Miracle-dz/UniFAR-FTUs huggingface dataset:
Multicenter Prevalence Study Comparing Molecular and Toxin Assays for Clostridioides difficile Surveillance, Switzerland

Public health authorities in the United States and Europe recommend surveillance for Clostridioides difficile infections among hospitalized patients, but differing diagnostic algorithms can hamper comparisons between institutions and countries. We compared surveillance based on detection of C. difficile by PCR or enzyme immunoassay (EIA) in a nationwide C. difficile prevalence study in Switzerland. We included all routinely collected stool samples from hospitalized patients with diarrhea in 76 hospitals in Switzerland on 2 days, 1 in winter and 1 in summer, in 2015. EIA C. difficile detection rates were 6.4 cases/10,000 patient bed-days in winter and 5.7 cases/10,000 patient bed-days in summer. PCR detection rates were 11.4 cases/10,000 patient bed-days in winter and 7.1 cases/10,000 patient bed-days in summer. We found PCR used alone increased reported C. difficile prevalence rates by <80% compared with a 2-stage EIA-based algorithm.
On the Plausibility of Virtual Body Animation Features in Virtual Reality

We present two experiments to assess the relative impact of different levels of body animation fidelity on plausibility illusion (Psi). The first experiment presents a virtual character that is not controlled by the user (<inline-formula><tex-math notation="LaTeX">$n=13$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>13</mml:mn></mml:mrow></mml:math><inline-graphic xlink:href="galvandebarba-ieq1-3025175.gif"/></alternatives></inline-formula>), while the second experiment presents a user-controlled virtual avatar (<inline-formula><tex-math notation="LaTeX">$n=24$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>24</mml:mn></mml:mrow></mml:math><inline-graphic xlink:href="galvandebarba-ieq2-3025175.gif"/></alternatives></inline-formula>, all male). Psi concerns how realistic and coherent the events in a virtual environment look and feel and is part of Slater's proposition of two orthogonal components of presence in virtual reality (VR). In the experiments, the face, hands, upper and lower bodies of the character or self-avatar were manipulated to present different degrees of animation fidelity, such as no animation, procedural animation, and motion captured animation. Participants started the experiment experiencing the best animation configuration. Then, animation features were reduced to limit the amount of captured information made available to the system. Participants had to move from this basic animation configuration towards a more complete one, and declare when the avatar animation realism felt equivalent to the initial and most complete configuration, which could happen before all animation features were maxed out. Participants in the self-avatar experiment were also asked to rate how each animation feature affected their sense of control of the virtual body. We found that a virtual body with upper and lower body animated using eight tracked rigid bodies and inverse kinematics (IK) was often perceived as equivalent to a professional capture pipeline relying on 53 markers. Compared to what standard VR kits in the market are offering, i.e., a tracked headset and two hand controllers, we found that foot tracking, followed by mouth animation and finger tracking, were the features that added the most to the sense of control of a self-representing avatar. In addition, these features were often among the first to be improved in both experiments.
A Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation

Supplemental Digital Content is available in the text. Objectives: Supplementation of antithrombin might decrease the amount of heparin needed to achieve a given anticoagulation target during extracorporeal membrane oxygenation. However, exogenous antithrombin itself may increase the risk of bleeding. We conceived a study to evaluate the effect of antithrombin supplementation in adult patients requiring venovenous extracorporeal membrane oxygenation for respiratory failure on heparin dose, adequacy of anticoagulation, and safety. Design: Prospective randomized controlled trial. Setting: ICUs of two Italian referral extracorporeal membrane oxygenation centers. Patients: Adult patients requiring venovenous extracorporeal membrane oxygenation for severe respiratory failure and unfractionated heparin for systemic anticoagulation. Interventions: Before extracorporeal membrane oxygenation start, patients were randomized to either receive antithrombin concentrate to maintain a plasmatic level 80–120% (treatment) or not (control) during the extracorporeal membrane oxygenation course. Measurements and Main Results: The primary outcome was the total amount of heparin required to maintain activated partial thromboplastin time ratio 1.5–2. Secondary outcomes were anti-factor Xa, the incidence of hemorrhagic and thrombotic events, and the amount of blood products transfused. Twenty-four patients in the treatment group and 24 in the control group were included in the intention-to-treat analysis. Antithrombin was 109.5% (93.0–123.0%) in the treatment group and 84.0% (68.5–98.0%) in the control group (p = 0.001). Supplementation of antithrombin did not decrease heparin dose (13.5 international units/kg/hr [9.6–17.9 international units/kg/hr] vs 15.1 international units/kg/hr [10.7–18.3 international units/kg/hr] in the treatment and control group, respectively; p = 0.33) and anti-Factor Xa levels (0.4 international units/mL [0.3–0.5 international units/mL] vs 0.3 international units/mL [0.2–0.5 international units/mL] in the treatment group and control group respectively; p = 0.65). Bleeding, blood product transfusions, and thrombosis were not different in the two groups. Conclusions: Antithrombin supplementation may not decrease heparin requirement nor diminish the incidence of bleeding and/or thrombosis in adult patients on venovenous extracorporeal membrane oxygenation.
TRIM21 Is Targeted for Chaperone-Mediated Autophagy during Salmonella Typhimurium Infection

Key Points IFN-I–inducible TRIM21 is degraded via CMA. S. Typhimurium activates mTORC2/Akt to impair CMA resulting in TRIM21 accumulation. High levels of TRIM21 contribute to S. Typhimurium–induced macrophage death. Visual Abstract Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative bacterium that induces cell death of macrophages as a key virulence strategy. We have previously demonstrated that the induction of macrophage death is dependent on the host’s type I IFN (IFN-I) response. IFN-I signaling has been shown to induce tripartite motif (TRIM) 21, an E3 ubiquitin ligase with critical functions in autoimmune disease and antiviral immunity. However, the importance and regulation of TRIM21 during bacterial infection remains poorly understood. In this study, we investigated the role of TRIM21 upon S. Typhimurium infection of murine bone marrow–derived macrophages. Although Trim21 expression was induced in an IFN-I–dependent manner, we found that TRIM21 levels were mainly regulated posttranscriptionally. Following TLR4 activation, TRIM21 was transiently degraded via the lysosomal pathway by chaperone-mediated autophagy (CMA). However, S. Typhimurium–induced mTORC2 signaling led to phosphorylation of Akt at S473, which subsequently impaired TRIM21 degradation by attenuating CMA. Elevated TRIM21 levels promoted macrophage death associated with reduced transcription of NF erythroid 2–related factor 2 (NRF2)–dependent antioxidative genes. Collectively, our results identify IFN-I–inducible TRIM21 as a negative regulator of innate immune responses to S. Typhimurium and a previously unrecognized substrate of CMA. To our knowledge, this is the first study reporting that a member of the TRIM family is degraded by the lysosomal pathway.
AVALIAÇÃO IN VITRO DA EFICÁCIA DO CLORFENVINFÓS E DA CIALOTRINA SOBRE O Boophilus microplus, COLHIDOS EM BOVINOS DA BACIA LEITEIRA DA MICRORREGIÃO DE GOIÂNIA–GOIÁS

Para a avaliacao da eficacia do clorfenvinfos e da cialotrina no combate ao Boophilus microplus na bacia lei teira de Goiânia (GO), amostras de femeas ingurgitadas do carrapato, colhidas de bovinos em 22 propriedades rurais da regiao, foram analisadas pelo teste de imersao de teleoginas. Os principios ativos foram avaliados nas concentracoes normalmente indicadas pelos fabricantes para uso em bovinos como carrapaticida, ou seja, de 500 ppm para o clorfenvinfos e de 45 ppm para a cialotrina. Como resultado, o tratamento com o clorfenvinfos apresentou eficacia de 100%, determinada atraves da percentagem de inibicao da reproducao das teleoginas, enquanto a cialotrina apresentou eficacia insatisfatoria como carrapaticida para uso em programas de controle do carrapato, com uma percentagem de inibicao da reproducao no valor de 77,2%. PALAVRAS-CHAVES: Clorfenvinfos, cialotrina, Boophilus microplus, organofosforado, piretroide.
Phototherapy as a Rational Antioxidant Treatment Modality in COVID-19 Management; New Concept and Strategic Approach: Critical Review

The COVID-19 pandemic has taken the entire globe by storm. The pathogenesis of this virus has shown a cytokine storm release, which contributes to critical or severe multi-organ failure. Currently the ultimate treatment is palliative; however, many modalities have been introduced with effective or minimal outcomes. Meanwhile, enormous efforts are ongoing to produce safe vaccines and therapies. Phototherapy has a wide range of clinical applications against various maladies. This necessitates the exploration of the role of phototherapy, if any, for COVID-19. This critical review was conducted to understand COVID-19 disease and highlights the prevailing facts that link phototherapy utilisation as a potential treatment modality for SARS-CoV-2 viral infection. The results demonstrated phototherapy’s efficacy in regulating cytokines and inflammatory mediators, increasing angiogenesis and enhancing healing in chronic pulmonary inflammatory diseases. In conclusion, this review answered the following research question. Which molecular and cellular mechanisms of action of phototherapy have demonstrated great potential in enhancing the immune response and reducing host–viral interaction in COVID-19 patients? Therefore, phototherapy is a promising treatment modality, which needs to be validated further for COVID-19 by robust and rigorous randomised, double blind, placebo-controlled, clinical trials to evaluate its impartial outcomes and safety.
V(DD)J recombination is an important and evolutionarily conserved mechanism for generating antibodies with unusually long CDR3s

The V(DD)J recombination is currently viewed as an aberrant and inconsequential variant of the canonical V(D)J recombination. Moreover, since the classical 12/23 rule for the V(D)J recombination fails to explain the V(DD)J recombination, the molecular mechanism of tandem D-D fusions has remained unknown since they were discovered three decades ago. Revealing this mechanism is a biomedically important goal since tandem fusions contribute to broadly neutralizing antibodies with ultralong CDR3s. We reveal previously overlooked cryptic nonamers in the recombination signal sequences of human IGHD genes and demonstrate that these nonamers explain the vast majority of tandem fusions in human repertoires. We further reveal large clonal lineages formed by tandem fusions in antigen-stimulated immunosequencing data sets, suggesting that such data sets contain many more tandem fusions than previously thought and that about a quarter of large clonal lineages with unusually long CDR3s are generated through tandem fusions. Finally, we developed the SEARCH-D algorithm for identifying D genes in mammalian genomes and applied it to the recently completed Vertebrate Genomes Project assemblies, nearly doubling the number of mammalian species with known D genes. Our analysis revealed cryptic nonamers in RSSs of many mammalian genomes, thus demonstrating that the V(DD)J recombination is not a “bug” but an important feature preserved throughout mammalian evolution.
Summarizing causal differences in survival curves in the presence of unmeasured confounding

Abstract Proportional hazard Cox regression models are frequently used to analyze the impact of different factors on time-to-event outcomes. Most practitioners are familiar with and interpret research results in terms of hazard ratios. Direct differences in survival curves are, however, easier to understand for the general population of users and to visualize graphically. Analyzing the difference among the survival curves for the population at risk allows easy interpretation of the impact of a therapy over the follow-up. When the available information is obtained from observational studies, the observed results are potentially subject to a plethora of measured and unmeasured confounders. Although there are procedures to adjust survival curves for measured covariates, the case of unmeasured confounders has not yet been considered in the literature. In this article we provide a semi-parametric procedure for adjusting survival curves for measured and unmeasured confounders. The method augments our novel instrumental variable estimation method for survival time data in the presence of unmeasured confounding with a procedure for mapping estimates onto the survival probability and the expected survival time scales.
Pain sensitivity and the primary sensorimotor cortices: a multimodal neuroimaging study.

The primary somatosensory cortex (SI) is a critical part of the neural substrate underlying interindividual differences in pain sensitivity. Here, we investigated whether resting-state functional connectivity, grey matter density (GMD) and GABA and Glx (glutamate and glutamine) levels of the sensorimotor cortices were related to pain thresholds and whether such imaging measures could predict high and low pain sensitivity. Functional, structural and spectroscopic magnetic resonance data was obtained from 48 healthy participants together with pain thresholds of the right index finger. Left and right sensorimotor networks (SMN) were extracted by means of independent component analysis and GMD was measured within the combined SMN by means of voxel-based morphometry. Spectroscopic data was acquired from the bilateral sensorimotor cortices. Within the left SMN, functional connectivity to the right SI correlated positively with pain thresholds. Additionally, GMD in the left SI and the GABA laterality index correlated positively with pain thresholds. A positive correlation was also found between the GABA laterality index and the left SMN connectivity to the right SI. Finally, the above mentioned functional connectivity and GMD measures could correctly predict high and low pain sensitivity in 83.7% of the study population. In summary, we showed that interindividual differences in pain sensitivity was related to the resting-state functional connectivity, interhemispheric GABA tone and GMD of the sensorimotor cortices. Furthermore, high and low pain sensitivity could be predicted with high accuracy using imaging measures from the primary sensorimotor cortices.
Transcription factor expression defines subclasses of developing projection neurons highly similar to single-cell RNA-seq subtypes

Significance Neurons of the cerebral cortex arise from a common progenitor pool that progressively generates different cell subtypes with distinct features, including deep layer (DL) and upper layer (UL) projection neurons. Several transcription factors (TFs) are known to specify whether a progenitor cell will become UL or DL; however, it is still unknown which upstream and downstream factors contribute to this fate decision. Here, we deeply characterize differential gene expression and chromatin accessibility of UL and DL neurons. We identify TFs that are highly differentially expressed and densely regulated and find that UL neurons retain the transcriptomic signature of their mother cells. We also discover a previously unknown role for the TF Myt1l in cell fate specification. We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than 50 unique types of mature cortical projection neurons defined by their distinct gene-expression profiles. Moreover, exactly how and when neurons diversify their function during development is unknown. Here we relate gene expression and chromatin accessibility of two subclasses of projection neurons with divergent morphological and functional features as they develop in the mouse brain between embryonic day 13 and postnatal day 5 in order to identify transcriptional networks that diversify neuron cell fate. We compare these gene-expression profiles with published profiles of single cells isolated from similar populations and establish that layer-defined cell classes encompass cell subtypes and developmental trajectories identified using single-cell sequencing. Given the depth of our sequencing, we identify groups of transcription factors with particularly dense subclass-specific regulation and subclass-enriched transcription factor binding motifs. We also describe transcription factor-adjacent long noncoding RNAs that define each subclass and validate the function of Myt1l in balancing the ratio of the two subclasses in vitro. Our multidimensional approach supports an evolving model of progressive restriction of cell fate competence through inherited transcriptional identities.
Impact of low‐intensity pulsed ultrasound on the growth of Schizochytrium sp. for omega‐3 production

Schizochytrium sp. is a microalga that is known for its high content of oils or lipids. It has a high percentage of polyunsaturated fatty acids in the accumulated oil, especially docosahexaenoic acid (DHA). DHA is an important additive for the human diet. Large‐scale production of Schizochytrium sp. can serve as an alternative source of DHA for humans as well as for fish feed, decreasing the burden on aqua systems. Therefore, research on improving the productivity of Schizochytrium attracts a lot of attention. We studied the potential of using low‐intensity pulsed ultrasound (LIPUS) in the growth cycle of Schizochytrium sp. in shake flasks. Different intensities and treatment durations were tested. A positive effect of LIPUS on biomass accumulation was observed in the Schizochytrium sp. culture. Specifically, LIPUS stimulation at the ultrasound intensity of 400 mW/cm2 with 20 min per treatment 10 times a day with equal intervals of 2.4 h between the treatments was found to enhance the growth of Schizochytrium biomass most effectively (by up to 20%). Due to the nature of cell division in Schizochytrium sp. which occurs via zoospore formation, LIPUS stimulation was inefficient if applied continuously during all 5 days of the growth cycle. Using microscopy, we studied the interval between zoospore formation in the culture and selected the optimal LIPUS application days (Days 0–1 and Days 4–5 of the 5‐day growth cycle). Microscopic images have also shown that LIPUS stimulation enhances zoospore formation in Schizochytrium sp. , leading to more active cell division in the culture. This study shows that LIPUS can serve as an additional tool for cost‐efficiency improvement in the large‐scale production of Schizochytrium as a sustainable and environmentally friendly source of omega‐3 (DHA).
Orthopaedic Injuries Associated With Cell Phone Use Resulting in Emergency Department Visits: A 20-Year Analysis

Introduction: Cell phones are an integral part of daily life but are distractors that can contribute to injury. The present study uses a large national emergency department (ED) database to evaluate the frequency, anatomic location, and type of injuries associated with cell phone use. We hypothesize that orthopaedic injuries related to cell phone use have increased over time and affect certain body parts and age groups more than others. Methods: The 1999 to 2018 Nation Electronic Injury Surveillance System was queried for cell phone-related injuries leading to ED visits (injuries to the head or face or involving a landline were excluded). Demographics, type of orthopaedic injury, and body part injured were tabulated, and injuries were then classified over time as direct mechanical or cell phone use-associated, as well as related to texting compared with talking. Results: A weighted national total of 44,599 injuries met inclusion criteria. A marked increase was noted in the incidence of cell phone use-associated injuries over the time (2,900%). Injuries occurred in persons with mean ± standard deviation age of 36.6 ± 19.9 years old, predominantly in women (60.6%), at home (32.8%) or on the street (22.4%), and while walking (31.6%) or driving (18.16%). The distribution of orthopaedic injuries was defined and occurred most frequently in the neck, lower torso/hip, and ankle. The most common types of injuries were sprain/strain (56.8%) and fracture (32.6%). The proportion of fracture injury types was significantly greater in adults aged greater than 65 (P < 0.001). The proportion of injuries related to texting on a cell phone was greatest in the 13- to 29-year-old age group and declined as age increased. Discussion: Orthopaedic injures related to cell phone use resulting in ED visits have markedly increased over time. The distribution and characteristics of such injuries can be used in targeted public health education and policy development.
Fatigue-Induced Hip Abductor Weakness and Changes in Biomechanical Risk Factors for Running-Related Injuries.

CONTEXT Despite overlap between hip abductor (HABD) weakness and fatigue-induced changes in running, the interaction of these theorized contributors to running injuries has been underevaluated. OBJECTIVE To assess the effects of a fatiguing run on HABD torque and evaluate the correlation between HABD torque and previously identified running-related injury pathomechanics while participants were rested or fatigued. DESIGN Crossover study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS A total of 38 healthy, physically active males (age = 21.61 ± 4.02 years, height = 1.78 ± 0.08 m, body mass = 76.00 ± 12.39 kg). INTERVENTION(S) Data collection consisted of rested-state collection, a fatiguing treadmill-run protocol, and fatigued-state collection. For theHABD measures, side-lying handheld-dynamometer isometric tests were performed and converted to torque using femur length. For the gait analysis, kinematic (240 Hz) and kinetic (960 Hz) running (4.0 m/s) data were collected for 3 trials. The fatigue protocol involved a graded exercise test and 80% o2max run to exhaustion. Immediately after the run, fatigued-state measures were obtained. MAIN OUTCOME MEASURE(S) Variables of interest were HABD torque and peak angles, velocities, and moments for hip and knee adduction and internal rotation. Differences between conditions were compared using paired t tests. Pearson correlation coefficients were calculated to evaluate relationships between HABD torque and biomechanical variables. RESULTS Fatigue decreased HABD torque and increased hip-adduction angle, knee-adduction velocity, and hip and knee internal-rotation velocities and moments (all P values < .05). In the rested state, HABD torque was correlated with hip-adduction velocity (r = -0.322, P = .049). In the fatigued state, HABD torque was correlated with hip-adduction velocity (r = -0.393, P = .015), hip internal-rotation velocity (r = -0.410, P = .01), and knee-adduction angle (r = 0.385, P = .017) and velocity (r = -0.378, P = .019). CONCLUSIONS Changes in joint velocities due to fatigue and correlations between HABD torque and hip- and knee-joint velocities highlight the need to consider not only the quantity of HABD strength but also the rate of eccentric control of HABDs.