bluuebunny/crossref_metadata_2025 huggingface dataset:
Chasing SARS-CoV-2 XBB.1.16 Recombinant Lineage in India and the Clinical Profile of XBB.1.16 cases in Maharashtra, India
Authors: Karyakarte Rajesh P. , Das Rashmita , Rajmane Mansi V. , Dudhate Sonali , Agarasen Jeanne , Pillai Praveena , Chandankhede Priyanka M. , Labhshetwar Rutika S. , Gadiyal Yogita , Kulkarni Preeti P. , Nizarudeen Safanah , Joshi Suvarna , Karmodiya Krishanpal , Potdar Varsha
Published: April 2023

Background

SARS-CoV-2 has evolved rapidly, resulting in emergence of lineages with competitive advantage over one another. Co-infections with different SARS-CoV-2 lineages can give rise to recombinant lineages. To date, XBB lineage is the most widespread recombinant lineage worldwide, with the recently named XBB.1.16 lineage causing a surge in the number of COVID-19 cases in India.

Methodology

The present study involved retrieval of SARS-CoV-2 genome sequences from India (between 1stDecember 2022 and 8thApril 2023) through GISAID; sequences were curated, followed by lineage and phylogenetic analysis. Demographic and clinical data from Maharashtra, India were collected telephonically, recorded in Microsoft® Excel, and analysed using IBM® SPSS statistics, version 29.0.0.0 (241).

Results

A total of 2,944 sequences were downloaded from the GISAID database, of which 2,856 were included in the study following data curation. The sequences from India were dominated by the XBB.1.16* lineage (36.17%) followed by XBB.2.3* (12.11%) and XBB.1.5* (10.36%). Of the 2,856 cases, 693 were from Maharashtra; 386 of these were included in the clinical study. The clinical features of COVID-19 cases with XBB.1.16* infection (XBB.1.16* cases, 276 in number) showed that 92% of those had a symptomatic disease, with fever (67%), cough (42%), rhinorrhoea (33.7%), body ache (14.5%) and fatigue (14.1%) being the most common symptoms. Presence of comorbidity was found in 17.7% of the XBB.1.16* cases. Among the XBB.1.16* cases, 91.7% were vaccinated with at least one dose of vaccine against COVID-19. While 74.3% of XBB.1.16* cases were home-isolated; 25.7% needed hospitalization/institutional quarantine, of these, 33.8% needed oxygen therapy. Out of 276 XBB.1.16* cases, seven (2.5%) cases succumbed to the disease. Majority of XBB.1.16* cases who died belonged to an elderly age group (60 years and above), had underlying comorbid condition/s, and needed supplemental oxygen therapy. The clinical features of COVID-19 cases infected with other co-circulating Omicron variants were similar to XBB.1.16* cases.

Conclusion

The study reveals that XBB.1.16* lineage has become the most predominant SARS-CoV-2 lineage in India. The study also shows that the clinical features and outcome of XBB.1.16* cases were similar to those of other co-circulating Omicron lineage infected cases in Maharashtra, India.
Screening for Post-Traumatic Stress Disorder following Childbirth using the Peritraumatic Distress Inventory
Authors: Jagodnik Kathleen M. , Ein-Dor Tsachi , Chan Sabrina J. , Ashkenazy Adi Titelman , Bartal Alon , Dekel Sharon
Published: April 2023

Background

Maternal psychiatric morbidities include a range of psychopathologies; one condition is post-traumatic stress disorder (PTSD) that develops following a traumatic childbirth experience and may undermine maternal and infant health. Although assessment for maternal mental health problems is integrated in routine perinatal care, screening for maternal childbirth-related PTSD (CB-PTSD) remains lacking. Acute emotional distress in response to a traumatic event strongly associates with PTSD. The brief 13-item Peritraumatic Distress Inventory (PDI) is a common tool to assess acute distress in non-postpartum individuals. How well the PDI specified to childbirth can classify women likely to endorse CB-PTSD is unknown.

Objectives

We sought to determine the utility of the PDI to detect CB-PTSD in the early postpartum period. This involved examining the psychometric properties of the PDI specified to childbirth, pertaining to its factorial structure, and establishing an optimal cutoff point for the classification of women with high vs. low likelihood of endorsing CB-PTSD.

Study Design

A sample of 3,039 eligible women who had recently given birth provided information about their mental health and childbirth experience. They completed the PDI regarding their recent childbirth event, and a PTSD symptom screen to determine CB-PTSD. We employed Exploratory Graph Analysis (EGA) and bootstrapping analysis to reveal the factorial structure of the PDI and the optimal PDI cutoff value for CB-PTSD classification.

Results

Factor analysis of the PDI shows two strongly correlated stable factors based on a modified 12-item version of the PDI consisting of (1) negative emotions and (2) bodily arousal and threat appraisal in regard to recent childbirth. This structure largely accords with prior studies of individuals who experienced acute distress resulting from other forms of trauma. We report that a score of 15 or higher on the modified PDI produces strong sensitivity and specificity. 88% of women with a positive CB-PTSD screen in the first postpartum months and 93% with a negative screen are identified as such using the established cutoff.

Conclusions

Our work reveals that a brief self-report screening concerning a woman’s immediate emotional reactions to childbirth that uses our modified PDI tool can detect women likely to endorse CB-PTSD in the early postpartum period. This form of maternal mental health assessment may serve as the initial step of managing symptoms to ultimately prevent chronic symptom manifestation. Future research is needed to examine the utility of employing the PDI as an assessment performed during maternity hospitalization stay in women following complicated deliveries to further guide recommendations to implement maternal mental health screening for women at high risk for developing CB-PTSD.
Comparison of three bioinformatics tools in the detection of ASD candidate variants from whole exome sequencing data
Authors: Shil Apurba , Levin Liron , Golan Hava , Meiri Gal , Michaelovski Analya , Tsadaka Yair , Aran Adi , Dinstein Ilan , Menashe Idan
Published: April 2023

Background

Autism spectrum disorder (ASD) is a heterogenous multifactorial neurodevelopmental condition with a significant genetic susceptibility component. Thus, identifying genetic variations associated with ASD is a complex task. Whole-exome sequencing (WES) is an effective approach for detecting extremely rare protein-coding single-nucleotide variants (SNVs) and short insertions/deletions (INDELs). However, interpreting these variants’ functional and clinical consequences requires integrating multifaceted genomic information.

Methods

We compared the concordance and effectiveness of three bioinformatics tools in detecting ASD candidate variants (SNVs and short INDELs) from WES data of 220 ASD family trios registered in the National Autism Database of Israel. We studied only rare (<1% population frequency) proband-specific variants. According to the American College of Medical Genetics (ACMG) guidelines, the pathogenicity of variants was evaluated by theInterVarandTAPEStools. In addition, likely gene-disrupting (LGD) variants were detected based on an in-house bioinformatics tool,Psi-Variant, that integrates results from seven in-silico prediction tools.

Results

Overall, 605 variants in 499 genes distributed in 193 probands were detected by these tools. The overlap between the tools was 64.1%, 17.0%, and 21.6% forInterVar–TAPES,InterVar–Psi-Variant, andTAPES–Psi-Variant, respectively. The intersection betweenInterVarandPsi-Variant(I∩P) was the most effective approach in detecting variants in known ASD genes (OR = 5.38, 95% C.I. = 3.25–8.53), while the union ofInterVarandPsi-Variant(IUP) achieved the highest diagnostic yield (30.9%).

Conclusions

Our results suggest that integrating different variant interpretation approaches in detecting ASD candidate variants from WES data is superior to each approach alone. The inclusion of additional criteria could further improve the detection of ASD candidate variants.
Perceived norms about male circumcision and personal circumcision status: a cross-sectional, population-based study in rural Uganda
Authors: Perkins Jessica M. , Kakuhikire Bernard , Baguma Charles , Jeon Sehee , Walker Sarah F. , Dongre Rohit , Kyokunda Viola , Juliet Mercy , Satinsky Emily N. , Comfort Alison B. , Siedner Mark , Ashaba Scholastic , Tsai Alexander C.
Published: April 2023

Introduction

Over the past decade, 15 high-priority countries in eastern and southern Africa have promoted voluntary medical male circucmsion for HIV and STI prevention. Despite male circumcision prevalence in Uganda nearly doubling from 26% in 2011 to 43% in 2016, it remained below the target level by 2020. Little is known about perceived norms of male circumcision and their association with circumcision uptake among men.

Methods

We conducted a cross-sectional study targeting all adult residents across eight villages in Rwampara District, southwestern Uganda in 2020-2022. We compared what men and women reported as the adult male circumcision prevalence within their village (perceived norm: >50% (most), 10% to <50% (some), <10%, (few), or do not know) to the aggregated prevalence of circumcision as reported by men aged <50 years. We used a modified multivariable Poisson regression model to estimate the association between perceived norms about male circumcision uptake and personal circumcision status among men.

Results

Overall, 167 (38%) men < 50 years old were circumcised (and 27% of all men were circumcised). Among all 1566 participants (91% response rate), 189 (27%) men and 177 (20%) women underestimated the male circumcision prevalence, thinking that few men in their own village had been circumcised. Additionally, 10% of men and 25% of women reported not knowing the prevalence. Men who underestimated the prevalence were less likely to be circumcised (aRR = 0.51, 95% CI 0.37 to 0.83) compared to those who thought that some village men were circumcised, adjusting for perceived personal risk of HIV, whether any same-household women thought most men were circumcised, and other sociodemographic factors.

Conclusions

Across eight villages, a quarter of the population underestimated the local prevalence of male circumcision. Men who underestimated circumcision uptake were less likely to be circumcised. Future research should evaluate norms-based approaches to promoting male circumcision uptake. Strategies may include disseminating messages about the increasing prevalence of adult male circumcision uptake in Uganda and providing personalized normative feedback to men who underestimated local rates about how uptake is greater than they thought.
Potential hiddenPlasmodium vivaxmalaria reservoirs from low parasitemia Duffy-negative Ethiopians: molecular evidence
Authors: Abebe Abnet , Bouyssou Isabelle , Mabilotte Solenne , Dugassa Sisay , Assefa Ashenafi , Juliano Jonathan J. , Lo Eugenia , Menard Didier , Golassa Lemu
Published: April 2023

Background

The interaction between thePlasmodium vivaxDuffy-binding protein and the corresponding Duffy Antigen Receptor for Chemokines (DARC) is primarily responsible for the invasion of reticulocytes byP. vivax. The Duffy-negative host phenotype, highly prevalent in sub-Saharan Africa, is caused by a single point mutation in the GATA-1 transcription factor binding site of the DARC gene promoter. The aim of this study was to assess the Duffy status of patients withP. vivaxinfection from different study sites in Ethiopia.

Methods

A cross-sectional study was conducted from February 2021 to September 2022 at five varying eco-epidemiological malaria endemic sites in Ethiopia. Outpatients who were diagnosed withP. vivaxinfection (pure and mixedP. vivax/P. falciparum) by microscopy were subjected to qPCR genotyping at the DARC promoter. The associations betweenP. vivaxinfection, host genotypes and other factors were evaluated.

Result

In total, 361 patients withP. vivaxinfection were included in the study. Patients with pureP. vivaxinfections accounted for 89.8% (324/361), while the remaining 10.2% (37/361) had mixedP. vivax/P. falciparuminfections. About 95.6% (345/361) of the participants were Duffy-positives (21.2% homozygous and 78.8%, heterozygous) and 4.4% (16/361) were Duffy-negatives. The mean asexual parasite density in homozygous and heterozygous Duffy-positives was 12,165 p/µl (IQR25-75: 1,640-24,234 p/µl) and11,655 p/µl (IQR25-75: 1,676-14,065 p/µl), respectively, significantly higher than that in Duffy-negatives (1,227p/µl; IQR25-75: 539-1,732p/µl).

Conclusion

This study confirms that Duffy-negativity does not provide complete protection againstP. vivaxinfection. The development ofP. vivax-specific elimination strategies, including alternative antimalarial vaccines should be facilitated by a better understanding of the epidemiological landscape ofvivaxmalaria in Africa. More importantly, low parasitemia associated withP. vivaxinfections in Duffy-negative patients may represent hidden reservoirs of transmission in Ethiopia.

Author Summary

Plasmodium vivaxgenerally receives less attention thanP. falciparumand was neglected in sub-Saharan Africa. However, the characteristics ofP. vivaxinfection in Duffy-negative individuals, and the distribution of Duffy blood group in different eco-epidemiological zones and ethnic groups of Ethiopia are not well documented. Here, we determined the Duffy genotypes ofP. vivaxinfected patients across broad regions of Ethiopia. It is clear that Duffy negative individuals in Ethiopia are not fully protected againstP. vivaxinfection, and that these infections in Duffy negatives are often associated with low parasitemia. Our findings lend support to the notion thatP. vivaxmay have developed a Duffy-independent erythrocyte invasion pathway and/or evolution in host immune responses.
Geospatial Patterns of Progress towards UNAIDS “95-95-95” Targets and Community Vulnerability in Zambia
Authors: Cuadros Diego F , Chowdhury Tuhin , Milali Masabho , Citron Daniel , Nyimbili Sulani , Vlahakis Natalie , Savory Theodora , Mulenga Lloyd , Sivile Suilanji , Zyambo Khozya , Bershteyn Anna
Published: April 2023

In sub-Saharan Africa, HIV/AIDS remains a leading cause of death. The UNAIDS established the “95-95-95” targets to improve HIV care continuum outcomes. Using geospatial data from the Zambia Population-based HIV Impact Assessment (ZAMPHIA), this study aims to investigate geospatial patterns in the “95-95-95” indicators and individual-level determinants that impede HIV care continuum in vulnerable communities, providing insights into the factors associated with gaps. This study used data from the 2016 ZAMPHIA to investigate the geospatial distribution and individual-level determinants of engagement across the HIV care continuum in Zambia. Gaussian kernel interpolation and optimized hotspot analysis were used to identify geospatial patterns in the HIV care continuum, while geospatial k-means clustering was used to partition areas into clusters. The study also assessed healthcare availability, access, and social determinants of healthcare utilization. Multiple logistic regression models were used to examine the association between selected sociodemographic and behavioral covariates and the three main outcomes of study. Varied progress towards the “95-95-95” targets were observed in different regions of Zambia. Each “95” displayed a unique geographic pattern, independent of HIV prevalence, resulting in four distinct geographic clusters. Factors associated with gaps in the “95s” include younger age, male sex, and low wealth, with younger individuals having higher odds of not being on ART and having detectable viral loads. Our study revealed significant spatial heterogeneity in the HIV care continuum in Zambia, with different regions exhibiting unique geographic patterns and levels of performance in the “95-95-95” targets, highlighting the need for geospatial tailored interventions to address the specific needs of different subnational regions. These findings underscore the importance of addressing differential regional gaps in HIV diagnosis, enhancing community-level factors, and developing innovative strategies to improve local HIV care continuum outcomes.
An unbiasedde novonetwork analysis uncovering causal genes and the developmental intersection between autism and co-occurring traits
Authors: Miller Catriona J. , Golovina Evgeniia , Wicker Joerg S , Jacobsen Jessie C , O’Sullivan Justin M.
Published: April 2023

Autism is a complex neurodevelopmental condition that manifests in various ways. Autism is often accompanied by other neurological disorders, such as ADHD, anxiety, and schizophrenia, which can complicate diagnosis and management. While research has investigated the role of specific genes in autism, their relationship with co-occurring traits is not fully understood.

To address this gap, we conducted a two-sample Mendelian Randomisation analysis and identified four genes located at the 17q21.31 locus that are causally linked to autism in fetal cortical tissue (i.e.LINC02210, LRRC37A4P, RP11-259G18.1, RP11-798G7.6). LINC02210was also identified as being causally related to autism in adult cortical tissue. By integrating data from expression quantitative trait loci [eQTLs], genes, and protein interactions we identified that the 17q21.31 locus contributes to the intersection between autism and other neurological traits and conditions in fetal cortical tissue. We also identified an additional distinct cluster of co-occurring traits, including cognition and worry, linked to genetic loci at 3p21.1.

Our results support the hypothesis that an individual’s autism phenotype is partially determined by their genetic risk for co-occurring conditions. Overall, our findings provide insights into the complex relationship between autism and co-occurring conditions, which could be used to develop predictive models for more accurate diagnosis and better clinical management.
Trends in Cardiac Arrest Outcomes & Management in Children with Cardiac Disease: An Analysis from the AHA Get With The Guidelines®-Resuscitation Registry
Authors: Gardner Monique M. , Morgan Ryan W. , Reeder Ron , Ghaffari Kimia , Ortmann Laura , Raymond Tia , Lasa Javier J. , Fowler Jessica , Dewan Maya , Nadkarni Vinay , Berg Robert A. , Sutton Robert , Topjian Alexis ,   the American Heart Association’s Get With The Guidelines®-Resuscitation Investigators
Published: April 2023

Introduction

Contemporary rates of survival after pediatric in-hospital cardiac arrest (IHCA) and trends in survival over the last 20 years have not been compared based on illness category. We hypothesized that survival to hospital discharge for surgical-cardiac category is higher than the non-cardiac category, and rates of survival after IHCA increased over time in all categories.

Methods

The AHA Get With The Guidelines®-Resuscitation registry was queried for index IHCA events in children <18 years of age from 2000-2021. Categories were surgical-cardiac (IHCA following cardiac surgery); medical-cardiac (IHCA in non-surgical cardiac disease); and non-cardiac (IHCA in patients without cardiac disease). The primary outcome was survival to hospital discharge. We compared eras 2000-2004, 2005-2009, 2010-2014, and 2015-2021 with mixed logistic regression models, including event year as a continuous predictor and site as a random effect.

Results

Of 17,696 index events, IHCA rates by illness category were: 18% surgical-cardiac, 18% medical-cardiac, and 64% non-cardiac. Surgical-cardiac category had the highest rate of survival to discharge compared to medical-cardiac and non-cardiac categories (56% vs. 43% vs. 46%; p<0.001). After controlling for age, location of event, and hospital size, the odds of survival were highest for surgical-cardiac category (aOR 1.28, 95% CI 1.16-1.40) and lower for medical-cardiac category (aOR 0.87, 0.80-0.95), compared to the non-cardiac category. Odds of survival increased for all illness categories from the 2000-2004 era to the 2015-2021 era. Rates of improvement differed among illness categories with medical-cardiac having the lowest increased odds per era. Surgical-cardiac patients had the highest rates of extracorporeal resuscitation (ECPR) (20% across the cohort), though the greatest increase in ECPR utilization was in the non-cardiac population (44% increased odds per era).

Conclusions

Over the last 20 years, both survival to hospital discharge and ECPR use has increased in all IHCA illness categories. Children with surgical-cardiac IHCA have higher odds of survival to hospital discharge compared to non-cardiac IHCA categories, whereas odds of survival were lowest with medical-cardiac IHCA.
CD3+T-cell: CD14+monocyte complexes are dynamic and increased with HIV and glucose intolerance
Authors: Obare Laventa M. , Simmons Joshua , Oakes Jared , Zhang Xiuqi , Nochowicz Cindy , Priest Stephen , Bailin Samuel S. , Warren Christopher M. , Mashayekhi Mona , Beasley Heather K. , Shao Jianqiang , Meenderink Leslie M. , Sheng Quanhu , Stolze Joey , Gangula Rama , Absi Tarek , Su Yan Ru , Neikirk Kit , Chopra Abha , Gabriel Curtis L. , Temu Tecla , Pakala Suman , Wilfong Erin M. , Gianella Sara , Phillips Elizabeth J. , Harrison David G. , Hinton Antentor , Kalams Spyros A. , Kirabo Annet , Mallal Simon A. , Koethe John R. , Wanjalla Celestine N.
Published: April 2023

An increased risk of cardiometabolic disease accompanies persistent systemic inflammation. Yet, the innate and adaptive immune system features in persons who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled HIV as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14+monocytes complexed to CD3+T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3+T-cell: CD14+monocyte complexes had more HIV copies compared to matched CD14+monocytes or CD4+T cells alone. Our results demonstrate that circulating CD3+T-cell:CD14+monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis and may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cell-monocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes.

Abstract Figure

Highlights

Circulating CD3+CD14+T cell-monocyte complexes are higher in individuals with diabetes.

CD3+CD14+T cell-monocytes complexes comprise a heterogenous group of functional and dynamic cell-cell interactions.

The proportion of CD3+CD14+T cell-monocyte complexes is positively associated with fasting blood glucose and negatively with plasma IL-10 levels and CD4+T regulatory cells.

CD3+CD14+T cell-monocyte complexes are metabolically flexible and can utilize both glycolysis and oxidative phosphorylation for their energy requirements.

In persons with treated HIV, CD3+CD14+T cell-monocytes have more detectable HIV DNA than circulating CD4+T cells alone.
REVEILLE2Thermosensitive Splicing: A Molecular Basis for the Integration of Nocturnal Temperature Information by the Arabidopsis Circadian Clock
Authors: James Allan B. , Sharples Chantal , Laird Janet , Armstrong Emily May , Guo Wenbin , Tzioutziou Nikoleta , Zhang Runxuan , Brown John W.S. , Nimmo Hugh G. , Jones Matthew A.
Published: April 2023

Cold stress is one of the major environmental factors that limit growth and yield of plants. However, it is still not fully understood how plants account for daily temperature fluctuations, nor how these temperature changes are integrated with other regulatory systems such as the circadian clock.

We demonstrate that REVEILLE2, a MYB-like transcription factor, exhibits a cold-induced alternative splicing switch from a non-translatable isoform at ambient temperature to a translatable isoform upon cold exposure. We explore the biological function ofREVEILLE2using a combination of molecular genetics, transcriptomics, and physiology.

Disruption of theREVEILLE2cooling switch alters regulatory gene expression, impairs circadian timing, and improves photosynthetic capacity. Changes in nuclear gene expression are particularly apparent in the initial hours following chilling, with chloroplast gene expression subsequently up-regulated.

TheREVEILLE2cold switch extends our understanding of plants immediate response to cooling. We propose that the circadian componentREVEILLE2restricts plants responses to nocturnal reductions in temperature, thereby enabling appropriate responses to daily environmental changes.

Plain language summary

Plants need to respond appropriately to temperature, accounting for the expected daily patterns of reduced temperatures that occur every night relative to the day. Here, we show that a gene expressed at night fulfils this function.
The ortholog of human REEP1-4 is required for autophagosomal enclosure of ER-phagy/nucleophagy cargos in fission yeast
Authors: Zou Chen-Xi , Ma Zhu-Hui , Jiang Zhao-Di , Pan Zhao-Qian , Xu Dan-Dan , Suo Fang , Shao Guang-Can , Dong Meng-Qiu , Du Li-Lin
Published: April 2023

Selective macroautophagy of the endoplasmic reticulum (ER) and the nucleus, known as ER-phagy and nucleophagy respectively, are processes whose mechanisms remain inadequately understood. Through an imaging-based screen, we find that in the fission yeastSchizosaccharomyces pombe, Yep1 (also known as Hva22 or Rop1), the ortholog of human REEP1-4, is essential for ER-phagy and nucleophagy, but not for bulk autophagy. In the absence of Yep1, the initial phase of ER-phagy and nucleophagy proceeds normally, with the ER-phagy/nucleophagy receptor Epr1 co-assembling with Atg8. However, ER-phagy/nucleophagy cargos fail to reach the vacuole. Instead, nucleus- and cortical-ER-derived membrane structures not enclosed within autophagosomes accumulate in the cytoplasm. Intriguingly, the outer membranes of nucleus-derived structures remain continuous with the nuclear envelope-ER network, suggesting a possible outer membrane fission defect during cargo separation from source compartments. We find that the ER-phagy role of Yep1 relies on its abilities to self-interact and shape membranes, and requires its C-terminal amphipathic helices. Moreover, we show that human REEP1-4 and budding yeast Atg40 can functionally substitute for Yep1 in ER-phagy, and Atg40 is a divergent ortholog of Yep1 and REEP1-4. Our findings uncover an unexpected mechanism governing the autophagosomal enclosure of ER-phagy/nucleophagy cargos and shed new light on the functions and evolution of REEP family proteins.
Spatio-temporal X-linked gene reactivation and site-specific retention of epigenetic silencing in the mouse germline
Authors: Roidor Clara , Syx Laurène , Beyne Emmanuelle , Zielinski Dina , Teissandier Aurélie , Lee Caroline , Walter Marius , Servant Nicolas , Chebli Karim , Bourc’his Déborah , Surani M. Azim , Borensztein Maud
Published: April 2023

Random X-chromosome inactivation (XCI) is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long non-coding RNAXist, occurs in the epiblast and is stably maintained to ensure proper dosage compensation of X-linked genes during life. However, this silencing is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling in developingin vivoPGC, we provide unprecedented detailed maps of gene reactivation. We demonstrated that PGC still carry a fully silent X chromosome on embryonic day (E) 9.5, despite the loss ofXistexpression. X-linked genes are then gradually reactivated outside theXistfirst-bound regions. At E12.5, a significant part of the inactive X chromosome (Xi) still resists reactivation, carrying an epigenetic memory of its silencing. Late-reactivated genes are enriched in repressive chromatin marks, including DNA methylation and H3K27me3 marks. Our results define the timing of reactivation of the silent X chromosome a key event in female PGC reprogramming with direct implications for reproduction.
Annelid adult cell type diversity and their pluripotent cellular origins
Authors: Álvarez-Campos Patricia , García-Castro Helena , Emili Elena , Pérez-Posada Alberto , Salamanca-Díaz David A. , Mason Vincent , Metzger Bria , Bely Alexandra E. , Kenny Nathan , Özpolat B. Duygu , Solana Jordi
Published: April 2023

Annelids are a broadly distributed, highly diverse, economically and environmentally important group of animals. Most species can regenerate missing body parts, and many are able to reproduce asexually. Therefore, many annelids can generate all adult cell types in adult stages. However, the putative adult stem cell populations involved in these processes, as well as the diversity of adult cell types generated by them, are still unknown. Here, we recover 75,218 single cell transcriptomes ofPristina leidyi, a highly regenerative and asexually-reproducing freshwater annelid. We characterise all major annelid adult cell types, and validate many of our observations by HCRin situhybridisation. Our results uncover complex patterns of regionally expressed genes in the annelid gut, as well as neuronal, muscle and epidermal specific genes. We also characterise annelid-specific cell types such as the chaetal sacs andglobin+ cells, and novel cell types of enigmatic affinity, including avigilin+ cell type, alumbrokinase+ cell type, and a diverse set of metabolic cells. Moreover, we characterise transcription factors and gene networks that are expressed specifically in these populations. Finally, we uncover a broadly abundant cluster of putative stem cells with a pluripotent signature. This population expresses well-known stem cell markers such asvasa, piwiandnanoshomologues, but also shows heterogeneous expression of differentiated cell markers and their transcription factors. In thesepiwi+ cells, we also find conserved expression of pluripotency regulators, including multiple chromatin remodelling and epigenetic factors. Finally, lineage reconstruction analyses reveal the existence of differentiation trajectories frompiwi+ cells to diverse adult types. Our data reveal the cell type diversity of adult annelids for the first time and serve as a resource for studying annelid cell types and their evolution. On the other hand, our characterisation of apiwi+cell population with a pluripotent stem cell signature will serve as a platform for the study of annelid stem cells and their role in regeneration.
De Novo Design of κ-Opioid Receptor Antagonists Using a Generative Deep Learning Framework
Authors: Salas-Estrada Leslie , Provasi Davide , Qui Xing , Kaniskan H. Ümit , Huang Xi-Ping , DiBerto Jeffrey F. , Ribeiro João Marcelo Lamim , Jin Jian , Roth Bryan L. , Filizola Marta
Published: April 2023

Likely effective pharmacological interventions for the treatment of opioid addiction include attempts to attenuate brain reward deficits during periods of abstinence. Pharmacological blockade of the κ-opioid receptor (KOR) has been shown to abolish brain reward deficits in rodents during withdrawal, as well as to reduce the escalation of opioid use in rats with extended access to opioids. Although KOR antagonists represent promising candidates for the treatment of opioid addiction, very few potent selective KOR antagonists are known to date and most of them exhibit significant safety concerns. Here, we used a generative deep learning framework for thede novodesign of chemotypes with putative KOR antagonistic activity. Molecules generated by models trained with this framework were prioritized for chemical synthesis based on their predicted optimal interactions with the receptor. Our models and proposed training protocol were experimentally validated by binding and functional assays.
Clathrin light chains CLCa and CLCb have non-redundant roles in epithelial lumen formation
Authors: Chen Yu , Briant Kit , Camus Marine D. , Brodsky Frances M.
Published: April 2023

To identify functional differences between vertebrate clathrin light chains (CLCa or CLCb), phenotypes of mice lacking genes encoding either isoform were characterised. Mice without CLCa displayed 50% neonatal mortality, reduced body weight, reduced fertility, and ∼40% of aged females developed uterine pyometra. Mice lacking CLCb displayed a less severe weight reduction phenotype compared to those lacking CLCa, and had no survival or reproductive system defects. Analysis of female mice lacking CLCa that developed pyometra revealed ectopic expression of epithelial differentiation markers (FOXA2 and K14) and a reduced number of endometrial glands, indicating defects in the lumenal epithelium. Defects in lumen formation and polarity of epithelial cysts derived from uterine or gut cell lines were also observed when either CLCa or CLCb were depleted, with more severe effects from CLCa depletion. In cysts, the CLC isoforms had different distributions relative to each other, while they converge in tissue. Together, these findings suggest differential and cooperative roles for CLC isoforms in epithelial lumen formation, with a dominant function for CLCa.
Genomic characterization of a pandrug-resistantKlebsiella pneumoniaebelonging to the high-risk ST11 in the Brazilian Amazon region
Authors: Fonseca Érica L. , Morgado Sérgio M. , Freitas Fernanda S. , Bighi Nathalia S. , Cipriano Rosângela , Vicente Ana Carolina P.
Published: April 2023

Pandrug-resistant (PDR)K. pneumoniaehas been reported sporadically in many countries and remains rare in Brazil. The lack of genomic studies limits the comprehension of the determinants mostly involved with the PDR emergence inK. pneumoniae. This study aimed to unravel the main genetic determinants involved with the PDR background of a clinical ST11K. pneumoniaerecovered in the Brazilian Amazon region. The carbapenem-resistant Kp196 was submitted to WGS and its intrinsic and acquired resistome was assessed by CARD and comparison with wild-type genes. Kp196 resistome was composed of acquired resistance determinants and mutations in chromosomal genes. Among the formers,blaCTX-M-15andblaNDM-1,blaOXA-9,blaOXA-1,aadA1, aacA4, strAB, aph(3’)-VI, aac(3)-IId, qnrS1, qnrB1, oqxAB, dfrA14, sul2, catB3were found in the vicinity of mobile genetic elements, which could contribute to their spread. Kp196 colistin resistance was multifactorial and attributed to modifications in ArnT (M114L/V117I/R372K), PhoQ (D150G), and themgrBdisruption by ISKpn25. Besides the presence ofqnrandoqxABgenes, Kp196 also presented altered GyrA (S83I) and ParC (S80I). Anin-blockdeletion in the repressor RamR, contributing toacrABoverexpression, and the presence of an enhanced-function AcrB variant (S966A), probably led to the Kp196 multidrug and tigecycline resistance. Insertions,in-blockdeletion, and missense mutations were involved withompK35-36-37inactivation, also accounting for the Kp196 multidrug resistance, including carbapenems. The Kp196 PDR profile, especially the carbapenem resistance, was due to the accumulation of different mechanisms, in which modifications in housekeeping genes accounted for a more stable resistome.
Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice
Authors: Lee Katherine S , Rader Nathaniel A , Miller Olivia A , Cooper Melissa , Wong Ting Y , Amin Md. Shahrier , Barbier Mariette , Bevere Justin R , Ernst Robert K , Damron F. Heath
Published: April 2023

As the COVID-19 pandemic transitions to endemic, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen- based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based agonist adjuvant, BECC 470. K18-hACE2 mice were primed and boosted at four-week intervals with either VLP-RBD-BECC or mRNA-1273. Both VLP-RBD-BECC and mRNA-1273 vaccination resulted in production of RBD-specific IgA antibodies in serum. RBD- specific IgA was also detected in the nasal wash and lung supernatants and were highest in VLP-RBD-BECC vaccinated mice. Interestingly, VLP-RBD-BECC vaccinated mice showed slightly lower levels of pre-challenge IgG responses, decreased RBD-ACE2 binding inhibition, and lower neutralizing activityin vitrothan mRNA-1273 vaccinated mice. Both VLP-RBD-BECC and mRNA-1273 vaccinated mice were protected against challenge with a lethal dose of Delta variant SARS-CoV-2. Both vaccines limited viral replication and viral RNA burden in the lungs of mice. CXCL10 is a biomarker of severe SARS-CoV-2 infection and we observed both vaccines limited expression of serum and lung CXCL10. Strikingly, VLP-RBD-BECC when administered intranasally, limited lung inflammation at early timepoints that mRNA-1273 vaccination did not. VLP-RBD-BECC immunization elicited antibodies that do recognize SARS-CoV-2 Omicron variant. However, VLP-RBD-BECC immunized mice were protected from Omicron challenge with low viral burden. Conversely, mRNA-1273 immunized mice had low to no detectable virus in the lungs at day 2. Together, these data suggest that VLP-based vaccines paired with BECC adjuvant can be used to induce protective mucosal and systemic responses against SARS- CoV-2.
The frequency of mutations in thepenA,mtrR,gyrA andparC genes ofNeisseria gonorrhoeae, the presence oftetM gene and antibiotic resistance/susceptibility: a systematic review and meta-analyses
Authors: Mendes Ana Clara , de Souza Renan Pedra , Bahia Diana
Published: April 2023

Sexually transmitted infections (STIs) are a major global public health problem and among the most common infectious diseases. Gonorrhoea is an STI that affects only humans, caused by the bacteriumNeisseria gonorrhoeae. In 2016, the WHO estimated that there were 86.9 million cases of gonorrhoea worldwide. Gonorrhoea is currently one of the most important STIs due to the increased spread and emergence of multiresistant strains. The main goal of this study was to analyse the relationship between resistance or decreased susceptibility to antibiotics inN. gonorrhoeaeand the presence of mutations in the genespenA,mtrR,tetM,gyrA andparC. Therefore, we conducted a systematic review following the PRISMA guidelines. We selected 19 studies for thepenA gene, 23 forgyrA andparC, 18 formtrR, and 12 fortetM using the Science Direct and PubMed databases. The included studies addressed susceptibility and resistance to antibiotics and mutations in the selected genes. Then, 21 different meta-analyses of the studies were performed. A meta-analysis was conducted when two or more studies were found for the same gene and the same antibiotic. Meta-analyses of isolates resistant to penicillin, cefixime, and ceftriaxone showed that more than 50% of the isolates had mutations in the genespenA andmtrR. Meanwhile, more than 50% of azithromycin-resistant isolates had mutations in themtrR gene, while more than 50% of the isolates resistant and intermediate-resistant to ciprofloxacin had mutations ingyrA. Moreover, less than 50% of isolates with intermediate resistance to ciprofloxacin had mutations inparC. The plasmid containing thetetM gene was found in more than 50% of tetracycline-resistant isolates. Infection monitoring and genetic studies are important to control the spread, which can improve the quality of life of infected individuals and lessen the financial burden on public healthcare systems.
MYT1L is required for suppressing earlier neuronal development programs in the adult mouse brain
Authors: Chen Jiayang , Fuhler Nicole A. , Noguchi Kevin K. , Dougherty Joseph D.
Published: April 2023

In vitro studies indicate the neurodevelopmental disorder gene myelin transcription factor 1-like (MYT1L) suppresses non-neuronal lineage genes during fibroblast-to-neuron direct differentiation. However, MYT1L's molecular and cellular functions in the adult mammalian brain have not been fully characterized. Here, we found that MYT1L loss leads to up-regulated deep layer (DL) gene expression, corresponding to an increased ratio of DL/UL neurons in the adult mouse cortex. To define potential mechanisms, we conducted Cleavage Under Targets & Release Using Nuclease (CUT&RUN) to map MYT1L binding targets and epigenetic changes following MYT1L loss in mouse developing cortex and adult prefrontal cortex (PFC). We found MYT1L mainly binds to open chromatin, but with different transcription factor co-occupancies between promoters and enhancers. Likewise, multiomic data set integration revealed that, at promoters, MYT1L loss does not change chromatin accessibility but increases H3K4me3 and H3K27ac, activating both a subset of earlier neuronal development genes as well asBcl11b, a key regulator for DL neuron development. Meanwhile, we discovered that MYT1L normally represses the activity of neurogenic enhancers associated with neuronal migration and neuronal projection development by closing chromatin structures and promoting removal of active histone marks. Further, we showed that MYT1L interacts with HDAC2 and transcriptional repressor SIN3B in vivo, providing potential mechanisms underlying repressive effects on histone acetylation and gene expression. Overall, our findings provide a comprehensive map of MYT1L binding in vivo and mechanistic insights into how MYT1L loss leads to aberrant activation of earlier neuronal development programs in the adult mouse brain.
Gender diversity, financial performance, and the moderating effect of CSR: empirical evidence from UK financial institutions
Authors: Ben Fatma Hanen , Chouaibi Jamel
Published: April 2023

Purpose

This study aims to examine the direct relationship between board gender diversity (BGD) and financial performance and the moderating role of corporate social responsibility (CSR) in the said relationship.

Design/methodology/approach

Using data collected from the Thomson Reuters Eikon ASSET4 database from 42 UK financial institutions listed in the ESG index for the period 2005–2019, this study used multivariate regression analysis on panel data to test the effect of BGD on financial performance and estimate the moderating effect of CSR between them. Moreover, to control the endogeneity problem, the authors conducted an additional analysis by testing the dynamic dimension of the data set through the generalized moment method.

Findings

The empirical results show that BGD is positively related to financial performance and that BGD increases firm performance with the moderating effect of CSR. Regarding the endogeneity problem, the existence of continuity between financial institution performances over time is demonstrated.

Research limitations/implications

The current paper sheds light on the importance of BGD in improving firm performance and the moderating role of CSR in strengthening the relationship between BGD and firm performance, thereby contributing to the agency theory, the resource dependency theory and the stakeholder theory. Therefore, regulators and policymakers in the UK can use the outcomes of this study to enforce the representation of female directors on boards to enhance the financial performance of financial institutions. Moreover, the findings could be useful for regulatory bodies to encourage financial institutions to practice CSR activities and disclose them in their annual reports.

Originality/value

To the best of the authors’ knowledge, this is the first study investigating the moderating role of CSR on the relationship between BGD and financial performance in the context of the financial sector. It is also the first study documenting that CSR reinforces the relationship between gender-diverse boards and financial institutions' performance. This study fills a research gap as it expands the existing literature that has generally focused on the impact of BGD on financial performance and has not reached similar results.
Exploring the topic structure and evolutionary trends of health informatics research in library and information science
Authors: Tian Peilin , Wang Le
Published: April 2023

Purpose

This study aims to reveal the topic structure and evolutionary trends of health informatics research in library and information science.

Design/methodology/approach

Using publications in Web of Science core collection, this study combines informetrics and content analysis to reveal the topic structure and evolutionary trends of health informatics research in library and information science. The analyses are conducted by Pajek, VOSviewer and Gephi.

Findings

The health informatics research in library and information science can be divided into five subcommunities: health information needs and seeking behavior, application of bibliometrics in medicine, health information literacy, health information in social media and electronic health records. Research on health information literacy and health information in social media is the core of research. Most topics had a clear and continuous evolutionary venation. In the future, health information literacy and health information in social media will tend to be the mainstream. There is room for systematic development of research on health information needs and seeking behavior.

Originality/value

To the best of the authors’ knowledge, this is the first study to analyze the topic structure and evolutionary trends of health informatics research based on the perspective of library and information science. This study helps identify the concerns and contributions of library and information science to health informatics research and provides compelling evidence for researchers to understand the current state of research.
The efficiency measurement of business intelligence systems in the big data-driven economy: a multidimensional model
Authors: Al-Okaily Aws , Teoh Ai Ping , Al-Okaily Manaf , Iranmanesh Mohammad , Al-Betar Mohammed Azmi
Published: April 2023

Purpose

There is a growing importance of business intelligence systems (BIS) adoption in today’s digital economy age which is characterized by uncertainty and ambiguity considering the magnitude and influence of data-related issues to be solved in contemporary businesses. This study aims to investigate critical success factors that affect business intelligence efficiency based on the DeLone and McLean model in Jordanian banking industry.

Design/methodology/approach

A quantitative research method through a questionnaire was used to collect data from actual users who depend on business intelligence tools to make operational and strategic decisions in Jordanian banks. The data obtained were tested using the partial least squares–structural equation modeling approach.

Findings

The survey findings attest that system quality, information quality, user quality, user satisfaction and user performance are important factors and contribute to business intelligence efficiency in the Jordanian banking industry.

Practical implications

The findings gained from this work can help policymakers in Jordanian banks to improve the business intelligence success and organizational performance.

Originality/value

To the best of the authors’ knowledge, this study is the first of its kind to propose a theoretical model to assess drivers of BIS efficiency from the Jordanian banks’ perspective.