bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper limb functional recovery in chronic stroke patients after COVID-19-interrupted rehabilitation: An observational study
Authors: Sakamoto Daigo , Hamaguchi Toyohiro , Nakayama Yasuhide , Hada Takuya , Abo Masahiro 
Published: June 2023

AbstractBackgroundUpper limb function of chronic stroke patients declined when outpatient rehabilitation was interrupted, and outings restricted, due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this study, we investigated whether these patients recovered upper limb function after resumption of outpatient rehabilitation.MethodsIn this observational study, 43 chronic stroke hemiplegic patients with impaired upper extremity function were scored for limb function via Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Action Research Arm Test (ARAT) after a structured interview, evaluation, and intervention. Scores at 6 months and 3 months before and 3 months after rehabilitation interruption were examined retrospectively, and scores immediately after resumption of care and at 3 and 6 months after resumption of care were examined prospectively. The amount of change for each time period and an analysis of covariance was performed with time as a factor and the change in FMA-UE and ARAT scores as dependent variables and by setting statistical significance at 5%.ResultsTime of evaluation significantly impacted total, part C, and part D of FMA-UE as well as total, pinch, and gross movement of ARAT. Post-hoc tests showed that the magnitude of change in limb function scores from immediately after resumption of rehabilitation to 3 months after resumption was significantly higher than the change from 3 months before to immediately after interruption for total, and part D of FMA-UE, and grip, and gross movement of ARAT (p<0.05).ConclusionsThe results suggest that upper limb functional decline in chronic stroke patients, caused by the SARS-CoV-2 pandemic-related therapy interruption and outing restrictions, was resolved after approximately 3 months of resumption of rehabilitation therapy. Our data can serve as reference standards for planning and evaluating treatment for chronic stroke patients with impaired upper limb function due to inactivity.
Evaluation of Mental Health and Quality of Life among Afghan Refugees in Iran
Authors: Saeidi Mahdieh , Sadr Saeed , Samimi Ardestani Seyed Mehdi , Nooraeen Sara 
Published: June 2023

AbstractBackgroundForced migration is significant in Middle Eastern countries. Afghanistan has a high rate of forced immigration due to decades of war and insecurity. This figure has risen, especially in the recent Taliban offensive. It is important to pay attention to the mental health of refugees and to evaluate the risk factors affecting the improvement of their mental health and quality of life. This study aims to investigate the mental health and quality of life among Afghan refugees living in Iran.MethodsThe study sample consisted of 200 Afghan refugees living in Tehran, Iran. Demographic characteristics, mental status and quality of life were investigated. One-sample t-test, chi-square, paired t-test, analysis of variance, and Scheffe post hoc test and logistic regression were used to analyze the data.ResultsAnxiety and insomnia were the most prevalent mental health symptoms among Afghan refugees. Depressive symptoms were higher in unemployed ones and women. Most of the participants (56.5%) had moderate quality of life and social relationship had the lowest score in quality-of-life domain.ConclusionsThe frequency of mental health disorders and low quality of life has been considerably high among Afghan Refugees in Iran. The mental health and quality of life of refugees should be further considered, especially after domestic wars and insecurities.
Volunteers of Third Sector Organizations in supporting older adults in the transition from hospital to home: A comparative case study
Authors: Nelson MLA , Singh H. , Saragosa M. 
Published: June 2023

ABSTRACTIntroductionWith increasing attention to models of transitional support delivered through multisectoral approaches, third sector organizations have supported community reintegration and independent living post hospitalization. This study aimed to identify core elements of these programs, facilitators and barriers to service implementation, and to understand the perspectives of providers and recipients.Methods and AnalysisA comparative case study was conducted, collecting data from two ‘Home from Hospital’ programs in the UK, and two transition support programs in Canada. An inductive thematic analysis generated rich descriptions of each program, and comparative analytical activities generated insights across the cases.ResultsPrograms provided a range of personalized support for older adults and address many post-discharge needs, including wellbeing assessments, support for instrumental activities of daily living, psychosocial support, and other individualized services directed by the needs and preferences of the service user. Results suggest that these types of programs can act as a ‘safety net’ and promote independent living. Skilled volunteers can positively impact older adults’ experience returning home.ConclusionsWhen the programs under study are considered in tandem with existing evidence, it facilitates a discussion of how TSO services could be made available more widely to support older adults in their transition experiences.
External validation of a paediatric SMART triage model for use in resource limited facilities
Authors: Kigo Joyce , Kamau Stephen , Mawji Alishah , Mwaniki Paul , Dunsmuir Dustin , Pillay Yashodani , Zhang Cherri , Pallot Katija , Ogero Morris , Kimutai David , Ouma Mary , Mohamed Ismael , Chege Mary , Thuranira Lydia , Kissoon Niranjan , Ansermino J. Mark , Akech Samuel 
Published: June 2023

AbstractIntroductionModels for digital triage of sick children at emergency departments of hospitals in resource poor settings have been developed. However, prior to their adoption, external validation should be performed to ensure their generalizability.MethodsWe externally validated a previously published nine-predictor paediatric triage model (SMART Triage) developed in Uganda using data from two hospitals in Kenya. Both discrimination and calibration were assessed, and recalibration was performed by optimizing the intercept for classifying patients into emergency, priority, or non-urgent categories based on low-risk and high-risk thresholds.ResultsA total of 2539 patients were eligible at Hospital 1 and 2464 at Hospital 2, and 5003 for both hospitals combined; admission rates were 8.9%, 4.5%, and 6.8%, respectively. The model showed good discrimination, with area under the receiver-operator curve (AUC) of 0.826, 0.784 and 0.821, respectively. The pre-calibrated model at a low-risk threshold of 8% achieved a sensitivity of 93% (95% confidence interval, (CI):89%-96%), 81% (CI:74%-88%), and 89% (CI:85%–92%), respectively, and at a high-risk threshold of 40%, the model achieved a specificity of 86% (CI:84%–87%), 96% (CI:95%-97%), and 91% (CI:90%-92%), respectively. Recalibration improved the graphical fit, but new risk thresholds were required to optimize sensitivity and specificity.ConclusionThe Smart Triage model showed good discrimination on external validation but required recalibration to improve the graphical fit of the calibration plot. There was no change in the order of prioritization of patients following recalibration in the respective triage categories. Recalibration required new site-specific risk thresholds that may not be needed if prioritization based on rank is all that is required. The Smart Triage model shows promise for wider application for use in triage for sick children in different settings.FunderWellcome Trust (UK)
Developmental hourglass: Verification by numerical evolution and elucidation by dynamical-systems theory
Authors: Kohsokabe Takahiro , Kuratanai Shigeru , Kaneko Kunihiko 
Published: June 2023

AbstractDetermining the general laws between evolution and development is a fundamental biological challenge. Developmental hourglasses have attracted increased attention as candidates for such laws, but the necessity of their emergence remains elusive. We conducted evolutionary simulations of developmental processes to confirm the emergence of the developmental hourglass and unveiled its establishment. We considered organisms consisting of cells containing identical gene networks that control morphogenesis and evolved them under selection pressure to induce more cell types. By computing the similarity between the spatial patterns of gene expression of two species that evolved from a common ancestor, a developmental hourglass was observed, that is, there was a correlation peak in the intermediate stage of development. The fraction of pleiotropic genes increased, whereas the variance in individuals decreased, consistent with previous experimental reports. Reduction of the unavoidable variance by initial or developmental noise, essential for survival, was achieved up to the hourglass bottleneck stage, followed by diversification in developmental processes, whose timing is controlled by the slow expression dynamics conserved among organisms sharing the hourglass. This study suggests why developmental hourglasses are observed within a certain phylogenetic range of species.Author SummaryUnderstanding the intriguing relationship between development and evolution in multicellular organisms has long been a challenge in biology. A recent hypothesis called the developmental hourglass proposes that there is a conserved middle stage during development across species of the same animal group. Despite growing evidence supporting this hypothesis, the underlying mechanisms and reasons for its emergence have remained elusive due to limited experimental data.To address this gap, we employed numerical evolution of gene regulation networks controlling pattern formation. Remarkably, our simulations revealed that species that diverged relatively recently in phylogeny displayed the highest similarity during the middle stage of development, which gradually diminished as they diverged further phylogenetically. Our findings satisfied not only the criteria of the developmental hourglass but also confirmed several essential characteristics of the developmental hourglass reported in recent experiments. Through theoretical analysis, we further demonstrated that the emergence of the developmental hourglass could be attributed to the acquisition of genes that change slowly and govern developmental processes, which also foster the robustness of development.By integrating computational simulations, theoretical insights, and previous experimental evidence, our study thus provides a comprehensive understanding of the developmental hourglass, which will unravel the intricate relationship between development and evolution.
Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids
Authors: Dingare Chaitanya , Yang Jenny , Steventon Ben 
Published: June 2023

AbstractPatterning and growth are fundamental features of embryonic development that must be tightly coordinated during morphogenesis. As metabolism can control cell growth while also providing mechanistic links to developmental signalling pathways, it is ideally placed to enable this coordination. To understand how metabolism impacts early mesoderm specification, we used mouse embryonic stem (ES) cell-derived gastruloids, as these enable temporal control over metabolic manipulations and can be generated in large quantities. Gastruloids show mosaic expression of two glucose transporters,Slc2a1andSlc2a3both of which co-express with the expression of both the mesodermal markerT/Braand the neural markerSox2. To understand the significance of cellular glucose uptake in development, we used the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG). 2-DG specifically blocks the expression ofT/Brawithout affecting the expression ofSox2and abolishes axial elongation in gastruloids. Surprisingly, removing glucose completely from the medium did not phenocopy 2-DG treatment despite a significant decline in glycolytic intermediates occurring under both conditions. As 2-DG can also act as a competitive inhibitor of mannose, we added mannose together with 2-DG and found that it could rescue the mesoderm specification. Together, our results show that while mannose is crucial for mesoderm specification, the glycolytic pathway is dispensable at early stages ofT/Braexpression in gastruloids.
Crystal structure of SUN1-KASH6 reveals an asymmetric LINC complex architecture compatible with nuclear membrane insertion
Authors: Gurusaran Manickam , Erlandsen Benedikte S. , Davies Owen R. 
Published: June 2023

AbstractThe LINC complex transmits cytoskeletal forces into the nucleus to control the structure and movement of nuclear contents. It is formed of nuclear SUN and cytoplasmic KASH proteins, which interact within the nuclear lumen, immediately below the outer nuclear membrane. However, the symmetrical location of KASH molecules within SUN-KASH complexes in previous crystal structures has been difficult to reconcile with the steric requirements for insertion of their immediately upstream transmembrane helices into the outer nuclear membrane. Here, we report the crystal structure of the SUN-KASH complex between SUN1 and JAW1/LRMP (KASH6) in an asymmetric 9:6 configuration. This intertwined assembly involves two distinct KASH conformations such that all six KASH molecules emerge on the same molecular surface. Hence, they are ideally positioned for insertion of upstream sequences into the outer nuclear membrane. Thus, we report the first structure of a SUN-KASH complex that is directly compatible with its biological role.
A novel, precise and high-throughput technology for viroid detection in cannabis (MFDetect™)
Authors: Fernandez i Marti Angel , Parungao Marcus , Selimotic Berin , Farrar Graham , Seyler Tristan , Anand Ajith , Ahmad Riaz 
Published: June 2023

AbstractHop latent viroid (HLVd) is a severe disease of cannabis, causing substantial economic losses in plant yield and crop value for growers worldwide. The best way to control the disease is early detection to limit the spread of the viroid in grow facilities. This study describes MFDetect™ as a rapid, highly sensitive, and high-throughput tool for detecting HLVd in the early stages of plant development. Furthermore, we compared MFDetect™ with RT-PCR in a time course experiment using different plant tissue, leaf, petiole, and roots at different plant development stages to demonstrate both technologies are comparable. Our study found leaf tissue is a suitable plant material for HLVd detection, with the viroid titer increasing in the infected leaf tissue with the age of plants. The study showed that other tissue types, including petiole and roots, were equally sensitive to detection via MFDetect™. The assay developed in this research allows the screening of thousands of plants in a week. The assay can be scaled easily to provide the growers with a quick turnaround and cost-effective diagnostic tool for screening many plants and tissue types at different stages of development.
Estimating the effectiveness of COVID-19 vaccination against COVID-19 hospitalisation and death: a cohort study based on the 2021 Census, England
Authors: Bermingham Charlotte , Nafilyan Vahe , Andrews Nick , Gethings Owen 
Published: June 2023

AbstractObjectiveTo estimate the effectiveness of COVID-19 vaccination against hospitalisation for COVID-19 and death involving COVID-19 in England using linked population level data sources including the 2021 Census.DesignRetrospective cohort study.SettingEngland, 21 March 2021 to 20 March 2022.ParticipantsIndividuals alive and aged 16+ on 21 March 2021, resident in England, enumerated in the 2021 Census as a usual resident, and able to link to an NHS number. A sample of 583,840 individuals was used for the analysis.ExposuresCOVID-19 vaccination: first dose, second dose and third dose/first booster dose, with categories for time since each dose.Main outcome measuresHospitalisation for COVID-19 or death involving COVID-19. An adjusted Cox proportional hazard model was used to estimate the hazard ratio for the outcomes for vaccinated participants for different doses and time since dose compared to unvaccinated individuals. Vaccine effectiveness was estimated as (1–hazard ratio)×100%. A control outcome of non-COVID-19 death was also assessed.ResultsVaccine effectiveness against hospitalisation for COVID-19 was 52.1% (95% confidence interval 51.3% to 52.8%) for a first dose, 55.6% (55.2% to 56.1%) for a second dose and 77.6% (77.3% to 78.0%) for a third dose, with a decrease in vaccine effectiveness 3+ months after the third dose.Vaccine effectiveness against COVID-19 mortality was 58.7% (52.7% to 63.9%) for a first dose, 88.5% (87.5% to 89.5%) for a second dose and 93.2% (92.9% to 93.5%) for a third dose, with evidence of waning 3+ months after the second and third doses.For the second dose, which is the most comparable across the different time-periods, vaccine effectiveness was higher against COVID-19 hospitalisation but slightly lower against COVID-19 mortality in the Omicron dominant period than the period before the Omicron variant became dominant. Vaccine effectiveness against both COVID-19 hospitalisation and mortality was higher in general for mRNA vaccines than non mRNA vaccines, however this could be influenced by the different populations given each vaccine vector. Non-zero VE against non-COVID-19 mortality indicates that residual confounding may impact the results, despite the inclusion of up-to-date socio-demographic adjustments and various sources of health data, with possible frailty bias, confounding by indication and a healthy vaccinee effect observed.ConclusionsThe vaccine effectiveness estimates show increased protection with number of doses and a high level of protection against both COVID-19 hospitalisation and mortality for the third/booster dose, as would be expected from previous research. However, despite the various sources of health data used to adjust the models, the estimates for different breakdowns and for non-COVID-19 mortality expose residual confounding by health status, which should be considered when interpreting estimates of vaccine effectiveness.
Metformin reduces SARS-CoV-2 in a Phase 3 Randomized Placebo Controlled Clinical Trial
Authors: Bramante Carolyn T , Beckman Kenneth B , Mehta Tanvi , Karger Amy B , Odde David J , Tignanelli Christopher J , Buse John B , Johnson Darrell M , Watson Ray H. B. , Daniel Jerry J , Liebovitz David M , Nicklas Jacinda M , Cohen Kenneth , Puskarich Michael A , Belani Hrishikesh K , Siegel Lianne K , Klatt Nichole R , Anderson Blake , Hartman Katrina M , Rao Via , Hagen Aubrey A , Patel Barkha , Fenno Sarah L , Avula Nandini , Reddy Neha V , Erickson Spencer M , Fricton Regina D. , Lee Samuel , Griffiths Gwendolyn , Pullen Matthew F , Thompson Jennifer L. , Sherwood Nancy , Murray Thomas A. , Rose Michael R. , Boulware David R , Huling Jared D. ,   the COVID-OUT study team
Published: June 2023

AbstractCurrent antiviral treatment options for SARS-CoV-2 infections are not available globally, cannot be used with many medications, and are limited to virus-specific targets.1-3Biophysical modeling of SARS-CoV-2 replication predicted that protein translation is an especially attractive target for antiviral therapy.4Literature review identified metformin, widely known as a treatment for diabetes, as a potential suppressor of protein translation via targeting of the host mTor pathway.5In vitro, metformin has antiviral activity against RNA viruses including SARS-CoV-2.6,7In the COVID-OUT phase 3, randomized, placebo-controlled trial of outpatient treatment of COVID-19, metformin had a 42% reduction in ER visits/hospitalizations/death through 14 days; a 58% reduction in hospitalizations/death through 28 days, and a 42% reduction in Long COVID through 10 months.8,9Here we show viral load analysis of specimens collected in the COVID-OUT trial that the mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (−0.56 log10copies/mL; 95%CI, -1.05 to -0.06, p=0.027) while there was no virologic effect for ivermectin or fluvoxamine vs placebo. The metformin effect was consistent across subgroups and with emerging data.10,11Our results demonstrate, consistent with model predictions, that a safe, widely available,12well-tolerated, and inexpensive oral medication, metformin, can be repurposed to significantly reduce SARS-CoV-2 viral load.
Estimation of the real magnitude of antimicrobial resistance ofMycoplasma genitaliumin Belgium by implementing a prospective surveillance programme
Authors: De Baetselier Irith , Smet Hilde , Kehoe Kaat , Loosen Imelda , Reynders Marijke , Mansoor Iqbal , Filippin Lorenzo , Cauchie Mathieu , Van Even Ellen , Makki Nadia , Schiettekatte Gilberte , Vandewal Wouter , Glibert Bart , Matheeussen Veerle , Van der Beken Yolien , Cartuyvels Reinoud , Steyaert Sophia , Lemmens Ann , Garrino Maria-Grazia , Paridaens Henry , Lazarova Elena , Lissoir Bénédicte , Deffontaine Marine , Heinrichs Amélie , Saegeman Veroniek , Padalko Elizaveta , Lecompte Amaryl , Berghe Wim Vanden , Kenyon Chris , Van den Bossche Dorien 
Published: June 2023

AbstractObjectivesAntimicrobial resistance ofMycoplasma genitalium(MG) is a growing concern worldwide. Because reliable data on the burden of resistant MG in Belgium are missing, an additional prospective surveillance program was implemented in 2022 to estimate the real burden of resistant MG in Belgium.MethodsBelgian laboratories (n=21) provided frozen remnants of MG positive samples to the National Reference Centre of Sexually Transmitted Infections from July to November 2022. The presence of macrolide and fluoroquinolones resistance associated mutations (RAMs) was assessed using Sanger sequencing of the 23SrRNA andparCgene. Differences in resistance patterns were correlated with surveillance methodology, socio-demographic and behavioral variables via Fisher’s exact test and logistic regression analysis.ResultsSequencing for both macrolide and fluoroquinolone RAMs was successful for 232/244 MG positive samples. Over half of the samples were resistant to macrolides (55.2%). All MG in samples from men who have sex with men (MSM) (24/24) were resistant to macrolides. The presence of fluoroquinolone RAMs was estimated to be 26% and did not differ with socio-demographic and sexual behaviour characteristics.ConclusionsGiven the considerable cost of macrolide resistance testing, our data suggest that the use of macrolide resistance testing in MSM does not seem justified in Belgium. However, the lower prevalence of macrolide resistance in other population groups, combined with further emergence of fluoroquinolone resistance provides evidence for macrolide resistance testing in these groups. Continued surveillance of resistance in MG in all groups will be crucial to guide national testing- and treatment strategies.