bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparing Adipogenic Hydrogel with Neo-Mechanical Isolated Adipose-Derived Extracellular Vesicles for Adipose Tissue Engineering
Authors: Nie Jia-ying , Zhu Yuan-zheng , Wang Jiang-wen , Hu Xuan , Wang Zhao-hui , Wu Shu , Yi Yang-yan 
Published: June 2021

Background:Subcutaneous transplantation of decellularized adipose tissue was capable of recellularization during soft tissue repair. However, further improvements are required to promote angiogenesis and adipogenesis. Here, the authors proposed a neo-mechanical protocol to isolate adipose tissue–derived extracellular vesicles (ATEVs) through lipoaspirate as a mediator for both angiogenesis and adipogenesis, and prepared ATEV-rich decellularized adipose tissue hydrogel for adipose tissue engineering.Methods:Adipose liquid extract and lipid-devoid adipose tissue were extracted through homogenization and repeated freeze and thaw cycles. ATEVs were isolated from adipose liquid extract by ultracentrifugation. Decellularized adipose tissue hydrogel was prepared by optimized decellularization of lipid-devoid adipose tissue. The optimum dose of ATEVs for angiogenesis and adipogenesis was estimated by co-culturing with vascular endothelial cells and 3T3-L1 cells, then mixed with the hydrogel. ATEV-enriched hydrogel was injected subcutaneously into the back of severe combined immunodeficiency mice, and then subjected to supplementary injection of ATEVs on postoperative day 14. ATEV-free decellularized adipose tissue hydrogel was injected as control. The newly formed tissue samples were harvested at postoperative weeks 2, 4, and 8 and subjected to volume measurement, hematoxylin and eosin staining, and immunofluorescence (CD31 and perilipin) staining.Results:The optimum dose of ATEVs for promoting angiogenesis and adipogenesis was 50 μg/ml. The newly formed tissue mediated by ATEV-enriched hydrogel had increased volume well as improved angiogenesis and adipogenesis at postoperative week 4 and 8.Conclusion:ATEV-enriched adipogenic hydrogel promotes enhanced angiogenesis and adipogenesis and could serve as a promising biomaterial for adipose tissue engineering.
Barriers and Facilitators to Engagement in Rehabilitation Among Stroke Survivors
Authors: Forgea Mary C. , Lyons Amy G. , Lorenz Rebecca A. 
Published: June 2021

Abstract

Background
Approximately 795,000 Americans experience a new or recurrent stroke every year, and it remains one of the leading causes of disability worldwide. Patient engagement in rehabilitation and physical activity has been associated with improvements in functional outcomes during inpatient rehabilitation. There is limited knowledge of the barriers and facilitators to patients’ engagement in stroke rehabilitation.

Methods
An integrative review with a systematic approach was conducted to explore the current available literature on barriers and facilitators to patient engagement in stroke inpatient rehabilitation.

Results
Twenty-five studies were included in the final review. Four major themes described the identified barriers and facilitators: (1) stroke impact, (2) self-efficacy, (3) therapeutic relationship, and (4) motivating factors. Individualized patient-centered goal setting was a commonly studied intervention found to successfully increase engagement.

Conclusion
Engagement in stroke rehabilitation is associated with improved patient outcomes. Using the identified themes from this review, nurses can develop focused interventions aimed at reducing barriers and increasing stroke patient engagement.
Real-time Alerting System for COVID-19 Using Wearable Data
Authors: Alavi Arash , Bogu Gireesh K , Wang Meng , Rangan Ekanath Srihari , Brooks Andrew W , Wang Qiwen , Higgs Emily , Celli Alessandra , Mishra Tejaswini , Metwally Ahmed A. , Cha Kexin , Knowles Peter , Alavi Amir A , Bhasin Rajat , Panchamukhi Shrinivas , Celis Diego , Aditya Tagore , Honkala Alexander , Rolnik Benjamin , Hunting Erika , Dagan-Rosenfeld Orit , Chauhan Arshdeep , Li Jessi W , Li Xiao , Bahmani Amir , Snyder Michael P 
Published: June 2021

AbstractEarly detection of infectious disease is crucial for reducing transmission and facilitating early intervention. We built a real-time smartwatch-based alerting system for the detection of aberrant physiological and activity signals (e.g. resting heart rate, steps) associated with early infection onset at the individual level. Upon applying this system to a cohort of 3,246 participants, we found that alerts were generated for pre-symptomatic and asymptomatic COVID-19 infections in 78% of cases, and pre-symptomatic signals were observed a median of three days prior to symptom onset. Furthermore, by examining over 100,000 survey annotations, we found that other respiratory infections as well as events not associated with COVID-19 (e.g. stress, alcohol consumption, travel) could trigger alerts, albeit at a lower mean period (1.9 days) than those observed in the COVID-19 cases (4.3 days). Thus this system has potential both for advanced warning of COVID-19 as well as a general system for measuring health via detection of physiological shifts from personal baselines. The system is open-source and scalable to millions of users, offering a personal health monitoring system that can operate in real time on a global scale.
The relative strength and timing of innate immune and CD8 T-cell responses underlie the heterogeneous outcomes of SARS-CoV-2 infection
Authors: Chatterjee Budhaditya , Sandhu Harshbir Singh , Dixit Narendra M. 
Published: June 2021

AbstractSARS-CoV-2 infection results in highly heterogeneous outcomes, from cure without symptoms to acute respiratory distress and death. While immunological correlates of disease severity have been identified, how they act together to determine the outcomes is unknown. Here, using a new mathematical model of within-host SARS-CoV-2 infection, we analyze diverse clinical datasets and predict that a subtle interplay between innate and CD8 T-cell responses underlies disease heterogeneity. Our model considers essential features of these immune arms and immunopathology from cytokines and effector cells. Model predictions provided excellent fits to patient data and, by varying the strength and timing of the immune arms, quantitatively recapitulated viral load changes in mild, moderate, and severe disease, and death. Additionally, they explained several confounding observations, including viral recrudescence after symptom loss, prolonged viral positivity before cure, and mortality despite declining viral loads. Together, a robust conceptual understanding of COVID-19 outcomes emerges, bearing implications for interventions.TeaserModeling explains how a subtle interplay between innate immune and CD8 T-cell responses determines the severity of COVID-19.
Endonuclease-based genotyping of the RBM, a first-line method for the surveillance of emergence or evolution of SARS-CoV-2 Variants
Authors: Lopez Eva , Barthélémy Margot , Baronti Cécile , Masse Shirley , Falchi Alessandra , Durbesson Fabien , Vincentelli Renaud , de Lamballerie Xavier , Charrel Rémi , Coutard Bruno 
Published: June 2021

AbstractSince the beginning of the Covid-19 pandemics, variants have emerged. Whereas most of them have no to limited selective advantage, some display increased transmissibility and/or resistance to immune response. To date, most of the mutations involved in the functional adaptation are found in the Receptor Binding Module (RBM), close to the interface with the human receptor ACE2. In this study, we thus developed and validated a fast and simple molecular assay allowing the detection and partial identification of the mutations in the RBM coding sequence. After the amplification of the region of interest, the amplicon is heat-denatured and hybridized with an amplicon of reference. The presence of a mutation in the heteroduplex can be cleaved by a mismatch-specific endonuclease and the cleavage pattern is analysed by capillary electrophoresis. The approach was first validated on viral RNA purified different SARS-CoV-2 variants produced in the lab before being implemented for clinical samples. The results highlighted the performance of the assay for the detection of mutations in the RBM from clinical samples. The procedure can be easily set up for high throughput identification of the presence of mutations and serve as a first-line screening to select the samples for full genome sequencing.
Seroprevalence of anti–SARS-CoV-2 antibodies in women attending antenatal care in eastern Ethiopia
Authors: Assefa Nega , Demissie Lemma , Teklemariam Zelalem , Oundo Joseph , Madrid Lola , Kebede Addisu , Dessie Yadeta , Scott J. Anthony G. 
Published: June 2021

AbstractInformation on the cumulative incidence of SARS-CoV-2 in East Africa is scarce. We conducted serosurveillance of anti–SARS-CoV-2 antibodies among pregnant women attending their first antenatal care visit in three health facilities in eastern Ethiopia.We collected data using questionnaire and a blood sample from 3,312 pregnant women between April 1, 2020 and March 31, 2021 at health facilities in Haramaya, Aweday and Harar. We selected 1,447 blood samples at random and assayed these for anti-SARS-CoV-2 antibodies at Hararghe Health Research laboratory using WANTAI® SARS-CoV-2 Rapid Test for total immunoglobulin. Temporal trends in seroprevalence were analysed with a χ2 test for trend and multivariable binomial regression.Among 1,447 sera tested, 83 were positive for anti–SARS-CoV-2 antibodies giving a crude seroprevalence of 5.7% (95% CI 4.6%, 7.0%). Of 160 samples tested in April-May, 2020, none was seropositive; the first seropositive sample was identified in June and seroprevalence rose steadily thereafter (χ2 test for trend, p=0.003) reaching a peak of 11.8% in February, 2021. In the multivariable model, seroprevalence was approximately 3% higher in first-trimester mothers compared to later presentations, and rose by 0.75% (95% CI 0.31%, 1.20%) per month of calendar time.This clinical convenience sample illustrates the dynamic of the SARS-CoV-2 epidemic in young adults in eastern Ethiopia; infection was rare before June 2020 but it spread in a linear fashion thereafter, rather than following intermittent waves, and reached 10% by the beginning of 2021. After one year of surveillance, most pregnant mothers remained susceptible.
Public health relevant consequences of the COVID-19 pandemic on malaria in sub-Saharan Africa: A scoping review
Authors: Heuschen Anna-Katharina , Lu Guangyu , Razum Oliver , Abdul-Mumin Alhassan , Sankoh Osman , Seidlein Lorenz von , D’Alessandro Umberto , Müller Olaf 
Published: June 2021

AbstractBackgroundThe COVID-19 pandemic has resulted in unprecedented challenges to health systems worldwide, including the control of non-COVID-19 diseases. Malaria cases and deaths may increase due to the direct and indirect effects of the pandemic in malaria endemic countries, particularly in sub-Saharan Africa (SSA).ObjectivesThis scoping review aims to summarize information on public health relevant effects of the COVID-19 pandemic on the malaria situation in SSA.MethodsReview of publications and manuscripts on preprint servers, in peer-reviewed journals and in grey literature documents from December 1, 2019, to June 9, 2021. A structured search was conducted on different databases using predefined eligibility criteria for the selection of articles.ResultsA total of 51 papers have been included in the analysis. Modeling papers have predicted a significant increase in malaria cases and malaria deaths in SSA due to the effects of the COVID-19 pandemic. Many papers provided potential explanations for expected COVID-19 effects on the malaria burden; these ranged from relevant diagnostical and clinical aspects, to reduced access to health care services, impaired availability of curative and preventive commodities and medications, and effects on malaria prevention campaigns. Compared to previous years, fewer country reports provided data on the actual number of malaria cases and deaths in 2020, with mixed results. While highly endemic countries reported evidence of decreased malaria cases in health facilities, low endemic countries reported overall higher numbers of malaria cases and deaths in 2020.ConclusionsThe findings from this review provide evidence for a significant but diverse impact of the COVID-19 pandemic on malaria in SSA. There is the need to further investigate the public health consequences of the COVID-19 pandemic on the malaria burden.
3D structure and in situ arrangements of CatSper channel in the sperm flagellum
Authors: Zhao Yanhe , Wang Huafeng , Wiesehoefer Caroline , Shah Naman B. , Reetz Evan , Hwang Jae Yeon , Huang Xiaofang , Lishko Polina V. , Davies Karen M. , Wennemuth Gunther , Nicastro Daniela , Chung Jean-Ju 
Published: June 2021

AbstractThe sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway into the sperm flagellum. However, CatSper’s complex subunit composition has impeded its reconstitution in vitro and structural elucidation. Here, we applied cryo-electron tomography to visualize the macromolecular organization of the native CatSper channel complex in intact mammalian sperm, as well as identified three additional CatSper-associated proteins. The repeating CatSper units form long zigzag-rows in four nanodomains along the flagella. In both mouse and human sperm, each CatSper repeat consists of a tetrameric pore complex. Murine CatSper contains an additional outwardly directed wing-structure connected to the tetrameric channel. The majority of the extracellular domains form a canopy above each pore-forming channel that interconnects to a zigzag-shaped roof. The intracellular domains link two neighboring channel complexes to a diagonal array. The loss of this intracellular link in Efcab9-/- sperm distorts the longitudinally aligned zigzag pattern and compromises flagellar movement. This work offers unique insights into the mechanisms underlying the assembly and transport of the CatSper complex to generate the nanodomains and provides a long-sought structural basis for understanding CatSper function in the regulation of sperm motility.
A tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion
Authors: Nadeem Aftab , Nagampalli Raghavendra , Toh Eric , Alam Athar , Myint Si Lhyum , Heidler Thomas V. , Dongre Mitesh , Zlatkov Nikola , Pace Hudson , Bano Fouzia , Sjöstedt Anders , Bally Marta , Uhlin Bernt Eric , Wai Sun Nyunt , Persson Karina 
Published: June 2021

ABSTRACTThe protein MakA was discovered as a motility-associated secreted toxin from Vibrio cholerae, Here, we show that MakA is part of a gene cluster encoding four additional proteins: MakB, MakC, MakD and MakE. The MakA, MakB and MakE proteins were readily detected in culture supernatants of wild type V. cholerae whereas secretion was very much reduced from a flagellum deficient mutant. Crystal structures of MakA, MakB and MakE revealed structural relationship to a superfamily of bacterial pore-forming proteins. Cloning and expression of MakA/B/E in Escherichia coli resulted in toxicity of the bacteria towards Caenorhabditis elegans used as a predatory organism model. None of these Mak proteins alone or in pairwise combinations were cytolytic but an equimolar mixture of MakA, MakB and MakE acted as a tripartite cytolytic toxin in vitro causing lysis of erythrocytes and cytotoxicity on cultured human colon carcinoma cells. Formation of oligomeric complexes on liposomes was observed by electron microscopy. Oligomer interaction with membranes was initiated by MakA membrane binding followed by MakB and MakE joining in formation of a pore structure. A predicted membrane insertion domain of MakA was shown by site-directed mutagenesis to be essential for toxicity towards C. elegans. Bioinformatic analyses revealed that the makCDBAE gene cluster is present as a novel genomic island in the vast majority of sequenced genomes of V. cholerae and the fish pathogen V. anguillarum. We suggest that the hitherto unrecognized cytolytic MakA/B/E toxin can contribute to Vibrionaceae fitness and virulence potential in different host environments and organisms.Significance StatementVibrio cholerae, responsible for outbreaks and pandemics of cholera disease, is a highly motile organism by virtue of a single flagellum. We describe that the flagellum facilitates the secretion of three V. cholerae proteins encoded by a hitherto unrecognized novel genomic island. The proteins MakA/B/E can form a tripartite cytolytic toxin that lyses erythrocytes and is cytotoxic to cultured human cells. A structural basis for the Mak protein cytolytic activity was obtained by X-ray crystallography. Flagellum-facilitated secretion, remarkably ensuring spatially co-ordinated delivery of Mak proteins, revealed a new role for the V. cholerae flagellum considered of particular significance for the bacterial environmental persistence. Our findings will pave the way for the development of new diagnostics and therapeutic strategies against pathogenic Vibrionaceae.
Determinants of Murine Skin Microbiota Composition in Homeostasis and Wound Healing
Authors: Galbraith Jack , Legrand Julien M. D. , Muller Nicholas , Baz Betoul , Togher Katie , Matigian Nicholas , Kang Seungha , Young Sylvia , Mortlock Sally , Roy Edwige , Morahan Grant , Walker Graeme , Morrison Mark , Khosrotehrani Kiarash 
Published: June 2021

AbstractAnimal microbiota have complex interactions with hosts and environment that determines its composition. Yet the ability of hosts to determine their microbiota composition is less well studied. In this study, to investigate the role host genetics in determining skin microbiota, we used 30 different mouse strains from the recombinant inbred panel, the Collaborative Cross. Murine skin microbiota composition was strongly dependent on murine strain with > 50% of the variation explained by murine strain. In particular, a quantitative trait locus on chromosome 4 associates both with Staphylococcus abundance and principal-component multi-trait analyses. Additionally, excisional wound associated changes in microbiota composition were not uniform across mouse strains and were host-specific, the genetic background accounting for about 40% of the variation in microbiota. Genetic background also had the highest effect on the healing speed of wounds accounting for over 50% of the variation while mouse age and microbiota composition change accounted only for 20% and 5% of the healing speed despite reaching statistical significance. In conclusion, host genetics has a significant impact on the skin microbiota composition during both homeostasis and wound healing. These findings have long reaching implications in our understanding of associations between microbiota dysbiosis and disease.
Population inter-connectivity over the past 120,000 years explains distribution and diversity of Central African hunter-gatherers
Authors: Padilla-Iglesias Cecilia , Atmore Lane M. , Olivero Jesús , Lupo Karen , Manica Andrea , Isaza Epifanía Arango , Vinicius Lucio , Migliano Andrea Bamberg 
Published: June 2021

AbstractThe evolutionary history of African hunter-gatherers holds key insights into modern human diversity. Here we combine ethnographic and genetic data on Central African hunter-gatherers (CAHG) to show that their current distribution and density is explained by ecology rather than by a displacement to marginal habitats due to recent farming expansions, as commonly assumed. We also predict hunter-gatherer presence across Central Africa over the past 120,000 years using paleoclimatic reconstructions, which were statistically validated by dated archaeological sites. Finally, we show that genomic estimates of separation times between CAHG groups match our ecological estimates of periods favouring population splits, and that recoveries of connectivity would have facilitated subsequent gene-flow. Our results reveal that CAHG stem from a deep history of partially connected populations. This form of sociality allowed the coexistence of relatively large effective population sizes and local differentiation, with important implications for the evolution of genetic and cultural diversity in Homo sapiens.
Reliable in silico ranking of engineered therapeutic TCR binding affinities with MMPB/GBSA
Authors: Crean Rory M. , Pudney Christopher R. , Cole David K. , van der Kamp Marc W. 
Published: June 2021

AbstractAccurate and efficient in silico ranking of protein-protein binding affinities is useful for protein design with applications in biological therapeutics. One popular approach to rank binding affinities is to apply the molecular mechanics Poisson Boltzmann/generalized Born surface area (MMPB/GBSA) method to molecular dynamics trajectories. Here, we identify protocols that enable the reliable evaluation of T-cell receptor (TCR) variants binding to their target, peptide-human leukocyte antigens (pHLAs). We suggest different protocols for variant sets with few (≤4) or many mutations, with entropy corrections important for the latter. We demonstrate how potential outliers could be identified in advance and that just 5-10 replicas of short (4 ns) MD simulations may be sufficient for reproducible and accurate ranking of TCR variants. The protocols developed here can be applied towards in silico screening during the optimization of therapeutic TCRs, potentially reducing both the cost and time taken for biologic development.
Adaptation of Drosophila larva foraging in response to changes in food distribution
Authors: Wosniack Marina E. , Hu Nan , Gjorgjieva Julijana , Berni Jimena 
Published: June 2021

AbstractWhen foraging, animals combine internal cues and sensory input from their environment to guide sequences of behavioral actions. Drosophila larva executes crawls, turns, and pauses to explore the substrate and find food sources. This exploration has to be flexible in the face of changes in the quality of food so that larvae feed in patches with favorable food and look for another source when the current location does not fulfill their nutritional needs. But which behavioral elements adapt, and what triggers those changes remain elusive. Using experiments and modeling, we investigate the foraging behavior of larvae in homogeneous environments with different food types and in environments where the food sources are patchy. Our work indicates that the speed of larval crawling and frequency of pauses is modulated by the food quality. Interestingly, we found that the genetic dimorphism in the foraging gene influences the exploratory behavior only when larvae crawl on yeast patches. While in a homogeneous substrate larvae maintain a turning bias in a specific orientation, in a patchy substrate larvae orient themselves towards the food when the patch border is reached. Therefore, by adapting different elements in their foraging behavior, larvae either increase the time inside nutritious food patches or continue exploring the substrate in less nutritious environments.