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BackgroundTreatment options for many cancers include immune checkpoint inhibitor (ICI) monotherapy and combination therapy with impressive clinical benefit across cancers. We sought to define the comparative cardiac risks of ICI combination and monotherapy.MethodsWe used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac ADRs (cADRs), such as carditis, heart failure, arrhythmia, myocardial infarction, and valvular dysfunction, related to ICI therapy. To explore possible relationships, we used the reporting odds ratio (ROR) as a proxy of relative risk. A lower bound of a 95% confidence interval of ROR > 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance.ResultsWe found 2278 cADR for ICI monotherapy and 353 for ICI combination therapy. Combination therapy was associated with significantly higher odds of carditis (ROR 6.9, 95% CI: 5.6-8.3) versus ICI monotherapy (ROR 5.0, 95% CI: 4.6-5.4). Carditis in ICI combination therapy was fatal in 23.4% of reported ADRs, compared to 15.8% for ICI monotherapy (P = 0.058).ConclusionsUsing validated pharmacovigilance methodology, we found increased odds of carditis for all ICI therapies, with the highest odds for combination therapy. Given the substantial risk of severe ADR and death, clinicians should consider these findings when prescribing checkpoint inhibitors.

The unique glia located in the olfactory system, called olfactory ensheathing cells (OECs), are implicated as an attractive choice for transplantation therapy following spinal cord injury because of their pro-regenerative characteristics. Adult OECs are thought to improve functional recovery and regeneration after injury by secreting neurotrophic factors and making cell-to-cell contacts with regenerating processes, but the mechanisms are not well understood. We show first that α7 integrin, a laminin receptor, is highly expressed at the protein level by OECs throughout the olfactory system, i.e., in the olfactory mucosa, olfactory nerve, and olfactory nerve layer of the olfactory bulb. Then we asked if OECs use the α7 integrin receptor directly to promote neurite outgrowth on permissive and neutral substrates, in vitro. We co-cultured α7+/+ and α7lacZ/lacZ postnatal cerebral cortical neurons with α7+/+ or α7lacZ/lacZ OECs and found that genotype did not effect the ability of OECs to enhance neurite outgrowth by direct contact. Loss of α7 integrin did however significantly decrease the motility of adult OECs in transwell experiments. Twice as many α7+/+ OECs migrated through laminin-coated transwells compared to α7+/+ OECs on poly-L-lysine (PLL). This is in contrast to α7lacZ/lacZ OECs, which showed no migratory preference for laminin substrate over PLL. These results demonstrate that OECs express α7 integrin, and that laminin and its α7 integrin receptor contribute to adult OEC migration in vitro and perhaps also in vivo.

The unique glia located in the olfactory system, called olfactory ensheathing cells (OECs), are implicated as an attractive choice for transplantation therapy following spinal cord injury because of their pro-regenerative characteristics. Adult OECs are thought to improve functional recovery and regeneration after injury by secreting neurotrophic factors and making cell-to-cell contacts with regenerating processes, but the mechanisms are not well understood. We show first that α7 integrin, a laminin receptor, is highly expressed at the protein level by OECs throughout the olfactory system, i.e., in the olfactory mucosa, olfactory nerve, and olfactory nerve layer of the olfactory bulb. Then we asked if OECs use the α7 integrin receptor directly to promote neurite outgrowth on permissive and neutral substrates, in vitro. We co-cultured α7+/+ and α7lacZ/lacZ postnatal cerebral cortical neurons with α7+/+ or α7lacZ/lacZ OECs and found that genotype did not effect the ability of OECs to enhance neurite outgrowth by direct contact. Loss of α7 integrin did however significantly decrease the motility of adult OECs in transwell experiments. Twice as many α7+/+ OECs migrated through laminin-coated transwells compared to α7+/+ OECs on poly-L-lysine (PLL). This is in contrast to α7lacZ/lacZ OECs, which showed no migratory preference for laminin substrate over PLL. These results demonstrate that OECs express α7 integrin, and that laminin and its α7 integrin receptor contribute to adult OEC migration in vitro and perhaps also in vivo.

Conventional banks are 'indirectly' allowed to take more risk under the shadow of sovereign guarantees. Banks commit moral hazards as any major banking crisis will be 'cushioned' by deposit insurance and bailed out using the taxpayer's money. This study offers an alternative explanation for the determinants of banks' credit risk, particularly those from the Islamic regions. Although conventional banks and Islamic banks may share state and social cushioning systems, Islamic banks are strictly prohibited by moral and religious principles from gambling with depositors' funds, even if there is a cushion available to bail them out. However, banks belonging to collective societies, such as those in the MENA area, may be inclined to take more risks due to the perception of having a larger safety net to protect them in the event of failure. We analyse these theoretical intersections by utilising a dataset consisting of 320 banks from 20 countries, covering the time span from 2006 to 2021. Our analysis employs a combination of Ordinary Least Squares (OLS), Fixed Effects (FE), and 2-step System-GMM methodologies. Our analysis reveals that Islamic banks are less exposed to credit risk compared to conventional banks. We contend that the stricter ethical and moral ground and multi-layer monitoring system amid protracted geopolitical and post-pandemic crises impacting Islamic countries contribute to the lower credit risk. We examine the consequences for credit and liquidity management in Islamic banks and the risk management strategies employed by Islamic banks, which can serve as a valuable reference for other banks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abdeljawad 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: Alcohol use disorder (AUD) is a major economic and healthcare burden in the United States. While there is evidence-based medication-assisted treatment (MAT) for AUD, few physicians implement these therapies on a regular basis., Objective: To determine the impact of a pharmacy-guided AUD discharge planning workflow on the rate of MAT prescriptions and inpatient readmissions., Methods: This was a single-centered pre-and-post intervention study over a 6-month period, with a 90-day pre-intervention period and a 90-day post-intervention period. The study included all patients over the age of 18 years admitted to a medicine or surgery floor bed who presented with alcohol withdrawal at any point during their hospital course. The intervention involved a pharmacy workflow, in which a list of patients admitted with alcohol withdrawal was automatically generated and referred to pharmacists, who then provided recommendations to the primary physician regarding prescriptions for naltrexone, acamprosate, and/or gabapentin. The patients were then contacted within 30 days after discharge for post-hospitalization follow-up. Our outcome measures were change in prescription rate of MATs, change in total and alcohol-related 90-day readmission rates, and change in total and alcohol-related 90-day emergency department (ED) visit rates., Results: The pre-intervention period consisted of 49 patients and the post-intervention period consisted of 41 patients. Our workflow demonstrated a 195% increase in the prescription rate of MATs at discharge (p < 0.001), 61% reduction in 90-day total readmission rate (p < 0.05), 40% reduction in 90-day total ED visit rate (p = 0.09), 92% reduction in 90-day alcohol-related readmission rate (p < 0.05), and 88% reduction in 90-day alcohol-related ED visit rate (p < 0.05)., Conclusions: Our intervention demonstrated that a pharmacy-based AUD discharge planning workflow has the potential to reduce inpatient readmissions and ED visits for patients with AUD, thus demonstrating improved patient outcomes with the potential to reduce healthcare costs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abiri 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.)

Object and scene perception are intertwined. When objects are expected to appear within a particular scene, they are detected and categorised with greater speed and accuracy. This study examined whether such context effects also moderate the perception of social objects such as faces. Female and male faces were embedded in scenes with a stereotypical female or male context. Semantic congruency of these scene contexts influenced the categorisation of faces (Experiment 1). These effects were bi-directional, such that face sex also affected scene categorisation (Experiment 2), suggesting concurrent automatic processing of both levels. In contrast, the more elementary task of face detection was not affected by semantic scene congruency (Experiment 3), even when scenes were previewed prior to face presentation (Experiment 4). This pattern of results indicates that semantic scene context can affect categorisation of faces. However, the earlier perceptual stage of detection appears to be encapsulated from the cognitive processes that give rise to this contextual interference., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Prunty 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: Treatment-related problems (TRPs) interfere with the ability to attain the desired goals of treatment, adding cost to healthcare systems. Patients hospitalized with acute conditions are at particular risk to experience TRPs. Data investigating such burden in patients with acute exacerbation of COPD (AECOPD) is generally scarce with no studies ever conducted in Jordan. This study aimed to investigate and categorize TRPs among patients hospitalized with AECOPD in Jordan, and to estimate their cost savings and cost avoidance., Methods: This was a retrospective population-based cohort study. Patients' cases of AECOPD admitted to the study site from Jan 2017 to Jul 2021 were identified from the electronic clinical database and screened for eligibility. TRPs were identified/categorized using AbuRuz tool and assessed for their severity. Cost saving was estimated by calculating all the extra costs. Cost avoidance was estimated according to Nesbit method., Results: A total of 1243 (mean±SD 3.1±1.5) and 503 (mean±SD 1.3±1.2) TRPs were identified during hospitalization and at discharge respectively, of which 49.4% and 66.7% were classified as "unnecessary drug therapy". In 54.5% of the cases, systemic corticosteroid was administered for a period longer than recommended. Most of the TRPs were of moderate severity. The total direct cost saving, and cost avoidance were estimated to be 15,745.7 USD and 340,455.5 USD respectively., Conclusion: The prevalence and cost of TRPs among AECOPD patients is a concern requiring attention. The study results implicate integrating interventions such as embracing clinical pharmacists' role in the respiratory care units to optimize patients' management., Competing Interests: The Author(s) declared that there is no conflict of interest., (Copyright: © 2024 Awwad 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 and Aims: Pericardial effusion (PE) is a prevalent form of pericardial involvement in chronic kidney disease (CKD). This study aims to investigate the clinical and laboratory features associated with PE severity in patients with CKD., Methods: In this cross-sectional study, we examined the medical records of patients admitted to tertiary hospitals with International Classification of Diseases 10th Revision (ICD-10) codes associated with CKD and PE. We included 112 CKD patients in stage 4 and 5 non-dialysis (ND) with PE for assessing the clinical and laboratory features of severity., Results: Patients were divided into two categories based on the severity of PE. Seventy-two patients had mild and 40 had moderate and severe PE. Univariate analysis of demographic and laboratory features on the date of admission demonstrated that chest pain, dyspnea, serum albumin, and neutrophil-to-lymphocyte ratio (NLR) are associated with the severity of PE. The univariate analysis on the date of echocardiography showed significantly higher white blood cell count (WBC), neutrophil count (percentage and absolute count), and NLR, along with significantly lower lymphocyte percentage and serum albumin among patients with moderate and severe PE. In the multivariable analysis of laboratory features, on admission hypoalbuminemia (p-value = 0.014, OR = 4.03, CI: 1.32-12.25) and NLR greater than 5.5 (p-value = 0.015, OR = 4.22, CI: 1.32-13.50) were significantly associated with moderate and severe PE. In a parallel matter, at the time of echocardiography hypoalbuminemia (p-value = 0.004, OR = 5.38, CI: 1.74-16.65) and neutrophilia (p-value = 0.005, OR = 7.94, CI: 1.89-33.44) were significantly associated with moderate and severe PE., Conclusion: Despite advancements in the diagnosis and treatment of CKD, PE is still a concerning issue in these patients. This study revealed that hypoalbuminemia, neutrophilia, and NLR greater than 5.5 could be predictive factors of moderate and severe PE in CKD patients with PE. Further prospective study with larger sample size is needed to confirm these results., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Eslami 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: Occupational musculoskeletal disorders are prevalent in ophthalmic surgeons and can impact surgeons' well-being and productivity. Heads-up displays may reduce ergonomic stress compared to conventional microscopes. This cross-sectional, non-interventional study compared ergonomic experience between heads-up display and conventional ocular microscopes., Methods: The study protocol was approved by the independent ethics committee and nonprofit organization MINS Institutional Review Board. An online questionnaire was distributed to a sample of ophthalmic surgeons in Japan with experience operating with heads-up display. The questionnaire captured surgeon-specific variables, the standardized Nordic Musculoskeletal Questionnaire, and custom questions to compare heads-up display and conventional microscope and understand long-term impacts of musculoskeletal disorders., Results: Analysis was conducted on responses from 67 surgeons with a mean 25 years of practice and 2.7 years using heads-up display. Many surgeons agreed or strongly agreed that heads-up display reduced the severity (40%) and frequency (40%) of pain and discomfort, improved posture (61%), and improved overall comfort (61%). Of respondents who experienced asthenopia (n = 59) or pain/discomfort during operation (n = 61), 54% reported improvement in asthenopia and 72% reported feeling less pain/discomfort since using heads-up display. Overall, 69% reported preference for heads-up display., Conclusion: This study provides novel data on musculoskeletal disorders and the long-term impacts of ergonomic strain reported by ophthalmologists building on existing literature demonstrating ergonomic and other advantages of heads-up display. Future studies with objective ergonomic assessment are warranted to validate these findings., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Motohiro Kamei, Hisaharu Suzuki, Rana Ghafouri, Margaret Ainslie-Garcia, Nicole Ferko, and Makoto Nakamura have received consulting fees from Alcon. Hideyuki Terayama and Derek O’Boyle are employees of Alcon. Hang Cheng was previously employed by Alcon. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Kamei 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.)

Research has identified Northwest Turkey as a key region for the development of dairying in the seventh millennium BCE, yet little is known about how this practice began or evolved there. This research studies Barcın Höyük, a site located in Bursa's Yenişehir Valley, which ranges chronologically from 6600 BCE, when the first evidence of settled life appears in the Marmara Region, to 6000 BCE, when Neolithic habitation at the site ceases. Using pottery sherds diagnostic by vessel category and type, this paper aims at identifying which ones may have been primarily used to store, process, or consume dairy products. Organic residue analysis of selected samples helped address the process of adoption and intensification of milk processing in this region over time. The lipid residue data discussed in this paper derive from 143 isotopic results subsampled from 173 organic residues obtained from 805 Neolithic potsherds and suggest that bowls and four-lugged pots may have been preferred containers for processing milk. The discovery of abundant milk residues even among the earliest ceramics indicates that the pioneer farmers arrived in the region already with the knowhow of dairying and milk processing. In fact, these skills and the reliance on secondary products may have given them one of the necessary tools to successfully venture into the unfarmed lands of Northwest Anatolia in the first place., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Özbal 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 Lebanon's economic crisis become uncontrollable, Lebanese pregnant women face malnutrition, with many having to skip meals and switch to resort to cheap and unhealthy alternatives altogether. The objectives of the study were to assess the dietary and lifestyle patterns of Lebanese pregnant women and to evaluate their diets compliance with the United States Department of Agriculture (USDA) pregnancy recommendations, before and during the Lebanese escalating economic crisis. A cross-sectional study was conducted between April 2021 and January 2022. A validated self-administrated questionnaire was administered during the first, second and third trimesters of pregnancy among 363 women in all Lebanese governorates. Most of the pregnant women were free of diseases. While the majority did not smoke, 14.1% smoked hookah / shisha during pregnancy. The adherence to the USDA recommendations in our sample did not significantly vary prior to and throughout the socioeconomic crisis, and it was generally low. Only the mean consumption of vegetables increased during the socioeconomic crisis (p<0.05). Regarding physical activity, while the proportion of active women slightly decreased during the socioeconomic crisis, around 55% were still active. In conclusion, higher attention should be given to the dietary habits and health of this critical population, through effective interventions that increase awareness and achieve measurable improvements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hoteit 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 decreasing status of on IUCN of Koklass pheasant (Pucrasia macrolopha) belongs to the family Phasianidae and the order Galliform needs the attention of researchers. The species with habitats as low as 6,000 feet and as high as 11,000 feet certainly cover a broad variety of habitats, such a wide altitude range embraces a diverse range of habitats. Insufficient research has been conducted on the suitability of moist temperate forests as a potential habitat for the Koklass pheasant. Therefore, this study was carried out to explore habitat suitability in 15 different sites which were located in the 4 districts of Hazara Division using GIS data science and environmental variables. A random sampling technique was used for laying out the transect. Overall, 45 line transects (Length 2-4 km, Width 10-30 m) were laid out in study sites. The size of sample plots for trees was 10x10m, for shrubs (4 x4m), and herbs and grasses 1x1m. The other habitat parameters like elevation, slope, cover, and frequency of plant at each point were also considered. We found the uneven distribution of Koklass pheasant in the Hazara Division. There were 59 occurrence points identified and highlighted the distribution of Koklass pheasant in the study area. Although all environmental variables were preferred by Koklass pheasant in its habitat statistical analysis proved that slope, level of disturbance, tree and shrub frequency of habitat contributed mostly to the presence of Koklass in each study site except the contribution of soil and herbs. The potential suitable habitat of Koklass pheasant was estimated to be 439.6 km2 areas starting from Abbottabad to Mansehra in the Hazara division. Awareness and enforcing legal protection are recommended for the conservation of Koklass Pheasant in Moist temperate forest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Badrulislam 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: Assessing parental satisfaction with healthcare services is crucial, particularly for parents and their children, who are the primary recipients of these services. In the context of Arabic-speaking parents, there is a notable absence of survey instruments tailored to measure their satisfaction. This study seeks to address this gap by validating a survey designed to evaluate parental satisfaction with rehabilitation services (RSs) provided to Jordanian children who have received cochlear implants (CIs)., Methods: The study included 92 participants and followed a four-step methodology: 1) a literature review and expert input; 2) cognitive interviews, pilot testing, and test-retest reliability testing; 3) data collection; 4) validity and reliability assessments., Results: The survey's validity was confirmed. Expert input and cognitive interviews improved content validity, and factor analysis established construct validity by revealing six factors explaining 82.33% of the variance in the survey scale. Convergent and discriminant validity were confirmed (composite reliability >0.7 and average variance extracted value >0.5). Cronbach's α exceeded 0.8 for each factor and reached 0.855 for the total scale. Survey results showed reliance on speech therapy and audiology, varied rehabilitation durations, and progress. Parents expressed overall satisfaction, particularly influenced by technical quality and efficacy/outcome dimensions. Parents' recommendations to enhance satisfaction with RSs included financial support, improved service accessibility, enhanced service delivery, specialized education, and increased public awareness., Conclusion: This study validates an Arabic satisfaction survey, emphasizing the significance of multidisciplinary, extended rehabilitation programs, skilled professionals, and positive outcomes. It emphasizes the necessity for improved access to specialized care and collaboration among healthcare, government, and media to shape parental perceptions of RSs. While the findings indicate overall satisfaction, they also reveal challenges faced by parents, highlighting the need for comprehensive support systems. These insights assist healthcare providers and policymakers in enhancing care quality and meeting the needs of CI children's families, thereby improving the RSs experience in Jordan., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alkhamra 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.)

Dietary self-monitoring is a behaviour change technique used to help elicit and sustain dietary changes over time. Current dietary self-monitoring tools focus primarily on itemizing foods and counting calories, which can be complex, time-intensive, and dependent on health literacy. Further, there are no dietary self-monitoring tools that conform to the plate-based approach of the 2019 Canada Food Guide (CFG), wherein the recommended proportions of three food groups are visually represented on a plate without specifying daily servings or portion sizes. This paper explored the perceptions of end-users (i.e., general public) and Registered Dietitians of iCANPlateTM-a dietary self-monitoring mobile application resembling the CFG. Qualitative data were collected through virtual focus groups. Focus group questions were based on the Capability, Opportunity, Motivation-Behaviour (COM-B) theoretical framework to explore perceptions of using the CFG and currently available dietary self-monitoring tools. The prototype iCANPlateTM (version 0.1) was presented to gain feedback on perceived barriers and facilitators of its use. Focus group discussions were audio recorded and verbatim transcribed. Trained researchers used thematic analysis to code and analyze the transcripts independently. Seven focus groups were conducted with Registered Dietitians (n = 44) and nine focus groups with members from the general public (n = 52). During the focus groups, participants mainly discussed the capabilities and opportunities required to use the current iteration of iCANPlateTM. Participants liked the simplicity of the application and its capacity to foster self-awareness of dietary behaviours rather than weight control or calorie counting. However, concerns were raised regarding iCANPlateTM's potential to improve adherence to dietary self-monitoring due to specific characteristics (i.e., insufficient classifications, difficulty in conceptualizing proportions, and lack of inclusivity). Overall, participants liked the simplicity of iCANPlateTM and its ability to promote self-awareness of dietary intakes, primarily through visual representation of foods on a plate as opposed to reliance on numerical values or serving sizes, were benefits of using the app. Findings from this study will be used to further develop the app with the goal of increasing adherence to plate-based dietary approaches., Competing Interests: None to declare., (Copyright: © 2023 Kheirmandparizi 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.)

Science, technology, engineering, mathematics, and medicine (STEMM) fields change rapidly and are increasingly interdisciplinary. Commonly, STEMM practitioners use short-format training (SFT) such as workshops and short courses for upskilling and reskilling, but unaddressed challenges limit SFT's effectiveness and inclusiveness. Education researchers, students in SFT courses, and organizations have called for research and strategies that can strengthen SFT in terms of effectiveness, inclusiveness, and accessibility across multiple dimensions. This paper describes the project that resulted in a consensus set of 14 actionable recommendations to systematically strengthen SFT. A diverse international group of 30 experts in education, accessibility, and life sciences came together from 10 countries to develop recommendations that can help strengthen SFT globally. Participants, including representation from some of the largest life science training programs globally, assembled findings in the educational sciences and encompassed the experiences of several of the largest life science SFT programs. The 14 recommendations were derived through a Delphi method, where consensus was achieved in real time as the group completed a series of meetings and tasks designed to elicit specific recommendations. Recommendations cover the breadth of SFT contexts and stakeholder groups and include actions for instructors (e.g., make equity and inclusion an ethical obligation), programs (e.g., centralize infrastructure for assessment and evaluation), as well as organizations and funders (e.g., professionalize training SFT instructors; deploy SFT to counter inequity). Recommendations are aligned with a purpose-built framework-"The Bicycle Principles"-that prioritizes evidenced-based teaching, inclusiveness, and equity, as well as the ability to scale, share, and sustain SFT. We also describe how the Bicycle Principles and recommendations are consistent with educational change theories and can overcome systemic barriers to delivering consistently effective, inclusive, and career-spanning SFT., Competing Interests: This work was supported by the National Science Foundation under DRL/EHR: 2027025 to JWW & RET. This funder played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Several co-authors are employed by commercial entities. These employers provided support in the form of salaries for BB, KLJ, EAB, and NC and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section., (Copyright: © 2023 Williams 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.)

Lower limb orthoses (LLOs) are externally-applied leg braces that are designed to improve or maintain mobility in people with a variety of health conditions that affect lower limb function. Clinicians and researchers are therefore often motivated to measure LLO users' mobility to select or assess the effectiveness of these devices. Patient-reported outcome measures (PROMs) can provide insights into important aspects of a LLO user's mobility for these purposes. However, few PROMs are available to measure mobility of LLO users. Those few that exist have issues that may limit their clinical or scientific utility. The objective of this study was to create a population-specific item bank for measuring mobility of LLO users. Previously-developed candidate items were administered in a cross-sectional study to a large national sample of LLO users. Responses from study participants (n = 1036) were calibrated to a graded response statistical model using Item Response Theory methods. A set of 39 items was found to be unidimensional, locally independent, and function without bias due to characteristics unrelated to mobility. The set of final calibrated items, termed the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M) item bank, was evaluated for initial evidence of convergent, divergent, and known groups construct validity. OPRO-M was strongly correlated with existing PROMs designed to measure aspects of physical function. Conversely, OPRO-M was weakly correlated with PROMs that measured unrelated constructs, like sleep disturbance and depression. OPRO-M also showed an ability to differentiate groups with expected mobility differences. Two fixed-length short forms were created from the OPRO-M item bank. Items on the short forms were selected based on statistical and clinical criteria. Collectively, results from this study indicate that OPRO-M can effectively measure mobility of LLO users, and OPRO-M short forms can now be recommended for use in routine clinical practice and research studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Balkman 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.)

Chronic skeletal muscle degeneration is characterized by fiber atrophy accompanied by deposition of extracellular matrix (ECM) components and fatty infiltration. Excessive accumulation of ECM leads to fibrosis via the contribution of fibro-adipogenic precursors (FAPs). Fibrosis also accompanies disuse atrophy and sarcopenia without significant inflammation. The present study aimed to comparatively analyze heterogeneous population of FAPs during acute injury and immobilization (tenotomy and denervation). The comparative analysis was accomplished based on the following 3 stromal cell subpopulations: i) CD140a(+)/Sca1(+); ii) CD140a(+)/Sca1(-); iii) CD140a(-)/Sca1(+). RNASeq analysis was employed to characterize and compare their quiescent and activated states. Whereas CD140a(-)/Sca1(+) was the most predominant activated subpopulation in tenotomy, denervation stimulated the CD140a(+)/Sca1(+) subpopulation. Immobilization models lacked myofiber damage and exhibited a minute increase in CD45(+) cells, as compared to acute injury. Transcriptome analysis showed common and discordant regulation of ECM components, without profound proliferative activation. Herein, we suggest unique surface markers for further identification of the investigated cell subpopulations. FAP subpopulations show similar activation kinetics in an inflammatory environment but the present findings highlight the fact that inflammation may not be a prerequisite for FAP activation. Delayed proliferation kinetics indicate that signals beyond inflammation might trigger FAP activation, leading to irreversible stromal changes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Özdemir 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: Human trafficking is considered a hidden global crime with unsubstantiated numbers. Despite the challenges in counting or measuring this crime, reports revealed the presence of around 40.3 million victims worldwide. Human trafficking results in severe detrimental impacts on both mental and physical health. Given the sensitivity and negative consequences of human trafficking on the global system and victims, and considering the scarce research in this area, our current study aimed at describing the (i) Sociodemographic profiles of anonymized victims, (ii) Means of control, and (iii) Purpose of trafficking, utilizing the largest anonymized and publicly available dataset on victims of human trafficking., Methods: This is a retrospective secondary analysis of the Counter-Trafficking Data Collaborative (CTDC) data pool in the period from 2010 to 2020. The utilized dataset is called the k-anonymized global victim of trafficking dataset, and it is considered the largest global dataset on victims of human trafficking. Data from the k-anonymized data pool were extracted and exported to Statistical Package for Social Sciences, SPSS® version 27.0 for Windows (IBM Corp. Version 27.0. Armonk, NY) for quality check and analysis using descriptive statistics., Results: A total of 87003 victims of human trafficking were identified in the period from 2010 to 2020. The most age category encountered among victims was 9-17 years with 10326 victims (11.9%), followed by 30-38 years with 8562 victims (9.8%). Females comprised 70% of the sample with 60938 victims. The United States (n = 51611), Russia (n = 4570), and the Philippines (n = 1988) comprised the most countries of exploitation/trafficking. Additionally, the year 2019 witnessed the greatest number of victims registered for assistance by anti-trafficking agencies with around 21312 victims (24.5%). Concerning means of control, threats, psychological abuse, restriction of the victim's movement, taking the victim's earnings, and physical abuse were the most reported means. 42685 victims (49.1%) reported sexual exploitation as the purpose of their trafficking, followed by forced labor with 18176 victims (20.9%)., Conclusion: Various means and methods can be used by traffickers to control the victims to be trafficked for many purposes, with sexual exploitation and forced labor being the most common ones. Global anti-trafficking efforts should be brought together in solidarity through utilizing the paradigm of protection of victims, prosecution of traffickers, prevention of trafficking, and inter-sectoral partnerships. Despite being a global concern with various reports that tried to capture the number of trafficked victims worldwide, human trafficking still has many unseen aspects that impose a significant challenge and adds to the global burden in combatting this threat., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Al-Tammemi 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.)

Elucidation of structure and dynamics of alternative higher-order structures of DNA such as in branched form could be targeted for therapeutics designing. Herein, we are reporting the intrinsically dynamic and folds transitions of an unusual DNA junction with sequence d(CGGCGGCCGC)4 which self-assembles into a four-way DNA junction form with sticky ends using long interval molecular simulations under various artificial physiological conditions. The original crystal structure coordinates (PDB ID: 3Q5C) for the selected DNA junction was considered for a total of 1.1 μs molecular dynamics simulation interval, including different temperature and pH, under OPLS-2005 force field using DESMOND suite. Following, post-dynamics structure parameters for the DNA junction were calculated and analyzed by comparison to the crystal structure. We show here that the self-assembly dynamics of DNA junction is mitigated by the temperature and pH sensitivities, and discloses peculiar structural properties as function of time. From this study it can be concluded on account of temperature sensitive and pH dependent behaviours, DNA junction periodic arrangements can willingly be synthesized and redeveloped for multiple uses like genetic biomarkers, DNA biosensor, DNA nanotechnology, DNA Zipper, etc. Furthermore, the pH dis-regulation behaviour may be used to trigger the functionality of DNA made drug-releasing nanomachines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Singh 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.)

Objectives: Hospital-acquired infections (HAIs) are significant problems as public health issues which need attention. Such infections are significant problems for society and healthcare organizations. This study aimed to carry out a systematic review and a meta-analysis to analyze the prevalence of HAIs globally., Methods: We conducted a comprehensive search of electronic databases including EMBASE, Scopus, PubMed and Web of Science between 2000 and June 2021. We found 7031 articles. After removing the duplicates, 5430 studies were screened based on the titles/ abstracts. Then, we systematically evaluated the full texts of the 1909 remaining studies and selected 400 records with 29,159,630 participants for meta-analysis. Random-effects model was used for the analysis, and heterogeneity analysis and publication bias test were conducted., Results: The rate of universal HAIs was 0.14 percent. The rate of HAIs is increasing by 0.06 percent annually. The highest rate of HAIs was in the AFR, while the lowest prevalence were in AMR and WPR. Besides, AFR prevalence in central Africa is higher than in other parts of the world by 0.27 (95% CI, 0.22-0.34). Besides, E. coli infected patients more than other micro-organisms such as Coagulase-negative staphylococci, Staphylococcus spp. and Pseudomonas aeruginosa. In hospital wards, Transplant, and Neonatal wards and ICU had the highest rates. The prevalence of HAIs was higher in men than in women., Conclusion: We identified several essential details about the rate of HAIs in various parts of the world. The HAIs rate and the most common micro-organism were different in various contexts. However, several essential gaps were also identified. The study findings can help hospital managers and health policy makers identify the reason for HAIs and apply effective control programs to implement different plans to reduce the HAIs rate and the financial costs of such infections and save resources., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Raoofi 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 risk of type-2 diabetes and cardiovascular disease is higher in subjects with metabolic syndrome, a cluster of clinical conditions characterized by obesity, impaired glucose metabolism, hyperinsulinemia, hyperlipidemia and hypertension. Diuretics are frequently used to treat hypertension in these patients, however, their use has long been associated with poor metabolic outcomes which cannot be fully explained by their diuretic effects. Here, we show that mice lacking the diuretic-sensitive Na+K+2Cl-cotransporter-1 Nkcc1 (Slc12a2) in insulin-secreting β-cells of the pancreatic islet (Nkcc1βKO) have reduced in vitro insulin responses to glucose. This is associated with islet hypoplasia at the expense of fewer and smaller β-cells. Remarkably, Nkcc1βKO mice excessively gain weight and progressive metabolic syndrome when fed a standard chow diet ad libitum. This is characterized by impaired hepatic insulin receptor activation and altered lipid metabolism. Indeed, overweight Nkcc1βKO but not lean mice had fasting and fed hyperglycemia, hypertriglyceridemia and non-alcoholic steatohepatitis. Notably, fasting hyperinsulinemia was detected earlier than hyperglycemia, insulin resistance, glucose intolerance and increased hepatic de novo gluconeogenesis. Therefore, our data provide evidence supporting the novel hypothesis that primary β-cell defects related to Nkcc1-regulated intracellular Cl-homeostasis and β-cell growth can result in the development of metabolic syndrome shedding light into additional potential mechanisms whereby chronic diuretic use may have adverse effects on metabolic homeostasis in susceptible individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Abdelgawad 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.)

Inverse odds of participation weighting (IOPW) has been proposed to transport clinical trial findings to target populations of interest when the distribution of treatment effect modifiers differs between trial and target populations. We set out to apply IOPW to transport results from an observational study to a target population of interest. We demonstrated the feasibility of this idea with a real-world example using a nationwide electronic health record derived de-identified database from Flatiron Health. First, we conducted an observational study that carefully adjusted for confounding to estimate the treatment effect of fulvestrant plus palbociclib relative to letrozole plus palbociclib as a second-line therapy among estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER2)-negative metastatic breast cancer patients. Second, we transported these findings to the broader cohort of patients who were eligible for a first-line therapy. The interpretation of the findings and validity of such studies, however, rely on the extent that causal inference assumptions are met., Competing Interests: No competing interests., (Copyright: © 2022 Ling 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: Cardiac rehabilitation improves prognosis and symptoms in cardiac patients. In 2020, due to the COVID-19 pandemic, cardiac rehabilitation services were temporarily suspended between April and August. We aimed to investigate the effect of cardiac rehabilitation suspension during the COVID-19 pandemic on patients' exercise capacity and metabolic parameters., Methods: Included were patients undergoing cardiac rehabilitation following hospital admission for ACS. Exercise capacity, weight and body fat percentage were compared between baseline, pre- and post-lockdown visits., Results: A total of 281 patients participated in the cardiac rehabilitation program prior to its suspension. Of them, only 198 (70%) patients returned to the program on its renewal and were included in the analysis. Exercise capacity improved significantly in the pre-lockdown stress test compared to baseline. However, there was a significant decrease in exercise capacity in the post compared to pre-lockdown test (8.1±6.3 and 7.1±2.1 METs in pre- and post-lockdown measurements, respectively, p<0.001). Of the 99 (50%) of patients that demonstrated at least 10% improvement in exercise capacity in the pre-lockdown test, 48(48.5%) patients returned to their baseline values in the post-lockdown test. Post-lockdown assessment demonstrated a significant weight gain (80.3 and 81.1kg, in pre- and post-lockdown measurements, respectively, p<0.001) as well as an increase in visceral fat level and body fat percentage., Conclusions: Cardiac rehabilitation suspension for 4 months during COVID-19 pandemic caused a significant reduction in exercise capacity and increased weight and body fat percent. These findings highlight the importance of remote cardiac rehabilitation services that can continue uninterrupted in times of pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Haskiah 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.)

This study was carried out to produce low-emitting biomass pellets biofuel from selected forest trees such as (Cedrus deodara and Pinus wallichiana) and agricultural crop residues such as (Zea mays and Triticum aestivum) in Gilgit-Baltistan, Pakistan using indigenously developed technology called pelletizer machine. Characterization, environmental life cycle impact assessment, and cumulative energy demand of biomass pellets biofuel produced from selected agriculture crops and forest tree residues were conducted. The primary data for biomass pellets production was collected by visiting various wood processing factories, sawmills, and agricultural crop fields in the study area. Biomass pellets are a type of biofuel that is often made by compressing sawdust and crushing biomass material into a powdery form. The particles are agglomerated as the raw material is extensively compressed and pelletized. Biomass pellets have lower moisture content, often less than 12%. Physically, the produced pellets were characterized to determine moisture content, pellet dimensions, bulk density, higher heating value, ash content, lower heating value, and element analysis. A functional unit of one kilogram (kg) biomass pellets production was followed in this study.The life cycle impact assessment of one kg biomass pellets biofuel produced from selected agro-forest species revealed environmental impact categories such as acidification (0.006 kg SO2 eq/kg pellets), abiotic depletion (0.018 kg Sb eq/kg pellets), marine aquatic ecotoxicity (417.803 kg 1,4-DB eq/kg pellets), human toxicity (1.107 kg 1,4-DB eq/kg pellets), freshwater aquatic ecotoxicity (0.191 kg 1,4-DB eq/kg pellets), eutrophication (0.001 kg PO4 eq/kg pellets), global warming (0.802 kg CO2 eq/kg pellets), and terrestrial ecotoxicity (0.008 kg 1,4-DB eq/kg pellets). Fossil fuel consumption was the hotspot source to all environmental impacts investigated. To measure the cumulative energy demand of biomass pellets made from different agroforestry species leftovers showed that the maximum cumulative energy was from wheat straw pellets (13.737 MJ), followed by corncob pellets (11.754 MJ), deodar sawdust pellets (10.905 MJ) and blue pine sawdust pellets (10.877 MJ). Among the various production activities, collection and transportation of primary raw material, crushing, screening, adding adhesives, pelletizing, cooling, final screening, and packing have the maximum contribution to the water scarcity index, followed by lubricating oil (0.00147m3). In contrast, the minimum contribution to water footprint was from electricity (0.00008m3) and wheat starch (0.00005m3). The highest contribution to the ecological footprint impact categories such as carbon dioxide, nuclear, and land occupation was lubricating oil and less contribution of wheat starch and electricity for manufacturing one kg pellets biofuel. It is concluded that physico-mechanical and combustion properties of the biomass pellets biofuel developed in the present study were following the Italian recommended standards. Therefore, it is strongly recommended that the Government of Pakistan should introduce the renewable biomass pellets industry in the country to reduce dependency on fossil fuels for cooking and heating purposes., Competing Interests: The authors have declared that no competing interests exist.

Seroprevalence of SARS-CoV-2 IgG among health care workers (HCWs) is crucial to inform infection control programs. Conflicting reports have emerged on the longevity of SARS-CoV-2 IgG. Our objective is to describe the prevalence of SARS-CoV-2 IgG in HCWs and perform 8 months longitudinal follow-up (FU) to assess the duration of detectable IgG. In addition, we aim to explore the risk factors associated with positive SARS-CoV-2 IgG. The study was conducted at a large COVID-19 public hospital in Riyadh, Saudi Arabia. All HCWs were recruited by social media platform. The SARS-CoV-2 IgG assay against SARS-CoV-2 nucleocapsid antigen was used. Multivariable logistic regression was used to examine association between IgG seropositive status and clinical and epidemiological factors. A total of 2528 (33% of the 7737 eligible HCWs) participated in the survey and 2523 underwent baseline serological testing in June 2020. The largest occupation groups sampled were nurses [n = 1351(18%)], physicians [n = 456 (6%)], administrators [n = 277 (3.6%)], allied HCWs [n = 205(3%)], pharmacists [n = 95(1.2%)], respiratory therapists [n = 40(0.5%)], infection control staff [n = 21(0.27%], and others [n = 83 (1%)]. The total cohort median age was 36 (31-43) years and 66.3% were females. 273 were IgG seropositive at baseline with a seroprevalence of 10.8% 95% CI (9.6%-12.1%). 165/185 and 44/112 were persistently IgG positive, at 2-3 months and 6 months FU respectively. The median (25th- 75th percentile) IgG level at the 3 different time points was 5.86 (3.57-7.04), 3.91 (2.46-5.38), 2.52 (1.80-3.99) respectively. Respiratory therapists OR 2.38, (P = 0.035), and those with hypertension OR = 1.86, (P = 0.009) were more likely to be seropositive. A high proportion of seropositive staff had prior symptoms 214/273(78%), prior anosmia was associated with the presence of antibodies, with an odds ratio of 9.25 (P<0.001), as well as fever and cough. Being a non-smoker, non-Saudi, and previously diagnosed with COVID-19 infection by PCR were statistically significantly different by seroprevalence status. We found that the seroprevalence of IgG against SARS-CoV-2 nucleocapsid antigen was 10.8% in HCWs at the peak of the pandemic in Saudi Arabia. We also observed a decreasing temporal trend of IgG seropositivity over 8 months follow up period., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Cystic fibrosis (CF) is a hereditary autosomal recessive disorder caused by a range of mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. This gene encodes the CFTR protein, which acts as a chloride channel activated by cyclic AMP (cAMP). This meta-analysis aimed to compare the responsiveness of induced pluripotent stem cells (iPSCs) to cAMP analogues to that of commonly used animal models., Methods: Databases searched included PubMed, Scopus, and Medline from inception to January 2020. A total of 8 and 3 studies, respectively, for animal models and iPSCs, were analyzed. Studies were extracted for investigating cAMP-stimulated anion transport by measuring the short circuit current (Isc) of chloride channels in different animal models and iPSC systems We utilized an inverse variance heterogeneity model for synthesis., Results: Our analysis showed considerable heterogeneity in the mean Isc value in both animal models and iPSCs studies (compared to their WT counterparts), and both suffer from variable responsiveness based on the nature of the underlying model. There was no clear advantage of one over the other., Conclusions: Studies on both animal and iPSCs models generated considerable heterogeneity. Given the potential of iPSC-derived models to study different diseases, we recommend paying more attention to developing reproducible models of iPSC as it has potential if adequately developed., Competing Interests: The authors have declared that no competing interests exist.

Shortly after the implementation of community mitigation measures in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), sharp declines in respiratory syncytial virus and influenza circulation were noted; post-mitigation circulation of other respiratory pathogens has gone unexplored. We retrospectively analyzed all records of a provider-ordered multiplex test between April 1, 2018, and July 31, 2021, in Nashville, Tennessee, and we noted disrupted historical seasonal patterns for common respiratory pathogens during the SARS-CoV-2 pandemic., Competing Interests: Natasha Halasa, MD, MPH receives grant support from Sanofi Pasteur, Quidel, and speaker compensation from an education grant supported by Genentech. Sanofi Pasteur also donated vaccines and influenza antibody testing for influenza vaccine trial. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Supporting small and nutritionally at-risk (potentially malnourished) infants under six months is a global health priority, albeit with a weak evidence-base. To inform policy and research in this area, we aimed to assess the perceptions and understanding of infant malnutrition and its management among carers, communities, and healthcare workers in rural Ethiopia., Methods: We conducted in-depth and key-informant interviews, from May-August 2020 in Jimma Zone and Deder District, Ethiopia. We used purposive sampling to recruit the participants. Interviews were transcribed into Amharic or Afaan Oromo and then translated into English. Atlas ti-7 was used to support data analysis. Findings were narrated based on the different themes arising from the interviews., Results: Carers/community members and healthcare workers reported on five different themes: 1) Perceptions about health and well-being: an 'ideal infant' slept well, fed well, was active and looked 'fat'; 2)Perceptions of feeding: overall knowledge of key recommendations like exclusive breastfeeding was good but practices were suboptimal, notably a cultural practice to give water to young infants; 3)Awareness about malnutrition: a key limitation was knowledge of exactly how to identify small and nutritionally at-risk infants; 4) Reasons for malnutrition: levels of understanding varied and included feeding problems and caregiver's work pressures resulting in the premature introduction of complementary feeds; 5) Perceptions about identification & treatment: carers prefer treatment close to home but were concerned about the quality of community-based services., Conclusion: To succeed, research projects that investigate programes that manage small and nutritionally at-risk infants under six months should understand and be responsive to the culture and context in which they operate. They should build on community strengths and tackle misunderstandings and barriers. Interventions beyond just focusing on knowledge and attitude of the carers and health workers are necessary to tackle the challenges around infants under 6 months of age at risk of malnutrition. Moreover, stakeholders beyond the health sector should also be involved in order to support the infants under 6 months and their mothers as some of the key reasons behind the at-risk infants are just beyond the capacity of the health sector or health system. Our list of themes could be used to inform infant nutrition work not just in Ethiopia but also in many others., Competing Interests: The authors have declared that no competing interests exist.

Objective: To compare the effect of stable supportive to flat flexible walking shoes on medial tibiofemoral contact force (MTCF) in people with medial knee osteoarthritis and varus malalignment., Design: This was a randomized cross-over study. Twenty-eight participants aged ≥50 years with medial knee osteoarthritis and varus malalignment were recruited from the community. Three-dimensional full-body motion, ground reaction forces and surface electromyograms from twelve lower-limb muscles were acquired during six speed-matched walking trials for flat flexible and stable supportive shoes, tested in random order. An electromyogram-informed neuromusculoskeletal model with subject-specific geometry estimated bodyweight (BW) normalized MTCF. Waveforms were analyzed using statistical parametric mapping with a repeated measures analysis of variance model. Peak MTCF, MTCF impulse and MTCF loading rates (discrete outcomes) were evaluated using a repeated measures multivariate analysis of variance model., Results: Statistical parametric mapping showed lower MTCF in stable supportive compared to flat flexible shoes during 5-18% of stance phase (p = 0.001). For the discrete outcomes, peak MTCF and MTCF impulse were not different between the shoe styles. However, mean differences [95%CI] in loading impulse (-0.02 BW·s [-0.02, 0.01], p<0.001), mean loading rate (-1.42 BW·s-1 [-2.39, -0.45], p = 0.01) and max loading rate (-3.26 BW·s-1 [-5.94, -0.59], p = 0.02) indicated lower measure of loading in stable supportive shoes compared to flexible shoes., Conclusions: Stable supportive shoes reduced MTCF during loading stance and reduced loading impulse/rates compared to flat flexible shoes and therefore may be more suitable in people with medial knee osteoarthritis and varus malalignment., Trial Registration: Australian and New Zealand Clinical Trials Registry (12619000622101)., Competing Interests: The authors have declared that no competing interests exist.

The type IIa family of receptor protein tyrosine phosphatases (RPTPs), including Lar, RPTPσ and RPTPδ, are well-studied in coordinating actin cytoskeletal rearrangements during axon guidance and synaptogenesis. To determine whether this regulation is conserved in other tissues, interdisciplinary approaches were utilized to study Lar-RPTPs in the Drosophila musculature. Here we find that the single fly ortholog, Drosophila Lar (Dlar), is localized to the muscle costamere and that a decrease in Dlar causes aberrant sarcomeric patterning, deficits in larval locomotion, and integrin mislocalization. Sequence analysis uncovered an evolutionarily conserved Lys-Gly-Asp (KGD) signature in the extracellular region of Dlar. Since this tripeptide sequence is similar to the integrin-binding Arg-Gly-Asp (RGD) motif, we tested the hypothesis that Dlar directly interacts with integrin proteins. However, structural analyses of the fibronectin type III domains of Dlar and two vertebrate orthologs that include this conserved motif indicate that this KGD tripeptide is not accessible and thus unlikely to mediate physical interactions with integrins. These results, together with the proteomics identification of basement membrane (BM) proteins as potential ligands for type IIa RPTPs, suggest a complex network of protein interactions in the extracellular space that may mediate Lar function and/or signaling in muscle tissue., Competing Interests: The authors have declared that no competing interests exist.

Background: Blood transfusion is a common, essential procedure when treating many different medical and surgical conditions. Efficient utilization of blood bank facilities by frequent auditing is crucial; however, few studies have examined blood utilization in Saudi Arabia. We aimed to review the blood ordering patterns and transfusion practices, and blood bank audit effectiveness at a single center in Saudi Arabia and compare our results with those of a similar study performed in the same center 20 years ago., Materials and Methods: This study was a retrospective descriptive chart review of all healthy blood donors and recipients from January 1, 2016, to December 31, 2020. We evaluated the crossmatching-to-transfusion ratio (C/T) as an indicator of blood bank utilization and compared the findings with those of the previous study. We also evaluated changes in blood bank utilization during the coronavirus disease 2019 pandemic., Results: Findings from 27,414 donors (men, 94.9%; mean age, 32.2 + 9.6 years) showed a 71% increase in blood donations compared to that of 2000. The donations gradually increased over the years, peaking just before COVID-19 pandemic started in March 2020. For 3,836 patients, 13,324 units of blood were crossmatched (average, 3.47 crossmatch/patient), with 23% of the crossmatch requests from surgical departments. The average C/T ratio, transfusion index, and transfusion probability (T%) were 1.37, 2.55, and 73.2%, respectively. The C/T ratio decreased by 54% between 2000 and 2020. During the pandemic, crossmatching decreased by 26% between 2019 and 2020, but with comparable C/T ratio in 2019 (1.45) and 2020 (1.39)., Conclusion: Our hospital blood bank utilization improved over the past 20 years, showing increased donations, reduced C/T ratio, and increased T%. This improvement emphasizes the importance of blood donation campaigns, blood bank auditing, restrictive transfusion guidelines, and physician education., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aimed to determine caregivers' perspectives on difficulties encountered while seeking care for adolescents with sickle cell disease (SCD). It explored the social, emotional, and financial impact of caring for an adolescent with SCD on their caregivers., Study Design: A mixed-method study in a major tertiary care hospital in Bahrain was conducted between June and August 2019. Cross-sectional questionnaires and thematic analyzed interviews were performed with 101 and 18 Bahraini caregivers of adolescents with SCD (aged 10-18 years), respectively., Results: Lack of parking lots (52.5%) and traffic jams (27%) were identified as the most common challenges in seeking hospital care for adolescents with SCD. These difficulties, including prolonged waiting in the emergency room, discouraged more than half of the caregivers who preferred to seek care from smaller healthcare centers. Most caregivers reported receiving a high degree of support from their families, who emotionally encouraged them to facilitate patient care (73.3%). Therefore, their relationships with their friends, colleagues, and relatives were not significantly affected. Catastrophic health expenditure occurred in 14.8% of caregivers. Qualitative themes that emerged were A) the intricacy of caring for adolescents with SCD, B) dissatisfaction with hospital facilities, and C) insufficient healthcare services, wherein caregivers reported adolescents' experiences with services during hospital visits. Subthemes for the intricacy of caring for adolescents with SCD were 1) the psychological tragedy, summarizing the initial caregivers' feelings after the confirmed diagnosis, 2) caregiving hardships that described the caregivers' emotional and health burden while accepting and adjusting to the disease, and 3) the cost of care on families, which highlights the financial burden of the disease on families., Conclusion: The caregivers of adolescents with SCD experienced several overwhelming challenges, including problems in accessing healthcare and receiving medical services, in addition to influences on the emotional, financial, and social aspects of their lives., Competing Interests: The authors have declared that no competing interests exist.

Responses to early life adversity differ greatly across individuals. Elucidating which factors underlie this variation can help us better understand how to improve health trajectories. Here we used a case:control study of refugee and non-refugee youth, differentially exposed to war-related trauma, to investigate the effects of genetics and psychosocial environment on response to trauma. We investigated genetic variants in two genes (serotonin transporter, 5-HTT, and catechol-O-methyltransferase, COMT) that have been implicated in response to trauma. We collected buccal samples and survey data from 417 Syrian refugee and 306 Jordanian non-refugee youth who were enrolled in a randomized controlled trial to evaluate a mental health-focused intervention. Measures of lifetime trauma exposure, resilience, and six mental health and psychosocial stress outcomes were collected at three time points: baseline, ~13 weeks, and ~48 weeks. We used multilevel models to identify gene x environment (GxE) interactions and direct effects of the genetic variants in association with the six outcome measures over time. We did not identify any interactions with trauma exposure, but we did identify GxE interactions with both genes and resilience; 1) individuals with high expression (HE) variants of 5-HTTLPR and high levels of resilience had the lowest levels of perceived stress and 2) individuals homozygous for the Val variant of COMT with high levels of resilience showed stable levels of post-traumatic stress symptoms. We also identified a direct protective effect of 5-HTTLPR HE homozygotes on perceived insecurity. Our results point to novel interactions between the protective effects of genetic variants and resilience, lending support to ideas of differential susceptibility and altered stress reactivity in a cohort of war-affected adolescents., Competing Interests: The authors have declared that no competing interests exist.

Epigenetic mechanisms regulate osteogenic lineage differentiation of mesenchymal stromal cells. Histone methylation is controlled by multiple lysine demethylases and is an important step in controlling local chromatin structure and gene expression. Here, we show that the lysine-specific histone demethylase Kdm1A/Lsd1 is abundantly expressed in osteoblasts and that its suppression impairs osteoblast differentiation and bone nodule formation in vitro. Although Lsd1 knockdown did not affect global H3K4 methylation levels, genome-wide ChIP-Seq analysis revealed high levels of Lsd1 at gene promoters and its binding was associated with di- and tri-methylation of histone 3 at lysine 4 (H3K4me2 and H3K4me3). Lsd1 binding sites in osteoblastic cells were enriched for the Runx2 consensus motif suggesting a functional link between the two proteins. Importantly, inhibition of Lsd1 activity decreased osteoblast activity in vivo. In support, mesenchymal-targeted knockdown of Lsd1 led to decreased osteoblast activity and disrupted primary spongiosa ossification and reorganization in vivo. Together, our studies demonstrate that Lsd1 occupies Runx2-binding cites at H3K4me2 and H3K4me3 and its activity is required for proper bone formation., Competing Interests: The authors have declared that no competing interests exist.

Background: Better understanding of the determinants of national life expectancy is crucial for economic development, as a healthy nation is a prerequisite for a wealthy nation. Many socioeconomic, nutritional, lifestyle, genetic and environmental factors can influence a nation's health and longevity. Environmental degradation is one of the critical determinants of life expectancy, which is still under-researched, as the literature suggests., Objectives: This study aims to investigate the determinants of life expectancy in 31 world's most polluted countries with particular attention on environmental degradation using the World Bank annual data and British Petroleum data over the period of 18 years (2000-2017)., Methods: The empirical investigation is based on the model of Preston Curve, where panel corrected standard errors (PCSE) and feasible general least square (FGLS) estimates are employed to explore the long-run effects. Pairwise Granger causality test is also used to have short-run causality among the variables of interest, taking into account the cross-sectional dependence test and other essential diagnostic tests., Results: The results confirm the existence of the Preston Curve, implying the positive effect of economic growth on life expectancy. Environmental degradation is found as a threat while health expenditure, clean water and improved sanitation affect the life expectancy positively in the sample countries. The causality test results reveal one-way causality from carbon emissions to life expectancy and bidirectional causalities between drinking water and life expectancy and sanitation and life expectancy., Conclusion: Our results reveal that environmental degradation is a threat to having improved life expectancy in our sample countries. Based on the results of this study, we recommend that: (1) policy marker of these countries should adopt policies that will reduce carbon emissions and thus will improve public health and productivity; (2) environment-friendly technologies and resources, such as renewable energy, should be used in the production process; (3) healthcare expenditure on a national budget should be increased; and (4) clean drinking water and basic sanitation facilities must be ensured for all people., Competing Interests: The authors have declared that no competing interests exist.

According to IPCC Annual Report (AR-5), environmental impact assessment of any product prototype is recommended before its large-scale commercialization; however, no environmental profile analysis of any biodiesel prototype has been conducted in Pakistan. Therefore, objective of this study was to conduct a comprehensive life cycle assessment (LCA), water footprint and cumulative energy demand (CED) of biodiesel production from Jatropha curcas L. (JC) seeds oil in Pakistan. A cradle-to-gate LCA approach was applied for 400 liter (L) JC biodiesel produced in Pakistan. JC biodiesel production chain was divided into three stages i.e., 1). cultivation of JC crop 2). crude oil extraction from JC seeds and 3). crude oil conversion to biodiesel. Primary data for all the stages were acquired through questionnaire surveys, field visits and measurements in the field. Potential environmental impacts were calculated in SimaPro v.9.2 software using Eco-indicator 99 methodology. Results showed that crude oil extraction stage accounted for highest emissions (77%) to the overall environmental impact categories evaluated, followed by oil conversion stage (21%) and JC cultivation stage (02%), respectively. The three stages of JC biodiesel production chain are major contributor to ecotoxicity with a contribution of 57% to this impact category. Higher contribution to ecotoxicity was due to agrochemicals used in the JC cultivation. Similarly, fossil fuels impact category was responsible for 38% of overall environmental impacts. In addition, water footprint of JC biodiesel production chain was 2632.54 m3/reference unit. Cumulative energy required for 400L JC biodiesel production chain was 46745.70 MJ in Pakistan. Fossil diesel consumption, synthetic fertilizers use and purchased electricity were major hotspot sources to environmental burdens caused by JC biodiesel production in Pakistan. By performing sensitivity analysis at 20% reduction of the baseline values of fossil diesel used, synthetic fertilizers and purchased electricity, a marked decrease in environmental footprint was observed. It is highly recommended that use of renewable energy instead of fossil energy would provide environmental benefits such as lower greenhouse gases and other toxic emissions as compared to conventional petroleum fuels. It is also recommended that JC as a biofuel plant, has been reported to have many desired characteristics such as quick growth, easy cultivation, drought resistance, pest and insect resistance, and mainly great oil content in JC seeds (27-40%). Therefore, JC plant is highly recommended to Billion Tree Afforestation Project (BTAP) for plantation on wasteland because it has multipurpose benefits., Competing Interests: The authors have declared that no competing interests exist.

Background: Abnormal fetal growth can be associated with factors during pregnancy and at postpartum., Objective: In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes associated with small-for-gestational age (SGA) and large-for-gestational age (LGA) infants., Methods: We performed a population-based retrospective study on 14,641 singleton live births registered in the PEARL-Peristat Study between April 2017 and March 2018 in Qatar. We estimated the incidence and examined the risk factors and outcomes using univariate and multivariate analysis., Results: SGA and LGA incidence rates were 6.0% and 15.6%, respectively. In-hospital mortality among SGA and LGA infants was 2.5% and 0.3%, respectively, while for NICU admission or death in labor room and operation theatre was 28.9% and 14.9% respectively. Preterm babies were more likely to be born SGA (aRR, 2.31; 95% CI, 1.45-3.57) but male infants (aRR, 0.57; 95% CI, 0.4-0.81), those born to parous (aRR 0.66; 95% CI, 0.45-0.93), or overweight (aRR, 0.64; 95% CI, 0.42-0.97) mothers were less likely to be born SGA. On the other hand, males (aRR, 1.82; 95% CI, 1.49-2.19), infants born to parous mothers (aRR 2.16; 95% CI, 1.63-2.82), or to mothers with gestational diabetes mellitus (aRR 1.36; 95% CI, 1.11-1.66), or pre-gestational diabetes mellitus (aRR 2.58; 95% CI, 1.8-3.47) were significantly more likely to be LGA. SGA infants were at high risk of in-hospital mortality (aRR, 226.56; 95% CI, 3.47-318.22), neonatal intensive care unit admission or death in labor room or operation theatre (aRR, 2.14 (1.36-3.22)., Conclusion: Monitoring should be coordinated to alleviate the risks of inappropriate fetal growth and the associated adverse consequences., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Studies have shown that acute kidney injury (AKI) occurrence post SARS-CoV-2 infection is complex and has a poor prognosis. Therefore, more studies are needed to understand the rate and the predications of AKI involvement among hospitalized COVID-19 patients and AKI's impact on prognosis while under different types of medications., Patients and Methods: This study is a retrospective observational cohort study conducted at Bahrain Defence Force (BDF) Royal Medical Services. Medical records of COVID-19 patients admitted to BDF hospital, treated, and followed up from April 2020 to October 2020 were retrieved. Data were analyzed using univariate and multivariate logistic regression with covariate adjustment, and the odds ratio (OR) and 95% confidence (95% CI) interval were reported., Results: Among 353 patients admitted with COVID-19, 47.6% developed AKI. Overall, 51.8% of patients with AKI died compared to 2.2% of patients who did not develop AKI (p< 0.001 with OR 48.6 and 95% CI 17.2-136.9). Besides, deaths in patients classified with AKI staging were positively correlated and multivariate regression analysis revealed that moderate to severe hypoalbuminemia (<32 g/L) was independently correlated to death in AKI patients with an OR of 10.99 (CI 95% 4.1-29.3, p<0.001). In addition, 78.2% of the dead patients were on mechanical ventilation. Besides age as a predictor of AKI development, diabetes and hypertension were the major risk factors of AKI development (OR 2.04, p<0.01, and 0.05 for diabetes and hypertension, respectively). Also, two or more comorbidities substantially increased the risk of AKI development in COVID-19 patients. Furthermore, high levels upon hospital admission of D-Dimer, Troponin I, and ProBNP and low serum albumin were associated with AKI development. Lastly, patients taking ACEI/ARBs had less chance to develop AKI stage II/III with OR of 0.19-0.27 (p<0.05-0.01)., Conclusions: The incidence of AKI in hospitalized COVID-19 patients and the mortality rate among AKI patients were high and correlated with AKI staging. Furthermore, laboratory testing for serum albumin, hypercoagulability and cardiac injury markers maybe indicative for AKI development. Therefore, clinicians should be mandated to perform such tests on admission and follow-up in hospitalized patients., Competing Interests: The authors have declared that no competing interests exist.

Meningioma is the second most common type of intracranial brain tumor. Immunohistochemical techniques have shown prodigious results in the role of epidermal growth factor receptor variant III (EGFR vIII) in glioma and other cancers. However, the role of EGFR vIII in meningioma is still in question. This study attempt the confer searches for the position attained by EGFR vIII in progression and expression of meningioma. Immunohistochemistry technique showed that EGFR vIII is highly expressed in benign tumors as compared to the atypical meningioma with a highly significant p-value (p<0.05). Further analysis by flow cytometry results supported these findings thus presented high intensity of EGFR vIII in low grades of meningioma. The study revealed that the significant Ki 67 values, to predictor marker for survival and prognosis of the patients. Higher expression of EGFR vIII in low grades meningiomas as compared to high-grade tumors indicate towards its oncogenic properties. To our knowledge, limited studies reported in literature expressing the EGFR vIII in meningioma tumors. Hence, Opinions regarding the role that EGFR vIII in tumorigenesis and tumor progression are clearly conflicting and, therefore, it is crucial not only to find out its mechanism of action, but also to definitely identify its role in meningioma., Competing Interests: The authors declare they have no conflicts of interest.

Background: Despite several intervention programs, the Bedouin population living in the Southern District of Israel has the highest mortality rate among children and adolescents from unintentional injuries. Our research questions asked: (1) How does increasing the involvement and participation of Bedouin community members influence the issue of unintentional injuries among children? (2) How does reframing of the technical issue of safety into security influence community involvement and cooperation?, Objectives: 1) To identify effective and efficacious positive deviance practices through community-based participatory research with adults, children, and professionals in the Bedouin community. 2) To create wider and deeper connections and cohesion between and among diverse Bedouin communities by seeding and sparking opportunities for social networking and cross-learning., Methods: The study used a qualitative multi-method approach to generate a hybrid intervention model for reducing unintentional childhood injuries among the Bedouins. To frame the issue of unintentional injuries from the lived perspective of the Bedouins, we employed the Positive Deviance (PD) and Community Based Participatory Research (CBPR) approach. Drawing upon theatrical traditions, entertainment-education (EE), was employed as a way to narratively engage and persuade the Bedouins., Results: Our research resulted in: (1) the emergence of several PD ideas and practices for preventing and avoiding children's injuries; (2) the actual creation of a safe and secure playroom for children at a neighborhood mosque; and (3) the creation of cascading and cross-learning social networks between and among members of the Bedouin community spread across various locations., Conclusion: This study helped in reframing the technical issue of accidents and safety into the notion of sacredness and security, enhanced the association between emotions and cognition by means of experiential and EE methods, and stimulated creative thinking and the emergence of new culturally and contextually relevant ideas and practices through the PD process. It demonstrated the synergistic power of using a hybrid model that combined the rigor and vigor of different health communication approaches to address a significant disparity in the burden of child accidents faced by the Bedouins. Our study generated solutions that emerged from, and directly benefitted, Bedouin children-those, who face overwhelming risk of injury and death from preventable accidents., Competing Interests: DE is Beterem Safe Kids Israel Head of Research and Data, and LVC is Beterem Safe Kids Israel Southern District manager. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: The credibility and the reliability of Internet webpages to seek medication-related information is questionable. The main objective of the current study was to evaluate perception and experience of pharmacists with the use of Internet-based medication information by their patients., Methods: This is a cross-sectional descriptive study that was conducted to evaluate perception and experience of pharmacists with the use of Internet-based medication information by their patients. During the study period, 200 pharmacists were approached to participate in the study using a paper-based survey to assess their perceptions and current experience with the use of Internet-based medication information by their patients. Data were analyzed using descriptive statistics (mean/standard deviation for continuous variables, and frequency/percentages for qualitative variables). Also, simple linear regression was utilized to screen factors affecting pharmacists' perception scores of the use of Internet-based medication information., Results: Among 161 recruited pharmacists, the majority (n = 129, 80.1%) reported receiving inquiries from patients about Internet-based medication information within the last year. Among them, only 22.6% (n = 29) of pharmacists believed that Internet-based medication information is somewhat or very accurate. Unfortunately, only 24.2% (n = 31) of them stated that they always had enough time for their patient to discuss their Internet-based medication information. Regarding pharmacists' perception of the use of Internet-based medication information by their patients, more than half of the pharmacists (>50%) believe that Internet-based medication information could increase the patient's role in taking responsibility. On the other hand, 54.7% (n = 88) of the pharmacists believed that Internet-based medication information would contribute to rising the healthcare cost by obtaining unnecessary medications by patients. Finally, pharmacists' educational level was found to significantly affect their perception scores toward patient use of Internet-based medication information where those with higher educational level showed lower perception score (r = -0.200, P-value = 0.011)., Conclusion: Although pharmacists felt that usage of Internet-based data by patients is beneficial, they also have believed that it has a negative impact in terms of rising the healthcare cost, and it promotes unnecessary fear or concern about medications. We suggest that pharmacists be trained on principles of critical appraisal to become professional in retrieval information on the Internet that might improve their delivery of healthcare information and their recommendations to patients., Competing Interests: The authors have declared that no competing interests exist.

Osteocytes remodel the perilacunar matrix and canaliculi. X-linked hypophosphatemia (XLH) is characterized by elevated serum levels of fibroblast growth factor 23 (FGF23), leading to decreased 1,25 dihydroxyvitamin D3 (1,25D) production and hypophosphatemia. Bones from mice with XLH (Hyp) have enlarged osteocyte lacunae, enhanced osteocyte expression of genes of bone remodeling, and impaired canalicular structure. The altered lacuno-canalicular (LCN) phenotype is improved with 1,25D or anti-FGF23 antibody treatment, pointing to roles for 1,25D and/or phosphate in regulating this process. To address whether impaired 1,25D action results in LCN alterations, the LCN phenotype was characterized in mice lacking the vitamin D receptor (VDR) in osteocytes (VDRf/f;DMP1Cre+). Mice lacking the sodium phosphate transporter NPT2a (NPT2aKO) have hypophosphatemia and high serum 1,25D levels, therefore the LCN phenotype was characterized in these mice to determine if increased 1,25D compensates for hypophosphatemia in regulating LCN remodeling. Unlike Hyp mice, neither VDRf/f;DMP1Cre+ nor NPT2aKO mice have dramatic alterations in cortical microarchitecture, allowing for dissecting 1,25D and phosphate specific effects on LCN remodeling in tibial cortices. Histomorphometric analyses demonstrate that, like Hyp mice, tibiae and calvariae in VDRf/f;DMP1Cre+ and NPT2aKO mice have enlarged osteocyte lacunae (tibiae: 0.15±0.02μm2(VDRf/f;DMP1Cre-) vs 0.19±0.02μm2(VDRf/f;DMP1Cre+), 0.12±0.02μm2(WT) vs 0.18±0.0μm2(NPT2aKO), calvariae: 0.09±0.02μm2(VDRf/f;DMP1Cre-) vs 0.11±0.02μm2(VDRf/f;DMP1Cre+), 0.08±0.02μm2(WT) vs 0.13±0.02μm2(NPT2aKO), p<0.05 all comparisons) and increased immunoreactivity of bone resorption marker Cathepsin K (Ctsk). The osteocyte enriched RNA isolated from tibiae in VDRf/f;DMP1Cre+ and NPT2aKO mice have enhanced expression of matrix resorption genes that are classically expressed by osteoclasts (Ctsk, Acp5, Atp6v0d2, Nhedc2). Treatment of Ocy454 osteocytes with 1,25D or phosphate inhibits the expression of these genes. Like Hyp mice, VDRf/f;DMP1Cre+ and NPT2aKO mice have impaired canalicular organization in tibia and calvaria. These studies demonstrate that hypophosphatemia and osteocyte-specific 1,25D actions regulate LCN remodeling. Impaired 1,25D action and low phosphate levels contribute to the abnormal LCN phenotype observed in XLH., Competing Interests: The authors have declared that no competing interests exist.

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of severity used in Covichem (accuracy 0.87, AUROC 0.91). Accuracy was 0.92 in the external validation cohort (89% sensitivity and 95% specificity). Covichem score could be useful as a rapid, costless and easy to implement severity assessment tool during acute COVID-19 pandemic waves., Competing Interests: The authors have declared that no competing interests exist.

Background: Matrix Metalloproteinase-9 (MMP-9) has been shown to play a key role in mediating inflammation and tissue damage in inflammatory bowel disease (IBD). In patients with IBD, the intestinal tight junction (TJ) barrier is compromised as characterized by an increase in intestinal permeability. MMP-9 is elevated in intestinal tissue, serum and stool of patients with IBD. Previous studies from our laboratory showed that MMP-9 causes an increase in intestinal epithelial TJ permeability and that the MMP-9 induced increase in intestinal permeability is an important pathogenic factor contributing to the development of intestinal inflammation in IBD. However, the intracellular mechanisms that mediate the MMP-9 modulation of intestinal barrier function remain unclear., Aims: The main aim of this study was to further elucidate the molecular mechanisms involved in MMP-9 induced increase in intestinal epithelial TJ permeability using Caco-2 monolayers as an in-vitro model system., Results: MMP-9 induced increase in Caco-2 TJ permeability was associated with activation and cytoplasmic-to-nuclear translocation of NF-κB p65. Knocking-down NF-κB p65 by siRNA transfection prevented the MMP-9 induced expression of the NF-κB target gene IL-8, myosin light chain kinase (MLCK) protein expression, and subsequently prevented the increase in Caco-2 TJ permeability. In addition, the effect of MMP-9 on Caco-2 intestinal epithelial TJ barrier function was not mediated by apoptosis or necrosis., Conclusion: Our data show that the MMP-9 induced disruption of Caco-2 intestinal epithelial TJ barrier function is regulated by NF-κB pathway activation of MLCK., Competing Interests: The authors have declared that no competing interests exist.

Since its emergence in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide including Pakistan. During the pandemic, whole genome sequencing has played an important role in understanding the evolution and genomic diversity of SARS-CoV-2. Although an unprecedented number of SARS-CoV-2 full genomes have been submitted in GISAID and NCBI, data from Pakistan is scarce. We report the sequencing, genomic characterization, and phylogenetic analysis of five SARS-CoV-2 strains isolated from patients in Pakistan. The oropharyngeal swabs of patients that were confirmed positive for SARS-CoV-2 through real-time RT-PCR at National Institute of Health, Pakistan, were selected for whole-genome sequencing. Sequencing was performed using NEBNext Ultra II Directional RNA Library Prep kit for Illumina (NEW ENGLAND BioLabs Inc., MA, US) and Illumina iSeq 100 instrument (Illumina, San Diego, US). Based on whole-genome analysis, three Pakistani SARS-CoV-2 strains clustered into the 20A (GH) clade along with the strains from Oman, Slovakia, United States, and Pakistani strain EPI&#95;ISL&#95;513925. The two 19B (S)-clade strains were closely related to viruses from India and Oman. Overall, twenty-nine amino acid mutations were detected in the current study genome sequences, including fifteen missense and four novel mutations. Notably, we have found a D614G (aspartic acid to glycine) mutation in spike protein of the sequences from the GH clade. The G614 variant carrying the characteristic D614G mutation has been shown to be more infectious that lead to its rapid spread worldwide. This report highlights the detection of GH and S clade strains and G614 variant from Pakistan warranting large-scale whole-genome sequencing of strains prevalent in different regions to understand virus evolution and to explore their genetic diversity., Competing Interests: The authors have declared that no competing interests exist.

Evidence-based models emphasizing on lifestyle behaviours for the treatment of drug use is still in its infancy. The development of multicomponent effective drug use intervention programs as part of health promotion is crucial to decrease risk of relapse. This study aims at exploring the lifestyle practices including dietary intake, physical activity and sleep of people who use drugs undergoing residential rehabilitation treatment in Lebanon with its perceived benefits and pitfalls. A purposive sample of 18 males and 9 females at different stages of recovery from drug use in rehabilitation centers participated in the qualitative discussions. The six phases thematic analysis revealed three themes: chaotic lifestyle, structuredlifestyle, benefits and pitfalls, and suggestions for making rehabilitation a better experience. Participants discussed their chaotic lifestyle during addiction with poor food intake, disrupted sleep and low physical activity moving to a more disciplined routine enforcing normality in lifestyle practices with social and professionlprofessional support. The early phases of treatment were marked with increased food intake and weight gain perceived as a health indicator and the sole divergent from drugs, moving towards more structured meals and efforts to lose weight in later stages. Lack of variety of Physical activity programs taking into consideration the motivational differences among the participants was also highlighted. Measures for improving rehabilitation services in terms of promoting healthy eating behaviours and environmental control were thoroughly addressed. These findings shed the light on the challenges faced in maintaining a healthy lifestyle in rehabilitation centers and the necessities of addressing them to improve the overall rehabilitation experience, prevent relapse and inform the development of future targeted intervention programs tackling all aspects of behavioural changes., Competing Interests: The authors have declared that no competing interests exist.

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. AUD is associated with a variety of physiological changes and is a substantial risk factor for numerous diseases. We aimed to characterize systemic alterations in immune responses using a well-established mouse model of chronic intermittent alcohol exposure to induce alcohol dependence. We exposed mice to chronic intermittent ethanol vapor for 4 weeks and analyzed the expression of cytokines IFN-γ, IL-4, IL-10, IL-12 and IL-17 by different immune cells in the blood, spleen and liver of alcohol dependent and non-dependent control mice through multiparametric flow cytometry. We found increases in IFN-γ and IL-17 expression in a cell type- and organ-specific manner. Often, B cells and neutrophils were primary contributors to increased IFN-γ and IL-17 levels while other cell types played a secondary role. We conclude that chronic alcohol exposure promotes systemic pro-inflammatory IFN-γ and IL-17 responses in mice. These responses are likely important in the development of alcohol-related diseases, but further characterization is necessary to understand the initiation and effects of systemic inflammatory responses to chronic alcohol exposure., Competing Interests: The authors have declared that no competing interests exist.