and with functional principal components analysis. We then fit linear and Cox proportional hazards models to evaluate whether usual gait speed and survival are associated with the stage-one model summaries. We also develop recommendations for identifying inadequately-fitting nonlinear model fits in a cohort setting with numerous heterogeneous response curves. These recommendations include: (1) defining a constrained parameter space that ensures biologically plausible model fits, (2) evaluating the relative discrepancy between predicted and observed responses of biological interest, and (3) identifying model fits that have notably poor model fit summary measures, such as [Formula: see text], relative to other fits in the cohort. The Ackerman model was unable to adequately fit 36% of the OGTT curves. The stage-two regression analyses found no associations between Ackerman model summaries and usual gait speed, nor with survival. The second functional principal component score was associated with faster gait speed (p<0.01) and improved survival (p<0.01)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The current research project investigates the correlation between economic growth, government spending, and public revenue in seventeen Indian states spanning the years 1990 to 2020. An analysis of the relationship between key fiscal policy variables and economic growth was conducted utilising a panel data approach, the Generalised Method of Moments (GMM), and fully modified Ordinary Least Squares (FMOLS & DOLS) estimation. In our investigation, we assessed the impacts of non-tax revenue, development plan expenditure, tax revenue, and development non-plan expenditure on (i) the net state domestic product (NSDP) and (ii) the NSDP per capita. The findings indicate that the selected fiscal variables are significantly related. The results indicate that expeditious expansion of the fiscal sector is obligatory to stimulate economic growth in India and advance the actual development of the economies of these states., Competing Interests: The authors declare no competing interest., (Copyright: © 2024 Sumandeep et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The Emergency Department Avoidability Classification (EDAC) retrospectively classifies emergency department (ED) visits that could have been safely managed in subacute primary care settings, but has not been validated against a criterion standard. A validated EDAC could enable accurate and reliable quantification of avoidable ED visits. We compared agreement between the EDAC and ED physician judgements to specify avoidable ED visits., Materials and Methods: We conducted a cluster randomized, single-blinded agreement study in an academic hospital in Hamilton, Canada. ED visits between January 1, 2019, and December 31, 2019 were clustered based on EDAC classes and randomly sampled evenly. A total of 160 ED visit charts were randomly assigned to ten participating ED physicians at the academic hospital for evaluation. Physicians judged if the ED visit could have been managed appropriately in subacute primary care (an avoidable visit); each ED visit was evaluated by two physicians independently. We measured interrater agreement between physicians with a Cohen's kappa and 95% confidence intervals (CI). We evaluated the correlation between the EDAC and physician judgements using a Spearman rank correlation and ordinal logistic regression with odds ratios (ORs) and 95% CIs. We examined the EDAC's precision to identify avoidable ED visits using accuracy, sensitivity and specificity., Results: ED physicians agreed on 139 visits (86.9%) with a kappa of 0.69 (95% CI 0.59-0.79), indicating substantial agreement. Physicians judged 96.2% of ED visits classified as avoidable by the EDAC as suitable for management in subacute primary care. We found a high correlation between the EDAC and physician judgements (0.64), as well as a very strong association to classify avoidable ED visits (OR 80.0, 95% CI 17.1-374.9). The EDACs avoidable and potentially avoidable classes demonstrated strong accuracy to identify ED visits suitable for management in subacute care (82.8%, 95% CI 78.2-86.8)., Discussion: The EDAC demonstrated strong evidence of criterion validity to classify avoidable ED visits. This classification has important potential for accurately monitoring trends in avoidable ED utilization, measuring proportions of ED volume attributed to avoidable visits and informing interventions intended at reducing ED use by patients who do not require emergency or life-saving healthcare., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Strum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mental health disorders are one of the most common causes that limit the ability of mothers to care for themselves and for their children. Recent data suggest high rates of distress among women in charge of young children in Zambia. Nevertheless, Zambia's public healthcare offers very limited treatment for common mental health distress. To address this treatment gap, this study aims to test the feasibility, acceptability, and potential efficacy of a context-adapted psychosocial intervention. A total of 265 mothers with mental health needs (defined as SRQ-20 scores above 7) were randomly assigned with equal probability to the intervention or control group. The intervention group will receive a locally adapted version of the Problem-Management Plus and "Thinking Healthy" interventions developed by the World Health Organization (WHO), combined with specific parts of the Strong Minds-Strong Communities intervention. Trained and closely supervised wellbeing-community health workers will provide the psychosocial intervention. Mental health distress and attendance to the intervention will be assessed at enrollment and 6 months after the intervention. We will estimate the impact of the intervention on mental health distress using an intention-to-treat approach. We previously found that there is a large necessity for interventions that aim to address mother anxiety/depression problems. In this study, we tested the feasibility and efficacy of an innovative intervention, demonstrating that implementing these mental health treatments in low-income settings, such as Zambia, is viable with an adequate support system. If successful, larger studies will be needed to test the effectiveness of the intervention with increased precision. Trial registration: This study is registered at clinicaltrials.gov as NCT05627206., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Falgas-Bague et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing Candida species viz., C. albicans, C. tropicalis and C. glabrata. Furthermore, the study validates 3BP's therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing >99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 μg/mL against all tested Candida spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all Candida strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of Candida spp., achieving a maximum eradication level of 90%. Toxicity/safety profiling in both in vitro erythrocyte lysis and in vivo Galleria mellonella survival assay authenticated the non-toxic nature of 3BP up to 512 μg/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against Candida species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jothi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tibiotalocalcaneal (TTC) arthrodesis is a procedure to treat severe ankle and subtalar arthropathy by providing pain free and stable fusion using IM nails. These nails can be manufactured with multiple materials and some feature the ability to dynamize the arthrodesis construct. However, the impact of IM nail material and nail dynamization on load-sharing and in the setting of bone resorption have not been quantified. This work utilized a patient-specific finite element analysis model of TTC arthrodesis to investigate IM nails with differing material moduli and the impact of nail dynamization on load-sharing and intersegmental compression in the setting of bone resorption. Each nail was virtually inserted into a patient-specific model of a hindfoot, which was segmented into the three bones of the TTC complex and assigned material properties based on the densitometry of the bone. Compression, amount of load-sharing, and stress distributions after simulated bone resorption were quantified and compared between the varying IM nails. Simulations revealed that bone segments were only subjected to 17% and 22% of dynamic gait forces in the titanium and carbon fiber nail constructs, whereas the pseudoelastic NiTi nail constructs allowed for 67% of the same. The titanium and carbon fiber nails lost all initial compression in less than 0.13mm of bone resorption, whereas the NiTi nail maintained compression through all simulated values of bone resorption. These data highlight the poor load-sharing of static nail TTC arthrodesis constructs and the ability of a pseudoelastic IM nail construct to maintain intersegmental compression when challenged with bone resorption., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Safranski and Dupont are paid employees of Enovis Foot & Ankle. Pacaccio is a paid consultant/advisor to Enovis Foot & Ankle. Safranski reports stock ownership and other compensation from MedShape-acquired by DJO during the conduct of this study and outside the submitted work. Dupont reports stock ownership and other compensation from MedShape-acquired by DJO during the conduct of this study and outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Terrill et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) and associated morbidity and mortality are increasing in sub-Saharan Africa (SSA). To facilitate access to quality care and improve treatment outcomes, there is a need for innovative community care models and optimized use of non-physician healthcare workers bringing diagnosis and care closer to patients' homes., Aim: We aimed to describe with a scoping review different models of community-based care for non-pregnant adults with T2DM in SSA, and to synthesize the outcomes in terms of engagement in care, blood sugar control, acceptability, and end-organ damage. We further aimed to critically appraise the different models of care and compare community-based to facility-based care if data were available., Methods: We searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Scopus, supplemented with backward and forward citation searches. We included cohort studies, randomized trials and case-control studies that reported on non-pregnant individuals diagnosed with T2DM in SSA, who received a substantial part of care in the community. Only studies which reported at least one of our outcomes of interest were included. A narrative analysis was done, and comparisons made between community-based and facility-based models, where within-study comparison was reported., Results: We retrieved 5,335 unique studies, four of which met our inclusion criteria. Most studies were excluded because interventions were facility-based; community care interventions described in the studies were only add-on features of a primarily facility-based care; and studies did not report outcomes of interest. The included studies reported on a total of 383 individuals with T2DM. Three different community care models were identified. 1) A community-initiated model where diagnosis, treatment and monitoring occurred primarily in the community. This model reported a higher linkage and engagement in care at 9 months compared to the corresponding facility model, but only slight reductions of average blood glucose levels at six months compared to baseline. 2) A facility-originated community model where after treatment initiation, a substantial part of follow-up was offered at community level. Two studies reported such a model of care, both had as core component home-delivery of medication. Acceptability of this approach was high. But neither study found improved T2DM control when compared to facility care 3) An eHealth model with high acceptability scores for both patients and care providers, and an absolute 1.76% reduction in average HbA1c levels at two months compared to baseline. There were no reported outcomes on end-organ damage. All four studies were rated as being at high risk for bias., Conclusion: Evidence on models of care for persons with T2DM in SSA where a substantial part of care is shifted to the community is scant. Whereas available literature indicates high acceptability of community-based care, we found no conclusive data on their effectiveness in controlling blood sugar and preventing complications. Evidence from larger scale studies, ideally randomized trials with clinically relevant endpoints is needed before roll-out of community-based T2DM care can be recommended in SSA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Firima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The work reported in present study deals with the development of a novel stochastic model and estimation of parameters to assess reliability characteristics for a turbogenerator unit of thermal power plant under classical and Bayesian frameworks. Turbogenerator unit consists of five components namely turbine lubrication, turbine governing, generator oil system, generator gas system and generator excitation system. The concepts of cold standby redundancy and Weibull distributed random variables are used in development of stochastic model. The shape parameter for all the random variables is same while scale parameter is different. Regenerative point technique and semi-Markov approach are used for evaluation of reliability characteristics. Sufficient repair facility always remains available in plant as well as repair done by the repairman is considered perfect. As the life testing experiments are time consuming, so to highlight the importance of proposed model Monte Carlo simulation study is carried out. A comparative analysis is done between true, classical and Bayesian results of MTSF, availability and profit function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Given the recent trends in the MPPT converters in PV systems, which have been researched extensively to improve design, modified closed-loop converter technology based on SoC is presented here. This paper aims to provide detailed information on the modern-day solar Maximum Power Point Tracking (MPPT) controller and Battery Management System (BMS). Most MPPT controller examination researched in the past is suitable only for fixed-rated battery capacity, which limits the converter capability and applications. The proposed paper uses the distributed energy management control technique to dispatch multi-battery charging based on the State of Charge (SoC). The converter construction is modified here as per the prerequisite of the model. The system hardware is developed and tested using Atmega2560 low power RISC based high-performance microcontroller. The batteries' SoC level and State of Health (SoH) are calculated using embedded sensors and communication platforms through the IoT platform and Global System Monitoring (GSM) technology. The GSM and IoT technology ensure that the different batteries are monitored periodically, and any irregularities are immediately addressed through the distributed energy management control technique. This ensures a safe, reliable, and effective charging of multiple batteries with increased accuracy, thereby maximizing battery life and reducing operational costs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Samikannu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Identify system-level features in HIV migration within a host across body tissues. Evaluate heterogeneity in the presence and magnitude of these features across hosts., Method: Using HIV DNA deep sequencing data generated across multiple tissues from 8 people with HIV, we represent the complex dependencies of HIV migration among tissues as a network and model these networks using the family of exponential random graph models (ERGMs). ERGMs allow for the statistical assessment of whether network features occur more (or less) frequently in viral migration than might be expected by chance. The analysis investigates five potential features of the viral migration network: (1) bi-directional flow between tissues; (2) preferential migration among tissues in the same biological system; (3) heterogeneity in the level of viral migration related to HIV reservoir size; (4) hierarchical structure of migration; and (5) cyclical migration among several tissues. We calculate the Cohran's Q statistic to assess heterogeneity in the magnitude of the presence of these features across hosts. The analysis adjusts for missing data on body tissues., Results: We observe strong evidence for bi-directional flow between tissues; migration among tissues in the same biological system; and hierarchical structure of the viral migration network. This analysis shows no evidence for differential level of viral migration with respect to the HIV reservoir size of a tissue. There is evidence that cyclical migration among three tissues occurs less frequent than expected given the amount of viral migration. The analysis also provides evidence for heterogeneity in the magnitude that these features are present across hosts. Adjusting for missing tissue data identifies system-level features within a host as well as heterogeneity in the presence of these features across hosts that are not detected when the analysis only considers the observed data., Discussion: Identification of common features in viral migration may increase the efficiency of HIV cure efforts as it enables targeting specific processes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Goyal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Repetitive, subconcussive events may adversely affect the brain and cognition during sensitive periods of development. Prevention of neurocognitive consequences of concussion in high school football is therefore an important public health priority. We aimed to identify the player positions and demographic, behavioral, cognitive, and impact characteristics that predict the frequency and acceleration of head impacts in high school football players., Methods: In this prospective study, three cohorts of adolescent male athletes (N = 53, 28.3% Hispanic) were recruited over three successive seasons in a high school American football program. Demographic and cognitive functioning were assessed at baseline prior to participating in football. Helmet sensors recorded impact frequency and acceleration. Each head impact was captured on film from five different angles. Research staff verified and characterized on-field impacts. Player-level Poisson regressions and year-level and impact-level linear mixed-effect models were used to determine demographic, behavioral, cognitive, and impact characteristics as predictors of impact frequency and acceleration., Results: 4,678 valid impacts were recorded. Impact frequency positively associated with baseline symptoms of hyperactivity-impulsivity [β(SE) = 1.05 impacts per year per unit of symptom severity (1.00), p = 0.01] and inattentiveness [β(SE) = 1.003 impacts per year per T-score unit (1.001), p = 0.01]. Compared to quarterbacks, the highest acceleration impacts were sustained by kickers/punters [β(SE) = 21.5 g's higher (7.1), p = 0.002], kick/punt returners [β(SE) = 9.3 g's higher (4.4), p = 0.03], and defensive backs [β(SE) = 4.9 g's higher (2.5), p = 0.05]. Impacts were more frequent in the second [β(SE) = 33.4 impacts (14.2), p = 0.02)] and third [β(SE) = 50.9 impacts (20.1), p = 0.01] year of play. Acceleration was highest in top-of-the-head impacts [β(SE) = 4.4 g's higher (0.8), p<0.001]., Conclusion: Including screening questions for Attention-Deficit/Hyperactivity Disorder in pre-participation evaluations can help identify a subset of prospective football players who may be at risk for increased head impacts. Position-specific strategies to modify kickoffs and correct tackling and blocking may also reduce impact burden., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 McAlister et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As clinical understanding of pediatric Post-Acute Sequelae of SARS CoV-2 (PASC) develops, and hence the clinical definition evolves, it is desirable to have a method to reliably identify patients who are likely to have post-acute sequelae of SARS CoV-2 (PASC) in health systems data. In this study, we developed and validated a machine learning algorithm to classify which patients have PASC (distinguishing between Multisystem Inflammatory Syndrome in Children (MIS-C) and non-MIS-C variants) from a cohort of patients with positive SARS- CoV-2 test results in pediatric health systems within the PEDSnet EHR network. Patient features included in the model were selected from conditions, procedures, performance of diagnostic testing, and medications using a tree-based scan statistic approach. We used an XGboost model, with hyperparameters selected through cross-validated grid search, and model performance was assessed using 5-fold cross-validation. Model predictions and feature importance were evaluated using Shapley Additive exPlanation (SHAP) values. The model provides a tool for identifying patients with PASC and an approach to characterizing PASC using diagnosis, medication, laboratory, and procedure features in health systems data. Using appropriate threshold settings, the model can be used to identify PASC patients in health systems data at higher precision for inclusion in studies or at higher recall in screening for clinical trials, especially in settings where PASC diagnosis codes are used less frequently or less reliably. Analysis of how specific features contribute to the classification process may assist in gaining a better understanding of features that are associated with PASC diagnoses., Competing Interests: “"Dr. Rao reports prior grant support from GSK and Biofire and is a consultant for Sequiris. Dr. Jhaveri is a consultant for AstraZeneca, Seqirus, Dynavax, receives an editorial stipend from Elsevier and Pediatric Infectious Diseases Society and royalties from Up To Date/Wolters Kluwer. Dr. Lee serves on the PASC Advisory Board for United Health Group. Dr Bailey has received grants from Patient-Centered Outcomes Research Institute All other authors have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2023 Lorman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Dystrophic epidermolysis bullosa (DEB) is due to variation in the COL7A1 gene. The clinical phenotype and severity depends on the type of variation and domain of the affected protein., Objectives: To characterize the spectrum of COL7A1 variations in a cohort of DEB patients from India, to correlate these findings with clinical phenotypes and to establish a genotype-phenotype correlation., Methods: This was a retrospective, observational study involving patients with DEB diagnosed on the basis of clinical manifestations, Immuno-fluorescence antigen mapping (IFM) and genetic analysis. A genotype-phenotype correlation was attempted and observations were further explained using IFM on skin biopsies and molecular dynamic simulations. Descriptive statistics were performed using SPSS version 20.0 with P values of <0.05 considered significant., Results: We report 68 unrelated Indian DEB patients classified as RDEB-Intermediate (RDEB-I), RDEB-Severe (RDEB-S) or DDEB based on the EB diagnostic matrix, immunofluorescence antigen mapping and genetic data. Of 68 DEB patients, 59 (86.76%) were inherited in a recessive pattern (RDEB) and 9 (13.24%) in a dominant pattern (DDEB). Limbal stem cell deficiency was seen in four cases of RDEB-S very early in the course of the disease. A total of 88 variants were detected of which 66 were novel. There were no hotspots and recurrent variations were seen in a very small group of patients. We found a high frequency of compound heterozygotes (CH) in RDEB patients born out of non-consanguineous marriage. RDEB patients older than two years who had oral mucosal involvement, and/or deformities, were more likely to have esophageal involvement. Genotype phenotype correlation showed a higher frequency of extracutaneous manifestations and deformities in patients with Premature Termination Codons (PTCs) than in patients with other variations. Molecular simulation studies in patients with missense mutations showed severe phenotype when they were localized in interrupted regions of GLY-X-Y repeats., Conclusion: This large study of DEB patients in South Asia adds to the continually expanding genetic database of this condition. This study has direct implications on management as this group of patients can be screened early and managed appropriately., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gupta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Pharmacotherapy is necessary for many people with psychiatric disorders and polypharmacy is common. The psychotropic drug-drug interaction (DDI) should be concerned and efficiently monitored by a proper instrument., Objectives: This study aimed to investigate the prevalence and associated factors of psychotropic DDI and to compare the identification utility from three databases: Drugs.com®, Lexicomp®, and Epocrates®., Methods: This was a retrospective cohort design. We collected demographic and clinical data of all patients hospitalised in the psychiatric inpatient unit in 2020. Psychotropic DDI profiles were examined through three databases. Descriptive statistics were used to report comprehensiveness of each database and prevalence of psychotropic DDI. The Fleiss' kappa index would be analysed to indicate agreement strength of DDI severity classification among three databases., Results: From 149 total admissions, the psychotropic DDIs were found in 148 admissions (99.3%). Thorough the study, there were 182 of both psychotropic and other agents prescribed under 1,357 prescriptions. In total, 2,825 psychotropic DDIs were identified by using Drugs.com® 2,500 times, Epocrates® 2,269 times, and Lexicomp® 2,265 times. Interactions with clonazepam was the three most frequent agents when co-administrated with quetiapine (n = 56), risperidone (n = 36), and valproic acid and derivatives (n = 36). Serious DDIs were comparatively lower in incidence and there was no evidence of its association with reported clinical adverse consequences. The study revealed slight and fair agreement regarding severity classification among the three databases was found. DDI events detected by Drugs.com® were greatest in number, but Lexicomp® provided the broadest list of medications prescribed in our study., Conclusion: Among three databases, interactions detected by Drugs.com® were greatest in number, whereas Lexicomp® provided the broadest list of medications. Development of such databases, based on both theoretical and clinical conceptions, should be focused to balance safety of patients and weariness of healthcare providers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pinkoh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The COVID-19 pandemic has increased social and emotional stressors globally, increasing mental health concerns and the risk of psychiatric illness worldwide. To date, relatively little is known about the impact of the pandemic on vulnerable groups such as women and children in low-resourced settings who generally have limited access to mental health care. We explore two rounds of data collected as part of an ongoing trial of early childhood development to assess mental health distress among mothers of children under 5-years-old living in two rural areas of Zambia during the COVID-19 pandemic. We examined the prevalence of mental health distress among a cohort of 1105 mothers using the World Health Organization's Self-Reporting Questionnaire (SRQ-20) before the onset of the COVID-19 pandemic in August 2019 and after the first two infection waves in October-November 2021. Our primary outcome was mental health distress, defined as SRQ-20 score above 7. We analyzed social, economic and family level characteristics as factors modifying to the COVID-19 induced changes in the mental health status. At baseline, 22.5% of women were in mental health distress. The odds of mental health distress among women increased marginally over the first two waves of the pandemic (aOR1.22, CI 0.99-1.49). Women under age 30, with lower educational background, with less than three children, and those living in Eastern Province (compared to Southern Province) of Zambia, were found to be at highest risk of mental health deterioration during the pandemic. Our findings suggest that the prevalence of mental health distress is high in this population and has further worsened during COVID-19 pandemic. Public health interventions targeting mothers' mental health in low resource settings may want to particularly focus on young mothers with limited educational attainment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Falgas-Bague et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The role of fiber orientation on a global chamber level in sustaining atrial fibrillation (AF) is unknown. The goal of this study was to correlate the fiber direction derived from Diffusion Tensor Imaging (DTI) with AF inducibility., Methods: Transgenic goats with cardiac-specific overexpression of constitutively active TGF-β1 (n = 14) underwent AF inducibility testing by rapid pacing in the left atrium. We chose a minimum of 10 minutes of sustained AF as a cut-off for AF inducibility. Explanted hearts underwent DTI to determine the fiber direction. Using tractography data, we clustered, visualized, and quantified the fiber helix angles in 8 different regions of the left atrial wall using two reference vectors defined based on anatomical landmarks., Results: Sustained AF was induced in 7 out of 14 goats. The mean helix fiber angles in 7 out of 8 selected regions were statistically different (P-Value < 0.05) in the AF inducible group. The average fractional anisotropy (FA) and the mean diffusivity (MD) were similar in the two groups with FA of 0.32±0.08 and MD of 8.54±1.72 mm2/s in the non-inducible group and FA of 0.31±0.05 (P-value = 0.90) and MD of 8.68±1.60 mm2/s (P-value = 0.88) in the inducible group., Conclusions: DTI based fiber direction shows significant variability across subjects with a significant difference between animals that are AF inducible versus animals that are not inducible. Fiber direction might be contributing to the initiation and sustaining of AF, and its role needs to be investigated further., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kamali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Model-based economic evaluations require conceptualization of the model structure. Our objectives were to identify important health states, events, and patient attributes to be included in a model-based cost-effectiveness analysis of fall prevention interventions, to develop a model structure to examine cost-effectiveness of fall prevention interventions, and to assess the face validity of the model structure., Methods: An expert panel comprising clinicians, health service researchers, health economists, a patient partner, and policy makers completed two rounds of online surveys to gain consensus on health states, events, and patient attributes important for fall prevention interventions. The surveys were informed by a literature search on fall prevention interventions for older adults (≥65 years) including economic evaluations and clinical practice guidelines. The results of the Delphi surveys and subsequent discussions can support the face validity of a state-transition model for an economic evaluation of fall prevention interventions., Results: In total, 11 experts rated 24 health states/events and 41 patient attributes. Consensus was achieved on 14 health states/events and 26 patient characteristics. The proposed model structure incorporated 12 of the 14 selected health states/events. Panelists confirmed the face validity of the model structure during teleconferences., Conclusions: There is a dearth of studies presenting the model conceptualization process; consequently, this study involving multiple end user partners with opportunities for input at several stages adds to the literature as another case study. This process is an example of how a fall prevention economic model was developed using a modified Delphi process and assessed for face validity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Saunders et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Breast cancer is heterogenous in development and cell population with prognoses being highly dependent on numerous factors from driving mutations, biomarker expression and variation in extracellular environment, all affecting response to therapies. Recently, much attention has been given to the role of metabolic alteration in cancers, expanding from the Warburg effect to highlight unique patterns in different cancer cell populations for improving diagnostic and therapeutic approaches. We recently reported on modulation of mannosylation of α-dystroglycan with the metabolite ribitol in breast cancer lines. Here we investigate the effects of pentose sugars ribitol, ribose, and xylitol media supplementation in breast cancer cells by metabolomics and differential gene expression profiling. This combined approach revealed distinctive patterns of alterations in metabolic pathways by ribitol, contrasted with the closely related pentose ribose and pentitol xylitol. Significantly, ribitol supplementation enhances utilization of glucose by glycolysis, whereas ribose improves oxidative phosphorylation and fatty acid synthesis. Ribitol supplementation also increased levels of reduced glutathione (associated with a decrease in oxidative phosphorylation, gluconeogenesis), where ribose supplementation elevated levels of oxidized glutathione (GSSG) indicating an increase in oxidative stress. Treatment with ribitol also enhanced nucleotide biosynthesis. The apparent TCA cycle dysregulation, with distinctive pattern in response to the individual pentitol and pentose, such as ribitol increasing succinate and fumarate while decreasing citrate, demonstrate the adaptive capability of cancer cells to nutritional environment. This metabolic reprogramming presents new avenues for developing targeted therapies to cancers with metabolites, especially in combination with other drug treatments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tucker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The rising prevalence of hepatitis C virus (HCV) infection and the availability of direct acting antivirals for HCV treatment has prompted a public health goal of HCV eradication. Despite the availability of treatment for HCV, treatment programs have generally excluded pregnant individuals. Our objective was to query patients and clinicians to identify barriers to including pregnant individuals in HCV treatment programs., Methods and Findings: This qualitative investigation included obstetricians and previously/currently pregnant individuals with HCV. Participants completed interviews regarding knowledge of and attitudes towards HCV treatment and perceived barriers to treatment during pregnancy. Data were analyzed using the constant comparative method. Obstetricians (N = 18) and patients (N = 21) described concerns about equity, access, and cost. Both expressed uncertainty about safety and confirmed a need for clinician education. Obstetricians emphasized the lack of professional guidelines. Although some clinicians expressed concern about patient adherence and engagement, patients were largely desirous of treatment; both groups identified potential benefits of antenatal treatment., Conclusions: Both patients and obstetricians were generally receptive to HCV treatment in pregnancy and recognized pregnancy as an important window of opportunity for treatment. Our findings suggest the need for further research on maternal-fetal safety of HCV treatment as well as on interventions to ensure fair and appropriate access to HCV treatment for pregnant individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Yee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adult acquired flatfoot deformity becomes permanent with stage III posterior tibialis tendon dysfunction and results in foot pain and difficulty walking and balancing. To prevent progression to stage III posterior tibialis tendon dysfunction when conservative treatment fails, a flexor digitorum longus to posterior tibialis tendon transfer is often conducted. However, since the flexor digitorum longus only has one-third the force-capability of the posterior tibialis, an osteotomy is typically also required. We propose the use of a novel implantable mechanism to replace the direct attachment of the tendon transfer with a sliding pulley to amplify the force transferred from the donor flexor digitorum longus to the foot arch. In this work, we created four OpenSim models of an arched foot, a flatfoot, a flatfoot with traditional tendon transfer, and a flatfoot with implant-modified tendon transfer. Paired with these models, we developed a forward dynamic simulation of the stance phase of gait that reproduces the medial/lateral distribution of vertical ground reaction forces. The simulation couples the use of a fixed tibia, moving ground plane methodology with simultaneous activation of nine extrinsic lower limb muscles. The arched foot and flatfoot models produced vertical ground reaction forces with the characteristic double-peak profile of gait, and the medial/lateral distribution of these forces compared well with the literature. The flatfoot model with implant-modified tendon transfer produced a 94.2% restoration of the medial/lateral distribution of vertical ground reaction forces generated by our arched foot model, which also represents a 2.1X improvement upon our tendon transfer model. This result demonstrates the feasibility of a pulley-like implant to improve functional outcomes for surgical treatment of adult acquired flatfoot deformity with ideal biomechanics in simulation. The real-world efficacy and feasibility of such a device will require further exploration of factors such as surgical variability, soft tissue interactions and healing response., Competing Interests: The authors have declared that no competing interests exist.

Background: Accurate restoration of joint line height and posterior offset in primary Total Knee Arthroplasty (TKA) have been shown to be important factors in post-operative range of movement and function. The aim of this study was to assess the accuracy of joint line and posterior offset restoration in a group of patients that underwent robotic-assisted TKA (raTKA). A matched cohort of patients that underwent a TKA using a conventional jig-based technique was assessed for comparison. The null hypothesis was that there would be no difference between groups., Methods: This study was a retrospective analysis of a cohort of 120 patients with end-stage knee osteoarthritis that received a TKA using the Navio Surgical System (n = 60), or Conventional manual TKA (n = 60). Procedures were performed between 1 January 2019 and 1 October 2019 at six different centres. Joint line height and posterior offset was measured pre-operatively and post-operatively on calibrated weight bearing plain radiographs of the knee. Two observers performed measurements using validated measuring tools. A BMI and age-matched cohort of patients that underwent TKA using a conventional technique in the same six centres were assessed for comparison. Mean values, standard deviations and confidence intervals are presented for change and absolute change in joint line height and posterior offset. Student's t-test was used to compare the changes between techniques., Results: Patients that underwent robotic-assisted TKA had joint line height and posterior offset restored more accurately than patients undergoing TKA using a conventional technique. Average change from pre-operative measurement in joint line height using raTKA was -0.38mm [95% CI: -0.79 to 0.03] vs 0.91 [0.14 to 1.68] with the conventional technique. Average absolute change in joint line height using raTKA was 1.96mm [1.74 to 2.18] vs 4.00mm [3.68 to 4.32] with the conventional technique. Average change in posterior offset using raTKA was 0.08mm [-0.40 to 0.56] vs 1.64mm [2.47 to 0.81] with the conventional technique. Average absolute change in posterior offset with raTKA was 2.19mm [1.92 to 2.46] vs 4.24mm [3.79 to 4.69] with the conventional technique. There was a significant difference when comparing absolute change in joint line height and posterior offset between groups (p<0.01)., Conclusion: Robotic-assisted primary TKA restores the joint line height and posterior offset more accurately than conventional jig-based techniques., Competing Interests: AA, PB, ME, SJ, JLV & DN are reimbursed for educational activities by Smith & Nephew. This does not alter our adherence to PLOS ONE policies on sharing data and materials

Depression is one of the significant mental health issues affecting all age groups globally. While it has been widely recognized to be one of the major disease burdens in populations, complexities in definitive diagnosis present a major challenge. Usually, trained psychologists utilize conventional methods including individualized interview assessment and manually administered PHQ-8 scoring. However, heterogeneity in symptomatic presentations, which span somatic to affective complaints, impart substantial subjectivity in its diagnosis. Diagnostic accuracy is further compounded by the cross-sectional nature of sporadic assessment methods during physician-office visits, especially since depressive symptoms/severity may evolve over time. With widespread acceptance of smart wearable devices and smartphones, passive monitoring of depression traits using behavioral signals such as speech presents a unique opportunity as companion diagnostics to assist the trained clinicians in objective assessment over time. Therefore, we propose a framework for automated depression classification leveraging alterations in speech patterns in the well documented and extensively studied DAIC-WOZ depression dataset. This novel tensor-based approach requires a substantially simpler implementation architecture and extracts discriminative features for depression recognition with high f1 score and accuracy. We posit that such algorithms, which use significantly less compute load would allow effective onboard deployment in wearables for improve diagnostics accuracy and real-time monitoring of depressive disorders., Competing Interests: The authors declare that they have no competing interests.

Background: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association., Methods: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes., Results: Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI., Conclusion: iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization., Competing Interests: The authors have declared that no competing interests exist.

Background: We retrospectively data-mined the case records of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients hospitalized to a tertiary care centre to derive mortality predictors and formulate a risk score, for prioritizing admission., Methods and Findings: Data on clinical manifestations, comorbidities, vital signs, and basic lab investigations collected as part of routine medical management at admission to a COVID-19 tertiary care centre in Chengalpattu, South India between May and November 2020 were retrospectively analysed to ascertain predictors of mortality in the univariate analysis using their relative difference in distribution among 'survivors' and 'non-survivors'. The regression coefficients of those factors remaining significant in the multivariable logistic regression were utilised for risk score formulation and validated in 1000 bootstrap datasets. Among 746 COVID-19 patients hospitalised [487 "survivors" and 259 "non-survivors" (deaths)], there was a slight male predilection [62.5%, (466/746)], with a higher mortality rate observed among 40-70 years age group [59.1%, (441/746)] and highest among diabetic patients with elevated urea levels [65.4% (68/104)]. The adjusted odds ratios of factors [OR (95% CI)] significant in the multivariable logistic regression were SaO2<95%; 2.96 (1.71-5.18), Urea ≥50 mg/dl: 4.51 (2.59-7.97), Neutrophil-lymphocytic ratio (NLR) >3; 3.01 (1.61-5.83), Age ≥50 years;2.52 (1.45-4.43), Pulse Rate ≥100/min: 2.02 (1.19-3.47) and coexisting Diabetes Mellitus; 1.73 (1.02-2.95) with hypertension and gender not retaining their significance. The individual risk scores for SaO2<95-11, Urea ≥50 mg/dl-15, NLR >3-11, Age ≥50 years-9, Pulse Rate ≥100/min-7 and coexisting diabetes mellitus-6, acronymed collectively as 'OUR-ARDs score' showed that the sum of scores ≥ 25 predicted mortality with a sensitivity-90%, specificity-64% and AUC of 0.85., Conclusions: The 'OUR ARDs' risk score, derived from easily assessable factors predicting mortality, offered a tangible solution for prioritizing admission to COVID-19 tertiary care centre, that enhanced patient care but without unduly straining the health system., Competing Interests: The authors have declared that no competing interests exist.

Background: There is a growing need to use green alternative larvicidal control for Aedes larvae compared to chemical insecticides. Substantial reliance on chemical insecticides caused insecticide resistance in mosquito populations. Thus, research for alternate chemical compounds from natural products is necessary to control Aedes larvae. This study explores the analysis of chemical compositions from Areca catechu nut as a potential larvicide for Aedes (Diptera: Culicidae)., Methods: The Areca catechu nut collected from Ipoh, Perak, Malaysia was grounded into powder and used for Soxhlet extraction. The chemical analysis of the extracts and their structures were identified using the GCMS-QP2010 Ultra (Shimadzu) system. National Institute of Standards and Technology (NIST) Chemistry WebBook, Standard Reference Database 69 (https://webbook.nist.gov/chemistry/) and PubChem (https://pubchem.ncbi.nlm.nih.gov/), the two databases used to retrieve the synonyms, molecular formula, molecular weight, and 2-dimensional (2D) structure of chemical compounds. Next, following WHO procedures for larval bioassays, the extracts were used to asses larvicidal activity against early 4th instar larvae of Aedes aegypti and Aedes albopictus., Results: The larvicidal activities were observed against early 4th stage larvae with different concentrations in the range from 200 mg/L to 1600 mg/L. The LC50 and LC95 of Aedes aegypti were 621 mg/L and 2264 mg/L respectively; whereas the LC50 and LC95 of Aedes albopictus were 636 mg/L and 2268 mg/L respectively. Mortality was not observed in the non-target organism test. The analysis using gas chromatography and mass spectrometer recovered several chemical compounds such as Arecaidine, Dodecanoic acid, Methyl tetradecanoate, Tetradecanoic acid , and n-Hexadecanoic acid bioactive components. These chemical constituents were used as additive formulations in pesticides, pest control, insect repellent, and insecticidal agents., Conclusions: Our study showed significant outcomes from the extract of Areca catechu nut and it deserves further investigation in relation to chemical components and larvicidal actions between different species of Aedes mosquitoes. Even though all these findings are fundamental, it may have some interesting potentials to be developed as natural bio-larvicidal products., Competing Interests: The authors have declared that no competing interests exist.

Formation of mature miRNAs and their expression is a highly controlled process. It is very much dependent upon the post-transcriptional regulatory events. Recent findings suggest that several RNA binding proteins beyond Drosha/Dicer are involved in the processing of miRNAs. Deciphering of conditional networks for these RBP-miRNA interactions may help to reason the spatio-temporal nature of miRNAs which can also be used to predict miRNA profiles. In this direction, >25TB of data from different platforms were studied (CLIP-seq/RNA-seq/miRNA-seq) to develop Bayesian causal networks capable of reasoning miRNA biogenesis. The networks ably explained the miRNA formation when tested across a large number of conditions and experimentally validated data. The networks were modeled into an XGBoost machine learning system where expression information of the network components was found capable to quantitatively explain the miRNAs formation levels and their profiles. The models were developed for 1,204 human miRNAs whose accurate expression level could be detected directly from the RNA-seq data alone without any need of doing separate miRNA profiling experiments like miRNA-seq or arrays. A first of its kind, miRbiom performed consistently well with high average accuracy (91%) when tested across a large number of experimentally established data from several conditions. It has been implemented as an interactive open access web-server where besides finding the profiles of miRNAs, their downstream functional analysis can also be done. miRbiom will help to get an accurate prediction of human miRNAs profiles in the absence of profiling experiments and will be an asset for regulatory research areas. The study also shows the importance of having RBP interaction information in better understanding the miRNAs and their functional projectiles where it also lays the foundation of such studies and software in future., Competing Interests: The authors declare that they have no competing interests.

Slow conduction areas and conduction block in the atria are considered pro-arrhythmic conditions. Studies examining the size and distribution of slow conduction regions in the context of persistent atrial fibrillation (AF) may help to develop improved therapeutic strategies for patients with AF. In this work, we studied the differences of size and number in slow conduction areas between control and persistent AF goats and the influence of propagation direction on the development of these pathological conduction areas. Epicardial atrial electrical activations from the left atrial roof were optically mapped with physiological pacing cycle lengths and for the shortest captured cycle lengths. The recordings were converted to local activation times and conduction velocity measures. Regions with slow conduction velocity (less than [Formula: see text]) were identified. The size of the connected regions and the number of non-connected regions were counted for propagation from different orthogonal directions. We found that regions of slow conduction significantly increases in our 15 persistent AF goat recordings in response to premature stimulation (24.4±4.3% increase to 36.6±4.4%, p < 0.001). This increase is driven by an increase of size from (3.70±0.89[mm2] to 6.36±0.91[mm2], p = 0.014) for already existing regions and not by generation of new slow conduction regions (11.6±1.8 vs. 13±1.9, p = 0.242). In 12 control goat recordings, no increase from baseline pacing to premature pacing was found. Similarly, size of the slow conduction areas and the count did not change significantly in control animals., Competing Interests: The authors have declared that no competing interests exist.

Background: Balance and functional strength training can improve muscle strength and physical functioning outcomes and decrease the risk of falls in older adults. To maximize the benefits of strength training, adequate protein intake is also important. However, the number of older individuals that consume enough protein or routinely engage in strength training remains low at less than 5% and even lower for activities that challenge balance. Our primary aim was to assess the feasibility of implementing a model (MoveStrong) of service delivery to teach older adults about balance and functional strength training and methods to increase protein intake., Methods: This study was a closed cohort stepped wedge randomized controlled trial. We recruited individuals ≥60 years considered pre-frail or frail with at least one chronic condition who were not currently engaging in regular strength training from Northern (rural) and Southern (urban) Ontario sites in Canada. The primary outcome was feasibility of implementation, defined by recruitment, retention, and adherence, and safety (defined by monitoring adverse events). We also reported participants' and providers' experience with MoveStrong, adaptations to the model based on participant's and provider's experience, and program fidelity., Results: We recruited 44 participants to the study and the average adherence rate was 72% with a retention of 71%. The program had a high-fidelity score. One person experienced a fall-related injury during exercise, while two other participants reported pain during certain activities. Five individuals experienced injuries or health problems that were not related to the program. Suggestions for future trials include modifying some exercises, exploring volunteer assistance, increasing the diversity of participants enrolled, and considering a different study design., Conclusions: Our pilot trial demonstrates the feasibility of recruitment and adherence for a larger multisite RCT of balance and functional strength training with attention to protein intake in pre-frail and frail older adults., Competing Interests: The authors have declared that no competing interests exist.

Background: Preservation of joint line height is an important factor in post-operative function after Total Knee Arthroplasty (TKA). This is the first study investigating the reliability of the novel Imperial Joint Line Congruency Measurement (IJLCM) technique for the assessment of joint line height using plain radiographs., Methods: The reliability of two techniques used to measure joint line height on pre-operative and post-operative plain radiographs is presented. 120 patients that underwent TKA from 6 different international centres were included. Measurements were performed using each technique by two senior orthopaedic surgeons at two different timepoints (test-retest). Two undergraduate medical students performed joint line measurements using the most reproducible of the two techniques on 40 pre-operative and post-operative images to establish the reliability of the measurement technique., Results: The IJLCM demonstrated an average absolute difference of 1.83mm (CI 1.56-2.10mm) and excellent inter and intra-rater reliability between senior orthopaedic surgeons (>0.92 (CI 0.88-0.94) when measuring joint line height on plain radiographs. Overall Crohnbach's alpha over 0.92 confirmed internal consistency. Measurements performed using the control technique as previously described by Figgie et al. had an average absolute difference of 5.75mm (5.17-6.32mm). Comparison of measurements by senior orthopaedic surgeons and medical students using the IJLCM technique with ANOVA and student's t-test demonstrated acceptable agreement and inter-rater reliability of >0.92 (0.87-0.95)., Conclusion: This study shows excellent accuracy, precision, and reliability of the novel IJLCM technique. Furthermore, excellent agreement between senior orthopaedic surgeons and medical students when using the IJLCM could be shown. The IJLCM technique is reliable for joint line assessment., Competing Interests: The authors have declared that no competing interests exist.

Chikungunya virus (CHIKV) is an arthropod-borne virus that causes large outbreaks world-wide leaving millions of people with severe and debilitating arthritis. Interestingly, clinical presentation of CHIKV arthritides have many overlapping features with rheumatoid arthritis including cellular and cytokine pathways that lead to disease development and progression. Currently, there are no specific treatments or vaccines available to treat CHIKV infections therefore advocating the need for the development of novel therapeutic strategies to treat CHIKV rheumatic disease. Herein, we provide an in-depth analysis of an efficacious new treatment for CHIKV arthritis with a semi-synthetic sulphated polysaccharide, Pentosan Polysulfate Sodium (PPS). Mice treated with PPS showed significant functional improvement as measured by grip strength and a reduction in hind limb foot swelling. Histological analysis of the affected joint showed local inflammation was reduced as seen by a decreased number of infiltrating immune cells. Additionally, joint cartilage was protected as demonstrated by increased proteoglycan staining. Using a multiplex-immunoassay system, we also showed that at peak disease, PPS treatment led to a systemic reduction of the chemokines CXCL1, CCL2 (MCP-1), CCL7 (MCP-3) and CCL12 (MCP-5) which may be associated with the reduction in cellular infiltrates. Further characterisation of the local effect of PPS in its action to reduce joint and muscle inflammation was performed using NanoString™ technology. Results showed that PPS altered the local expression of key functional genes characterised for their involvement in growth factor signalling and lymphocyte activation. Overall, this study shows that PPS is a promising treatment for alphaviral arthritis by reducing inflammation and protecting joint integrity., Competing Interests: This study was funded by a joint research grant funded from Paradigm Biopharmaceuticals Ltd (https://paradigmbiopharma.com/), Advance Queensland mid-career fellowship awarded to PAR and Griffith University. RK and CJMS are paid employees of Paradigm Biopharmaceuticals Ltd. As staff members of Paradigm Biopharmaceuticals Ltd, RK and CJMS are entitled to long term and short-term incentives. LJH was a paid part-time consultant for Paradigm Biopharmaceuticals Ltd. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript beyond those specified. This research may lead to the use of PPS towards the treatment of CHIKV disease. Paradigm Biopharmaceuticals Ltd. hold the following patents PCT/AU2016/050408 “Treatment of Alphavirus-Induced Inflammation” (published as WO2017/201563) and the Australian patent number is 2016407635 “Treatment of Alphavirus-Induced Inflammation”. Furthermore, iPPS will be available in Australia via Australian infectious disease physicians through the TGA Special Access Scheme (SAS) for patients with chronic RRV-induced arthritis where there are no other treatment options. Access will be available in Q2 CY 2021 as a pay-for-use program, providing a path to first revenues for Paradigm. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Urban greenspace is a valuable component of the urban form that has the potential to improve the health and well-being of residents. Most quantitative studies of relationships between health and greenspace to date have investigated associations only with what greenspace exists in the local environment (i.e. provision of greenspace), rather than to what extent it is used. This is due to the difficulty of obtaining usage data in large amounts. In recent years, GPS functionality integrated into mobile phones has provided a potential solution to this problem by making it possible to track which parts of the environment people experience in their day-to-day lives. In this paper, we demonstrate a method to derive cleaned, trip-level information from raw GPS data collected by a mobile phone app, then use this data to investigate the characteristics of trips to urban greenspace by residents of the city of Sheffield, UK. We find that local users of the app spend an average of an hour per week visiting greenspaces, including around seven trips per week and covering a total distance of just over 2.5 km. This may be enough to provide health benefits, but is insufficient to provide maximal benefits. Trip characteristics vary with user demographics: ethnic minority users and users from more socioeconomically deprived areas tend to make shorter trips than White users and those from less deprived areas, while users aged 34 years and over make longer trips than younger users. Women, on average, make more frequent trips than men, as do those who spent more time outside as a child. Our results suggest that most day-to-day greenspace visits are incidental, i.e. travelling through rather than to greenspace, and highlight the importance of including social and cultural factors when investigating who uses and who benefits from urban greenspace., Competing Interests: The authors have declared that no competing interests exist.

Agri-food systems are besieged by malnutrition, yield gaps, and climate vulnerability, but integrated, research-based responses in public policy, agricultural, value chains, and finance are constrained by short-termism and zero sum thinking. As they respond to current and emerging agri-food system challenges, decision makers need new tools that steer toward multi-sector, evidence-based collaboration. To support national agri-food system policy processes, the Integrated Agri-food System Initiative (IASI) methodology was developed and validated through case studies in Mexico and Colombia. This holistic, multi-sector methodology builds on diverse existing data resources and leverages situation analysis, modeled predictions, and scenarios to synchronize public and private action at the national level toward sustainable, equitable, and inclusive agri-food systems. Culminating in collectively agreed strategies and multi-partner tactical plans, the IASI methodology enabled a multi-level systems approach by mobilizing design thinking to foster mindset shifts and stakeholder consensus on sustainable and scalable innovations that respond to real-time dynamics in complex agri-food systems. To build capacity for these types of integrated, context-specific approaches, greater investment is needed in supportive international institutions that function as trusted in-region 'innovation brokers.' This paper calls for a structured global network to advance adaptation and evolution of essential tools like the IASI methodology in support of the One CGIAR mandate and in service of positive agri-food systems transformation., Competing Interests: No competing interests. Versant Vision LLC has no competing commercial affiliation and therefore this does not alter our adherence to PLOS ONE policies on sharing data and materials.”

Objectives: Social media use is associated with developing communities of practice that promote the rapid exchange of information across traditional institutional and geographical boundaries faster than previously possible. We aimed to describe and share our experience using #neoEBM (Neonatal Evidence Based Medicine) hashtag to organise and build a digital community of neonatal care practice., Materials and Methods: Analysis of #neoEBM Twitter data in the Symplur Signals database between 1 May 2018 to 9 January 2021. Data on tweets containing the #neoEBM hashtag were analysed using online analytical tools, including the total number of tweets and user engagement., Results: Since its registration, a total of 3 228 distinct individual Twitter users used the hashtag with 23 939 tweets and 37 259 710 impressions generated. The two days with the greatest number of tweets containing #neoEBM were 8 May 2018 (n = 218) and 28 April 2019 (n = 340), coinciding with the annual Pediatric Academic Societies meeting. The majority of Twitter users made one tweet using #neoEBM (n = 1078), followed by two tweets (n = 411) and more than 10 tweets (n = 347). The number of individual impressions (views) of tweets containing #neoEBM was 37 259 710. Of the 23 939 tweets using #neoEBM, 17 817 (74%) were retweeted (shared), 15 643 (65%) included at least one link and 1 196 (5%) had at least one reply. As #neoEBM users increased over time, so did tweets containing #neoEBM, with each additional user of the hashtag associated with a mean increase in 7.8 (95% CI 7.7-8.0) tweets containing #neoEBM., Conclusion: Our findings support the observation that the #neoEBM community possesses many of the characteristics of a community of practice, and it may be an effective tool to disseminate research findings. By sharing our experiences, we hope to encourage others to engage with or build online digital communities of practice to share knowledge and build collaborative networks across disciplines, institutions and countries., Competing Interests: AK, RP, CW, SM, AS, OE and BK are current or previous social media editors and NB is immediate past lead social media editor for the International Society for Evidence-Based Neonatology (ebneo.org) and all tweet as part of these roles as @EBNEO. None are compensated for their role as social media editors. The authors have no financial relationships with the online analytical platform Symplur. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Certain oral bacterial pathogens may play a role in oral carcinogenesis. We assessed the feasibility of conducting a population-based study in India to examine the distributions and levels of Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia in relation to oral leukoplakia (a potentially malignant disorder) and other participant characteristics., Methods: This exploratory case-control study was nested within a large urban Indian cohort and the data included 22 men and women with oral leukoplakia (cases) and 69 leukoplakia-free controls. Each participant provided a salivary rinse sample, and a subset of 34 participants (9 cases; 25 controls) also provided a gingival swab sample from keratinized gingival surface for quantitative polymerase chain reaction (qPCR)., Results: Neither the distribution nor the levels of pathogens were associated with oral leukoplakia; however, individual pathogen levels were more strongly correlated with each other in cases compared to controls. Among controls, the median level of total pathogens was the highest (7.55×104 copies/ng DNA) among persons of low socioeconomic status. Salivary rinse provided better DNA concentration than gingival swab for qPCR analysis (mean concentration: 1.8 ng/μl vs. 0.2 ng/μl)., Conclusions: This study confirms the feasibility of population studies evaluating oral microbiome in low-resource settings and identifies promising leads for future research., Competing Interests: We declare the commercial affiliation (Genentech Roche, CA, USA) of one of our authors (PKD). This does not alter our adherence to Plos One policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research.

Objectives: The study aims to investigate GPs' experiences of how UK COVID-19 policies have affected the management and safety of complex elderly patients, who suffer from multimorbidity, at the primary care level in North West London (NWL)., Design: This is a service evaluation adopting a qualitative approach., Setting: Individual semi-structured interviews were conducted between 6 and 22 May 2020, 2 months after the introduction of the UK COVID-19 Action Plan, allowing GPs to adapt to the new changes and reflect on their impact., Participants: Fourteen GPs working in NWL were interviewed, until data saturation was reached., Outcome Measures: The impact of COVID-19 policies on the management and safety of complex elderly patients in primary care from the GPs' perspective., Results: Participants' average experience was fourteen years working in primary care for the NHS. They stated that COVID-19 policies have affected primary care at three levels, patients' behaviour, work conditions, and clinical practice. GPs reflected on the impact through five major themes; four of which have been adapted from the Safety Attitudes Questionnaire (SAQ) framework, changes in primary care (at the three levels mentioned above), involvement of GPs in policy making, communication and coordination (with patients and in between medical teams), stressors and worries; in addition to a fifth theme to conclude the GPs' suggestions for improvement (either proposed mitigation strategies, or existing actions that showed relative success). A participant used an expression of "infodemic" to describe the GPs' everyday pressure of receiving new policy updates with their subsequent changes in practice., Conclusion: The COVID-19 pandemic has affected all levels of the health system in the UK, particularly primary care. Based on the GPs' perspective in NWL, changes to practice have offered opportunities to maintain safe healthcare as well as possible drawbacks that should be of concern., Competing Interests: The authors have declared that no competing interests exist.

This paper examines recent changes in the life trajectories of Indian women. We use data from four major national population surveys that span the years 1998-2016. We look at several cohorts of women across the states and regions. We compare decisions related to education, marriage, childbearing and participation in the labor force. Though there is considerable diversity across states and regions, as well as religious groups, we find some consistent patterns that emerge everywhere. First, educational attainment and the age at marriage have been steadily increasing. Women who do not complete secondary school are more likely to marry early. Second, caste and religion (rather than education) play a significant role in decisions after marriage, such as the timing of births, the use of contraception and labor force participation. Third, women from disadvantaged communities continue to have very different life trajectories than other social groups. They are more likely to use contraception and participate in the labor force. Lower levels of schooling also appear to exacerbate the disadvantages of social identity. The pace of these changes varies sharply across states as well as regions of the country., Competing Interests: The authors have declared that no competing interests exist.

Age and sex differences in brain metabolite concentrations in early life are not well understood. We examined the associations of age and sex with brain metabolite levels in healthy neonates, and investigated the associations between neonatal brain metabolite concentrations and developmental outcomes. Forty-one infants (36-42 gestational weeks at birth; 39% female) of predominantly Hispanic/Latina mothers (mean 18 years of age) underwent MRI scanning approximately two weeks after birth. Multiplanar chemical shift imaging was used to obtain voxel-wise maps of N-acetylaspartate (NAA), creatine, and choline concentrations across the brain. The Bayley Scales of Infant and Toddler Development, a measure of cognitive, language, and motor skills, and mobile conjugate reinforcement paradigm, a measure of learning and memory, were administered at 4 months of age. Findings indicated that postmenstrual age correlated positively with NAA concentrations in multiple subcortical and white matter regions. Creatine and choline concentrations showed similar but less pronounced age related increases. Females compared with males had higher metabolite levels in white matter and subcortical gray matter. Neonatal NAA concentrations were positively associated with learning and negatively associated with memory at 4 months. Age-related increases in NAA, creatine, and choline suggest rapid development of neuronal viability, cellular energy metabolism, and cell membrane turnover, respectively, during early life. Females may undergo earlier and more rapid regional developmental increases in the density of viable neurons compared to males., Competing Interests: The authors have declared that no competing interests exist.

Karnataka, a state in south India, reported its first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on March 8, 2020, more than a month after the first case was reported in India. We used a combination of contact tracing and genomic epidemiology to trace the spread of SARS-CoV-2 in the state up until May 21, 2020 (1578 cases). We obtained 91 genomes of SARS-CoV-2 which clustered into seven lineages (Pangolin lineages-A, B, B.1, B.1.80, B.1.1, B.4, and B.6). The lineages in Karnataka were known to be circulating in China, Southeast Asia, Iran, Europe and other parts of India and are likely to have been imported into the state both by international and domestic travel. Our sequences grouped into 17 contact clusters and 24 cases with no known contacts. We found 14 of the 17 contact clusters had a single lineage of the virus, consistent with multiple introductions and most (12/17) were contained within a single district, reflecting local spread. In most of the 17 clusters, the index case (12/17) and spreaders (11/17) were symptomatic. Of the 91 sequences, 47 belonged to the B.6 lineage, including eleven of 24 cases with no known contact, indicating ongoing transmission of this lineage in the state. Genomic epidemiology of SARS-CoV-2 in Karnataka suggests multiple introductions of the virus followed by local transmission in parallel with ongoing viral evolution. This is the first study from India combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response., Competing Interests: FH is an employee of TruFactor-InMobi group company, however, he was permitted to participate as a volunteer in this study and his employer neither had access to data, nor any say in the design of the study or the decision to publish. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors are employees of state (PD, PK) or central government. The employers had no role in the design of the study or the decision to publish. The authors declare that they do not have any other financial or non-financial relationships that could present a conflict of interest.

The present study investigates if the total replacement of dietary fishmeal (FM) with poultry by-product meal (PBM), supplemented with methionine influences the muscle fatty acids composition, normal gut morphology, histological traits of the liver, muscle, and gill, liver enzymes, immune and antioxidant response, and stress-related gene in juvenile barramundi, Lates calcarifer in relation to growth and feed utilization. Barramundi (3.58±0.01g) were randomly distributed into six 300 L seawater recirculating tanks (25 fish/tank) and fed two formulated isonitrogenous and isolipidic diets for 6 weeks. The control diet had FM as the sole animal protein source, whereas other test diet had only PBM as an animal protein source. Dietary PBM affected the fish performance and feed utilization. Regarding muscle fatty acid profile, total saturated fatty acids and monounsaturated fatty acids elevated while total PUFA particularly n-3 LC-PUFA and EPA decreased in PBM fed fish than control diet fed fish. Liver, muscle, gill, and intestinal histology showed no obvious alteration in control diet fed fish, however, more lipid droplets and hepatic vacuolization in the liver, necrotic myotome in muscle, hyperplasia in secondary lamellae in gill and short and broken folds in the intestine were observed in PBM fed fish. Similar to light microscopy observation of intestinal morphology, the transmission electron microscopy (TEM) analysis revealed shorter and smaller microvilli in fish fed PBM. Histopathological alterations in the liver of PBM fed fish were further associated with the elevated levels of aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) and the significant upregulation of stress-related genes, HSP70 and HSP90. Also, a negative influence on lysozyme activity, and antioxidant enzymatic activities were recorded in fish fed PBM. Overall, it can be concluded that a total substitution of FM protein by methionine supplemented PBM negatively influenced the growth performance, liver health, histological traits of different organs, immune and antioxidant response, and expression of stress-related genes in juvenile barramundi., Competing Interests: The authors declare no competing interests.

Background: Aboriginal and Torres Strait Islander people experience a greater burden of disease and die younger than non-Indigenous Australians, with Aboriginal people living in remote areas of the Northern Territory of Australia having the lowest life expectancy estimates. Despite a high burden of chronic disease among Aboriginal and Torres Strait Islander people, access to specialist health services remains low and models of care that increase engagement, may improve health outcomes., Methods: We describe client and staff perspectives of a model of clinical genetics services provided by the MJD Foundation (MJDF) in geographically and culturally complex contexts within the Northern Territory of Australia. We seek to understand the MJDF model's success in supporting Aboriginal families with the familial, neurodegenerative condition Machado-Joseph disease and how it could be applied in the provision of other specialist services. Thematic analysis was undertaken on semi-structured interviews with primary health care staff (n = 2), Non-Aboriginal MJDF Staff (n = 7) and Aboriginal MJDF Clients / Community workers (n = 13)., Results: Four key themes regarding the MJDF model of service delivery were identified with the service being; 1) client led 2) accepting of various understandings of genetic disease causation 3) focused on relationships, continuity and trust between the service provider and the clients, and 4) committed to incorporating an inclusive whole-of-family practice. The MJDF model takes a community-based, person-and family-centred approach to successfully deliver effective specialist genetic health services in remote community settings. We propose that these approaches have broad application in the future design and delivery of specialist health services particularly in culturally complex settings., Competing Interests: LM and DLG are employees of the MJD Foundation. This does not alter our adherence to PLOS ONE policies on sharing data and material.