bluuebunny/crossref_metadata_2025_split huggingface dataset:
BIMAM—a tool for imputing variables missing across datasets using a Bayesian imputation and analysis model
Authors: Elfadaly Fadlalla G , Adamson Alex , Patel Jaymini , Potts Laura , Potts James , Blangiardo Marta , Thompson John , Minelli Cosetta 
Published: August 2021

AbstractMotivationCombination of multiple datasets is routine in modern epidemiology. However, studies may have measured different sets of variables; this is often inefficiently dealt with by excluding studies or dropping variables. Multilevel multiple imputation methods to impute these ‘systematically’ missing data (as opposed to ‘sporadically’ missing data within a study) are available, but problems may arise when many random effects are needed to allow for heterogeneity across studies. We show that the Bayesian IMputation and Analysis Model (BIMAM) implemented in our tool works well in this situation.General featuresBIMAM performs imputation and analysis simultaneously. It imputes both binary and continuous systematically and sporadically missing data, and analyses binary and continuous outcomes. BIMAM is a user-friendly, freely available tool that does not require knowledge of Bayesian methods. BIMAM is an R Shiny application. It is downloadable to a local machine and it automatically installs the required freely available packages (R packages, including R2MultiBUGS and MultiBUGS).AvailabilityBIMAM is available at [www.alecstudy.org/bimam].
Prevalence and predictors of long-acting reversible contraceptive use among sexually active women in 26 sub-Saharan African countries
Authors: Bolarinwa Obasanjo Afolabi , Nwagbara Ugochinyere Ijeoma , Okyere Joshua , Ahinkorah Bright Opoku , Seidu Abdul-Aziz , Ameyaw Edward Kwabena , Igharo Victor 
Published: August 2021

Abstract

Background
Long-acting reversible contraceptives (LARCs) are associated with high efficacy rates and continuity of use. Based on the foregoing, we sought to examine the prevalence and factors associated with LARC use among sexually active women in 26 countries in sub-Saharan Africa(SSA).

Methods
Secondary data from Demographic and Health Surveys conducted in 26 countries in SSA between January 2010 and December 2019 were pooled and analysed. A total of 56 067 sexually active women 15–49 y of age met the inclusion criteria. Bivariate and multivariate regression analyses were performed to examine the association between selected factors and the use of LARCs in SSA. Results were presented as crude odds ratios and adjusted odds ratios (aORs) with statistical precision at &lt;0.05.

Results
The prevalence of LARC use was 21.73%, ranging from 1.94% in Namibia to 54.96% in Benin. Sexually active women with secondary or higher education (aOR 1.19 [95% confidence interval {CI} 1.08 to 1.32]), those cohabiting (aOR 1.25 [95% CI 1.06 to 1.47]) and those with four or more children (aOR 2.22 [95% CI 1.78 to 2.78]) were more likely to use LARCs compared with those without education, never married and with no biological child.

Conclusions
The use of LARCs in the 26 countries in SSA was relatively low. Hence, the identified contributory factors of LARC use should be tackled with appropriate interventions. These include continuous campaigns on the efficacy of LARCs in reducing unintended pregnancy, maternal mortality and morbidity.
Reciprocal regulation of IgA and the gut microbiota: a key mutualism in the intestine
Authors: Takeuchi Tadashi , Ohno Hiroshi 
Published: August 2021

Abstract
The mammalian intestine is home to trillions of microbes, and their colonization contributes to host physiology through the production of indispensable metabolites and competition against pathogens. However, it is also important to balance this symbiotic relationship, as overgrowth and translocation of microbes could trigger a fatal infection. IgA is the major immunoglobulin class produced and secreted in the intestine and is considered to play a pivotal role in maintaining homeostasis. In this review, we summarize recent studies exploring the interactions between IgA and the gut microbiota and explain how different types of IgA could coexist to regulate the gut microbiota. In particular, we discuss two important aspects of IgA in controlling the gut microbes: function and specificity. Differences in these two aspects appear attributable to how IgA is induced and are associated with the functions of IgA as well. Together, our review delineates a recent understanding of IgA–microbiome interactions and proposes a future direction to clarify its complexity.
Hormonal orchestration of root apical meristem formation and maintenance in Arabidopsis
Authors: Yamoune Amel , Cuyacot Abigail Rubiato , Zdarska Marketa , Hejatko Jan 
Published: August 2021

AbstractPlant hormones are key regulators of a number of developmental and adaptive responses in plants, integrating the control of intrinsic developmental regulatory circuits with environmental inputs. Here we provide an overview of the molecular mechanisms underlying hormonal regulation of root development. We focus on key events during both embryonic and post-embryonic development, including specification of the hypophysis as a future organizer of the root apical meristem (RAM), hypophysis asymmetric division, specification of the quiescent centre (QC) and the stem cell niche (SCN), RAM maturation and maintenance of QC/SCN activity, and RAM size. We address both well-established and newly proposed concepts, highlight potential ambiguities in recent terminology and classification criteria of longitudinal root zonation, and point to contrasting results and alternative scenarios for recent models. In the concluding remarks, we summarize the common principles of hormonal control during root development and the mechanisms potentially explaining often antagonistic outputs of hormone action, and propose possible future research directions on hormones in the root.
An African American Male Patient with Rare Type B Insulin Resistance Syndrome
Authors: Jialal Ishwarlal , Devaraj Sridevi 
Published: August 2021

Abstract
Syndromes of severe insulin resistance can result from mutations in the insulin receptor gene or autoantibodies to the insulin receptor. The type B syndrome of insulin resistance results from autoantibodies to the insulin receptor and occurs predominantly in women under age 50 years. Here we report on a 64 year old African American man with systemic lupus erythematosus (SLE) and acanthosis nigricans who had severe insulin resistance requiring up to 5000 units of insulin per day. He was diagnosed with type B insulin resistance syndrome based on his clinical presentation and demonstration of autoantibodies to the insulin receptor in his serum. This case study underscores the importance of assaying for autoantibodies to the insulin receptors especially in African American patients with severe insulin resistance and diabetes requiring excessive doses of insulin, in the setting of an autoimmune disease like SLE. It also behooves reference laboratories to develop and offer this assay because these patients have a very high mortality.
A supernova remnant association for the fast-moving pulsar PSR J0908–4913
Authors: Johnston Simon , Lower Marcus E 
Published: August 2021

ABSTRACT
A recent measurement of the proper motion of PSR J0908–4913 shows that it is a fast-moving object at a distance of some 3 kpc. Here, we present evidence that the pulsar is located at the edge of a previously unknown, filled-centre supernova remnant (SNR), G270.4–1.0. The velocity vector of the pulsar points directly away from the centre of the remnant. The putative association of the pulsar with SNR G270.4–1.0 implies the pulsar is ∼12 kyr old, significantly less than its characteristic age of 110 kyr. We show that the rotation axis of the pulsar points in the direction of the proper motion. Rotation measure and dispersion measure variations are seen over time, likely indicating the pulsar is passing behind a filament of the remnant.
The Rsm (Csr) post-transcriptional regulatory pathway coordinately controls multiple CRISPR–Cas immune systems
Authors: Campa Aroa Rey , Smith Leah M , Hampton Hannah G , Sharma Sahil , Jackson Simon A , Bischler Thorsten , Sharma Cynthia M , Fineran Peter C 
Published: August 2021

Abstract
CRISPR–Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, pathways regulating their activity are not well defined. We recently developed a high-throughput genome-wide method (SorTn-seq) and used this to uncover CRISPR–Cas regulators. Here, we demonstrate that the widespread Rsm/Csr pathway regulates the expression of multiple CRISPR–Cas systems in Serratia (type I-E, I-F and III-A). The main pathway component, RsmA (CsrA), is an RNA-binding post-transcriptional regulator of carbon utilisation, virulence and motility. RsmA binds cas mRNAs and suppresses type I and III CRISPR–Cas interference in addition to adaptation by type I systems. Coregulation of CRISPR–Cas and flagella by the Rsm pathway allows modulation of adaptive immunity when changes in receptor availability would alter susceptibility to flagella-tropic phages. Furthermore, we show that Rsm controls CRISPR–Cas in other genera, suggesting conservation of this regulatory strategy. Finally, we identify genes encoding RsmA homologues in phages, which have the potential to manipulate the physiology of host bacteria and might provide an anti-CRISPR activity.
Steroids use in non-oxygen requiring COVID-19 patients: a systematic review and meta-analysis
Authors: Sahu A K , Mathew R , Bhat R , Malhotra C , Nayer J , Aggarwal P , Galwankar S 
Published: August 2021

Summary

Background
Corticosteroids have become the mainstay treatment in severe COVID-19. However, its role is mild disease is controversial due to lack of robust scientific evidence. This systematic review and meta-analysis were conducted to assess effect of steroids in mild COVID-19 patients.

Methods
PubMed, EMBASE, Web of Science and medRxiv were searched from 31 December 2019 to 14 May 2021 for studies that reported effectiveness of steroids in non-oxygen requiring COVID-19 patients in terms of progressing to severe disease, mortality, duration of fever, duration of viral clearance and length of hospital stay (LOHS). Studies on inhalational steroids, case reports and reviews were excluded. Risk of bias (ROB) was assessed by the Cochrane's ROB tool and ROBANS tool. Quantitative data synthesis was done using the generic inverse variance method.

Results
A total of 6411 studies were identified, 2990 articles were screened after exclusion. Seven studies which fit the criteria (involving 2214 non-oxygen requiring COVID-19 patients) were included and analysed. Overall odds of progression to severe disease among the non-oxygen requiring COVID-19 patients receiving steroids was 5.97 [95% confidence interval (CI): 1.27–27.99, I2 = 0%] and odds of death (OR: 1.35, 95% CI: 1.01–1.79; I2 = 0%) as compared to the patients not receiving steroids. Mean duration of fever (7.4 days), duration to viral clearance (18.9 days) and LOHS (20.8 days) were significantly higher in the steroid arm, as compared to that in no-steroid arm (6.7, 16.5 and 15.2 days, respectively).

Conclusion
Steroids in non-oxygen requiring COVID-19 patients can be more detrimental than beneficial.

Protocol registration
The study was prospectively registered in PROSPERO (CRD 42021254951).
Growth of ‘CandidatusLiberibacter asiaticus’ in Commercial Grapefruit Juice-Based Media Formulations Reveals Common Cell Density-Dependent Transient Behaviors
Authors: Merfa Marcus V. , Naranjo Eber , Shantharaj Deepak , De La Fuente Leonardo 
Published: August 2021

The phloem-restricted, insect-transmitted bacterium ‘Candidatus Liberibacter asiaticus’ (CLas) is associated with huanglongbing (HLB), the most devastating disease of citrus worldwide. The inability to culture CLas impairs the understanding of its virulence mechanisms and the development of effective management strategies to control this incurable disease. Previously, our research group used commercial grapefruit juice (GJ) to prolong the viability of CLas in vitro. In the present study, GJ was amended with a wide range of compounds and incubated under different conditions to optimize CLas growth. Remarkably, results showed that CLas growth ratios were inversely proportional to the initial inoculum concentration. This correlation is probably regulated by a cell density-dependent mechanism, because diluting samples between subcultures allowed CLas to resume growth. Moreover, strategies to reduce the cell density of CLas, such as subculturing at short intervals and incubating samples under flow conditions, allowed this bacterium to multiply and reach maximum growth as early as 3 days after inoculation, although no sustained exponential growth was observed under any tested condition. Unfortunately, cultures were only transient, because CLas lost viability over time; nevertheless, we obtained populations of about 105genome equivalents/ml repeatedly. Finally, we established an ex vivo system to grow CLas within periwinkle calli that could be used to propagate bacterial inoculum in the lab. In this study we determined the influence of a comprehensive set of conditions and compounds on CLas growth in culture. We hope our results will help guide future efforts toward the long-sought goal of culturing CLas axenically.
Are flexible school start times associated with higher academic grades? A 4-year longitudinal study
Authors: Biller Anna M. , Molenda Carmen , Obster Fabian , Zerbini Giulia , Förtsch Christian , Roenneberg Till , Winnebeck Eva C. 
Published: August 2021

AbstractThe mismatch between teenagers’ late sleep phase and early school start time results in acute and chronic sleep reductions. This is not only harmful for students’ learning in the short-term but may impact on students’ career prospects and widen social inequalities. Delaying school start times has been shown to improve sleep but whether this translates to better achievement is unresolved. The current evidence is limited due to a plethora of outcome measures and the many factors influencing sleep and grade/score trajectories. Here, we studied whether 0.5-1.5 years of exposure to a flexible school start system, with the daily choice of an 8AM or 8:50AM-start (intervention), allowed secondary school students (n=63-157, 14-19 years) to improve their quarterly school grades in a 4-year longitudinal pre-post design. We investigated whether sleep, changes in sleep or frequency of later starts predicted grade improvements in the flexible system. Our mixed model regressions with 5,111-16,724 official grades as outcomes did not indicate meaningful grade improvements in the flexible system per se or with previously observed sleep variables (nor their changes) – the covariates academic quarter, discipline and grade level had a greater, more systematic effect in our sample. Importantly, this finding does not preclude improvements in learning and cognition in our sample. However, at the ‘dose’ received here, intermittent sleep benefits did not obviously translate into detectable grade changes, which is in line with several other studies and highlights that grades are suboptimal to evaluate timetabling interventions despite their importance for future success.Significance statementEarly school start times worldwide clash with teenagers’ delayed sleep-wake rhythms. This mismatch results in sleep restrictions below healthy amounts, which compromises health and performance and further aggravates social disparities. Since adequate sleep is important for learning and concentration, there is the strong expectation that counteracting sleep deprivation with delayed school starts results in better academic achievement. We add important high-resolution, longitudinal data to this unresolved scientific debate. When controlling for confounders, our results do not support that improved sleep leads to grade changes within 1.5 years in a flexible start system. While grades are suboptimal to measure later school start effects on performance, they nevertheless open doors to higher education worldwide and thus determine future trajectories.
Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
Authors: Ryan Feargal J. , Hope Christopher M. , Masavuli Makutiro G. , Lynn Miriam A. , Mekonnen Zelalem A. , Lip Yeow Arthur Eng , Garcia-Valtanen Pablo , Al-Delfi Zahraa , Gummow Jason , Ferguson Catherine , O’Connor Stephanie , Reddi Benjamin AJ , Shaw David , Kok-Lim Chuan , Gleadle Jonathan M. , Beard Michael R. , Barry Simon C. , Grubor-Bauk Branka , Lynn David J. 
Published: August 2021

AbstractIncreasing evidence suggests immune dysregulation in individuals recovering from SARS- CoV-2 infection. We have undertaken an integrated analysis of immune responses at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 individuals recovering from mild, moderate, severe, or critical COVID-19. Anti-Spike and anti-RBD IgG responses were largely stable up to 24wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+monocytes) and adaptive immune populations (T helper, T follicular helper and regulatory T cells) in COVID-19 convalescents compared to healthy controls, which were most strongly evident at 12 and 16wpi. RNA sequencing suggested ongoing immune and metabolic dysregulation in convalescents months after infection. Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.
The Arabidopsis m6A-binding proteins ECT2 and ECT3 bind largely overlapping mRNA target sets and influence target mRNA abundance, not alternative polyadenylation
Authors: Arribas-Hernández Laura , Rennie Sarah , Schon Michael , Porcelli Carlotta , Enugutti Balaji , Andersson Robin , Nodine Michael , Brodersen Peter 
Published: August 2021

AbstractGene regulation viaN6-methyladenosine (m6A) in mRNA involves RNA-binding proteins that recognize m6A via a YT521-B homology (YTH) domain. The plant YTH domain proteins ECT2 and ECT3 act genetically redundantly in stimulating cell proliferation during organogenesis, but several fundamental questions regarding their mode of action remain unclear. Here, we use HyperTRIBE (targets of RNA-binding proteins identified by editing) to show that most ECT2 and ECT3 targets overlap, with only few examples of preferential targeting by either of the two proteins. HyperTRIBE in different mutant backgrounds also provides direct views of redundant and specific target interactions of the two proteins. We also show that contrary to conclusions of previous reports, ECT2 does not accumulate in the nucleus. Accordingly, inactivation ofECT2,ECT3and their surrogateECT4does not change patterns of polyadenylation site choice in ECT2/3 target mRNAs, but does lead to lower steady state accumulation of target mRNAs. In addition, mRNA and microRNA expression profiles show indications of stress response activation inect2/ect3/ect4mutants, likely via indirect effects. Thus, previous suggestions of control of alternative polyadenylation by ECT2 are not supported by evidence, and ECT2 and ECT3 act largely redundantly to regulate target mRNA, including its abundance, in the cytoplasm.
Eelbrain: A Python toolkit for time-continuous analysis with temporal response functions
Authors: Brodbeck Christian , Das Proloy , Gillis Marlies , Kulasingham Joshua P. , Bhattasali Shohini , Gaston Phoebe , Resnik Philip , Simon Jonathan Z. 
Published: August 2021

1AbstractEven though human experience unfolds continuously in time, it is not strictly linear; instead, it entails cascading processes building hierarchical cognitive structures. For instance, during speech perception, humans transform a continuously varying acoustic signal into phonemes, words, and meaning, and these levels all have distinct but interdependent temporal structures. Time-lagged regression usingtemporal response functions (TRFs)has recently emerged as a promising tool for disentangling electrophysiological brain responses related to such complex models of perception. Here we introduce the Eelbrain Python toolkit, which makes this kind of analysis easy and accessible. We demonstrate its use, using continuous speech as a sample paradigm, with a freely available EEG dataset of audiobook listening. A companion GitHub repository provides the complete source code for the analysis, from raw data to group level statistics. More generally, we advocate a hypothesis-driven approach in which the experimenter specifies a hierarchy of time-continuous representations that are hypothesized to have contributed to brain responses, and uses those as predictor variables for the electrophysiological signal. This is analogous to a multiple regression problem, but with the addition of a time dimension. TRF analysis decomposes the brain signal into distinct responses associated with the different predictor variables by estimating a multivariate TRF (mTRF), quantifying the influence of each predictor on brain responses as a function of time(-lags). This allows asking two questions about the predictor variables: 1) Is there a significant neural representation corresponding to this predictor variable? And if so, 2) what are the temporal characteristics of the neural response associated with it? Thus, different predictor variables can be systematically combined and evaluated to jointly model neural processing at multiple hierarchical levels. We discuss applications of this approach, including the potential for linking algorithmic/representational theories at different cognitive levels to brain responses through computational models with appropriate linking hypotheses.
The CHK-2 antagonizing phosphatase PPM-1.D regulates meiotic entry via catalytic and non-catalytic activities
Authors: Baudrimont Antoine , Paouneskou Dimitra , Mohammad Ariz , Lichtenberger Raffael , Blundon Joshua , Kim Yumi , Hartl Markus , Falk Sebastian , Schedl Tim , Jantsch Verena 
Published: August 2021

SummaryThe transition from the stem cell/progenitor fate to meiosis is mediated by several redundant post-transcriptional regulatory pathways in C. elegans. Interfering with all three branches causes tumorous germlines. SCFPROM-1 comprises one branch and mediates a scheduled degradation step at entry into meiosis. prom-1 mutants show defects in timely initiation of events of meiotic prophase I, resulting in high rates of embryonic lethality. Here, we identify the phosphatase PPM-1.D/Wip1 as crucial substrate for PROM-1. We report that PPM-1.D antagonizes CHK-2 kinase, a key regulator for meiotic prophase initiation e.g., DNA double strand breaks, chromosome pairing and synaptonemal complex formation. We propose that PPM-1.D controls the amount of active CHK-2 by both catalytic and non-catalytic activities, where strikingly the non-catalytic regulation seems to be crucial at meiotic entry. PPM-1.D sequesters CHK-2 at the nuclear periphery and programmed SCFPROM-1 mediated degradation of PPM-1.D liberates the kinase and promotes meiotic entry.