bluuebunny/crossref_metadata_2025_split huggingface dataset:
What is known from the existing literature about the available treatments for pelvic floor dysfunction among female athletes? A scoping review protocol
Authors: Giagio Silvia , Salvioli Stefano , Pillastrini Paolo , Fiorucci Marika , Innocenti Tiziano 
Published: May 2021

ABSTRACTBackgroundPelvic floor dysfunction (PFD) is a term used to describe a variety of symptoms, signs and conditions involving different impairments on the pelvic floor muscles.The existing literature suggests that some sports may lead to a higher risk of developing PFD, in particular among female athletes. Despite a recent scoping review highlighted a great number of studies dealing with epidemiologic data on this topic, no study has been conducted to map the available treatments.In this framework, the aim of the present scoping review will be to map and summarize the literature to identify the available evidence concerning the treatments for PFD among female athletes.Inclusion criteriaStudies considering female athletes practicing sports at any performance level with any type of PFD will be eligible for inclusion. Any treatment options (i.e. preventive, conservative, surgery) reported by each study and any context will be considered.MethodsThis scoping review will be performed in accordance with the Joanna Briggs Institute methodology. MEDLINE, Cochrane Central, Scopus, CINAHLComplete, Embase, PEDro and SPORTDiscus database will be searched from inception to May 2021. Additional records will be identified through searching in grey literature and the reference lists of all relevant studies. No study design, publication type, data and language restrictions will be applied.Two reviewers will independently screen all abstracts and full-text studies for inclusion. A data collection form will be developed by the research team to extract the characteristics of the studies included. A tabular and accompanying narrative summary of the information will be provided.ConclusionsThis will be the first scoping review to provide a comprehensive overview of the topic. The results will add meaningful information for clinicians in the management of PFD among female athletes. Furthermore, any knowledge gaps of the topic will be identified. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
Methodological proposal to explore and design future health innovation policies and opportunities for Responsible Research and Innovation (RRI)
Authors: Argüello Arturo , Ortega-Rodriguez Alicia , Álvarez Pablo 
Published: May 2021

AbstractResponsible Research and Innovation (RRI) seeks to align the research results with the needs of society to respond to current and future problems, also encompassing financial instruments, innovative public policies, and the distribution of resources. These policies should prioritize research in those areas with the greatest impact on society, and particularly in health research, this impact should be focused on responding to clinical problems of the population rather than economic impact. A methodology is proposed that uses information from open sources to identify discrepancies between the results of the most translational research of a region and its health needs, in order to provide useful information for the formulation of innovation policies.
Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B
Authors: Liu Jun , Budylowski Patrick , Samson Reuben , Griffin Bryan D. , Babuadze Giorgi , Rathod Bhavisha , Colwill Karen , Abioye Jumai A. , Schwartz Jordan A , Law Ryan , Yip Lily , Ahn Sang Kyun , Chau Serena , Naghibosadat Maedeh , Arita Yuko , Hu Queenie , Yue Feng Yun , Banerjee Arinjay , Mossman Karen , Mubareka Samira , Kozak Robert A. , Pollanen Michael S. , Orozco Natalia Martin , Gingras Anne-Claude , Marcusson Eric G. , Ostrowski Mario A. 
Published: May 2021

AbstractSafe and effective vaccines are needed to end the COVID-19 pandemic caused by SARS-CoV-2. Here we report the preclinical development of a lipid nanoparticle (LNP) formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern (VOCs), including the B.1.1.7, B.1.351 and P.1 lineages. No adverse effects were induced by PTX-COVID19-B in both mice and hamsters. These preclinical results indicate that PTX-COVID19-B is safe and effective. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 1 clinical trial ongoing (ClinicalTrials.govnumber:NCT04765436).One Sentence SummaryPTX-COVID19-B is a SARS-CoV-2 mRNA vaccine that is highly immunogenic, safe, and effective in preventing SARS-CoV-2 infection in mice and hamsters and is currently being evaluated in human clinical trials.
Early cross-coronavirus reactive signatures of protective humoral immunity against COVID-19
Authors: Kaplonek Paulina , Wang Chuangqi , Bartsch Yannic , Fischinger Stephanie , Gorman Matthew J. , Bowman Kathryn , Kang Jaewon , Dayal Diana , Martin Patrick , Nowak Radoslaw , Hsieh Ching-Lin , Feldman Jared , Julg Boris , Nilles Eric J. , Musk Elon R. , Menon Anil S. , Fischer Eric S. , McLellan Jason S. , Schmidt Aaron , Goldberg Marcia B. , Filbin Michael , Hacohen Nir , Lauffenburger Douglas A , Alter Galit 
Published: May 2021

AbstractThe introduction of vaccines has inspired new hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against COVID-19, thus we profiled the earliest humoral signatures in a large cohort of severe and asymptomatic COVID-19 individuals. While a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, non-survivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibody evolution. Given the conservation of S2 across β-coronaviruses, we found the early development of SARS-CoV-2-specific immunity occurred in tandem with pre-existing common β-coronavirus OC43 humoral immunity in survivors, which was selectively also expanded in individuals that develop paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.
The recent evolutionary rescue of a staple crop depended on over half a century of global germplasm exchange
Authors: Muleta Kebede T. , Felderhoff Terry , Winans Noah , Walstead Rachel , Charles Jean Rigaud , Armstrong J. Scott , Mamidi Sujan , Plott Chris , Vogel John P. , Lemaux Peggy G. , Mockler Todd C. , Grimwood Jane , Schmutz Jeremy , Pressoir Gael , Morris Geoffrey P. 
Published: May 2021

ABSTRACTRapid environmental change can lead to extinction of populations or evolutionary rescue via genetic adaptation. In the past several years, smallholder and commercial cultivation of sorghum (Sorghum bicolor), a global cereal and forage crop, has been threatened by a global outbreak of an aggressive new biotype of sugarcane aphid (SCA;Melanaphis sacchari). Here we characterized genomic signatures of adaptation in a Haitian sorghum breeding population, which had been recently founded from admixed global germplasm, extensively intercrossed, and subjected to intense selection under SCA infestation. We conducted evolutionary population genomics analyses of 296 post-selection Haitian lines compared to 767 global accessions at 159,683 single nucleotide polymorphisms. Despite intense selection, the Haitian population retains high nucleotide diversity through much of the genome due to diverse founders and an intercrossing strategy. A genome-wide fixation (FST) scan and geographic analyses suggests that adaptation to SCA in Haiti is conferred by a globally-rare East African allele ofRMES1, which has also spread to other breeding programs in Africa, Asia, and the Americas.De novogenome sequencing data for SCA resistant and susceptible lines revealed putative causative variants atRMES1. Convenient low-cost markers were developed from theRMES1selective sweep and successfully predicted resistance in independent U.S. × African breeding lines and eight U.S. commercial and public breeding programs, demonstrating the global relevance of the findings. Together, the findings highlight the potential of evolutionary genomics to develop adaptive trait breeding technology and the value of global germplasm exchange to facilitate evolutionary rescue.
Comparison of Approaches to Transcriptomic Analysis in Multi-Sampled Tumors
Authors: Ku Anson T. , Wilkinson Scott , Sowalsky Adam G. 
Published: May 2021

ABSTRACTIntratumoral heterogeneity is a well-documented feature of human cancers associated with outcome and treatment resistance. However, a heterogeneous tumor transcriptome contributes an unknown level of variability to analyses of differentially expressed genes that may contribute to phenotypes of interest, including treatment response. Although current clinical practice and the vast majority of research studies use a single sample from each patient, decreasing costs in sequencing technologies and computing costs have made repeated-measures analyses increasingly economical. Repeatedly sampling the same tumor increases the statistical power of differentially expressed gene analysis that is indispensable towards downstream analysis and also increases ones understanding of within-tumor variance that may affect conclusions. Here, we compared five different methods for analyzing gene expression profiles derived from repeated sampling of human prostate tumors in two separate cohorts of patients. We also benchmarked the sensitivity of generalized linear models to linear mixed models for identifying differentially expressed genes contributing to relevant prostate cancer pathways based on a ground truth model.
Absolute proteome quantification in the gas-fermenting acetogen Clostridium autoethanogenum
Authors: Valgepea Kaspar , Talbo Gert , Takemori Nobuaki , Takemori Ayako , Ludwig Christina , Mueller Alexander P. , Tappel Ryan , Köpke Michael , Simpson Séan Dennis , Nielsen Lars Keld , Marcellin Esteban 
Published: May 2021

ABSTRACTMicrobes that can recycle one-carbon (C1) greenhouse gases into fuels and chemicals are vital for the biosustainability of future industries. Acetogens are the most efficient known microbes for fixing carbon oxides CO2 and CO. Understanding proteome allocation is important for metabolic engineering as it dictates metabolic fitness. Here, we use absolute proteomics to quantify intracellular concentrations for >1,000 proteins in the model-acetogen Clostridium autoethanogenum grown on three gas mixtures. We detect prioritisation of proteome allocation for C1 fixation and significant expression of proteins involved in the production of acetate and ethanol as well as proteins with unclear functions. The data also revealed which isoenzymes are important. Integration of proteomic and metabolic flux data demonstrated that enzymes catalyse high fluxes with high concentrations and high in vivo catalytic rates. We show that flux adjustments were dominantly accompanied with changing enzyme catalytic rates rather than concentrations. Our work serves as a reference dataset and advances systems-level understanding and engineering of acetogens.
Dissecting and Tuning Primer Editing by Proofreading Polymerases
Authors: Gohl Daryl M. , Auch Benjamin , Certano Amanda , LeFrançois Brice , Bouevitch Anne , Doukhanine Evgueni , Fragel Christina , Macklaim Jean , Hollister Emily , Garbe John , Beckman Kenneth B. 
Published: May 2021

ABSTRACTProofreading polymerases have 3’ to 5’ exonuclease activity that allows the excision and correction of mis-incorporated bases during DNA replication. In a previous study, we demonstrated that in addition to correcting substitution errors and lowering the error rate of DNA amplification, proofreading polymerases can also edit PCR primers to match template sequences. Primer editing is a feature that can be advantageous in certain experimental contexts, such as amplicon-based microbiome profiling. Here we develop a set of synthetic DNA standards to report on primer editing activity and use these standards to dissect this phenomenon. The primer editing standards allow next-generation sequencing-based enzymological measurements, reveal the extent of editing, and allow the comparison of different polymerases and cycling conditions. We demonstrate that proofreading polymerases edit PCR primers in a concentration-dependent manner, and we examine whether primer editing exhibits any sequence specificity. In addition, we use these standards to show that primer editing is tunable through the incorporation of phosphorothioate linkages. Finally, we demonstrate the ability of primer editing to robustly rescue the drop-out of taxa with 16S rRNA gene-targeting primer mismatches using mock communities and human skin microbiome samples.
Inferring population structure in biobank-scale genomic data
Authors: Chiu Alec M. , Molloy Erin K. , Tan Zilong , Talwalkar Ameet , Sankararaman Sriram 
Published: May 2021

AbstractInferring the structure of human populations from genetic variation data is a key task in population and medical genomic studies. While a number of methods for population structure inference have been proposed, current methods are impractical to run on biobank-scale genomic datasets containing millions of individuals and genetic variants. We introduce SCOPE, a method for population structure inference that is orders of magnitude faster than existing methods while achieving comparable accuracy. SCOPE infers population structure in about a day on a dataset containing one million individuals and variants as well as on the UK Biobank dataset containing 488,363 individuals and 569,346 variants. Furthermore, SCOPE can leverage allele frequencies from previous studies to improve the interpretability of population structure estimates.
Validity and Reliability of a Behavior Assessment Questionnaire for Children with Obesity
Authors: Paek So Yeon , Roy Lonnie C. , DeHaven Mark J. , Carson Elyse , Barlow Sarah E. , Kridelbaugh LeAnn 
Published: May 2021

AbstractThe 10-item Behavior Assessment Questionnaire (BAQ) was developed to assess parent-report of child screen time, physical activity, and food consumption during the past 3 months in children with obesity. Response options were on a 5-point scale, converted to 0-100, with higher scores indicating healthier behavior. To evaluate, two convenience samples of parents of children 5-18 years completed the questionnaire: a cohort presenting to an obesity program (n=83) and a cohort of community events attenders and hospital employee parents (n=147). Scores had a normal distribution without floor or ceiling effects. Cronbach’s alpha for the 10-item scale was .71. Factor analysis yielded three component factors with Cronbach’s alpha of .66, .75, and .59 for the Screen Time, Physical Activity, and Food Consumption dimensions respectively. Scores of the obesity group (49.02 [SD 14.52]) were lower than scores of the community group (55.44 [SD 13.55]), p=.001. The BAQ demonstrated reliability and validity for use as an index of lifestyle behaviors.Key MessagesA short, easily administered questionnaire, completed by parents, about obesity-associated lifestyle behaviors of children demonstrates reliability and validityThis questionnaire could help pediatric providers assess behaviors in order to provide more targeted lifestyle counseling for children to reduce obesity risk.
The Impact of Universal Transport Media and Viral Transport Media Liquid Samples on a SARS-CoV-2 Rapid Antigen Test
Authors: Mayfield J , Hesse P , Ledden D 
Published: May 2021

AbstractThe impact of universal transport media (UTM) and viral transport media (VTM) liquid samples on the performance of the Healgen Scientific Rapid COVID-19 Antigen Test was investigated. Twelve different UTM/VTM liquid samples were added at different dilutions to the extraction buffer, and 2 of 12 generated false-positive results. To understand the cause of these false-positive results, the effect of extraction buffer dilution on sample pH, surfactant concentration, and ionic strength were investigated. The most important factor in UTM/VTM liquid sample dilution of the extraction buffer was ionic strength as measured by conductivity. Dilutions with conductivity below ∼17 mS/cm can induce a false-positive result. It was also noted that the ionic strength of UTM/VTMs can vary, and those with low ionic strength can be problematic. To rule out the effect of other common components found in UTMs/VTMs, several materials were mixed with extraction buffer and tested at high concentrations. None was shown to produce false-positive results.
Syntrophic H2 production enhances the performance of primarily acetate-supplemented reactors treating sulphate contaminated solutions
Authors: Hessler Tomas , Harrison Susan T.L. , Banfield Jillian F. , Huddy Robert J. 
Published: May 2021

AbstractBiological sulfate reduction (BSR) represents a promising bioremediation strategy, yet the impact of metabolic interactions on performance has been largely unexplored. Here, genome-resolved metagenomics was used to characterise 17 microbial communities associated with reactors operated with defined sulfate-contaminated solutions. Pairs of reactors were supplemented with lactate or with acetate plus a small amount of fermentable substrate. At least thirty draft quality genomes, representing all the abundant bacteria, were recovered from each metagenome. All of the 22 SRB genomes encode genes for H2 consumption. And of the total 163 genomes recovered, 130 encode 321 NiFe and FeFe hydrogenases. The lactate-supplemented packed-bed bioreactor was particularly interesting as it resulted in stratified microbial communities that were distinct in their predominant metabolisms. Pathways for fermentation of lactate and hydrogen production were enriched towards the inlet whereas increased autotrophy and acetate-oxidizing SRB were evident towards the end of the flow path. We hypothesized that high sulfate removal towards the end of the flow path, despite acetate being an electron donor that typically sustains low SRB growth rates, was stimulated by H2 consumption. This hypothesis was supported by sustained performance of the predominantly acetate-supplemented stirred-tank reactor, which was dominated by diverse fermentative, hydrogen-evolving bacteria and low-abundance SRB capable of acetate and hydrogen consumption. We conclude that the performance of BSR reactors supplemented with inexpensive acetate can be improved by the addition of a low concentration of fermentable material due to stimulation of syntrophic relationships among hydrogen-producing non-SRB and dual hydrogen- and acetate-utilising SRB.
microRNA-138 controls hippocampal interneuron function and short-term memory
Authors: Daswani R. , Gilardi C. , Soutschek M. , Nanda P. , Weiss K. , Bicker S. , Fiore R. , Dieterich C. , Germain P.L. , Winterer J , Schratt G 
Published: May 2021

AbstractThe proper development and function of neuronal circuits relies on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, e.g. schizophrenia. microRNA-dependent gene regulation in pyramidal neurons is important for excitatory synaptic function and cognition, but its role in inhibitory interneurons is poorly understood. Here, we identify miR-138-5p as a regulator of short-term memory and inhibitory synaptic transmission in the hippocampus. Sponge-mediated miR-138-5p inactivation specifically in parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioural phenotypes associated with miR-138-5p inactivation are paralleled by an upregulation of the schizophrenia-associated Erbb4, which we validated as a direct miR-138-5p target gene. Our findings suggest that miR-138-5p is a critical regulator of PV interneuron function, with implications for cognition and schizophrenia. More generally, they provide evidence that microRNAs orchestrate neural circuit development by fine-tuning both excitatory and inhibitory synaptic transmission.
Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole cell mechanics
Authors: Vahabikashi Amir , Sivagurunathan Suganya , Nicdao Fiona Ann Sadsad , Han Yu Long , Park Chan Young , Wong Xianrong , Tran Joseph R. , Gundersen Gregg G. , Reddy Karen L. , Luxton G.W. Gant , Guo Ming , Fredberg Jeffrey J. , Zheng Yixian , Adam Stephen A. , Goldman Robert D. 
Published: May 2021

AbstractThe ability of a cell to regulate its mechanical properties is central to its function. Emerging evidence suggests that interactions between the cell nucleus and cytoskeleton influence cell mechanics through poorly understood mechanisms. Here we show that A- and B-type nuclear lamin isoforms distinctively modulate both nuclear and cellular volume and selectively stabilize the linker of nucleoskeleton and cytoskeleton (LINC) complexes that couple the nucleus to cytoskeletal actin and vimentin. We reveal, further, that loss of each of the four-known lamin isoforms in the mouse embryonic fibroblasts differentially affects cortical and cytoplasmic stiffness as well as cellular contractility, and then propose a LINC complex mediated model that explains these impaired mechanical phenotypes. Finally, we demonstrate that loss of each lamin isoform softens the nucleus in a manner that correlates with loss of heterochromatin. Together, these findings uncover distinctive roles for each lamin isoform in maintaining cellular and nuclear mechanics.
Visuo-proprioceptive integration and recalibration with multiple visual stimuli
Authors: Debats Nienke B , Heuer Herbert , Kayser Christoph 
Published: May 2021

SUMMARYTo organize the plethora of sensory signals from our environment into a coherent percept, our brain relies on the processes of multisensory integration and sensory recalibration. We here asked how visuo-proprioceptive integration and recalibration are shaped by the presence of more than one potentially relevant visual stimulus, hence paving the way to studying multisensory perception under more naturalistic settings with multiple signals per sensory modality. By manipulating the spatio-temporal correspondence between the hand position and two visual stimuli during a cursor-control task, we contrasted two alternative accounts: that only the temporally more proximal signal enters integration and recalibration similar to a winner-takes-all process, or that the influences of both visual signals superpose. Our results show that integration - and likely also recalibration - are shaped by the superposed contributions of multiple stimuli rather than by only individual ones.