bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the quality of in-patient neonatal routine data as a pre-requisite for monitoring and improving quality of care at scale: A multi-site retrospective cohort study in Kenyan hospitals
Authors: Tuti Timothy , Aluvaala Jalemba , Chelangat Daisy , Mbevi George , Wainaina John , Mumelo Livingstone , Wairoto Kefa , Mochache Dolphine , Irimu Grace , Maina Michuki , English Mike 
Published: June 2022

AbstractObjectivesThe objectives of this study were to (1) determine if membership of a clinical information network (CIN) was associated with an improvement in the quality of documentation of in-patient neonatal care provided over time, and (2) characterise accuracy of prescribing for basic treatments provided to neonatal in-patients if data are adequate.Design and SettingsThis was a retrospective cohort study involving all children aged ≤28 days admitted to New-Born Units (NBUs) between January 2018 and December 2021 in 20 government hospitals with an interquartile range of annual NBU inpatient admissions between 550 and 1640 in Kenya. These hospitals participated in routine audit and feedback processes on quality of documentation and care over the study period.OutcomesThe study’s outcomes were the number of patients as a proportion of all eligible patients with (1) complete domain-specific documentation scores, and (2) accurate domain-specific treatment prescription scores at admission.Findings80060 NBU admissions were eligible for inclusion. Upon joining the CIN, documentation scores in the monitoring (vital signs), other physical examination and bedside testing, discharge information, and maternal history domains demonstrated a statistically significant month-to-month relative improvement in number of patients with complete documentation of 7.6%, 2.9%, 2.4%, and 2.0% respectively. There was also statistically significant month-to-month improvement in prescribing accuracy after joining the CIN of 2.8% and 1.4% for feeds and fluids but not for Antibiotic prescriptions. Findings suggest that much of the variation observed is due to hospital-level factors.ConclusionsIt is possible to introduce tools that capture important clinical data at least 80% of the time in routine African hospital settings but analyses of such data will need to account for missingness using appropriate statistical techniques. These data allow trends in performance to be explored and could support better impact evaluation, performance benchmarking, exploration of links between health system inputs and outcomes and scrutiny of variation in quality and outcomes of hospital care.
Sleep Duration, Quality, and Risk of Peripheral Artery Disease: Multinational Cohort and Mendelian Randomization Studies
Authors: Yuan Shuai , Levin Michael G. , Titova Olga E , Chen Jie , Sun Yuhao ,   VA Million Veteran Program, Åkesson Agneta , Li Xue , Damrauer Scott M. , Larsson Susanna C. 
Published: June 2022

AbstractBackgroundSleep duration and quality has been associated with cardiovascular disease, however the effect of sleep on peripheral artery disease (PAD) specifically remains unestablished. We conducted cohort, case-control, and Mendelian randomization (MR) analyses to assess the associations of sleep duration and quality with PAD risk.MethodsSleep traits were assessed for associations with incident PAD using cohort analysis among 53,416 Swedish adults. Replicated was sought in a case-control study of 28,123 PAD cases and 128,459 controls from the VA Million Veteran Program (MVP) and a cohort study of 452,028 individuals from the UK Biobank study (UKB). Two-sample Mendelian randomization (MR) was used for casual inference-based analyses of sleep-related traits and PAD (31,307 PAD cases 211,753 controls).ResultsObservational analyses demonstrated a U-shaped association between sleep duration and PAD risk. In Swedish adults, incident PAD risk was higher in those with short sleep (<5 hours; hazard ratio (HR), 1.74; 95% confidence interval (CI) 1.31-2.31) or long sleep (≥8 hours; HR 1.24; 95% CI 1.08-1.43), compared to individuals with a sleep duration of 7 to <8 hours/night. This finding was supported by case-control analysis in MVP and cohort analysis in UKB. Observational analysis also revealed positive associations between poor sleep quality (HR, 1.81; 95% CI 1.13-2.90) and daytime napping (HR, 1.32; 95% CI 1.18-1.49) with PAD. MR analysis supported an inverse association between sleep duration (odds ratio per hour increase, 0.79, 95% CI, 0.55, 0.89) and PAD, and an association between short sleep and increased PAD (odds ratio, 1.20, 95% CI, 1.04-1.38). MR also found an association between insomnia with PAD (OR, 1.10; 95% CI 1,05-1.15) and a reverse association of PAD on shorter sleep (OR, 1.05; 95% CI 1.01-1.10).ConclusionsMaintenance of healthy sleep habits, especially avoiding habitual short sleep, may prevent PAD.
A high confidencePhyscomitrium patensplasmodesmata proteome by iterative scoring and validation reveals diversification of cell wall proteins during evolution
Authors: Gombos Sven , Miras Manuel , Howe Vicky , Xi Lin , Pottier Mathieu , Kazemein Jasemi Neda S. , Schladt Moritz , Ejike Jona , Neumann Ulla , Hänsch Sebastian , Kuttig Franziska , Zhang Zhaoxia , Dickmanns Marcel , Xu Peng , Stefan Torsten , Baumeister Wolfgang , Frommer Wolf B. , Simon Rüdiger , Schulze Waltraud X. 
Published: June 2022

AbstractCells of multicellular organisms exchange nutrients, building blocks and information. In animals, this happens via gap junctions, in plants via plasmodesmata (PD). PD have striking properties, translocating a large range of molecules from ions, to metabolites, RNA and proteins up to 40 kDa. PD are hard to characterize due to being deeply embedded into cell walls and the presence of several membranes. While previous studies of protein composition of PD from angiosperms identified large lists of proteins, few were validated. Here, we developed a PD scoring approach in conjunction with systematic localization on a large scale to define a high-confidence PD proteome ofPhyscomitrium patens. This high confidence PD proteome comprises nearly 300 proteins, which together with thebona fidePD proteins from literature, are made available in the public PDDB database. Conservation of localization across plant species strengthens the reliability of plant PD proteomes and provides a basis for exploring the evolution of this important organelle. In particular, theP. patensPD proteome was highly enriched in cell wall modifying proteins. Callose-degrading glycolyl hydrolase family 17 (GHL17) proteins are presented as an abundant PD protein family with representatives across an evolutionary scale. Exclusively members of the alpha-clade of the GHL17 family are shown to be PD localized and their orthologs occur only in plant species which have developed PD. Members of the EXORDIUM-family and xyloglucan transglycosylases are additional cell-wall located proteins highly abundant in theP. patensPD proteome also showing evolutionary diversification of PD localized family members from other clade members.
Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping combined with genome sequence analysis
Authors: N’Guessan Arnaud , Kailasam Senthilkumar , Mostefai Fatima , Poujol Raphael , Grenier Jean-Christophe , Contini Paola , De Palma Raffaele , Haber Carsten , Stadler Volker , Bourque Guillaume , Hussin Julie G. , Shapiro B. Jesse , Fritz Jörg H. , Piccirillo Ciriaco A. 
Published: June 2022

ABSTRACTA deeper understanding of the molecular determinants that drive humoral responses to coronaviruses, and in particular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is critical for improving and developing diagnostics, therapies and vaccines. Moreover, viral mutations can change key antigens in a manner that alters the ability of the immune system to detect and clear infections. In this study, we exploit a deep serological profiling strategy coupled with an integrated, computational framework for the analysis of SARS-CoV-2 humoral immune responses of asymptomatic or recovered COVID-19-positive patients relative to COVID-19-negative patients. We made use of a novel high-density peptide array (HDPA) spanning the entire proteomes of SARS-CoV-2 and endemic human coronaviruses to rapidly identify B cell epitopes recognized by distinct antibody isotypes in patients’ blood sera. Using our integrated computational pipeline, we then evaluated the fine immunological properties of detected SARS-CoV-2 epitopes and relate them to their evolutionary and structural properties. While some epitopes are common across all CoVs, others are private to specific hCoVs. We also highlight the existence of hotspots of pre-existing immunity and identify a subset of cross-reactive epitopes that contributes to increasing the overall humoral immune response to SARS-CoV-2. Using a public dataset of over 38,000 viral genomes from the early phase of the pandemic, capturing both inter- and within-host genetic viral diversity, we determined the evolutionary profile of epitopes and the differences across proteins, waves and SARS-CoV-2 variants, which have important implications for genomic surveillance and vaccine design. Lastly, we show that mutations in Spike and Nucleocapsid epitopes are under stronger selection between than within patients, suggesting that most of the selective pressure for immune evasion occurs upon transmission between hosts.
Characterization of entry pathways, species-specific ACE2 residues determining entry, and antibody neutralization evasion of Omicron BA.1, BA.1.1, BA.2, and BA.3 variants
Authors: Neerukonda Sabari Nath , Wang Richard , Vassell Russell , Baha Haseebullah , Lusvarghi Sabrina , Liu Shufeng , Wang Tony , Weiss Carol D. , Wang Wei 
Published: June 2022

AbstractThe SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) have since rapidly emerged. Studies characterizing the mechanisms of Omicron variant infection and sensitivity to neutralizing antibodies induced upon vaccination are ongoing by several groups. In the present study, we used pseudoviruses to show that the transmembrane serine protease 2 (TMPRSS2) enhances infection of BA.1, BA.1.1, BA.2, and BA.3 Omicron variants to lesser extent compared to ancestral D614G. We further show that Omicron variants have higher sensitivity to inhibition by soluble angiotensin converting enzyme 2 (ACE2) and the endosomal inhibitor chloroquine compared to D614G. The Omicron variants also more efficiently used ACE2 receptors from nine out of ten animal species tested, and unlike the D614G variant, used mouse ACE2 due to the Q493R and Q498R spike substitutions. Finally, neutralization of the Omicron variants by antibodies induced by three doses of Pfizer/BNT162b2 mRNA vaccine was 7-8-fold less potent than the D614G, and the Omicron variants still evade neutralization more efficiently.
Precise and stable edge orientation signaling by human first-order tactile neurons
Authors: Sukumar Vaishnavi , Johansson Roland S. , Pruszynski J. Andrew 
Published: June 2022

AbstractFast-adapting type 1 (FA-1) and slow-adapting type 1 (SA-1) first-order neurons in the human tactile system have distal axons that branch in the skin and form many transduction sites, yielding receptive fields with many highly sensitive zones or ‘subfields’. We previously demonstrated that this arrangement allows FA-1 and SA-1 neurons to signal the geometric features of touched objects, specifically the orientation of raised edges scanned with the fingertips. Here we show that such signaling operates for fine edge orientation differences (5-20°) and is stable across a broad range of scanning speeds (15-180 mm/s); that is, under conditions relevant for real-world hand use. We found that both FA-1 and SA-1 neurons weakly signal fine edge orientation differences via the intensity of their spiking responses and only when considering a single scanning speed. Both neuron types showed much stronger edge orientation signaling in the sequential structure of the evoked spike trains and FA-1 neurons performed better than SA-1 neurons. Represented in the spatial domain, the sequential structure was strikingly invariant across scanning speeds, especially those naturally used in tactile spatial discrimination tasks. This speed invariance suggests that neurons’ responses are structured via sequential stimulation of their subfields and thus links this capacity to their terminal organization in the skin. Indeed, the spatial precision of elicited action potentials rationally matched spatial acuity of subfield arrangements, which typically corresponds to the dimension of individual fingertip ridges.Significance StatementThe distal axons of human first-order tactile neurons branch and innervate many mechanosensitive end organs in the skin. For those neurons terminating in end organs associated with fingerprint ridges (Meissner and Merkel), this branching results in cutaneous receptive fields with multiple subfields spread across several ridges. Consequently, when a fingertip scans the surface of an object, the spatial coincidence between a neuron’s subfields and the tactile stimulus defines the sequential structure of the evoked spike train (i.e., the presence of action potential bursts and the gaps between them). Here we show that, for surfaces composed of oriented edges, this sequential structure signals information about edge orientation differences at the limit of what people can feel and that the spatial precision of the structuring is maintained across a broad range of speeds relevant for real-world hand use. We submit that, to be of human relevance, models of higher order tactile processing must consider the impact of multifocal receptive fields in the periphery. For example, the speed invariance of tactile fine-form/texture perception may arise simply because the same subsets of peripheral subfields in the population of first-order tactile neurons are stimulated together regardless of speed.
Roles of RodZ and Class A PBP1b in the Assembly and Regulation of the Peripheral Peptidoglycan Elongasome in Ovoid-Shaped Cells ofStreptococcus pneumoniaeD39
Authors: Lamanna Melissa M. , Manzoor Irfan , Joseph Merrin , Ye Ziyun A. , Benedet Mattia , Zanardi Alessia , Ren Zhongqing , Wang Xindan , Massidda Orietta , Tsui Ho-Ching T. , Winkler Malcolm E. 
Published: June 2022

SUMMARYRodZ of rod-shaped bacteria functions to link MreB filaments to the Rod peptidoglycan (PG) synthase complex that moves circumferentially perpendicular to the long cell axis, creating hoop-like sidewall PG. Ovoid-shaped bacteria, such asStreptococcus pneumoniae(pneumococcus;Spn) that lack MreB, use a different modality for peripheral PG elongation that emanates from the midcell of dividing cells. Yet,S. pneumoniaeencodes a RodZ homolog similar to RodZ in rod-shaped bacteria. We show here that the helix-turn-helix and transmembrane domains of RodZ(Spn) are essential for growth at 37°C. ΔrodZmutations are suppressed by Δpbp1a,mpgA(Y488D), and ΔkhpAmutations that suppress ΔmreC, but not ΔcozE. Consistent with a role in PG elongation, RodZ(Spn) co-localizes with MreC and aPBP1a throughout the cell cycle and forms complexes and interacts with PG elongasome proteins and regulators. Depletion of RodZ(Spn) results in aberrantly shaped, non-growing cells and mislocalization of elongasome proteins MreC, PBP2b, and RodA. Moreover, Tn-seq reveals that RodZ(Spn), but not MreCD(Spn), displays a specific synthetic-viable genetic relationship with aPBP1b, whose function is unknown. We conclude that RodZ(Spn) acts as a scaffolding protein required for elongasome assembly and function and that aPBP1b, like aPBP1a, plays a role in elongasome regulation and possibly peripheral PG synthesis.Graphical Summary
Recording large-scale, cellular-resolution neuronal activity from freely-moving mice
Authors: Das Aniruddha , Holden Sarah , Borovicka Julie , Icardi Jacob , Patel Davina , Patel Rushik , Raber Jacob , Dana Hod 
Published: June 2022

AbstractCurrent methods for recording large-scale neuronal activity from behaving mice with single-cell resolution require either fixing the mouse head under a microscope or attachment of a recording device to the animal’s skull. Both of these options significantly affect the animal behavior and hence also the recorded brain activity patterns. Here, we introduce a new method to acquire snapshots of single-cell cortical activity maps from freely-moving mice using a calcium sensor called CaMPARI. CaMPARI has a unique property of irreversibly changing its color from green to red inside active neurons when illuminated with 400nm light. We capitalize on this property to demonstrate cortex-wide activity recording without any head fixation or attachment of a miniaturized device to the mouse’s head. Multiple cortical regions were recorded while the mouse was performing a battery of behavioral and cognitive tests. We identified task-dependent activity patterns across motor and somatosensory cortices, with significant differences across sub-regions of the motor cortex. This new CaMPARI-based recording method expands the capabilities of recording neuronal activity from freely-moving and behaving mice under minimally-restrictive experimental conditions and provides large-scale volumetric data that are not accessible otherwise.
Accurate pan-cancer tumor purity estimation from gene expression data
Authors: Revkov Egor , Kulshrestha Tanmay , Sung Ken Wing-Kin , Jacobsen Skanderup Anders 
Published: June 2022

AbstractTumors are complex masses composed of malignant and non-malignant cells. Variation in tumor purity (proportion of cancer cells in a sample) can both confound integrative analysis and enable studies of tumor heterogeneity. Here we developed PUREE, which uses a weakly supervised learning approach to infer tumor purity from a tumor gene expression profile. PUREE was trained on gene expression data and genomic consensus purity estimates from 7864 solid tumor samples. PUREE predicted purity with high accuracy across distinct solid tumor types and generalized to tumor samples from unseen tumor types and cohorts. Gene features of PUREE were further validated using single-cell RNA-seq data from distinct tumor types. In a comprehensive benchmark, PUREE outperformed existing transcriptome-based purity estimation approaches. Overall, PUREE is a highly accurate and versatile method for estimating tumor purity and interrogating tumor heterogeneity from bulk tumor gene expression data.
An epigenetic barrier sets the timing of human neuronal maturation
Authors: Ciceri Gabriele , Cho Hyunwoo , Kshirsagar Meghana , Baggiolini Arianna , Aromolaran Kelly A , Walsh Ryan M , Goldstein Peter A , Koche Richard P. , Leslie Christina S , Studer Lorenz 
Published: June 2022

AbstractThe pace of human brain development is highly protracted compared to most other species. The maturation of cortical neurons is particularly slow, extending over months to years to reach adult-like functions. Remarkably, such protracted timing is retained in cortical neurons derived from human pluripotent stem cell (hPSC) during in vitro differentiation or upon transplantation into the murine brain in vivo. Those findings suggest the presence of a cell intrinsic clock that sets the pace of neuronal maturation, though the molecular nature of such a clock has remained elusive.Here, we identify an epigenetic developmental program which sets the timing of human neuronal maturation. First, we developed a human PSC-based approach to synchronize the birth of cortical neurons in vitro which allowed us to define a detailed atlas of progressive morphological, functional, and molecular maturation in human cortical neurons. Interestingly, we observed a slow, temporal unfolding of maturation programs that is limited by the retention of a specific set of epigenetic factors. Loss-of-function studies for several of those factors in cortical neurons enables precocious molecular and physiological maturation. Remarkably, transient inhibition of EZH2, EHMT1/2 or DOT1L, at the progenitor stage primes newly born neurons to rapidly acquire mature properties upon differentiation. Therefore, our findings reveal that the rate at which human neurons mature is set well before neurogenesis through the establishment of an “epigenetic barrier” in progenitor cells. Mechanistically, this barrier acts by holding transcriptional maturation programs in a poised state that gets gradually released during neuronal differentiation to ensure the prolonged timeline characteristic of human cortical neuron maturation.
TSignal: A transformer model for signal peptide prediction
Authors: Dumitrescu Alexandru , Jokinen Emmi , Kellosalo Juho , Paavilainen Ville , Lähdesmäki Harri 
Published: June 2022

AbstractSignal peptides are short amino acid segments present at the N-terminus of newly synthesized proteins that facilitate protein translocation into the lumen of the endoplasmic reticulum, after which they are cleaved off. Specific regions of signal peptides influence the efficiency of protein translocation, and small changes in their primary structure can abolish protein secretion altogether. The lack of conserved motifs across signal peptides, sensitivity to mutations, and variability in the length of the peptides, make signal peptide prediction a challenging task that has been extensively pursued over the years. We introduce TSignal, a deep transformer-based neural network architecture that utilizes BERT language models (LMs) and dot-product attention techniques. TSignal predicts the presence of signal peptides (SPs) and the cleavage site between the SP and the translocated mature protein. We show improved accuracy in terms of cleavage site and SP presence prediction for most of the SP types and organism groups. We further illustrate that our fully data-driven trained model identifies useful biological information on heterogeneous test sequences.