bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescribed footwear and orthoses are not prophylactic in preventing lower extremity injuries in military tactical athletes. A systematic review with meta-analysis
Authors: Paradise Scott L. , Beer Joshua R. , Cruz Chris A. , Fechner Ken M. , MacGregor Andrew J. , Fraser John J. 
Published: June 2021

ABSTRACTIntroductionMilitary members are exposed to high cumulative physical loads that frequently lead to injury. Prescribed footwear and orthoses have been used to prevent injury. The purpose of this systematic review with meta-analysis was to assess if prescribed prophylactic footwear or foot orthoses reduced lower extremity injury risk in military tactical athletes.MethodsMEDLINE, Embase, Web of Science, CINAHL, SportDiscus, and DTIC databases were searched for randomized controlled trials published at any time that compared foot orthoses or prescribed footwear (to include shock-absorbing insoles and socks) to a placebo intervention or a no-treatment control. Methodological quality was assessed and numbers of injuries, population at risk, and the duration of the study epoch were extracted and relative risk (RR) calculated. An omnibus meta-analysis was performed assessing all prescribed footwear and orthoses intervention studies, with subgroup analyses conducted on studies with similar interventions [i.e., basketball athletic shoes; athletic shoes (prescribed by foot type); foot orthoses; shock-absorbing insoles; socks; tropical combat boots].ResultsOf 1,673 studies identified, 22 studies were included. Three of eight studies that employed orthoses demonstrated significantly reduced overuse injuries compared to no treatment controls (RR range: 0.34-0.68); one study showed neoprene insoles significantly decreased overuse injuries (RR: 0.75). There were no other significant effects in the individual studies, and no protective effects observed in the omnibus meta-analysis or in the component sub analyses.ConclusionsPrescribed footwear and orthoses do not appear to have a prophylactic effect on lower quarter MSKI in military members and cannot be recommended at this time.
Intensified stimulation targeting lateral and medial prefrontal cortices for the treatment of social anxiety disorder: A randomized, double-blind, parallel-group, dose-comparison study
Authors: Jafari Eisa , Alizadehgoradel Jaber , Koluri Fereshteh Pourmohseni , Nikoozadehkordmirza Ezzatollah , Refahi Meysam , Taherifard Mina , Nejati Vahid , Hallajian Amir-Homayun , Ghanavati Elham , Vicario Carmelo M. , Nitsche Michael A. , Salehinejad Mohammad Ali 
Published: June 2021

AbstractBackgroundSocial Anxiety Disorder (SAD) is the most common anxiety disorder while remains largely untreated. Disturbed amygdala-frontal network functions are central to the pathophysiology of SAD, marked by hypoactivity of the lateral prefrontal cortex (PFC), and hypersensitivity of the medial PFC and amygdala. The objective of this study was to determine whether modulation of dorsolateral and medial PFC activity with a novel intensified stimulation protocol reduces SAD core symptoms, improves treatment-related variables, and reduces attention bias to threatening stimuli.MethodsIn this randomized, sham-controlled, double-blind trial, we assessed the efficacy of an intensified stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) in two intensities (1 vs 2 mA) compared to sham stimulations. 45 patients with SAD were randomized in three tDCS arms. SAD symptoms, treatment-related variables (worries, depressive state, emotion regulation, quality of life), and attention bias to threatening stimuli (dot-probe paradigm) were assessed before and right after the intervention. SAD symptoms were also assessed at 2-month follow-up.ResultsBoth 1 mA and 2mA protocols significantly reduced fear/avoidance symptoms, worries and improved, emotion regulation and quality of life after the intervention compared to the sham group. Improving effect of the 2 mA protocol on avoidance symptoms, worries and depressive state was significantly larger than the 1 mA group. Only the 2 mA protocol reduced attention bias to threat-related stimuli, the avoidance symptom at follow-up, and depressive states, as compared to the sham group.ConclusionsModulation of lateral-medial PFC activity with intensified stimulation can improve cognitive control, motivation and emotion networks in SAD and thereby results in therapeutic effects. These effects can be larger with 2 mA vs 1 mA intensities, though a linear relationship between intensity and efficacy should not be concluded.
A year of Covid-19 GWAS results from the GRASP portal reveals potential SARS-CoV-2 modifiers
Authors: Thibord Florian , Chan Melissa V. , Chen Ming-Huei , Johnson Andrew D. 
Published: June 2021

AbstractHost genetic variants influence the susceptibility and severity of several infectious diseases, and the discovery of novel genetic associations with Covid-19 phenotypes could help developing new therapeutic strategies to reduce its burden.Between May 2020 and June 2021, we used Covid-19 data released periodically by UK Biobank and performed 65 Genome-Wide Association Studies (GWAS) in up to 18 releases of Covid-19 susceptibility (N=18,481 cases in June 2021), hospitalization (N=3,260), severe outcomes (N=1,244) and death (N=1,104), stratified by sex and ancestry.In coherence with previous studies, we observed 2 independent signals at the chr3p21.31 locus (rs73062389-A, OR=1.21, P=4.26×10−15 and rs71325088-C, OR=1.62, P=2.25×10−9) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A, OR=1.10, P=3.30×10−12), suggesting an increased risk of infection in non-O blood groups carriers. Additional signals at the APOE (associated with severity and death) LRMDA (susceptibility in non-European) and chr2q32.3 (susceptibility in women) loci were also identified but did not replicate in independent datasets. We then devised an original approach to extract variants exhibiting an increase in significance over time. When applied to the susceptibility, hospitalization and severity analyses, this approach revealed the known DPP9, RPL24 and MAPT loci, amongst thousands of other signals. Finally, this significance trajectory analysis was applied to the larger Covid-19hgi meta-analyses, where additional loci of interest, related to the immune system, were identified.These results, freely available on the GRASP portal, provide new insights on the genetic mechanisms involved in Covid-19 phenotypes.
Multiscale dynamics underlying neocortical slow oscillations
Authors: Mattia Maurizio , Perez-Zabalza Maria , Tort-Colet Núria , Dasilva Miguel , Muñoz Alberto , Sanchez-Vives Maria V. 
Published: June 2021

ABSTRACTSlow oscillations in the sleeping and anesthetized brain invariantly emerge as an alternation between Up (high firing) and Down (almost quiescent) states. In cortex, they occur simultaneously in cell assemblies in different layers and propagate as traveling waves, a concerted activity at multiple scales whose interplay and role is still under debate. Slow oscillations have been reported to start in deep layers, more specifically in layer 5. Here, we studied the laminar organization of slow oscillations in the anesthetized rat cortex and we found that the activity leading to Up states actually initiates in layer 6, then spreads towards upper layers. Layer 5 cell assemblies have a threshold-like activation that can persist after layer 6 inactivation, giving rise to hysteresis loops like in “flip-flop” computational units. We found that such hysteresis is finely tuned by the columnar circuitry depending on the recent history of the local ongoing activity. Furthermore, thalamic inactivation reduced infragranular excitability without affecting the columnar activation pattern. We propose a role for layer 6 acting as a hub unraveling a hierarchy of cortical loops.
All-optical mechanobiology interrogation of YAP in human cancer and normal cells using a novel multi-functional system
Authors: Luo Qin , Huang Miao , Liang Chenyu , Zhang Justin , Lin Gaoming , Yu Sydney , Tanaka Mai , Lepler Sharon , Guan Juan , Siemann Dietmar , Tang Xin 
Published: June 2021

ABSTRACTLong-term multi-functional imaging and analysis of live cells require streamlined functional coordination of various hardware and software platforms. However, manual control of various equipment produced by different manufacturers is labor-intensive and time-consuming, potentially decreasing the accuracy, reproducibility, and quality of acquired data. Therefore, an all-in-one and user-programmable system that enables automatic, multi-functional, and long-term image acquisition and is compatible with most fluorescent microscopy platforms can desirably benefit the scientific community. In this paper, we introduce the full operating protocols of utilizing a novel integrated software system that consists of (1) a home-built software program, titled “Automatic Multi-functional Integration Program (AMFIP)”, which enables automatic multi-channel imaging acquisition, and (2) a suite of quantitative imaging analysis and cell traction computation packages. We applied this integrated system to reveal the previously unknown relationship between the spatial-temporal distribution of mechano-sensitive Yes-associated protein (YAP) and the cell mechanics, including cell spreading and traction, in human normal cells (B2B) and lung cancer cells (PC9). Leveraging our system’s capability of multi-channel control and readout, we found: (1) B2B normal cells and PC9 cancer cells show distinct YAP expression, traction, and cell dynamics relationship during cell spreading and migration processes; and (2) PC9 cancer cells apply noticeable peri-nuclear forces on substrates. In summary, this paper presents a detailed stepwise protocol on how to utilize an integrated user-programmable system that enables automatic multi-functional imaging and analysis to elucidate YAP mechanosensitivity. These tools open the possibility for detailed explorations of multifaceted signaling dynamics in the context of cell physiology and pathology.SUMMARYThis paper presents a detailed stepwise protocol on how to utilize an integrated user-programmable system that enables all-optical electro-mechanobiology interrogation to elucidate YAP mechanosensitivity.
Inferring global-scale temporal latent topics from news reports to predict public health interventions for COVID-19
Authors: Wen Zhi , Powell Guido , Chafi Imane , Buckeridge David , Li Yue 
Published: June 2021

SummaryThe COVID-19 pandemic has highlighted the importance of non-pharmacological interventions (NPI) for controlling epidemics of emerging infectious diseases. Despite their importance, NPI have been monitored mainly through the manual efforts of volunteers. This approach hinders measurement of the NPI effectiveness and development of evidence to guide their use to control the global pandemic. We present EpiTopics, a machine learning approach to support automation of the NPI prediction and monitoring at both the document-level and country-level by mining the vast amount of unlabelled news reports on COVID-19. EpiTopics uses a 3-stage, transfer-learning algorithm to classify documents according to NPI categories, relying on topic modelling to support result interpretation. We identified 25 interpretable topics under 4 distinct and coherent COVID-related themes. Importantly, the use of these topics resulted in significant improvements over alternative automated methods in predicting the NPIs in labelled documents and in predicting country-level NPIs for 42 countries.
Functional redundancy of WDR31 with GTPase-activating proteins ELMOD and RP2 in regulating IFT trains via BBSome
Authors: Cevik Sebiha , Peng Xiaoyu , Beyer Tina , Pir Mustafa S. , Yenisert Ferhan , Woerz Franziska , Hoffmann Felix , Altunkaynak Betul , Pir Betul , Boldt Karsten , Karaman Asli , Cakiroglu Miray , Sadik Oner S. , Cao Ying , Ueffing Marius , Kaplan Oktay I. 
Published: June 2021

AbstractThe correct intraflagellar transport (IFT) assembly at the ciliary base and the IFT turnaround at the ciliary tip are key for the IFT to perform its function, but we still have poor understanding about how these processes are regulated. Here, we identify WDR31 as a new ciliary protein, and analysis from zebrafish andCaenorhabditis elegansreveals the role ofWDR31in regulating the cilia morphology. We find that loss of WDR-31 together with RP-2 and ELMD-1 (the sole ortholog ELMOD1-3) results in ciliary accumulations of IFT Complex B components and KIF17 kinesin, with fewer IFT/BBSome particles traveling along cilia in both anterograde and retrograde directions, suggesting that the IFT/BBSome entry into cilia and exit from cilia are impacted. Furthermore, anterograde IFT in the middle segment travel at increased speed inwdr-31;rpi-2;elmd-1. Remarkably, a non-ciliary protein leaks into cilia ofwdr-31;rpi-2;elmd-1possible due to IFT defects. This work reveals WDR31-RP-2-ELMD-1 as IFT and BBSome trafficking regulators.
NDR1 and the Arabidopsis Plasma Membrane ATPase AHA5 are Required for Processes that Converge on Drought Tolerance and Immunity
Authors: Lu Yi-Ju , Chen Huan , Corrion Alex , Buyuk Ilker , Li Pai , Samaradivakara Saroopa , Wai Ching Man , Sakamoto Hikaru , Santos Patrícia , VanBuren Robert , Kim Yongsig , Day Brad 
Published: June 2021

AbstractNON-RACE-SPECIFIC DISEASE RISISTANCE1 (NDR1) is a key component of plant immune signaling, required for defense against the bacterial pathogen Pseudomonas syringae. Plant stress responses have overlapping molecular, physiological, and cell biology signatures, and given the central role of NDR1 during biotic stress perception and signaling, we hypothesized that NDR1 also functions in abiotic stress responses, including in a role that mediates signaling at the plasma membrane (PM) - cell wall (CW) continuum. Here, we demonstrate that NDR1 is required for the induction of drought stress responses in plants, a role that couples stress signaling in an abscisic acid-dependent manner. We show that NDR1 physically associates with the PM-localized H+-ATPases AHA1, AHA2, and AHA5 and is required for proper regulation of H+-ATPase activity and stomatal guard cell dynamics, providing a mechanistic function of NDR1 during drought responses. In the current study, we demonstrate that NDR1 functions in signaling processes associated with both biotic and abiotic stress response pathways, a function we hypothesize represents NDR1’s role in the maintenance of cellular homeostasis during stress. We propose a role for NDR1 as a core transducer of signaling between cell membrane processes and intercellular stress response activation.
Identification of ACE2 modifiers by CRISPR screening
Authors: Sherman Emily J. , Mirabelli Carmen , Tang Vi T. , Khan Taslima G. , Kennedy Andrew A. , Graham Sarah E. , Willer Cristen J. , Tai Andrew W. , Sexton Jonathan Z. , Wobus Christiane E. , Emmer Brian T. 
Published: June 2021

ABSTRACTSARS-CoV-2 infection is initiated by binding of the viral spike protein to its receptor, ACE2, on the surface of host cells. ACE2 expression is heterogeneous both in vivo and in immortalized cell lines, but the molecular pathways that govern ACE2 expression remain unclear. We now report high-throughput CRISPR screens for functional modifiers of ACE2 surface abundance. We identified 35 genes whose disruption was associated with a change in the surface abundance of ACE2 in HuH7 cells. Enriched among these ACE2 regulators were established transcription factors, epigenetic regulators, and functional networks. We further characterized individual cell lines with disruption of SMAD4, EP300, PIAS1, or BAMBI and found these genes to regulate ACE2 at the mRNA level and to influence cellular susceptibility to SARS-CoV-2 infection. Collectively, our findings clarify the host factors involved in SARS-CoV-2 entry and suggest potential targets for therapeutic development.
Point-estimating observer models for latent cause detection
Authors: Lee Jennifer Laura , Ma Wei Ji 
Published: June 2021

AbstractThe spatial distribution of visual items allows us to infer the presence of latent causes in the world. For instance, a spatial cluster of ants allows us to infer the presence of a common food source. However, optimal inference requires the integration of a computationally intractable number of world states in real world situations. For example, optimal inference about whether a common cause exists based on N spatially distributed visual items requires marginalizing over both the location of the latent cause and 2N possible affiliation patterns (where each item may be affiliated or non-affiliated with the latent cause). How might the brain approximate this inference? We show that subject behaviour deviates qualitatively from Bayes-optimal, in particular showing an unexpected positive effect of N (the number of visual items) on the false-alarm rate. We propose several “point-estimating” observer models that fit subject behaviour better than the Bayesian model. They each avoid a costly computational marginalization over at least one of the variables of the generative model by “committing” to a point estimate of at least one of the two generative model variables. These findings suggest that the brain may implement partially committal variants of Bayesian models when detecting latent causes based on complex real world data.
Brain-wide analysis of the supraspinal connectome reveals anatomical correlates to functional recovery after spinal injury
Authors: Wang Zimei , Romanski Adam , Mehra Vatsal , Wang Yunfang , Campbell Benjamin C. , Petsko Gregory A. , Tsoulfas Pantelis , Blackmore Murray 
Published: June 2021

AbstractThe supraspinal connectome is essential for normal behavior and homeostasis and consists of numerous sensory, motor, and autonomic projections from brain to spinal cord. Study of supraspinal control and its restoration after damage has focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. We now provide an experimental platform and associated web-based resource to rapidly profile the entire supraspinal mesoconnectome in adult mice. Optimized viral labeling, 3D imaging, and registration to a mouse digital neuroanatomical atlas assigned tens of thousands of supraspinal neurons to more than 60 identified regions. We demonstrate the approach’s ability to clarify essential points of topographic mapping between spinal levels, to measure population-specific sensitivity to spinal injury, and to resolve previously unexplained variability in functional recovery. This work will spur progress by broadening understanding and enabling analyses of essential but understudied supraspinal populations.
A CRISPR toolbox for generating intersectional genetic mice for functional, molecular, and anatomical circuit mapping
Authors: Lusk Savannah J. , McKinney Andrew , Hunt Patrick J. , Fahey Paul G. , Patel Jay , Chang Andersen , Sun Jenny J. , Martinez Vena K. , Zhu Ping Jun , Egbert Jeremy R. , Allen Genevera , Jiang Xiaolong , Arenkiel Benjamin R. , Tolias Andreas S. , Costa-Mattioli Mauro , Ray Russell S. 
Published: June 2021

ABSTRACTBackgroundA full understanding of circuits and cellular mechanisms governing health and disease requires the dissection and multi-faceted study of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic response alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical study. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allow for more defined target expression. Although the application of this method is becoming increasingly popular, the expense and difficulty associated with production of customized intersectional mouse lines have limited widespread application to more common allele manipulations that are often commercially produced at great expense.ResultsWe present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production. Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study how functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase-responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle.ConclusionsLines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.
Identifying proximal RNA interactions from cDNA-encoded crosslinks with ShapeJumper
Authors: Christy Thomas W. , Giannetti Catherine A. , Laederach Alain , Weeks Kevin M. 
Published: June 2021

AbstractSHAPE-JuMP is a concise strategy for identifying close-in-space interactions in RNA molecules. Nucleotides in close three-dimensional proximity are crosslinked with a bi-reactive reagent that covalently links the 2’-hydroxyl groups of the ribose moieties. The identities of crosslinked nucleotides are determined using an engineered reverse transcriptase that jumps across crosslinked sites, resulting in a deletion in the cDNA that is detected using massively parallel sequencing. Here we introduce ShapeJumper, a bioinformatics pipeline to process SHAPE-JuMP sequencing data and to accurately identify through-space interactions. ShapeJumper identifies proximal interactions with near-nucleotide resolution using an alignment strategy that is optimized to tolerate the unique non-templated reverse-transcription profile of the engineered crosslink-traversing reverse-transcriptase. JuMP-inspired strategies are now poised to replace adapter-ligation for detecting RNA-RNA interactions in most crosslinking experiments.