bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change in incidence of cardiovascular diseases during the covid-19 pandemic and vaccination campaign: data from the nationwide French hospital discharge database
Authors: Boudemaghe Thierry , Léger Lucas , Perez-Martin Antonia , Suehs Carey M. , Gris Jean-Christophe 
Published: August 2022

AbstractImportanceThe covid-19 pandemic induced a severe disruption in hospital activity. Cardiovascular illnesses represent a major health burden in industrialised countries and are second in terms of hospital bed occupancy in France. Considering the resources mobilized and the public health issue involved, it is necessary to study the impact of the pandemic on their incidences.ObjectiveTo monitor changes in the incidence of cardiovascular diseases during years 2020 and 2021 compared to 2019.DesignNationwide population-based cohort study.SettingFrench hospital discharge database between January 1 and October 30 in 2019, 2020 and 2021.ParticipantsNew patients hospitalized for vascular disease in Metropolitan France. A patient was considered as incident for a morbidity if not present in the database in the previous two years with the morbidity as the primary reason for admission.Main outcome measuresStandardized hospitalization incidence difference and relative risk of hospitalization for a series of targeted vascular diseases from January 1 to October 31 for 2021 versus 2019. Demographic data from 2019 were used for the standardization of patient counts by 10-year age strata for each morbidity and year.ResultsWhile the relative risk of hospitalization in 2021 versus 2019 decreased for almost all diseases, an increase in relative risk was observed for myocarditis (28.0%) and pulmonary embolisms (10.0%).In 2020, the relative risk of hospitalization versus 2019 also decreased for almost all diseases but remained stable for myocarditis and increased by 4.0% for pulmonary embolisms.In 2021, the difference in myocarditis coincided with the vaccination campaign in young individuals. The increase in pulmonary embolism occurred predominantly in older women, with a weak but still noticeable coincidence with the vaccination campaign.ConclusionsThe deficit in care for patients with acute atherothrombotic manifestations in 2021 and 2020 shows a failure by the French healthcare system to rectify the deficiencies of 2020. The risk excess for pulmonary embolism cannot be entirely explained by covid-19 or by vaccine-induced immune thrombotic thrombocytopenia. This warrants investigating the risk/efficacy ratio of a temporary thromboprophylaxis in individuals at risk before vaccine.
A Multicenter Randomized Comparison of High-Intensity Interval Training and Moderate-Intensity Exercise to Recover Walking Post-Stroke: Results of the HIT-Stroke Trial
Authors: Boyne Pierce , Billinger Sandra A. , Reisman Darcy S. , Awosika Oluwole O. , Buckley Sofia , Burson Jamiah , Carl Daniel , DeLange Matthew , Doren Sarah , Earnest Melinda , Gerson Myron , Henry Madison , Horning Alli , Khoury Jane , Kissela Brett , Laughlin Abigail , McCartney Kiersten , McQuaid Thomas , Miller Allison , Moores Alexandra , Palmer Jacqueline A. , Sucharew Heidi , Thompson Elizabeth , Wagner Erin , Ward Jaimie , Wasik Emily , Whitaker Alicen A. , Wright Henry , Dunning Kari 
Published: August 2022

ABSTRACTIntroductionFor walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. This trial aimed to determine the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8 or 12 weeks) needed to maximize immediate improvement in walking capacity in chronic stroke.MethodsPersons with chronic post-stroke gait dysfunction at three centers were randomized to high-intensity interval training (HIT) or moderate intensity aerobic training (MAT), each involving 45 minutes of treadmill and overground walking exercise with a physical therapist, 3 times per week for 12 weeks. The HIT protocol used repeated 30 second bursts of walking at maximum safe speed, alternated with 30-60 second recovery periods, targeting an average aerobic intensity above 60% heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40 ± 5% HRR, progressing by 5% HRR every 2 weeks, up to 60% HRR as tolerated. Blinded assessment at baseline and after 4, 8 and 12 weeks of training included the 6-minute walk test (6MWT) as the primary measure of walking capacity.ResultsRandomized participants (N=55) attended 1,675 (85%) of 1,980 planned treatment sessions and 197 (90%) of 220 planned testing sessions. No serious adverse events related to study procedures occurred. Compared with MAT, HIT involved significantly higher training speeds (161% vs 96% baseline fastest 10-meter speed, p<0.0001) and mean aerobic intensity (61% vs 46% HRR, p<0.0001) across treatment visits. There was no significant between-group difference in 6MWT changes after 4 weeks of training (HIT +27 meters [95% CI: 6-48], MAT +12 meters [-9-33], p=0.28), but randomization to HIT resulted in significantly greater gains than MAT after 8 weeks (+58 [39-76] vs +29 [9-48] meters, p=0.02) and 12 weeks (+71 [49-94] vs +27 [3-50] meters, p=0.005) of training. HIT also showed significantly greater improvements than MAT on some measures of gait speed, fatigue and exercise capacity.DiscussionThese findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In chronic stroke, vigorous walking exercise can produce significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks are needed to maximize immediate gains.
Prognostic early snapshot stratification of autism based on adaptive functioning
Authors: Mandelli Veronica , Landi Isotta , Busuoli Elena Maria , Courchesne Eric , Pierce Karen , Lombardo Michael V. 
Published: August 2022

AbstractA major goal of precision medicine is to predict prognosis based on individualized information at the earliest possible points in development. Using early snapshots of adaptive functioning and unsupervised data-driven discovery methods, we uncover highly stable early autism subtypes that yield information relevant to later prognosis. Data from the National Institute of Mental Health Data Archive (NDA) (n=1,098) was used to uncover 3 early subtypes (<72 months) that generalize with 97% accuracy. Outcome data from NDA (n=2,561; mean age, 13 years) also reproducibly clusters into 3 subtypes with 99% generalization accuracy. Early snapshot subtypes predict developmental trajectories in non-verbal cognitive, language, and motor domains and are predictive of membership in different adaptive functioning outcome subtypes. Robust and prognosis-relevant subtyping of autism based on early snapshots of adaptive functioning may aid future clinical and research work (e.g., clinical trials, intervention), via prediction of these subtypes with our open web-based app (https://landiit.shinyapps.io/vineland_statification_proj/).
Clarifying the role of Cortico-Cortical and Amygdalo-Cortical brain dysconnectivity associated with Conduct Problems
Authors: Dugré Jules R. , Potvin Stéphane 
Published: August 2022

ABSTRACTBackgroundRecent evidence suggests that adolescents exhibiting conduct problems (CP) may have disrupted brain connectivity at rest. However, these studies are generally characterized by small sample sizes and differ in terms of neuroimaging methodologies and chosen psychometric scales to assess CP. In parallel, evidence from genetic and structural imaging studies suggests that aggregating measures may increase generalizability and reproducibility in results. Our primary aim was to identify deficits in functional brain connectivity that were replicable across two distinct measures of CP.MethodsIn a large sample of adolescents (n=1416), we assessed the relationship between resting-state functional connectome (including the amygdala bilaterally) and two distinct measures of conduct problems. Positive and negative brain connectivity measures were derived from the intersection of both scales. The utility of these aggregated scores was assessed in comparison with variants of psychopathy and clinical diagnoses.ResultsPsychometrics scales assessing CP were significantly related to 231 & 269 disrupted functional connectivity. Only 21 brain connectivity were shared between the two scales (10 positively and 11 negatively associated with CP. These brain connectivity scores differed between adolescents with variants of psychopathy and healthy controls and were specifically associated with disruptive disorders, but not other pediatric psychiatric disorders.ConclusionThe current study provides the evidence that different measures of CP may yield distinct results. Nonetheless, it also highlights that functional brain connectivity that intersected between the two scales may be robust and reliable neurobiological markers of severity of CP. Finally, brain connectivity scores may be generalizable to variants of psychopathy and specific to disruptive disorders.
How talin allosterically activates vinculin
Authors: Franz Florian , Tapia-Rojo Rafael , Winograd-Katz Sabina , Boujemaa-Paterski Rajaa , Li Wenhong , Unger Tamar , Albeck Shira , Aponte-Santamaria Camilo , Garcia-Manyes Sergi , Medalia Ohad , Geiger Benjamin , Gräter Frauke 
Published: August 2022

AbstractThe talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces and regulate one another remains unclear. By combining single molecule magnetic tweezer experiments, Molecular Dynamics simulations, actin bundling assays, and adhesion assembly experiments in live cells, we here discover a two-ways allosteric network within vinculin as a regulator of the talin-vinculin interaction. We directly observe a maturation process of vinculin upon talin binding which reinforces the binding to talin at a rate of 0.03 s−1. This allosteric transition can compete with force-induced dissociation of vinculin from talin only at 7-10 pN. Mimicking the allosteric activation by mutation yields a vinculin molecule that bundles actin and localizes to focal adhesions in a force-independent manner. Hence, the allosteric switch confines talin-vinculin interactions and focal adhesion build-up to intermediate force levels. The ‘allosteric vinculin mutant’ is a valuable molecular tool to further dissect the mechanical and biochemical signalling circuits at focal adhesions and elsewhere.
A conserved isoleucine in the binding pocket of RIG-I controls immune tolerance to mitochondrial RNA
Authors: de Regt Ann Kristin , Anand Kanchan , Ciupka Katrin , Gatterdam Karl , Putschli Bastian , Fusshöller David , Hilbig Daniel , Kirchhoff Alexander , Hunkler Charlotte , Wolter Steven , Grünewald Agathe , Schuberth-Wagner Christine , Ludwig Janos , Paeschke Katrin , Bartok Eva , Zillinger Thomas , Hagelueken Gregor , Hartmann Gunther , Geyer Matthias , Schlee Martin 
Published: August 2022

SUMMARYRIG-I is a cytosolic receptor of viral RNA essential for the immune response to numerous RNA viruses. Accordingly, RIG-I must sensitively detect viral RNA yet tolerate abundant self-RNA species. The basic binding cleft and an aromatic amino acid of the RIG-I C-terminal domain(CTD) mediate high-affinity recognition of 5’triphosphorylated and 5’base-paired RNA(dsRNA). Here, we found that, while 5’unmodified hydroxyl(OH)-dsRNA demonstrated residual activation potential, 5’-monophosphate(5’p)-termini, present on most cellular RNAs, prevented RIG-I activation. Determination of CTD/dsRNA co-crystal structures and mutant activation studies revealed that the evolutionarily conserved I875 within the CTD sterically inhibits 5’p-dsRNA binding. RIG-I(I875A) was activated by both synthetic 5’p-dsRNA and endogenous long dsRNA within the polyA-rich fraction of total cellular RNA. RIG-I(I875A) specifically interacted with a long, highly structured, polyA-bearing, non-coding mitochondrial(mt) RNA, and depletion of mtRNA from total RNA abolished its activation. Altogether, our study demonstrates that avoidance of 5’p-RNA recognition is crucial to preventing mtRNA-triggered RIG-I-mediated autoinflammation.
A novel in silico method employs chemical and protein similarity algorithms to accurately identify chemical transformations in the human gut microbiome
Authors: Bustion Annamarie , Agrawal Ayushi , Turnbaugh Peter J. , Pollard Katherine S. 
Published: August 2022

AbstractBacteria within the gut microbiota possess the ability to metabolize a wide array of human drugs, foods, and toxins, but the responsible enzymes for these chemical events remain largely uncharacterized due to the time consuming nature of current experimental approaches. Attempts have been made in the past to computationally predict which bacterial species and enzymes are responsible for chemical transformations in the gut environment, but with low accuracy due to minimal chemical representation and sequence similarity search schemes. Here, we present an in silico approach that employs chemical and protein Similarity algorithms that Identify MicrobioMe Enzymatic Reactions (SIMMER). We show that SIMMER predicts the chemistry and responsible species and enzymes for a queried reaction with high accuracy, unlike previous methods. We demonstrate SIMMER use cases in the context of drug metabolism by predicting previously uncharacterized enzymes for 88 drug transformations known to occur in the human gut. Bacterial species containing these enzymes are enriched within human donor stool samples that metabolize the query compound. After demonstrating its utility and accuracy, we chose to make SIMMER available as both a command-line and web tool, with flexible input and output options for determining chemical transformations within the human gut. We present SIMMER as a computational addition to the microbiome researcher’s toolbox, enabling them to make informed hypotheses before embarking on the lengthy laboratory experiments required to characterize novel bacterial enzymes that can alter human ingested compounds.
Global convergence of dominance and neglect in flying insect diversity
Authors: Srivathsan Amrita , Ang Yuchen , Heraty John M. , Hwang Wei Song , Jusoh Wan F.A. , Kutty Sujatha Narayanan , Puniamoorthy Jayanthi , Yeo Darren , Roslin Tomas , Meier Rudolf 
Published: August 2022

ABSTRACTMost of arthropod biodiversity is unknown to science. For this reason, it has been unclear whether insect communities around the world are dominated by the same or different taxa. This question can be answered through standardized sampling of biodiversity followed by estimation of species diversity and community composition with DNA sequences. This approach is here applied to flying insects sampled by 39 Malaise traps placed in five biogeographic regions, eight countries, and numerous habitats (>220,000 specimens belonging to >25,000 species in 463 families). Unexpectedly, we find that 20 insect families account for >50% of local species diversity regardless of continent, climatic region, and habitat type. These consistent differences in family-level dominance explain two-thirds of variation in community composition despite massive levels of species turnover, with most species (>97%) in the top 20 families encountered at a single site only. Alarmingly, the same families that dominate global insect diversity also suffer from extreme taxonomic neglect with little signs of increasing activities in recent years. Tackling the biodiversity of these “dark taxa” thereby emerges as an urgent priority because the arthropod groups comprising most of the global flying insect diversity are particularly poorly known.
Concomitant immunity to M. tuberculosis infection
Authors: Joslyn Louis R. , Flynn JoAnne L. , Kirschner Denise E. , Linderman Jennifer J. 
Published: August 2022

AbstractSome persistent infections provide a level of immunity that protects against reinfection with the same pathogen, a process referred to as concomitant immunity. To explore the phenomenon of concomitant immunity duringMycobacterium tuberculosisinfection, we utilizedHostSim, a previously published virtual host model of the immune response following Mtb infection. By simulating reinfection scenarios and comparing with data from non-human primate studies, we predict that the durability of a concomitant immune response against Mtb is intrinsically tied to levels of tissue resident memory T cells (Trms) during primary infection, with a secondary but important role for circulating Mtb-specific T cells. Further, we compareHostSimreinfection experiments to observational TB studies from the pre-antibiotic era to predict that the upper bound of the lifespan of resident memory T cells in human lung tissue is likely 2-3 years. To the authors’ knowledge, this is the first estimate of resident memory T-cell lifespan in humans. Our findings are a first step towards demonstrating the important role of Trms in preventing disease and suggest that the induction of lung Trms is likely critical for vaccine success.
TP53-dependent CRISPR-Cas9 sex bias across cancer types affects MYC, PIK3CA, and SUV39H1 mediated by factors including SOX9, FOXO4, and PRC1
Authors: Guo Mengbiao , Xiong Yuanyan 
Published: August 2022

AbstractCRISPR-Cas9 system has emerged as the dominant technology for gene editing and has great potential for large-scale clinical applications. One major concern is its off-target issue and other potential side effects after the introduction of exogenous CRISPR-Cas9 into cells. Several previous studies investigated CRISPR-Cas9 interactions with p53 mainly in non-transformed cells, such as RPE1 (retinal pigmented epithelium cells) and H9 (embryonic stem cells [ESC]). Recently, it has been reported that Cas9 alone can activate the p53 pathway and select for p53-inactivating mutations after studying hundreds of cancer cell lines. We reanalyzed the reported data of Cas9-associated p53-inactivating mutations and observed large significant sex difference when comparing Cas9 activities in p53-wildtype and p53-mutant cell lines. To expand the impact of this finding, we further examined all protein-coding genes screening by the CRISPR-Cas9 system in a large-scale dataset from the DepMap project. We highlight the p53 status-dependent sex bias of CRISPR-Cas9 effect across cancer cell types (genes includingMYC, PIK3CA, KAT2B, KDM4E, SUV39H1, FANCB, TLR7, and APC2) and potential mechanisms (mediated by transcriptional factors including SOX9, FOXO4, LEF1, and RYBP) underlying this phenomenon, which suggest that the p53-dependent sex bias effect may need to be considered in future clinical applications, especially in cancer, when using this genome editing system.
A long interval between priming and boosting SARS-CoV-2 mRNA vaccine doses enhances B cell responses with limited impact on T cell immunity
Authors: Nicolas Alexandre , Sannier Gérémy , Dubé Mathieu , Nayrac Manon , Painter Mark M. , Goel Rishi R. , Laporte Mélanie , Medjahed Halima , Williams Justine C. , Brassard Nathalie , Niessl Julia , Gokool Laurie , Morrisseau Chantal , Arlotto Pascale , Tremblay Cécile , Martel-Laferrière Valérie , Finzi Andrés , Greenplate Allison R. , Wherry E. John , Kaufmann Daniel E. 
Published: August 2022

SUMMARYSpacing the first two doses of SARS-CoV-2 mRNA vaccines beyond 3-4 weeks raised initial concerns about vaccine efficacy. While studies have since shown that long-interval regimens induce robust antibody responses, their impact on B and T cell immunity is poorly known. Here, we compare in SARS-CoV-2 naïve donors B and T cell responses to two mRNA vaccine doses administered 3-4 versus 16 weeks apart. After boost, the longer interval results in higher magnitude and a more mature phenotype of RBD-specific B cells. While the two geographically distinct cohorts present quantitative and qualitative differences in T cell responses at baseline and after priming, the second dose led to convergent features with overall similar magnitude, phenotype and function of CD4+ and CD8+ T cell responses at post-boost memory timepoints. Therefore, compared to standard regimens, a 16-week interval has a favorable impact on the B cell compartment but minimally affects T cell immunity.
Large deviations for the stochastic functional integral equation with nonlocal condition
Authors: Shruthi Gopal , Suvinthra Murugan 
Published: August 2022

PurposeThe purpose of this paper is to study large deviations for the solution processes of a stochastic equation incorporated with the effects of nonlocal condition.Design/methodology/approachA weak convergence approach is adopted to establish the Laplace principle, which is same as the large deviation principle in a Polish space. The sufficient condition for any family of solutions to satisfy the Laplace principle formulated by Budhiraja and Dupuis is used in this work.FindingsFreidlin–Wentzell type large deviation principle holds good for the solution processes of the stochastic functional integral equation with nonlocal condition.Originality/valueThe asymptotic exponential decay rate of the solution processes of the considered equation towards its deterministic counterpart can be estimated using the established results.
Critical plane-based fatigue life model under multiaxial random loading
Authors: Wang Jie , Liu Jianhui , Hua Feilon , He Yingbao , Wang Xuexue 
Published: August 2022

PurposeEngineering components/structures are usually subjected to complex and variable loads, which result in random multiaxial stress/strain states. However, fatigue analysis methods under constant loads cannot be directly applied to fatigue life prediction analysis under random loads. Therefore, the purpose of this study is how to effectively evaluate fatigue life under multiaxial random loading.Design/methodology/approachFirst, the average phase difference is characterized as the ratio of the number of shear strain cycles to the number of normal strain cycles, and the new non-proportional additional hardening factor is proposed. Then, the determined random typical load spectrum is processed into a simple variable amplitude load spectrum, and the damage in each plane is calculated according to the multiaxial fatigue life prediction model and Miner theory. Meanwhile, the cumulative damage can be calculated separately by projection method. Finally, the maximum projected cumulative damage plane is defined as the critical plane of multiaxial random fatigue.FindingsThe fatigue life prediction capability of the method is verified based on test data of TC4 titanium alloy under random multiaxial loading. Most of the predicting results are within double scatter bands.Originality/valueThe objective of this study is to provide a reference for the determination of critical plane and non-proportional additional hardening factor under multiaxial random loading, and to promote the development of multiaxial fatigue from experimental studies to practical engineering applications.