bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors and risk factors of short-term and long-term outcomes among women with gestational diabetes mellitus (GDM) and their offspring: Moving toward precision prognosis?
Authors: Semnani-Azad Zhila , Gaillard Romy , Hughes Alice E , Boyle Kristen E. , Tobias Deirdre K. , Perng Wei ,   ADA/EASD PMDI
Published: April 2023

ABSTRACTAs part of the American Diabetes Association Precision Medicine in Diabetes Initiative (PMDI) – a partnership with the European Association for the Study of Diabetes (EASD) – this systematic review is part of a comprehensive evidence evaluation in support of the 2ndInternational Consensus Report on Precision Diabetes Medicine. Here, we sought to synthesize evidence from empirical research papers published through September 1st, 2021 to evaluate and identify prognostic conditions, risk factors, and biomarkers among women and children affected by gestational diabetes mellitus (GDM), focusing on clinical endpoints of cardiovascular disease (CVD) and type 2 diabetes (T2D) among women with a history of GDM; and adiposity and cardiometabolic profile among offspring exposed to GDMin utero.We identified a total of 107 observational studies and 12 randomized controlled trials testing the effect of pharmaceutical and/or lifestyle interventions. Broadly, current literature indicates that greater GDM severity, higher maternal body mass index, belonging to racial/ethnic minority group; and unhealthy lifestyle behaviors would predict a woman’s risk of incident T2D and CVD, and an unfavorable cardiometabolic profile among offspring. However, the level of evidence is low (Level 4 according to the Diabetes Canada 2018 Clinical Practice Guidelines for diabetes prognosis) largely because most studies leveraged retrospective data from large registries that are vulnerable to residual confounding and reverse causation bias; and prospective cohort studies that may suffer selection and attrition bias. Moreover, for the offspring outcomes, we identified a relatively small body of literature on prognostic factors indicative of future adiposity and cardiometabolic risk. Future high-quality prospective cohort studies in diverse populations with granular data collection on prognostic factors, clinical and subclinical outcomes, high fidelity of follow-up, and appropriate analytical approaches to deal with structural biases are warranted.
A Systematic Review of the use of Precision Diagnostics in Monogenic Diabetes
Authors: Murphy Rinki , Colclough Kevin , Pollin Toni I. , Ikle Jennifer M. , Svalastoga Pernille , Maloney Kristin A. , Saint-Martin Cécile , Molnes Janne ,   ADA/EASD Precision Medicine Diabetes Initiative, Misra Shivani , Aukrust Ingvild , de Franco AIElisa , Flanagan Sarah E. , Njølstad Pål R. , Billings Liana K. , Owen Katharine R , Gloyn Anna L 
Published: April 2023

AbstractMonogenic forms of diabetes present opportunities for precision medicine as identification of the underlying genetic cause has implications for treatment and prognosis. However, genetic testing remains inconsistent across countries and health providers, often resulting in both missed diagnosis and misclassification of diabetes type. One of the barriers to deploying genetic testing is uncertainty over whom to test as the clinical features for monogenic diabetes overlap with those for both type 1 and type 2 diabetes. In this review, we perform a systematic evaluation of the evidence for the clinical and biochemical criteria used to guide selection of individuals with diabetes for genetic testing and review the evidence for the optimal methods for variant detection in genes involved in monogenic diabetes. In parallel we revisit the current clinical guidelines for genetic testing for monogenic diabetes and provide expert opinion on the interpretation and reporting of genetic tests. We provide a series of recommendations for the field informed by our systematic review, synthesizing evidence, and expert opinion. Finally, we identify major challenges for the field and highlight areas for future research and investment to support wider implementation of precision diagnostics for monogenic diabetes.Plan Language SummarySince monogenic diabetes misclassification can occur and lead to missed opportunities for optimal management, and several diagnostic technologies are available, we systematically review the yield of monogenic diabetes using different criteria to select people with diabetes for genetic testing and the technologies used.
Addressing Acute Febrile Illness Using a Syndromic Approach During A Chikungunya Epidemic in Rio de Janeiro, Brazil: A Prospective Observational Study
Authors: Moreira José , Fernandez-Carballo B. Leticia , Escadafal Camille , Dittrich Sabine , Brasil Patrícia , Siqueira André M 
Published: April 2023

AbstractBackgroundIdentifying etiologies of acute febrile illness (AFI) is challenging in settings with limited laboratory capacity. We aimed to describe the causes of AFI among non-severe patients seeking care at the primary level in Rio de Janeiro, Brazil when a large chikungunya virus (CHIKV) epidemic was ongoing.Methodology/Principal FindingsWe conducted a 10-month prospective AFI study in participants aged 2-65 seeking care at public emergency departments and outpatient clinics. Patients with fever ≤ 7 days were offered enrollment, and clinical, and laboratory data were gathered for consecutive participants. A syndrome-driven approach comprising culture, molecular and serologic tests were adopted to investigate the cause of fever. Logistic regression model determined predictors of laboratory-positive CHIKV. Follow-up visits were conducted 14-28 days after the index visit. Five hundred participants (median age 26 [15-41] years, 50.4% females) yielded 824 diagnoses, and 249/500 (49.8%) of whom had multiple diagnoses. Systemic infection (382/500, 76%), followed by acute respiratory infection (155/500, 31%), and urinary infection (23/500, 4.6%) were the most common febrile syndromes. CHIKV was the primary etiology found in 284 (56.8%) participants. Viral upper respiratory infection accounted for 40/155 (25.8%) of the respiratory infections, of which Rhinovirus and Influenza A were the main viruses commonly detected. None of the diagnostic tests were positive in 124/500 (25%). Predictors of laboratory-positive CHIKV were the absence of cough, arthralgia, rash, high temperature, and leucopenia. Of those 297/500 (59.4%) who returned for the follow-up, 120/297 (40%) persisted with symptoms. CHIKV-positive patients were more likely to experience persistent arthritis than CHIKV negative [OR: 10.18 (3.64-28.45)].Conclusions/SignificanceUsing a syndromic approach to identify the etiology of fever during an epidemic of CHIKV in Rio, we found evidence of other pathogens associated with AFI. Clinical and laboratory markers might allow early identification and accurate distinction of patients with CHIKV from other AFI to guide proper clinical management. Future research should assess whether a syndromic approach to febrile illness in resource-limited settings improves patient outcomes and rationale antimicrobial use.Clinicaltrials.govregistration number:NCT03047642
Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism
Authors: Marine Huillet , Frédéric Lasserre , Marie-Pierre Gratacap , Beatrice Engelmann , Justine Bruse , Arnaud Polizzi , Tiffany Fougeray , Céline Martin , Clémence Rives , Anne Fougerat , Claire Naylies , Yannick Lippi , Géraldine Garcia , Elodie Rousseau- Bacquie , Cécile Canlet , Laurent Debrauwer , Ulrike Rolle-Kampczyk , Martin von Bergen , Bernard Payrastre , Elisa Boutet-Robinet , Laurence Gamet-Payrastre , Hervé Guillou , Nicolas Loiseau , Sandrine Ellero-Simatos 
Published: April 2023

ABSTRACTBackground and AimsThe constitutive androstane receptor (CAR) is a nuclear receptor able to recognize a large panel of xenobiotics leading to the modulation of the expression of its target genes involved in xenobiotic detoxication and energy metabolism. While CAR hepatic activity is thought to be higher in women than in men, its response to an acute pharmacological activation has never been investigated in both sexes.MethodsHepatic transcriptome, plasma and hepatic metabolome, have been analyzed inCar+/+andCar-/-male and female mice treated either with the CAR-specific agonist, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), or with vehicle.ResultsWhile 90% of TCPOBOP-sensitive genes were modulated in a sex- independent way, the remaining 10% were almost exclusively impacted in female liver specifically. These female-specific CAR-sensitive genes were mainly involved in xenobiotic metabolism, inflammation and extracellular matrix organization. CAR activation also induced higher hepatic oxidative stress and hepatocyte cytolysis in females than in males. Data mining on human data confirmed that CAR activation may be involved in sexually-dimorphic drug-induced liver injury. Hepatic expression of flavin monooxygenase 3(Fmo3)was almost abolished and associated with a decrease of hepatic trimethylamine-N-oxide (TMAO) concentration in TCPOBOP-treated females. In line with a possible role in the control of TMAO homeostasis, CAR activation decreased platelet hyperresponsiveness in female mice supplemented with dietary choline.ConclusionsOur results demonstrate that more than 10% of CAR-sensitive genes are sex-specific and influence hepatic and systemic response such as platelet aggregation. Also, CAR activation may be an important mechanism of sexually- dimorphic drug-induced liver injury.
The impact of innate immunity on malaria parasite infection dynamics
Authors: Herbert-Mainero Alejandra , Spence Philip J. , Reece Sarah E. , Kamiya Tsukushi 
Published: April 2023

1AbstractDecades of research have investigated the molecular and cellular mechanisms that control the immune response to malaria. Yet, many studies offer conflicting results on the functional impact of innate immunity for controlling parasite replication early in infection. We conduct a meta-analysis to probe for consensus on the effect of innate immunity on parasite replication, examining three different species of rodent malaria parasite. Screening published studies that span four decades of research we collate, curate and statistically analyse infection dynamics in immune deficient or augmented mice to identify and quantify consensus and identify sources of disagreement among studies. Additionally, we estimate whether host factors or experimental methodology shape the impact of immune perturbations on parasite burden. First, we detected meta-analytic mean effect sizes (absolute Cohen’s h) for the difference in parasite burden between treatment and control groups ranging from 0.1498 to 0.2321 across parasite species. This range is considered a small effect size and translates to a modest change in parasitaemia of roughly 6-12% on average at the peak of infection. Second, we reveal that variation across studies usingP. chabaudiorP. yoeliiis best explained by stochasticity (due to small sample sizes) rather than by host factors or experimental design. Third, we find that forP. bergheithe impact of immune perturbation is increased when young or female mice are used and is greatest when effector molecules (as opposed to upstream signalling molecules) are disrupted (up to an 18% difference in peak parasitaemia). Finally, we find little evidence of publication bias suggesting that our results are robust. The small effects sizes we observe, across three parasite species, following experimental perturbations of the innate immune system may be explained by redundancy in a complex biological system or by incomplete (or inappropriate) data reporting for meta-analysis. Alternatively, our findings might indicate a need to re-evaluate the efficiency with which innate immunity controls parasite replication early in infection. Testing these explanations is necessary to translate understanding from model systems to human malaria infections, manage immunopathology, and facilitate realism in mathematical models.
Cryo-EM structure of the mycobacterial 70S ribosome in complex with ribosome hibernation promotion factor RafH, reveals the unique mode of mycobacterial ribosome hibernation
Authors: Kumara Niraj , Sharmaa Shivani , Kaushala Prem S. 
Published: April 2023

AbstractRibosome hibernation is a key survival strategy bacteria adopt under environmental stress, where a protein, hibernation promotion factor (HPF), transitorily inactivates the ribosome and slows down its overall protein synthesis. The mechanism is well studied in enteric bacteria, which mainly hibernate its ribosome in 100S disome form through a dual domain, long HPF (HPFlong) or a single domain, short HPF (HPFshort) in concert with another ribosome modulation factor. Mycobacteria under hypoxia (low oxygen) stress overexpresses RafH protein regulated under DosR regulon, a critical factor for its survival. The RafH, a dual domain HPF, an orthologue of bacterial HPFlong, hibernates ribosome in 70S monosome form only. Here we report the cryo-EM structure ofMycobacterium smegmatis, a close homologue ofM. tuberculosis, 70S ribosome in complex with the RafH factor at an overall 2.8 Å resolution. The RafH N-terminus domain (NTD) is conserved and binds to the decoding center of the ribosomal small subunit, a similar binding site of HPFlongNTD, but additionally it also interacts with the inter subunit bridge, B2a. Contrary to the HPFlongCTD, the RafH CTD, which is larger, binds to a unique site at the platform binding center of the ribosomal small subunit and sandwiches between bS1 and uS11 ribosomal proteins. The two domain connecting linker regions, which remain mostly disordered in earlier reported HPFlongstructures, interacts mainly with the anti-Shine Dalgarno sequence of the 16S rRNA. The helix H54a of 23S rRNA, unique to the mycobacterial ribosome, adopts a different conformation and come close to RafH CTD, suggesting its role in ribosome hibernation. RafH inhibitsin-vitroprotein synthesis in a concentration dependent manner. Further, the modeling studies provided the structural basis for the incompatibility of mycobacterial ribosomes forming 100S like hibernating ribosomes.
A quantitative characterization of early neuron generation in the developing zebrafish telencephalon
Authors: Gimeno Glòria Casas , Dvorianinova Ekaterina , Lembke Carla-Sophie , Dijkstra Emma SC , Abbas Hussam , Liu Yuanyuan , Paridaen Judith TML 
Published: April 2023

AbstractThe adult brain is made up of anatomically and functionally distinct regions with specific neuronal compositions. At the root of this neuronal diversity are neural stem and progenitor cells (NPCs) that produce many neurons throughout embryonic development. During development, NPCs switch from initial expanding divisions to neurogenic divisions, which marks the onset of neurogenesis. Here, we aimed to understand when NPCs switch division modes to generate the first neurons in the anterior-most part of the zebrafish brain, the telencephalon. To this end, we used the deep learning-based segmentation method Cellpose and clonal analysis of individual NPCs to assess production of neurons by NPCs in the first 24 hours of zebrafish telencephalon development. Our results provide a quantitative atlas detailing the production of telencephalic neurons and NPC division modes between 14 and 24 hours post-fertilization. We find that within this timeframe, the switch to neurogenesis is gradual, with considerable heterogeneity in individual NPC neurogenic potential and division rates. This quantitative characterization of initial neurogenesis in the zebrafish telencephalon establishes a basis for future studies aimed at illuminating the molecular mechanisms and regulators of early neurogenesis.
A critical role for CaMKII in behavioral timescale synaptic plasticity in hippocampal CA1 pyramidal neurons
Authors: Xiao Kuo , Li Yiding , Chitwood Raymond A. , Magee Jeffrey C. 
Published: April 2023

AbstractBehavioral timescale synaptic plasticity (BTSP) is a type of non-Hebbian synaptic plasticity reported to underlie place field formation in the hippocampal CA1 neurons. Despite this important function, the molecular mechanisms underlying BTSP are poorly understood. The α-Calcium-calmodulin-dependent protein kinase II (αCaMKII) is activated by synaptic transmission-mediated calcium influx and its subsequent phosphorylation is central to synaptic plasticity. Because the activity of αCaMKII is known to outlast the event triggering phosphorylation, we hypothesized it could be involved in the extended timescale of the BTSP process. To examine the role of αCaMKII in BTSP, we performed whole-cell in-vivo and in-vitro recordings in CA1 pyramidal neurons from mice engineered to have a point mutation at the autophosphorylation site (T286A) causing accelerated signaling kinetics. Here we demonstrate a profound deficit in synaptic plasticity, strongly suggesting that αCaMKII signaling is required for BTSP. This study elucidates part of the molecular mechanism of BTSP and provides insight into the function of αCaMKII in place cell formation and ultimately learning and memory.TeaserThe molecular mechanisms of BTSP have been revealed to require the autophosphorylation of CaMKII.
Dynamic expectations: Behavioral and electrophysiological evidence of sub-second updates in reward predictions
Authors: Marciano Déborah , Bellier Ludovic , Mayer Ida , Ruvalcaba Michael , Lee Sangil , Hsu Ming , Knight Robert T. 
Published: April 2023

AbstractExpectations are often dynamic: any sports fan knows that expectations are rapidly updated as games unfold. Yet expectations have traditionally been studied as static. Here, using slot machines as a case study, we provide parallel behavioral and electrophysiological evidence of sub-second moment-to-moment changes in expectations. In Study 1, we show that the dynamics of the EEG signal before the slot machine stopped differed depending on the nature of the outcome, including not only whether the participant won or lost, but also how close they came to winning. In line with our predictions, Near Win Before outcomes (the slot machine stops one item before a match) were similar to Wins, but different than Near Win After (the machine stops one item after a match) and Full Miss (the machine stops two or three items from a match). In Study 2, we designed a novel behavioral paradigm to measure moment-to-moment changes in expectations via dynamic betting. We found that different outcomes also elicited unique expectation trajectories in the deceleration phase. Notably, these behavioral expectation trajectories paralleled Study 1’s EEG activity in the last second prior to the machine’s stop. In Studies 3 (EEG) and 4 (behavior) we replicated these findings in the loss domain where a match entails a loss. Again, we found a significant correlation between behavioral and EEG results. These four studies provide the first evidence that dynamic sub-second updates in expectations can be behaviorally and electrophysiologically measured. Our findings open up new avenues for studying the ongoing dynamics of reward expectations and their role in healthy and unhealthy cognition.
An accurate and interpretable model for antimicrobial resistance in pathogenicEscherichia colifrom livestock and companion animal species
Authors: Chung Henri C. , Foxx Christine L. , Hicks Jessica A. , Stuber Tod P. , Friedberg Iddo , Dorman Karin S. , Harris Beth 
Published: April 2023

AbstractUnderstanding the microbial genomic contributors to antimicrobial resistance (AMR) is essential for early detection of emerging AMR infections, a pressing global health threat in human and veterinary medicine. Here we used whole genome sequencing and antibiotic susceptibility test data from 980 disease causingEscherichia coliisolated from companion and farm animals to model AMR genotypes and phenotypes for 24 antibiotics. We determined the strength of genotype-to-phenotype relationships for 197 AMR genes with elastic net logistic regression. Model predictors were designed to evaluate different potential modes of AMR genotype translation into resistance phenotypes. Our results show a model that considers the presence of individual AMR genes and total number of AMR genes present from a set of genes known to confer resistance was able to accurately predict isolate resistance on average (mean F1score = 98.0%, SD = 2.3%, mean accuracy = 98.2%, SD = 2.7%). However, fitted models sometimes varied for antibiotics in the same class and for the same antibiotic across animal hosts, suggesting heterogeneity in the genetic determinants of AMR resistance. We conclude that an interpretable AMR prediction model can be used to accurately predict resistance phenotypes across multiple host species and reveal testable hypotheses about how the mechanism of resistance may vary across antibiotics within the same class and across animal hosts for the same antibiotic.
A gendered discourse on truthful disclosure of financial fraud practices among accountants in China: implications to corporate governance
Authors: Tan Kim-Lim , Liu Yuming , Ye Qiuting 
Published: April 2023

Purpose
With the worsening of corporate fraud and consequential loss, the growing importance of truthful disclosure is globally advocated. This study aims to examine corporate governance’s role in accountants’ intention to disclose fraudulent practices honestly. At the same time, this study examines intergender differences concerning the formation of the disclosure intention.

Design/methodology/approach
Based on the theory of planned behavior (TPB), data from 256 accountants working in China have been collected via an online survey. This data is subsequently analyzed with the partial least square (PLS) structural equation modeling method.

Findings
The results revealed that integrity and corporate governance significantly positively affect employees’ attitudes, subjective norms and perceived behavioral control toward disclosure intention. At the same time, it shows that only subjective norm and perceived behavioral control established a significant positive relationship with disclosure intention. It also shows that males display higher attitudes and perceived behavioral control in developing the intention.

Originality/value
This study helps understand accountants’ disclosure intention of fraud practices, especially during shock events such as the COVID-19 pandemic. To the best of the authors’ knowledge, this study is the first to extend the TPB incorporating corporate governance and integrity as antecedents to disclosure intention. At the same time, this study contributes to the existing literature by being the first attempt to investigate intergender differences. Finally, it advances the body of knowledge on employees’ behavior and contributes methodologically by introducing the PLS approach.