bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical usability, reliability, and repeatability of noncontact scanners in measuring residual limb volume in persons with transtibial amputation
Authors: Kofman Rianne , Winter Raoul E , Emmelot Cornelis H , Geertzen Jan HB , Dijkstra Pieter U 
Published: December 2021

Background:
In previous studies, noncontact 3D scanners were found to be the most reliable in measuring volume of the residual limb after a transtibial amputation (TTA). Meanwhile newly developed noncontact scanners became available to measure residual limb volume after TTA but should be tested for clinical usability and reliability.

Objective:
To determine the clinical usability, reliability, and repeatability of noncontact scanners in measuring residual limb volume in persons with a TTA.

Study design:
Original research report; repeated measurements.

Methods:
Three noncontact scanners (Rodin4D, Omega Tracer, and Biosculptor) were used to measure the residual limb volume on two occasions by two observers in 30 persons with an unilateral or bilateral TTA. Clinical usability was assessed as scores of the Post-Study System Usability Questionnaire, participant satisfaction (0–10 scale), and time to take the measurement.

Results:
The usability score of the Omega Scanner 3D (123.4) and Rodin4D (121.3) was significantly better compared with the Biosculptor (117.8). Participant experience was equal for all. The residual variance was 8.4%, where participant and scanning system explained most of the error variance (80.7%). Repeatability coefficients of the systems were 16.5 cc (Omega Scanner 3D), 26.4 cc (Rodin4D), and 32.8 cc (Biosculptor). The time to perform the measurements was significantly longer (+80 seconds) for the Omega Scanner 3D.

Conclusions
For measuring residual limb volume in TT amputees, Omega software (state version 12.2) combined with the Rodin4D scanner was more usable and reliable than the Rodin 4D or Biosculptor systems, when operated by staff with limited experience and training.
Fluvoxamine for Outpatient COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-Analysis
Authors: Lee Todd C. , Vigod Simone , Bortolussi-Courval Émilie , Hanula Ryan , Boulware David R. , Lenze Eric J. , Reiersen Angela M. , McDonald Emily G. 
Published: December 2021

AbstractImportanceWidely available and affordable options for the outpatient management of COVID-19 are needed, particularly therapies that prevent hospitalization.ObjectivePerform a meta-analysis of the available randomized clinical trial evidence for fluvoxamine in the outpatient management of COVID-19.Data SourcesWorld Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov.Study SelectionCompleted outpatient trials with available results which compared fluvoxamine to placebo.Data Extraction and SynthesisWe followed the PRISMA 2020 guidelines. We extracted study details in terms of inclusion criteria, trial demographics and the pre-specified outcome of all-cause hospitalization. Risk of bias was assessed by the Cochrane Risk of Bias 2 tool. We conducted a frequentist random effects meta-analysis, as well as two sensitivity analyses using a Bayesian random effects meta-analysis with different estimates of prior probability: a weakly neutral prior (50% chance of efficacy with 95% confidence interval for Risk Ratio [RR] between 0.5 and 2) and a moderately optimistic prior (85% chance of efficacy). We contextualized the results by estimating the probability of any effect (RR ≤1) and moderate effect (RR ≤0.9) on reducing hospitalization.Main Outcome(s) and Measure(s)All cause hospitalization.Results2196 participants were included from 3 identified trials. The risk ratios for hospitalization were 0.75 (95%CI, 0.57-0.97) for the frequentist analysis, 0.78 (95%CI 0.58-1.08) for the Bayesian weakly neutral prior, and 0.73 (95%CI, 0.53-1.01) for the Bayesian moderately optimistic prior. Depending on the scenario, the probability of any effect on hospitalization ranged from 94.1% to 98.3% and a moderate effect from 81.6% to 91.1%.Conclusions and RelevanceUnder a variety of assumptions, fluvoxamine shows a high probability of preventing hospitalization in outpatients with COVID-19. While ongoing randomized trials are important to evaluate alternative doses, explore the effectiveness in vaccinated patients, and provide further refinement to these estimates, fluvoxamine could be recommended as a treatment option, particularly in resource-limited settings or persons without access to SARS-CoV-2 monoclonal antibody therapy or direct antivirals.Key PointsQuestionDoes early administration of fluvoxamine prevent hospitalization in symptomatic adult outpatients with confirmed COVID-19?FindingsIn this meta-analysis with Bayesian sensitivity analyses that accounted for varying prior probabilities, there was a high probability (94.1% to 98.3%) that fluvoxamine reduces hospitalization with frequentist risk ratio of 0.75 (95%CI 0.57-0.97).MeaningFluvoxamine is a widely available and inexpensive option that prevents hospitalization in patients with early COVID-19 based on randomized controlled trial evidence to date.
A Computational Dissection of Spike protein of SARS-CoV-2 Omicron Variant
Authors: Rehman Zaira , Umair Massab , Ikram Aamer , Salman Muhammad , Haider Syed Adnan , Ammar Muhammad 
Published: December 2021

AbstractThe emergence of SARS-CoV-2 omicron variant in late November, 2021 and its rapid spread to different countries, warns the health authorities to take initiative to work on containing its spread. The omicron SARS-CoV-2 variant is unusual from the other variants of concerns reported earlier as it harbors many novel mutations in its genome particularly with >30 mutations in the spike glycoprotein alone. The current study investigated the variation in binding mechanism which it carries compared to the wild type. The study also explored the interaction profile of spike-omicron with human ACE2 receptor. The structure of omicron spike glycoprotein was determined though homology modeling. The interaction analysis was performed through docking using HADDOCK followed by binding affinity calculation. Finally, the comparison of interactions were performed among spike-ACE2 complex of wild type, delta and omicron variants. The interaction analysis has revealed the involvement of highly charged and polar residues (H505, Arg498, Ser446, Arg493, and Tyr501) in the interactions. The important novel interactions in the spike-ACE2-omicron complex was observed as S494:H34, S496:D38, R498:Y41, Y501:K353, and H505:R393 and R493:D38. Moreover, the binding affinity of spike-ACE2-omicron complex (−17.6Kcal/mol) is much higher than wild type-ACE2 (−13.2Kcal/mol) and delta-ACE2 complex (−13.3Kcal/mol). These results indicate that the involvement of polar and charged residues in the interactions with ACE2 may have an impact on increased transmissibility of omicron variant.
Mitochondria-mediated Maternal-fetal Interactions and Consequences of Mitochondrial Dysregulation Indicate New Roles for Mitochondria in Hypertensive Pregnancies
Authors: Ricci Contessa A. , Reid Danielle M. , Sun Jie , Santillan Donna A. , Santillan Mark K. , Goulopoulou Styliani , Phillips Nicole R. 
Published: December 2021

AbstractOxidative stress, placental mitochondrial morphological alterations, and impaired bioenergetics are associated with hypertensive disorders of pregnancy. Here we examined mitochondrial DNA mutational load in pregnant women with pregnancy-induced hypertension and reanalyzed publicly available high-throughput transcriptomic datasets from maternal and fetal tissues from normotensive and hypertensive pregnancies. Mitochondrial dysregulation was indicated by aberrant mitochondrial gene expression, and putative consequences were examined. Women with hypertensive pregnancy had elevated mitochondrial DNA mutational load. Maternal mitochondrial dysregulation in hypertensive pregnancies was associated with pathways involved in inflammation, cell death/survival, and placental development. In fetal tissues from hypertensive pregnancies, mitochondrial dysregulation was associated with increased extracellular vesicle production. Our study demonstrates mitochondria-mediated maternal-fetal interactions during healthy pregnancy and maternal mitochondrial dysregulation in hypertensive pregnancy development.
The Roles of APOBEC-mediated RNA Editing in SARS-CoV-2 Mutations, Replication and Fitness
Authors: Kim Kyumin , Calabrese Peter , Wang Shanshan , Qin Chao , Rao Youliang , Feng Pinghui , Chen Xiaojiang S. 
Published: December 2021

ABSTRACTDuring COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A, APOBEC1, and APOBEC3G can edit on specific sites of SARS-CoV-2 RNA to produce C-to-U mutations. However, SARS-CoV-2 replication and viral progeny production in Caco-2 cells are not inhibited by the expression of these APOBECs. Instead, expression of wild-type APOBEC3 greatly promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the random mutations, this study suggests the predictability of all possible viral genome mutations by these APOBECs based on the UC/AC motifs and the viral genomic RNA structure.One-sentence summaryEfficient Editing of SARS-CoV-2 genomic RNA by Host APOBEC deaminases and Its Potential Impacts on the Viral Replication and Emergence of New Strains in COVID-19 Pandemic
Short-term Ketogenic Diet Induces a Molecular Response that is Distinct from Dietary Protein Restriction
Authors: Kalafut Krystle C. , Mitchell Sarah J. , MacArthur Michael R. , Mitchell James R. 
Published: December 2021

AbstractThere is increasing interest in utilizing short-term dietary interventions in the contexts of cancer, surgical stress and metabolic disease. These short-term diets may be more feasible than extended interventions and may be designed to complement existing therapies. In particular, the high-fat, low-carbohydrate ketogenic diet (KD), traditionally used to treat epilepsy, has gained popularity as a potential strategy for weight loss and improved metabolic health. In mice, long-term KD improves insulin sensitivity and extends lifespan and healthspan. Dietary protein restriction (PR) causes increased energy expenditure, weight loss and improved glucose homeostasis. Since KD is inherently a low-protein diet (10% of calories from protein vs. 20% in control diet), here we evaluated the potential for mechanistic overlap between PR and KD via activation of a PR response. Mice were fed control, protein-free, or one of four ketogenic diets with varying protein content for 8 days. PF and KD diets both decreased body weight, fat mass, and liver weights, and reduced fasting glucose and insulin levels, compared to mice fed the control diet. However, PF and KD differed with respect to insulin tolerance and hepatic insulin sensitivity, which were increased in PF-fed mice and impaired in KD-fed mice relative to controls. Furthermore, contrary to the PF-fed mice, mice fed ketogenic diets containing at least 5% protein did not increase hepatic Fgf21 or brown adipose Ucp1 expression. Interestingly, mice fed KD lacking protein demonstrated greater elevations in hepatic Fgf21 than mice fed a low-fat PF diet. To further elucidate potential mechanistic differences between PF and KD diets and the interplay between dietary protein and carbohydrate restriction, we conducted RNA-seq analysis on livers from mice fed each of the six diets and identified distinct gene sets which respond to dietary protein content, dietary fat content, and ketogenesis. We conclude that KD with 10% of energy from protein does not induce a protein restriction response, and that the overlapping metabolic benefits of KD and PF diets occur via distinct underlying mechanisms.
A tRNA-acetylating toxin and detoxifying enzyme inMycobacterium tuberculosis
Authors: Tomasi Francesca G. , Hall Alexander M. J. , Schweber Jessica T. P. , Dulberger Charles L. , McGowen Kerry , Liu Qingyun , Fortune Sarah M. , Helaine Sophie , Rubin Eric J. 
Published: December 2021

AbstractToxin-antitoxin (TA) systems allow bacteria to adapt to changing environments without altering gene expression. Despite being overrepresented inMycobacterium tuberculosis(Mtb), their individual physiological roles remain elusive. We describe a TA system inMtbwhich we have named TacAT due to its homology to previously discovered systems in Salmonella. The toxin, TacT, blocks growth by acetylating glycyl-tRNAs and inhibiting translation. Its effects are reversed by the enzyme peptidyl tRNA hydrolase (Pth), which also cleaves peptidyl tRNAs that are prematurely released from stalled ribosomes. Pth is essential in most bacteria and thereby has been proposed as a promising drug target for complex pathogens likeMtb. Transposon sequencing data suggest that thetacAToperon is nonessential forMtbgrowthin vitro, and premature stop mutations in this TA system present in some clinical isolates suggest that it is also dispensablein vivo. We assessed whether TacT modulatespthessentiality inMtb, as drugs targeting Pth might be ineffective if TacAT is disrupted. We find thatpthessentiality is unaffected by the absence oftacAT. These results highlight a fundamental aspect of mycobacterial biology and indicate that Pth’s essential role hinges on its peptidyl-tRNA hydrolase activity. Our work underscores Pth’s potential as a viable target for new antibiotics.
Amino acid availability determines plant immune homeostasis in the rhizosphere microbiome
Authors: Liu Yang , Han Jiatong , Wilson Andrew J. , O’Sullivan Lucy , Haney Cara H. 
Published: December 2021

AbstractMicrobes possess conserved microbe-associated molecular patterns (MAMPs) such as flagellin that are recognized by plant receptors to induce immunity. Despite containing the same MAMPs as pathogens, commensals thrive in the plant rhizosphere microbiome indicating they must suppress or evade host immunity. The beneficial bacteria Pseudomonas capeferrum WCS358 can suppress Arabidopsis root immunity via acidification by secreting gluconic acid. While gluconic acid is sufficient to suppress immunity, we found that it is not necessary in a second beneficial strain Pseudomonas simiae WCS417, which produces more gluconic acid than WCS358. To uncover mechanisms that contribute to the suppression of Arabidopsis immunity, we performed a forward genetic screen in EMS-mutagenized P. simiae WCS417 using a flagellin-inducible CYP71A12pro:GUS reporter as an Arabidopsis immune readout. We identified a mutant that cannot suppress flagellin-elicited CYP71A12pro:GUS expression or acidify the rhizosphere. Next generation sequencing revealed a mutation in the catabolic site of an ornithine carbamoyltransferase argF, which is required for arginine biosynthesis. The mutant could be complemented by expression of argF from a plasmid, and a ΔargF mutant could not suppress immunity. Fungal pathogens can use alkalization through production of ammonia and glutamate, the arginine biosynthetic precursors, to promote their own growth and virulence. Therefore, we hypothesized that the biosynthesis of specific amino acids may be necessary to reduce levels of ammonia and glutamate to prevent rhizosphere alkalization and bacterial overgrowth. Genetically blocking arginine, glutamine, or proline biosynthesis, or by adding corresponding exogenous amino acids, resulted in rhizosphere alkalization. Interestingly, exogenous amino acids caused bacterial overgrowth in a gluconic acid-deficient mutants. Our findings show that bacterial amino acid biosynthesis contributes to acidification by preventing accumulation of glutamate precursors and the resulting alkalization. Collectively this work shows that by regulating nutrient availability, plants have the potential to regulate their immune homeostasis in the rhizosphere microbiome.
Platr4is an ESC-specific lncRNA that exhibits its function downstream on meso/endoderm lineage commitment
Authors: Hazra Rasmani , Brine Lily , Garcia Libia , Benz Brian , Chirathivat Napon , Shen Michael M. , Wilkinson John Erby , Lyons Scott K. , Spector David L. 
Published: December 2021

SummaryThe mammalian genome encodes thousands of long non-coding RNAs (lncRNAs) that are developmentally regulated and differentially expressed across tissues, suggesting possible roles in cellular differentiation. Despite this expression pattern, little is known about how lncRNAs influence lineage commitment at the molecular level. Here, we reveal that perturbation of an embryonic stem cell (ESC)-specific lncRNA,Pluripotency associated transcript 4(Platr4), in ESCs directly influences the downstream meso/endoderm differentiation program without affecting pluripotency. We further show thatPlatr4interacts with the TEA domain transcription factor 4 (Tead4) to regulate the expression of a downstream target gene crucial in the cardiac lineage program known as connective tissue growth factor (Ctgf). Importantly,Platr4knockout mice exhibit myocardial atrophy, valve mucinous degenration associated with reduced cardiac output and sudden heart failure. Together, our findings provide evidence thatPlatr4expression in undifferentiated ESCs is critical for downstream lineage differentiation, highlighting its importance in disease modeling and regenerative medicine.
Nonmuscle myosin IIA dynamically guides regulatory light chain phosphorylation and assembly of nonmuscle myosin IIB
Authors: Weißenbruch Kai , Fladung Magdalena , Grewe Justin , Baulesch Laurent , Schwarz Ulrich S. , Bastmeyer Martin 
Published: December 2021

AbstractNonmuscle myosin II minifilaments have emerged as central elements for force generation and mechanosensing by mammalian cells. Each minifilament can have a different composition and activity due to the existence of the three nonmuscle myosin II isoforms A, B and C and their respective phosphorylation pattern. We have used CRISPR/Cas9-based knockout cells, quantitative image analysis and mathematical modelling to dissect the dynamic processes that control the formation and activity of heterotypic minifilaments and found a strong asymmetry between isoforms A and B. Loss of NM IIA completely abrogates regulatory light chain phosphorylation and reduces the level of assembled NM IIB. Activated NM IIB preferentially co-assembles into pre-formed NM IIA minifilaments and stabilizes the filament in a force-dependent mechanism. NM IIC is only weakly coupled to these processes. We conclude that NM IIA and B play clearly defined complementary roles during assembly of functional minifilaments. NM IIA is responsible for the formation of nascent pioneer minifilaments. NM IIB incorporates into these and acts as a clutch that limits the force output to prevent excessive NM IIA activity. Together these two isoforms form a balanced system for regulated force generation.
Neuronal circuits integrating visual motion information in Drosophila
Authors: Shinomiya Kazunori , Nern Aljoscha , Meinertzhagen Ian A. , Plaza Stephen M. , Reiser Michael B. 
Published: December 2021

SummaryThe detection of visual motion enables sophisticated animal navigation, and studies in flies have provided profound insights into the cellular and circuit basis of this neural computation. The fly’s directionally selective T4 and T5 neurons respectively encode ON and OFF motion. Their axons terminate in one of four retinotopic layers in the lobula plate, where each layer encodes one of four cardinal directions of motion. While the input circuitry of the directionally selective neurons has been studied in detail, the synaptic connectivity of circuits integrating T4/T5 motion signals is largely unknown. Here we report a 3D electron microscopy reconstruction, wherein we comprehensively identified T4/T5’s synaptic partners in the lobula plate, revealing a diverse set of new cell types and attributing new connectivity patterns to known cell types. Our reconstruction explains how the ON and OFF motion pathways converge. T4 and T5 cells that project to the same layer, connect to common synaptic partners symmetrically, that is with similar weights, and also comprise a core motif together with bilayer interneurons, detailing the circuit basis for computing motion opponency. We discovered pathways that likely encode new directions of motion by integrating vertical and horizontal motion signals from upstream T4/T5 neurons. Finally, we identify substantial projections into the lobula, extending the known motion pathways and suggesting that directionally selective signals shape feature detection there. The circuits we describe enrich the anatomical basis for experimental and computations analyses of motion vision and bring us closer to understanding complete sensory-motor pathways.
Board level “Picture-Understanding-Action”: a new way of looking at quality
Authors: Martin Jennifer , Flynn Maureen A. , Khurshid Zuneera , Fitzsimons John J. , Moore Gemma , Crowley Philip 
Published: December 2021

PurposeThe purpose of this study is to present a quality improvement approach titled “Picture-Understanding-Action” used in Ireland to enhance the role of healthcare boards in the oversight of healthcare quality and its improvement.Design/methodology/approachThe novel and practical “Picture-Understanding-Action” approach was implemented using the Model for Improvement to iteratively introduce changes across three quality improvement projects. This approach outlines the concepts and activities used at each step to support planning and implementation of processes that allow a board to effectively achieve its role in overseeing and improving quality. This approach matured over three quality improvement projects.FindingsThe “Picture” included quantitative and qualitative aspects. The quantitative “Picture” consisted of a quality dashboard/profile of board selected outcome indicators representative of the health system using statistical process control (SPC) charts to focus discussion on real signals of change. The qualitative picture was based on the experience of people who use and work in health services which “people-ised” the numbers. Probing this “Picture” with collective grounding, curiosity and expert training/facilitation developed a shared “Understanding”. This led to “Action(s)” from board members to improve the “Picture” and “Understanding” (feedback action), to ask better questions and make better decisions and recommendations to the executive (feed-forward action). The Model for Improvement, Plan-Do-Study-Act cycles and a co-design approach in design and implementation were key to success.Originality/valueTo the authors’ knowledge, this is the first time a board has undertaken a quality improvement (QI) project to enhance its own processes. It addresses a gap in research by outlining actions that boards can take to improve their oversight of quality of care.