bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can a knee sleeve influence ground reaction forces and knee joint power during a step-down hop in participants following ACL reconstruction? An explanatory analysis
Authors: Sole Gisela , Pataky Todd , Hammer Niels , Lamb Peter 
Published: August 2022

AbstractPurposeElastic knee sleeves are often worn following anterior cruciate ligament reconstruction but mechanisms underlying observed changes in movement patterns are still unclear. The aim of this study was to determine the immediate and 6-week effects of wearing a knee sleeve on ground reaction forces (GRF) and knee joint power during a step-down hop task.MethodsUsing a cross-over design, we estimated GRF and knee kinematics and kinetics during a step-down hop for 30 participants (age 26.1 [SD 6.7] years, 14 women) following ACL reconstruction (median 16 months post-surgery) with and without wearing a knee sleeve. In a subsequent randomised clinical trial, participants in the ‘Sleeve Group’ (n=9) then wore the sleeve for 6 weeks at least 1 hour daily, while a ‘Control Group’ (n=9) did not wear the sleeve. Statistical parametric mapping (SPM) was used to compare (1) GRF trajectories in the three planes as well as knee joint power between three conditions at baseline (uninjured side, unsleeved injured and sleeved injured side); (2) within-participant changes for GRF and knee joint power trajectories from baseline to follow-up between groups. We also compared discrete peak GRFs and power, rate of (vertical) force development, and mean knee joint power in the first 5% of stance phase.ResultsGRF did not differ for the (unsleeved) injured compared to the uninjured sides based on SPM analysis. Discrete variables showed lower peak anterior (propulsive) GRF for the injured side, and lower peak eccentric and concentric power, and mean power in the first 5% of stance. When wearing the sleeve on the injured side, mean power in the first 5% of stance increased significantly [mean difference (95% CIs) 1.3 (0.6, 2.0) N/BW*ht] from a concentric to an eccentric power when wearing the knee sleeve. After six weeks, the direction of change for vertical GRF differed between the groups: while the Control Group had slightly decreased forces, the Sleeve Group presented increased forces.ConclusionsIncreased knee power in the first 5% of landing when wearing the knee sleeve, combined with greater knee flexion, may indicate a protective response for ACL ruptures, most commonly occurring during that early phase of landing. The directional change of increased vertical GRF for the Sleeve group, combined with shorter stance duration at follow-up, may indicate enhanced performance when being prescribed such sleeve.
Clinical Validation of Segmentation-Based Detection of Glioma Progression
Authors: Damasceno Pablo F. , Gleason Tyler , Hawkins James , Luks Tracy , Majumdar Sharmila , Lupo Janine M. , Crane Jason C. , Villanueva-Meyer Javier E. 
Published: August 2022

PurposeTo evaluate whether an AI-based method could be used routinely as part of patient care to assist in detecting non-enhancing glioma progression.Materials and MethodsA 3D U-Net trained (n=481) and validated (n=121) to segment post-surgical lower grade gliomas was used to measure tumor volumes over time and assess progression in a clinical test set. Eight prospective and eight retrospective patients (total 72 exams) who were suspected of progression during their routine outpatient imaging were clinically assessed. Gold standards for progression were derived from clinical reports a posteriori using visual read, and radiologists were blinded to the AI decision at time of reporting.ResultsProgression assessments were presented to radiologists via an easy-to-use, interactive, and interpretable environment in under 10 minutes. Combining prospective and retrospective cases, a final sensitivity of 0.72 and specificity of 0.75 was achieved at progression detection.ConclusionsAutomated detection of glioma progression would provide valuable decision support for routine use.
Effectiveness of fourth dose COVID-19 vaccine against the Omicron variant compared to no vaccination
Authors: Zeng Jessie , Szanyi Joshua , Blakely Tony 
Published: August 2022

AbstractIn response to enhanced immune evasion properties of the Omicron SARS-CoV-2 variant and waning COVID-19 vaccine effectiveness (VE), several jurisdictions have rolled out fourth dose vaccination programs. Using a system of logistic regression equations and VE estimates for a fourth dose relative to a third dose reported in an Israeli study, we estimated absolute vaccine effectiveness for third and fourth doses of mRNA COVID-19 vaccine (c.f. no vaccination) against Omicron, by clinical outcome. We found that a fourth dose restores or even enhances protection conferred by a third dose at the same time since vaccination.
Cohort monitoring of 29 Adverse Events of Special Interest prior to and after COVID-19 vaccination in four large European electronic healthcare data sources
Authors: Sturkenboom Miriam , Messina Davide , Paoletti Olga , de Burgos-Gonzalez Airam , García-Poza Patricia , Huerta Consuelo , Llorente- García Ana , Martin-Perez Mar , Martinez Maria , Martin Ivonne , Overbeek Jetty , Padros-Goossens Marc , Souverein Patrick , Swart Karin , Klungel Olaf , Gini Rosa 
Published: August 2022

SettingPrimary and/or secondary health care data from four European countries: Italy, the Netherlands, the United Kingdom, SpainParticipantsIndividuals with complete data for the year preceding enrollment or those born at the start of observation time. The cohort comprised 25,720,158 subjects.InterventionsFirst and second dose of Pfizer, AstraZeneca, Moderna, or Janssen COVID-19 vaccine.Main outcome measures29 adverse events of special interest (AESI): acute aseptic arthritis, acute coronary artery disease, acute disseminated encephalomyelitis (ADEM), acute kidney injury, acute liver injury, acute respiratory distress syndrome, anaphylaxis, anosmia or ageusia, arrhythmia, Bells’ palsy, chilblain-like lesions death, erythema multiforme, Guillain Barré Syndrome (GBS), generalized convulsion, haemorrhagic stroke, heart failure, ischemic stroke, meningoencephalitis, microangiopathy, multisystem inflammatory syndrome, myo/pericarditis, myocarditis, narcolepsy, single organ cutaneous vasculitis (SOCV), stress cardiomyopathy, thrombocytopenia, thrombotic thrombocytopenia syndrome (TTS) venous thromboembolism (VTE)Results12,117,458 individuals received at least a first dose of COVID-19 vaccine: 54% with Comirnaty (Pfizer), 6% Spikevax (Moderna), 38% Vaxzevria (AstraZeneca) and 2% Janssen Covid-19 vaccine. AESI were very rare <10/100,000 PY in 2020, only thrombotic and cardiac events were uncommon. After adjustment for factors associated with severe COVID, 10 statistically significant associations of pooled incidence rate ratios remained based on dose 1 and 2 combined. These comprised anaphylaxis after AstraZeneca vaccine, TTS after both AstraZeneca and Janssen vaccine, erythema multiforme after Moderna, GBS after Janssen vaccine, SOCV after Janssen vaccine, thrombocytopenia after Janssen and Moderna vaccine and VTE after Moderna and Pfizer vaccines. The pooled rate ratio was more than two-fold increased only for TTS, SOCV and thrombocytopenia.ConclusionWe showed associations with several AESI, which remained after adjustment for factors that determined vaccine roll out. Hypotheses testing studies are required to establish causality.
Impact of galvanic vestibular stimulation electrode current density on brain current flow patterns: Does electrode size matter?
Authors: Troung Dennis Q , Guillen Alexander , Nooristani Mujda , Maheu Maxime , Champoux Francois , Datta Abhishek 
Published: August 2022

AbstractBackgroundGalvanic vestibular stimulation (GVS) uses at least one electrode placed on the mastoid process with one or multiple placed over other head areas to stimulate the vestibular system. The exact electrode size used is not given much importance in the literature and has not been reported in several studies. In a previous study, we compared the clinical effects of using different electrode sizes (3 cm2 and 35 cm2) with placebo but with the same injected current, on postural control. We observed significant improvement using the smaller size electrode but not with the bigger size electrode. The goal of this study was to simulate the current flow patterns with the intent to shed light and potentially explain the experimental outcome.MethodsWe used an ultra-high-resolution structural dataset and developed a model to simulate the application of different electrode sizes. We considered current flow in the brain and in the vestibular labyrinth.ResultsOur simulation results verified the focality increase using smaller electrodes that we postulated as the main reason for our clinical effect. The use of smaller size electrodes in combination with the montage employed also result in higher induced electric field (E-field) in the brain.ConclusionsElectrode size and related current density is a critical parameter to characterize any GVS administration as the choice impacts the induced E-field. It is evident that the higher induced E-field likely contributed to the clinical outcome reported in our prior study.
Allosteric Inhibition of the T Cell Receptor by a Designed Membrane Ligand
Authors: Ye Yujie , Morita Shumpei , Wilhelm Kiera B. , Groves Jay T. , Barrera Francisco N. 
Published: August 2022

AbstractThe T cell receptor (TCR) is a complex molecular machine that directs the activation of T cells, allowing the immune system to fight pathogens and cancer cells. Despite decades of investigation, the molecular mechanism of TCR activation is still controversial. One of the leading activation hypotheses is the allosteric model. This model posits that binding of pMHC at the extracellular domain triggers a dynamic change in the transmembrane (TM) domain of the TCR subunits, which leads to signaling at the cytoplasmic side. We sought to test this hypothesis by creating a TM ligand for TCR. Previously we described a method to create a soluble peptide capable of inserting into membranes and bind to the TM domain of the receptor tyrosine kinase EphA2 (Alves et al., eLife 2018). Here we show that the approach is generalizable to complex membrane receptors, by designing a membrane ligand for TCR. We observed that the designed peptide caused a reduction of Lck phosphorylation of TCR at the CD3ζ subunit. As a result, in the presence of this Peptide Inhibitor of TCR (PITCR), the proximal signaling cascade downstream of TCR activation was significantly dampened in T cells. Co-localization and co-immunoprecipitation results in DIBMA native nanodiscs confirmed that PITCR was able to bind to the TCR. We propose that PITCR binds into a crevice present between the TM helices of the CD3ζ and CD3ε(δ) subunits. Our results additionally indicate that PITCR disrupts the allosteric changes in the compactness of the TM bundle that occur upon TCR activation, lending support to the allosteric TCR activation model. The TCR inhibition achieved by PITCR might be useful to treat inflammatory and autoimmune diseases and to prevent organ transplant rejection, as in these conditions aberrant activation of TCR contributes to disease.
Effects of HSP70 chaperones Ssa1 and Ssa2 on Ste5 scaffold and the mating mitogen-activated protein kinase (MAPK) Pathway in Saccharomyces cerevisiae
Authors: Farley Francis W. , McCully Ryan R. , Maslo Paul B. , Yu Lu , Sheff Mark A. , Sadeghi Homayoun , Elion Elaine A. 
Published: August 2022

AbstractSte5 is a prototype of scaffold proteins that regulate activation of mitogen-activated protein kinase (MAPK) cascades in all eukaryotes. Ste5 associates with many proteins including Gβγ (Ste4), Ste11 MAPKKK, Ste7 MAPKK, Fus3 and Kss1 MAPKs, Bem1, Cdc24. Here we show that Ste5 also associates with heat shock protein 70 chaperone (Hsp70) Ssa1 and that Ssa1 and its ortholog Ssa2 are together important for Ste5 function and efficient mating responses. The majority of purified overexpressed Ste5 associates with Ssa1. Loss of Ssa1 and Ssa2 has deleterious effects on Ste5 abundance, integrity, and localization particularly when Ste5 is expressed at native levels. The status of Ssa1 and Ssa2 influences Ste5 electrophoresis mobility and formation of high molecular weight species thought to be phosphorylated, ubiquitinylated and aggregated and lower molecular weight fragments. A Ste5 VWA domain mutant with greater propensity to form punctate foci has reduced predicted propensity to bind Ssa1 near the mutation sites and forms more punctate foci when Ssa1 Is overexpressed, supporting a dynamic protein quality control relationship between Ste5 and Ssa1. Loss of Ssa1 and Ssa2 reduces activation of Fus3 and Kss1 MAPKs and FUS1 gene expression and impairs mating shmoo morphogenesis. Surprisingly, ssa1, ssa2, ssa3 and ssa4 single, double and triple mutants can still mate, suggesting compensatory mechanisms exist for folding. Additional analysis suggests Ssa1 is the major Hsp70 chaperone for the mating and invasive growth pathways and reveals several chaperone-network proteins required for mating morphogenesis.
A shift in the pathotype diversity and complexity of Phytophthora sojae, causal agent of root and stem rot of soybean, in Brazil
Authors: Batista I.C.A. , Silva M.P.C. , Silva Junior A. L. , Gonzalez M.P. , Camargo M. P. , Figueiredo A. , Hora Junior B.T. , Mizubuti E.S.G. 
Published: August 2022

AbstractSoybean root rot disease caused by the oomycete Phytophthora sojae is particularly destructive, once it is a host-specific pathogen that can infect and kill soybean plants at any stage of growth. The use of resistant cultivars is the most effective method of controlling the disease. Therefore, monitoring changes in the adaptability of P. sojae population to resistance genes (Rps) is extremely important not only from an epidemiological point of view but mainly for the management of the disease and durability of the Rps genes. We investigated the pathotypes of 40 isolates of P. sojae, sampled from the region with a higher incidence of soybean root rot in Brazil, using a set of 14 soybean differentials. The first study investigating pathotype diversity in Brazil was published in 2013. A decade later, we are reporting a major shift in pathotype diversity and complexity. This information can be useful for breeding programs aiming at developing soybean cultivars with resistance to root and stem rot and optimize the usage of genes and germplasm.
Redefining the structure of tip-links in hair-cells
Authors: Kaur Veerpal , Ghosh Sanat K. , Bhatia Tripta , Rakshit Sabyasachi 
Published: August 2022

AbstractTip-link, the gating-spring in hearing, modulates the mechanoelectrotransduction process and protects the hearing sensory machineries from overexcited auditory inputs. Tip-links are formed by two exceptionally long cadherins, cadherin-23 and protocadherin-15. It is proposed that both the cadherins first independently form cis-dimers through lateral interactions and finally, engage in trans-interactions to form the heterotetrameric assembly in tip-links. In fact, the molecular details of the protocadherin cis-dimers are well-understood. However, little structural and molecular details are known for independent cis-dimer of cadherin-23. Using photo-induced cross-linking of unmodified proteins in solution and on lipid-membranes, we observed no trace of cadherin-23 cis-dimers, rather we captured trans-homodimers of cadherin-23. We thus, redefine the tip-link structure where protocadherin-15 remains as cis-dimers, however, two individual cadherin-23 binds to protocadherin-15 cis-dimer for tip linking.
Emerging fish pathogens Lactococcus petauri and L. garvieae in Nile tilapia (Oreochromis niloticus) farmed in Brazil
Authors: Egger Renata Catão , Rosa Júlio César Câmara , de Pádua Santiago Benites , de Oliveira Barbosa Fernanda , Zerbini Mariana Taíse , Tavares Guilherme Campos , Figueiredo Henrique César Pereira 
Published: August 2022

AbstractLactococcosis in fish has been associated with Lactococcus garvieae and the recently described L. petauri. However, the relevance of these emerging fish pathogens to Nile tilapia still requires thorough understanding. This study investigated lactococcosis outbreaks in Nile tilapia on Brazilian farms and characterized the isolates through molecular identification of the bacterial species, multilocus sequence typing (MLST) analysis, virulence to Nile tilapia, and antimicrobial susceptibility. Lactococcosis outbreaks were monitored from 2019 to 2022 throughout Brazil. The outbreaks occurred mainly during warmer months, and co-infections were observed in four farms, whereas concurrent bacterial infections were identified in all farms. Since the sequence of the 16S rRNA was not capable of differentiating between L. petauri and L. garvieae, Lactococcus spp. isolates were identified at the species level using the gyrB gene sequence. In total, 30 isolates were classified as L. petauri and two as L. garvieae. All L. petauri isolates were grouped in ST24, except for one isolate which belonged to the newly described ST47. A new ST was also described for the L. garvieae isolates identified, ST46. Furthermore, L. petauri ST24 and ST47 were characterized as singletons, whereas L. garvieae ST46 was grouped with ST16 and ST17 and formed CC17. For the challenge trial, an L. petauri ST24 isolate was chosen considering that this MLST lineage was the most frequently observed. L. petauri was reisolated from challenged Nile tilapia, confirming the pathogenicity of this bacterium to Nile tilapia. The infection in the fish progressed very rapidly, and within 48 h post-challenge clinical signs and the first mortalities were observed. The estimated LD50 was 5.74 × 103 CFU 15 days post-challenge. Provisional epidemiological cutoff values were determined for L. petauri for six antimicrobial agents from different drug classes. All isolates were characterized as wild type (WT) for neomycin and oxytetracycline, whereas 96.67 % of the isolates were characterized as WT for amoxicillin, erythromycin, and florfenicol, and 83.33 % were WT for norfloxacin. Of the 14 outbreaks analyzed, 12 were caused by L. petauri and two by L. garvieae. The gyrB gene sequence was used to differentiate L. petauri from L. garvieae and allowed for the correct identification of these pathogens. Two MSLT lineages of L. petauri were identified and ST24 was observed in different regions of the country, illustrating a rapid expansion of this bacterial lineage.Highlights of the manuscriptLactococcus petauri is pathogenic to Nile tilapia.The MLST lineage most observed was L. petauri ST24, indicating its adaption to infect Nile tilapia.The analysis of the gyrB gene sequence allowed for the correct identification of L. petauri and L. garvieae.
The Nematode Oscheius tipulae as A Genetic Model for Programmed DNA Elimination
Authors: Dockendorff Thomas C. , Estrem Brandon , Reed Jordan , Simmons James R. , Zadegan Sobhan Bahrami , Zagoskin Maxim V. , Terta Vincent , Seaberry Erin , Wang Jianbin 
Published: August 2022

SUMMARYProgrammed DNA elimination (PDE) is a notable exception to the paradigm of genome integrity. In metazoa, PDE often occurs during early embryogenesis, coincident with germline to somatic cell differentiation. During PDE, portions of genomic DNA are lost, resulting in reduced somatic genomes. Recent studies have described the sequences lost and chromosome behavior in metazoa. However, a system for studying the mechanisms and consequences of PDE in metazoa is lacking. Here, we established a functional and genetic model for PDE in the free-living nematode Oscheius tipulae, a member of the Rhabditidae family, which includes Caenorhabditis elegans. O. tipulae was recently suggested to eliminate DNA. Using staged embryos, we show that O. tipulae PDE occurs during embryogenesis at the 2-16 cell stages, similar to the human/pig parasitic nematode Ascaris. We identified a conserved motif, named Sequence For Elimination (SFE), for all 12 break sites on the six chromosomes at the junction of retained and eliminated DNA. SFE mutants exhibit a “fail-to-eliminate” phenotype only at the modified sites. END-seq revealed that breaks can occur at multiple positions within the SFE, with extensive end resection followed by telomere addition to both retained and eliminated ends. We identified through END-seq in the wild-type embryos, genome sequencing of SFE mutants, and comparative genomics of 23 wild isolates a large number of functional SFEs at the chromosome ends. We suggest these alternative SFEs provide flexibility in the sequences eliminated and a fail-safe mechanism for PDE. These studies establish O. tipulae as a new, attractive model to study the mechanisms and consequences of PDE in a metazoan.
Leveraging microfluidic dielectrophoresis to distinguish compositional variations of lipopolysaccharide inE. coli
Authors: Wang Qianru , Kim Hyungseok , Halvorsen Tiffany M. , Chen Sijie , Hayes Christopher S. , Buie Cullen R. 
Published: August 2022

AbstractLipopolysaccharide (LPS) is the unique feature that composes the outer leaflet of the Gram-negative bacterial cell envelope. Variations in LPS structures affect a number of physiological processes, including outer membrane permeability, antimicrobial resistance, recognition by the host immune system, biofilm formation, and interbacterial competition. Rapid characterization of LPS properties is crucial for studying the relationship between these LPS structural changes and bacterial physiology. However, current assessments of LPS structures require LPS extraction and purification followed by cumbersome proteomic analysis. This paper demonstrates one of the first high-throughput and noninvasive strategies to directly distinguishEscherichia coliwith different LPS structures. Using a combination of three-dimensional insulator-based dielectrophoresis (3DiDEP) and cell tracking in a linear electrokinetics assay, we elucidate the effect of structural changes inE. coliLPS oligosaccharides on electrokinetic mobility and polarizability. We show that our platform is sufficiently sensitive to detect LPS structural variations at the molecular level. To correlate electrokinetic properties of LPS with the outer membrane permeability, we further examined effects of LPS structural variations on bacterial susceptibility to colistin, an antibiotic known to disrupt the outer membrane by targeting LPS. Our results suggest that microfluidic electrokinetic platforms employing 3DiDEP can be a useful tool for isolating and selecting bacteria based on their LPS glycoforms. Future iterations of these platforms could be leveraged for rapid profiling of pathogens based on their surface LPS structural identity.
IL-2 secreting T helper cells promote EF B cell maturation via intrinsic regulation of B cell mTOR/AKT/Blimp-1 axis
Authors: Faliti Caterina E. , Mesina Maria , Choi Jinyong , Bélanger Simon , Schief William R. , Crotty Shane 
Published: August 2022

SUMMARYB cells are fundamental players in the secretion of antibodies and the establishment of long-term memory-based immunity. Integration of signals from TLRs, BCR stimulation, and T helper cell-derived cytokines can all dictate B cell differentiation and their metabolic state. However, while important components of this interaction have been described, the precise signaling networks and mechanisms regulating B cell fate are not fully understood. Here, we elucidated the role of interleukin-2 (IL-2) in determining early B cell fate decisions and inducing plasma cell reprogramming. Using both in vitro culture systems and in vivo models of immunization, alongside CRISPR-based genome editing of antigen-specific T and B cells, we identify a role for T helper-secreted IL-2 in inducing high expression of Irf4 and Blimp-1 in activated cognate B cells, enhancing plasma cell differentiation. Induction of this cascade promotes their differentiation and drives metabolic reprogramming through the regulation of mTOR/AKT/Blimp-1 axis.