bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial analysis of methicillin-resistantStaphylococcus aureuscarriage (MRSA) at hospital admission in a livestock dense region
Authors: Arntzen Vera H. , Feenstra Sabiena G. , Benincà Elisa , Le T.T.N. , Mascini Ellen M. , Nabuurs-Franssen Marrigje H. , Voss Andreas , Marik Agi M. , de Jong Eefje , Silvis Welmoed , Schijffelen Maarten J. , Schneeberger Peter , Hopman Joost , Korthals Altes Hester , Wertheim Heiman F.L.
Published: May 2023

Title

Spatial analysis of methicillin-resistantStaphylococcus aureuscarriage (MRSA) screening yield at hospital admission in a livestock-dense region

Purpose

In the Netherlands, patients with a risk factor for methicillin-resistantStaphylococcus aureus(MRSA) carriage, such as foreign hospital stay and contact with livestock (pigs, veal calves and/or broilers) are actively screened upon hospital admission. This study aimed to give insight in the geographical clustering patterns of MRSA carriage among these patients in a livestock-dense region.

Methods

A retrospective study was performed using medical records and laboratory results of MRSA screened patients admitted to seven hospitals in the provinces of Gelderland and Noord-Brabant, covering the period from 01/2011 to 02/2017. SaTScan spatial scanning identified cluster areas with an increased MRSA carriage risk in postal codes compared to the surrounding areas.

Results

15 546 patients were included, among which 10.0% (n=1499) were MRSA carriers. Four significant, typically highly pig-dense MRSA carriage hotspots were identified, where the relative risk of carriage ranged from 2.1 to 3.4 compared to the surrounding area.

Conclusion

MRSA carriage risk clustered in certain areas, suggesting an association between livestock density (mainly pigs) and the MRSA carriage risk for the screened population at hospital admission. It needs to be explored when proximity (not contact) to livestock should be considered a risk factor. Considering analytical difficulties we encountered it is recommended to harmonize culture methods and data acquisition across hospitals to facilitate analysis for improving MRSA screening policy.

Impacts

The fraction MRSA carriers among patients with livestock contact notified in the hospital system in this study was 22.7%, showing the effectiveness of the Search and Destroy policy.

MRSA carriage in the Dutch Province Gelderland is clustered in certain hotspots, located in pig-dense areas.

Culture methods and data acquisition should be harmonized across hospitals to facilitate analysis for improving MRSA screening policy.
Hear my Voice: Understanding how community health workers in the Peruvian Amazon expanded their roles to mitigate the impact of the COVID-19 pandemic through Community-Based Participatory Action Research
Authors: Samsamshariat Tina , Madhivanan Purnima , Reyes Alexandra , Moya Eva M. , Meza-Sánchez Graciela , Reinders Stefan , Blas Magaly M.
Published: May 2023

Introduction

The COVID-19 pandemic led to the collapse of the Peruvian health system, which disrupted healthcare access for indigenous communities in the Amazon. We aimed to understand how the COVID-19 pandemic transformed the responsibilities of community health workers (CHWs) from indigenous communities in the Peruvian Amazon so policymakers can support indigenous health efforts.

Methods

Fourteen CHWs from Loreto, Peru participated in a community-based Participatory Action Research (CBPR) project using Photovoice, a technique that encourages vulnerable groups to take photos and develop stories illustrating their lived experiences. Participants were recruited fromMamás del Río, a local university-based program, through purposive sampling. CHWs were trained in Photovoice and asked to photograph how the pandemic affected their lives and work. Participants met four times over five months to share photos and develop action items. Data were organized into key themes using a general inductive method. Final photos and action items were shared with policymakers during galleries in Iquitos and Lima.

Results

CHWs took a total of 36 photos with 33 accompanying texts highlighting their roles during the pandemic. Four core themes emerged: (1) the collapse of social infrastructure, (2) the use of medicinal plants versus pharmaceuticals, (3) the community adaptations and struggles, and (4) the importance of CHWs. CHWs expanded their responsibilities or leveraged their leadership across these themes to support COVID-19 patients, vaccination, and mandates without training or resources from the government. CHWs asked policymakers for formal integration into the health system, standardization of CHW training, and better management of community pharmacies.

Conclusion

CHWs, who work on a voluntary basis, took on additional roles during the pandemic with little to no training from the government. CHWs demonstrated how their roles could be better supported by the government to ameliorate future health catastrophes in the Peruvian Amazon.

Short Summary

Health care delivery in the Peruvian Amazon collapsed during the COVID-19 pandemic. Community health workers provided frontline care, education, and logistical support without formal training, resources, or compensation from the Ministry of Health. The government can better leverage, supervise, recognize, and integrate the role of community health workers to strengthen the health system.
Association of SARS-CoV-2 Infection and Cardiopulmonary Long COVID with Exercise Capacity and Chronotropic Incompetence among People with HIV
Authors: Durstenfeld Matthew S. , Peluso Michael J. , Spinelli Matthew A. , Li Danny , Hoh Rebecca , Gandhi Monica , Henrich Timothy J. , Aras Mandar A. , Long Carlin S. , Deeks Steven G. , Hsue Priscilla Y.
Published: May 2023

Background

Long COVID has been associated with reduced exercise capacity, but whether SARS-CoV-2 infection or Long COVID is associated with reduced exercise capacity among people with HIV (PWH) has not been reported. We hypothesized that PWH with cardiopulmonary post-acute symptoms of COVID-19 (PASC) would have reduced exercise capacity due to chronotropic incompetence.

Methods

We conducted cross-sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH. We evaluated associations of HIV, prior SARS-CoV-2 infection, and cardiopulmonary PASC with exercise capacity (peak oxygen consumption, VO2) and adjusted heart rate reserve (AHRR, chronotropic measure) with adjustment for age, sex, and body mass index.

Results

We included 83 participants (median age 54, 35% female). All 37 PWH were virally suppressed; 23 (62%) had prior SARS-CoV-2 infection, and 11 (30%) had PASC. Peak VO2was reduced among PWH (80% predicted vs 99%; p=0.005), a difference of 5.5 ml/kg/min (95%CI 2.7-8.2, p<0.001). Chronotropic incompetence more prevalent among PWH (38% vs 11%; p=0.002), and AHRR was reduced among PWH (60% vs 83%, p<0.0001). Among PWH, exercise capacity did not vary by SARS-CoV-2 coinfection, but chronotropic incompetence was more common among PWH with PASC: 3/14 (21%) without SARS-CoV-2, 4/12 (25%) with SARS-CoV-2 without PASC, and 7/11 (64%) with PASC (p=0.04 PASC vs no PASC).

Conclusions

Exercise capacity and chronotropy are lower among PWH compared to SARS-CoV-2 infected individuals without HIV. Among PWH, SARS-CoV-2 infection and PASC were not strongly associated with reduced exercise capacity. Chronotropic incompetence may be a mechanism limiting exercise capacity among PWH.
Open science practices in research published in surgical journals: A cross-sectional study
Authors: Pathak Kavya , Marwaha Jayson S. , Chen Hao Wei , Krumholz Harlan M. , Matthews Jeffrey B.
Published: May 2023

Open science practices are research tools used to improve research quality and transparency. These practices have been used by researchers in various medical fields, though the usage of these practices in the surgical research ecosystem has not been quantified. In this work, we studied the use of open science practices in general surgery journals. Eight of the highest-ranked general surgery journals by SJR2 were chosen and their author guidelines were reviewed. From each journal, 30 articles published between January 1, 2019 and August 11, 2021 were randomly chosen and analyzed. Five open science practices were measured (preprint publication prior to peer-reviewed publication, use of Equator guidelines, study protocol preregistration prior to peer-reviewed publication, published peer review, and public accessibility of data, methods, and/or code). Across all 240 articles, 82 (34%) used one or more open science practices. Articles in theInternational Journal of Surgeryshowed greatest use of open science practices, with a mean of 1.6 open science practices compared to 0.36 across the other journals (p<.001). Adoption of open science practices in surgical research remains low, and further work is needed to increase utilization of these tools.
A multi-ancestry genome-wide meta-analysis, fine-mapping, and gene prioritization approach to characterize the genetic architecture of adiponectin
Authors: Sarsani Vishal , Brotman Sarah M. , Xianyong Yin , Silva Lillian Fernandes , Laakso Markku , Spracklen Cassandra N.
Published: May 2023

Previous genome-wide association studies (GWAS) for adiponectin, a complex trait linked to type 2 diabetes and obesity, identified >20 associated loci. However, most loci were identified in populations of European ancestry, and many of the target genes underlying the associations remain unknown. We conducted a multi-ancestry adiponectin GWAS meta-analysis in ≤46,434 individuals from the METSIM cohort and the ADIPOGen and AGEN consortiums. We combined study-specific association summary statistics using a fixed-effects, inverse variance-weighted approach. We identified 22 loci associated with adiponectin (P< 5×10−8), including 15 known and 7 previously unreported loci. Among individuals of European ancestry, GCTA-COJO identified 14 additional distinct signals at theADIPOQ,CDH13,HCAR1, andZNF664loci. Leveraging the multi-ancestry data, FINEMAP + SuSiE identified 46 causal variants (PP>0.9), which also exhibited potential pleiotropy for cardiometabolic traits. To prioritize target genes at associated loci, we propose a combinatorial likelihood scoring formalism (“GPScore”) based on measures derived from 11 gene prioritization strategies and the physical distance to the transcription start site. With “GPScore”, we prioritize the 30 most probable target genes underlying the adiponectin-associated variants in the multi-ancestry analysis, including well-known causal genes (e.g.,ADIPOQ,CDH13) and novel genes (e.g.,CSF1,RGS17). Functional association networks revealed complex interactions of prioritized genes, their functionally connected genes, and their underlying pathways centered around insulin and adiponectin signaling, indicating an essential role in regulating energy balance in the body, inflammation, coagulation, fibrinolysis, insulin resistance, and diabetes. Overall, our analyses identify and characterize adiponectin association signals and inform experimental interrogation of target genes for adiponectin.
Genomic variation associated with cardiovascular disease progression following preeclampsia: A systematic review
Authors: Krishnamurthy Gayathry , Nguyen Phuong Tram , Tran Bao Ngoc , Phan Hoang T , Brennecke Shaun P. , Moses Eric K , Melton Phillip E.
Published: May 2023

Background

Women with a history of preeclampsia (PE) have been shown to have up to five times the risk of developing later-life cardiovascular disease (CVD). While PE and CVD are known to share clinical and molecular characteristics, there are limited studies investigating their shared genomics (genetics, epigenetics or transcriptomics) variation over time. Therefore, we sought to systematically review the literature to identify longitudinal studies focused on the genomic progression to CVD following PE.

Methods

A literature search of primary sources through PubMed, Scopus, Web of Science and Embase via OVID was performed. Studies published from January 1st, 1980, to February 02nd, 2023, that investigated genomics in PE and CVD were eligible for inclusion. Studies that did not include CVD or related risk factors as outcome, were in non-human species or focused on pregnancy complications other than PE were excluded. Included studies were screened based on Cochrane systematic review guidelines in conjunction with the PRISMA 2020 checklist. Eligible articles were further assessed for quality using the Newcastle-Ottawa scale.

Results

A total of 8929 articles were screened with 14 studies subjected to quality assessment. Following further evaluation, six studies were included for final review. All six of these studies were heterogenous in regard to CVD/risk factor as outcome, gene mapping approach, and in different targeted genes. The only common variable across all six studies was use of a case-control study design.

Conclusions

Our results provide critical insight into the heterogeneous nature of genomic studies investigating CVD following PE and highlight the urgent need for longitudinal studies to further investigate the genetic variation underlying the progression to CVD following PE.
A global catalog of whole-genome diversity from 233 primate species
Authors: Kuderna Lukas F.K. , Gao Hong , Janiak Mareike C. , Kuhlwilm Martin , Orkin Joseph D. , Bataillon Thomas , Manu Shivakumara , Valenzuela Alejandro , Bergman Juraj , Rouselle Marjolaine , Silva Felipe Ennes , Agueda Lidia , Blanc Julie , Gut Marta , de Vries Dorien , Goodhead Ian , Harris R. Alan , Raveendran Muthuswamy , Jensen Axel , Chuma Idriss S. , Horvath Julie , Hvilsom Christina , Juan David , Frandsen Peter , Schraiber Joshua G. , de Melo Fabiano R. , Bertuol Fabricio , Byrne Hazel , Sampaio Iracilda , Farias Izeni , Amaral João Valsecchi do , Messias Malu , da Silva Maria N. F. , Trivedi Mihir , Rossi Rogerio , Hrbek Tomas , Andriaholinirina Nicole , Rabarivola Clément J. , Zaramody Alphonse , Jolly Clifford J. , Phillips-Conroy Jane , Wilkerson Gregory , Abee Christian , Simmons Joe H. , Fernandez-Duque Eduardo , Kanthaswamy Sree , Shiferaw Fekadu , Wu Dongdong , Zhou Long , Shao Yong , Zhang Guojie , Keyyu Julius D. , Knauf Sascha , Le Minh D. , Lizano Esther , Merker Stefan , Navarro Arcadi , Nadler Tilo , Khor Chiea Chuen , Lee Jessica , Tan Patrick , Lim Weng Khong , Kitchener Andrew C. , Zinner Dietmar , Gut Ivo , Melin Amanda , Guschanski Katerina , Schierup Mikkel Heide , Beck Robin M. D. , Umapathy Govindhaswamy , Roos Christian , Boubli Jean P. , Rogers Jeffrey , Farh Kyle , Bonet Tomas Marques
Published: May 2023

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology, and is urgent given severe threats these species are facing. Here, we present high coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human-specific. This study will open a wide range of research avenues for future primate genomic research.

One-Sentence Summary

The whole genome sequences of 233 primate species provide insight into the determinants of genetic diversity, phylogenomics, and human uniqueness.
High-density volumetric super-resolution microscopy
Authors: Daly Sam , Fernandes João Ferreira , Bruggeman Ezra , Handa Anoushka , Peters Ruby , Benaissa Sarah , Zhang Boya , Beckwith Joseph S. , Sanders Edward W. , Sims Ruth R. , Klenerman David , Davis Simon J. , O’Holleran Kevin , Lee Steven F.
Published: May 2023

Volumetric super-resolution microscopy typically encodes the 3D position of single-molecule fluorescence into a 2D image by changing the shape of the point spread function (PSF) as a function of depth. However, the resulting large and complex PSF spatial footprints reduce temporal resolution by requiring lower labelling densities to avoid overlapping fluorescent signals. We quantitatively compare the density dependence of single-molecule light field microscopy (SMLFM) to other 3D PSFs (astigmatism, double helix and tetrapod) showing that SMFLM enables an order-of-magnitude speed improvement compared to the double helix PSF by resolving overlapping emitters through parallax. We then experimentally demonstrate the high accuracy (>99.2 ± 0.1%, 0.1 locs μm−2) and sensitivity (>86.6 ± 0.9%, 0.1 locs μm−2) of SMLFM at point detection through whole-cell (scan-free) imaging and tracking of single membrane proteins in live primary B cells. We also exemplify high density volumetric imaging (0.15 locs μm−2) in dense cytosolic tubulin datasets.
Stealth liposomes encapsulating a potent ACAT1/SOAT1 inhibitor F12511: pharmacokinetic, biodistribution and toxicity studies in wild-type mice, and efficacy studies in triple transgenic Alzheimer Disease mice
Authors: Torre Adrianna L. De La , Huynh Thao N. , Chang Catherine C.Y. , Pooler Darcy B. , Ness Dylan , Lewis Lionel , Pannem Sanjana , Feng Yichen , Samkoe Kimberley S. , Hickey William F. , Chang Ta Yuan
Published: May 2023

Cholesterol is essential to cellular function and is stored as cholesteryl esters (CEs). CEs biosynthesis is responsible by the enzymes acyl-CoA: cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2), with ACAT1 as the primary isoenzyme in most cells in humans. ACATs are targets for atherosclerosis therapies and may also be promising targets for treating Alzheimer’s Disease (AD). F12511 is a high-affinity ACAT1 inhibitor that has passed phase 1 safety tests for anti-atherosclerosis. Previously, we had developed a nanoparticle system to encapsulate a large concentration of F12511 into a stealth liposome (DSPE-PEG2000with egg phosphatidylcholine). Here, we injected the nanoparticle encapsulated F12511 (nanoparticle F) intravenously (IV) to wild-type (WT) mice and performed HPLC/MS/MS analysis and ACAT enzyme activity measurement. The results demonstrated that F12511 was present within the mouse brain after a single IV but did not over-accumulate in the brain or other tissues after repeated IVs. Histological examination showed that F12511 did not cause overt neurological or systemic toxicity. We then showed that 2-week IV delivery of nanoparticle F to aging 3xTg AD mice ameliorated amyloidopathy, reduced hyperphosphorylated tau and non-phosphorylated tau, and reduced neuroinflammation. This work lays the foundation with nanoparticle F as a possible therapy for AD and other neurodegenerative diseases.
Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons
Authors: Sørensen Erik F. , Harris R. Alan , Zhang Liye , Raveendran Muthuswamy , Kuderna Lukas F. K. , Walker Jerilyn A. , Storer Jessica M. , Kuhlwilm Martin , Fontsere Claudia , Seshadri Lakshmi , Bergey Christina M. , Burrell Andrew S. , Bergmann Juraj , Phillips-Conroy Jane E. , Shiferaw Fekadu , Chiou Kenneth L. , Chuma Idrissa S. , Keyyu Julius D. , Fischer Julia , Gingras Marie-Claude , Salvi Sejal , Doddapaneni Harshavardhan , Schierup Mikkel H. , Batzer Mark A. , Jolly Clifford J. , Knauf Sascha , Zinner Dietmar , Farh Kyle K.-H. , Marques-Bonet Tomas , Munch Kasper , Roos Christian , Rogers Jeffrey
Published: May 2023

Baboons (genusPapio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high coverage whole genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and inter-species gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal novel patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes.

One-Sentence Summary

Genomic data for 225 baboons reveal novel sites of inter-species gene flow and local effects due to differences in admixture.
High-content microscopy reveals a morphological signature of bortezomib resistance
Authors: Kelley M.E. , Berman A.Y. , Stirling D.R. , Cimini B.A. , Han Y. , Singh S. , Carpenter A.E. , Kapoor T.M. , Way G.P.
Published: May 2023

Drug resistance is a challenge in anticancer therapy, particularly with targeted therapeutics and cytotoxic compounds. In many cases, cancers can be resistant to the drug prior to exposure, i.e., possess intrinsic drug resistance. However, we lack target-independent methods to anticipate resistance in cancer cell lines or characterize intrinsic drug resistance without a priori knowledge of its cause. We hypothesized that cell morphology could provide an unbiased readout of drug sensitivity prior to treatment. We therefore isolated clonal cell lines that were either sensitive or resistant to bortezomib, a well-characterized proteasome inhibitor and anticancer drug to which many cancer cells possess intrinsic resistance. We then measured high-dimensional single-cell morphology profiles using Cell Painting, a high-content microscopy assay. Our imaging- and computation-based profiling pipeline identified morphological features typically different between resistant and sensitive clones. These features were compiled to generate a morphological signature of bortezomib resistance, which correctly predicted the bortezomib treatment response in seven of ten cell lines not included in the training dataset. This signature of resistance was specific to bortezomib over other drugs targeting the ubiquitin-proteasome system. Our results provide evidence that intrinsic morphological features of drug resistance exist and establish a framework for their identification.
A leaky integrate-and-fire computational model based on the connectome of the entire adultDrosophilabrain reveals insights into sensorimotor processing
Authors: Shiu Philip K. , Sterne Gabriella R. , Spiller Nico , Franconville Romain , Sandoval Andrea , Zhou Joie , Simha Neha , Kang Chan Hyuk , Yu Seongbong , Kim Jinseop S. , Dorkenwald Sven , Matsliah Arie , Schlegel Philipp , Yu Szi-chieh , McKellar Claire E. , Sterling Amy , Costa Marta , Eichler Katharina , Jefferis Gregory S.X.E. , Murthy Mala , Bates Alexander Shakeel , Eckstein Nils , Funke Jan , Bidaye Salil S. , Hampel Stefanie , Seeds Andrew M. , Scott Kristin
Published: May 2023

The forthcoming assembly of the adultDrosophila melanogastercentral brain connectome, containing over 125,000 neurons and 50 million synaptic connections, provides a template for examining sensory processing throughout the brain. Here, we create a leaky integrate-and-fire computational model of the entireDrosophilabrain, based on neural connectivity and neurotransmitter identity, to study circuit properties of feeding and grooming behaviors. We show that activation of sugar-sensing or water-sensing gustatory neurons in the computational model accurately predicts neurons that respond to tastes and are required for feeding initiation. Computational activation of neurons in the feeding region of theDrosophilabrain predicts those that elicit motor neuron firing, a testable hypothesis that we validate by optogenetic activation and behavioral studies. Moreover, computational activation of different classes of gustatory neurons makes accurate predictions of how multiple taste modalities interact, providing circuit-level insight into aversive and appetitive taste processing. Our computational model predicts that the sugar and water pathways form a partially shared appetitive feeding initiation pathway, which our calcium imaging and behavioral experiments confirm. Additionally, we applied this model to mechanosensory circuits and found that computational activation of mechanosensory neurons predicts activation of a small set of neurons comprising the antennal grooming circuit that do not overlap with gustatory circuits, and accurately describes the circuit response upon activation of different mechanosensory subtypes. Our results demonstrate that modeling brain circuits purely from connectivity and predicted neurotransmitter identity generates experimentally testable hypotheses and can accurately describe complete sensorimotor transformations.
Syndecan-4 is the Key Proteoglycan Mediating LPS-induced Sepsis-associated Lung Injury
Authors: Zhu Zhipeng , Ling Xiaoyan , Zhou Hongmei , Xie Junran
Published: May 2023

The occurrence of acute sepsis-associated lung injury (ALI) is closely related to vascular endothelial cell dysfunction, but the exact isoform of the functional syndecans (SDCs) located in the inner endothelial membrane of blood vessels and involved in regulating inflammation is not clear. The present study aimed to clarify whether SDC2 and/or 4 is involved in the inflammation process.Using the Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) were extracted and analyzed. A bioinformatic analysis was conducted using R language, gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) with the aim of predicting SDC2 and 4 expression levels. Subsequently, the expression profiles of these two proteins were examined after construction of a sepsis-associated ALI mmodel was constructed in both human lung vascular endothelial cells (HLVEC) and animal models under inflammatory conditions. Eventually, the transcription factors (TF) of SDC2/4 were predicted based on the available dataset, and their involvement in septic inflammation was indirectly assessed. The GSE 5883 microarray gene-chip data profile was found to be suitable for analyzing lipopolysaccharide (LPS)-induced endothelial inflammatory injury. After analyzing the DEGs, 224 and 102 genes were found to be up- and down-regulated, respectively. All DEGs were involved in modulating receptor ligand and signaling receptor activator activities, cytokine receptor binding in biological processes, such as responses to lipopolysaccharide (LPS) and molecules from bacterial origins, positive regulation of cell adhesion, and other functions. In the case of localization of cellular components, most DEGs were enriched in cytoplasmic ribonucleoprotein granules, transcription regulator complex, and membrane rafts and were involved in the tumor necrosis factor (TNF) signaling and cytokine receptor interaction pathways. When compared with the control group, SDC4 gene expression in the LPS group increased by 4.5-fold, and comparable results were found in terms of SDC2 gene expression. From an experimental aspect, SDC4 was found to be markedly up-regulated with respect to mRNA and protein expression levels in response to inflammatory injury; moreover, down-regulation of SDC4 could severely exacerbate inflammatory responses either in in vivo or in vitro models. Altogether, SDC4, rather than SDC2, was found to be involved in LPS-induced sepsis-associated ALI.
Host-Microbiome Associations in Saliva Predict COVID-19 Severity
Authors: Alqedari Hend , Altabtbaei Khaled , Espinoza Josh L. , Bin-Hasan Saadoun , Alghounaim Mohammad , Alawady Abdullah , Altabtabae Abdullah , AlJamaan Sarah , Devarajan Sriraman , AlShammari Tahreer , Ben Eid Mohammed , Matsuoka Michele , Jang Hyesun , Dupont Christopher L. , Freire Marcelo
Published: May 2023

Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following Severe Acute Respiratory Syndrome Coronavirus 2 – SARS-CoV-2 – there are coordinated microbiome and inflammatory responses within the mucosal and systemic compartments that are unknown. The specific roles that the oral microbiota and inflammatory cytokines play in the pathogenesis of COVID-19 are yet to be explored. We evaluated the relationships between the salivary microbiome and host parameters in different groups of COVID-19 severity based on their Oxygen requirement. Saliva and blood samples (n = 80) were collected from COVID-19 and from non-infected individuals. We characterized the oral microbiomes using 16S ribosomal RNA gene sequencing and evaluated saliva and serum cytokines using Luminex multiplex analysis. Alpha diversity of the salivary microbial community was negatively associated with COVID-19 severity. Integrated cytokine evaluations of saliva and serum showed that the oral host response was distinct from the systemic response. The hierarchical classification of COVID-19 status and respiratory severity using multiple modalities separately (i.e., microbiome, salivary cytokines, and systemic cytokines) and simultaneously (i.e., multi-modal perturbation analyses) revealed that the microbiome perturbation analysis was the most informative for predicting COVID-19 status and severity, followed by the multi-modal. Our findings suggest that oral microbiome and salivary cytokines may be predictive of COVID-19 status and severity, whereas atypical local mucosal immune suppression and systemic hyperinflammation provide new cues to understand the pathogenesis in immunologically naïve populations.

Significance Statement

The oral mucosa is one of the first sites encountered by bacterial and viral infections, including SARS-CoV-2. It consists of a primary barrier occupied by a commensal oral microbiome. The primary function of this barrier is to modulate immunity and provide protection against invading infection. The occupying commensal microbiome is an essential component that influences the immune system’s function and homeostasis. The present study showed that the host oral immune response performs unique functions in response to SARS-CoV-2 when compared to systemic responses during the acute phase. We also demonstrated that there is a link between oral microbiome diversity and COVID-19 severity. Additionally, the salivary microbiome was predictive of not only disease status but also severity.
Ribosomal Frameshifting Selectively Modulates the Assembly, Function, and Pharmacological Rescue of a Misfolded CFTR Variant
Authors: Carmody Patrick , Roushar Francis J , Tedman Austin , Wang Wei , Herwig Madeline , Kim Minsoo , McDonald Eli Fritz , Noguera Karen , Wong-Roushar Jennifer , Poirier Jon-Luc , Zelt Nathan , Pockrass Ben , McKee Andrew G , Kuntz Charles P , Raju S Vamsee , Plate Lars , Penn Wesley D , Schlebach Jonathan P
Published: May 2023

The cotranslational misfolding of the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR) plays a central role in the molecular basis of cystic fibrosis (CF). The misfolding of the most common CF variant (ΔF508) remodels both the translational regulation and quality control of CFTR. Nevertheless, it is unclear how the misassembly of the nascent polypeptide may directly influence the activity of the translation machinery. In this work, we identify a structural motif within the CFTR transcript that stimulates efficient -1 ribosomal frameshifting and triggers the premature termination of translation. Though this motif does not appear to impact the interactome of wild-type CFTR, silent mutations that disrupt this RNA structure alter the association of nascent ΔF508 CFTR with numerous translation and quality control proteins. Moreover, disrupting this RNA structure enhances the functional gating of the ΔF508 CFTR channel at the plasma membrane and its pharmacological rescue by the CFTR modulators contained in the CF drug Trikafta. The effects of the RNA structure on ΔF508 CFTR appear to be attenuated in the absence of the ER membrane protein complex (EMC), which was previously found to modulate ribosome collisions during preemptive quality control of a misfolded CFTR homolog. Together, our results reveal that ribosomal frameshifting selectively modulates the assembly, function, and pharmacological rescue of a misfolded CFTR variant. These findings suggest interactions between the nascent chain, quality control machinery, and ribosome may dynamically modulate ribosomal frameshifting in order to tune the processivity of translation in response to cotranslational misfolding.
Endothelial specific reduction in Arf6 impairs insulin-stimulated vasodilation and skeletal muscle blood flow resulting in systemic insulin resistance
Authors: Islam Md Torikul , Cai Jinjin , Allen Shanena , Moreno Denisse G , Bloom Samuel I , Bramwell R Colton , Mitton Jonathan , Horn Andrew G , Zhu Weiquan , Donato Anthony J , Holland William L , Lesniewski Lisa A
Published: May 2023

Background

Much of what we know about insulin resistance is based on studies from metabolically active tissues such as liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance, however, the underlying mechanisms remain incompletely understood. ADP ribosylation factor 6 (Arf6) is a small GTPase that plays a critical role in endothelial cell (EC) function. Here, we tested the hypothesis that the deletion of endothelial Arf6 will result in systemic insulin resistance.

Methods

We used mouse models of constitutive EC-specific Arf6 deletion (Arf6f/-Tie2Cre) and tamoxifen inducible Arf6 knockout (Arf6f/fCdh5Cre). Endothelium-dependent vasodilation was assessed using pressure myography. Metabolic function was assessed using a battery of metabolic assessments including glucose- and insulin-tolerance tests and hyperinsulinemic-euglycemic clamps. A fluorescence microsphere-based technique was used to measure tissue blood flow. Intravital microscopy was used to assess skeletal muscle capillary density.

Results

Endothelial Arf6 deletion impaired insulin-stimulated vasodilation in white adipose tissue (WAT) and skeletal muscle feed arteries. The impairment in vasodilation was primarily due to attenuated insulin-stimulated nitric oxide (NO) bioavailability but independent of altered acetylcholine- or sodium nitroprusside-mediated vasodilation. In vitro Arf6 inhibition resulted in suppressed insulin stimulated phosphorylation of Akt and endothelial NO synthase. Endothelial cell-specific deletion of Arf6 also resulted in systematic insulin resistance in normal chow fed mice and glucose intolerance in high fat diet fed obese mice. The underlying mechanisms of glucose intolerance were reductions in insulin-stimulated blood flow and glucose uptake in the skeletal muscle and were independent of changes in capillary density or vascular permeability.

Conclusion

Results from this study support the conclusion that endothelial Arf6 signaling is essential for maintaining insulin sensitivity. Reduced expression of endothelial Arf6 impairs insulin-mediated vasodilation and results in systemic insulin resistance. These results have therapeutic implications for diseases that are associated with endothelial cell dysfunction and insulin resistance such as diabetes.
Role of sociodemographic, clinical, behavioral, and molecular factors in precision prevention of type 2 diabetes: a systematic review
Authors: Bodhini Dhanasekaran , Morton Robert W. , Santhakumar Vanessa , Nakabuye Mariam , Pomares-Millan Hugo , Clemmensen Christoffer , Fitzpatrick Stephanie L. , Guasch-Ferre Marta , Pankow James S. , Ried-Larsen Mathias , Franks Paul W. ,   ADA/EASD Precision Medicine in Diabetes Initiative, Tobias Deirdre K. , Merino Jordi , Mohan Viswanathan , Loos Ruth J.F.
Published: May 2023

The variability in the effectiveness of type 2 diabetes (T2D) preventive interventions highlights the potential to identify the factors that determine treatment responses and those that would benefit the most from a given intervention. We conducted a systematic review to synthesize the evidence to support whether sociodemographic, clinical, behavioral, and molecular characteristics modify the efficacy of dietary or lifestyle interventions to prevent T2D. Among the 80 publications that met our criteria for inclusion, the evidence was low to very low to attribute variability in intervention effectiveness to individual characteristics such as age, sex, BMI, race/ethnicity, socioeconomic status, baseline behavioral factors, or genetic predisposition. We found evidence, albeit low certainty, to support conclusions that those with poorer health status, particularly those with prediabetes at baseline, tend to benefit more from T2D prevention strategies compared to healthier counterparts. Our synthesis highlights the need for purposefully designed clinical trials to inform whether individual factors influence the success of T2D prevention strategies.
Autophagy is a cell-intrinsic driver of neural stem cell quiescence in hippocampal dentate gyrus development
Authors: Calatayud-Baselga Isabel , Casares-Crespo Lucía , Franch-Ibáñez Carmina , Guijarro-Nuez José , Sanz Pascual , Mira Helena
Published: May 2023

Neurogenesis in the adult mammalian brain relies on the lifelong persistence of quiescent neural stem cell (NSC) reservoirs. Little is known about the mechanisms that lead to the initial establishment of NSC quiescence during development. Here, we show that protein aggregates and autophagy machinery components accumulate in quiescent NSCs and that pharmacological blockade of autophagy disrupts quiescence. Conversely, increasing autophagy through AMPK/ULK1 activation instructs the acquisition of the quiescent state. Selective ablation ofAtg7, a critical gene for autophagosome formation, in hippocampal radial-glia like NSCs at early and late postnatal stages compromises the initial acquisition and maintenance of quiescence during the formation of the dentate gyrus SGZ niche. Therefore, we demonstrate that autophagy is cell-intrinsically required to establish radial glia-like NSC quiescence during hippocampal development. Our results uncover a fundamental role of autophagy in the transition of developmental NSCs into their dormant adult form, paving the way for studies directed at further understanding the mechanisms of stem cell niche formation and maintenance in the mammalian brain.
Crystal structure and Hirshfeld surface analysis of 2-amino-6-[(1-phenylethyl)amino]-4-(thiophen-2-yl)pyridine-3,5-dicarbonitrile
Authors: Naghiyev Farid N. , Khrustalev Victor N. , Asadov Khammed A. , Akkurt Mehmet , Khalilov Ali N. , Bhattarai Ajaya , Mamedov İbrahim G.
Published: May 2023

In the title compound, C19H15N5S, the thiophene ring is disordered in a 0.6:0.4 ratio by an approximate 180° rotation of the ring around the C—C bond linking it to the pyridine ring. In the crystal, the molecules are linked by N—H...N hydrogen bonds into dimers with an R
2
2(12) motif, forming chains along the b-axis direction. These chains are connected to each other by further N—H...N hydrogen bonds, forming a three-dimensional network. Furthermore, N—H...π and π–π [centroid–centroid separations = 3.899 (8) and 3.7938 (12) Å] interactions also contribute to the crystal cohesion. A Hirshfeld surface analysis indicated that the most important contributions to the surface contacts are from H...H (46.1%), N...H/H...N (20.4%) and C...H/H...C (17.4%) interactions.
(2,2′-Bipyridyl)(η6-p-cymene)iodidoruthenium(II) hexafluoridophosphate
Authors: Kelani Monsuru T. , Muller Alfred , Lammertsma Koop
Published: May 2023

The title compound, having the molecular formula [RuI(η6-C10H14)(C10H8N2)]PF6, crystallizes in the triclinic P\overline{1} (Z = 2) space group as a half-sandwich complex resembling a three-legged piano stool. Important geometrical parameters include Ru—cymene centroid = 1.6902 (17) Å, Ru—I = 2.6958 (5) Å, [Ru—N]avg = 2.072 (3) Å, N1—Ru—N2 = 76.86 (12)° and a dihedral angle between the planes of the two rings of the bipyridyl system of 5.9 (2)°. The PF6
− ion was treated with a twofold disorder model, refining to a 65.0 (8):35.0 (8) occupancy ratio. The crystal packing features C—H...F/I interactions.
ICT adoption and youth employment in Nigeria's agricultural sector
Authors: Osabohien Romanus
Published: May 2023

Purpose

This paper argues that through information and communication technology (ICT) adoption, the youth will be engaged in all nodes of the agricultural value chains, thereby improving the level of employment and reducing post-harvest losses. The study examines the determinants of ICT adoption among the youth. In addition, it estimates the impact of ICT adoption on youth employment in agriculture towards the actualisation of the Sustainable Development Goals (SDGs), particularly SDG-8, to promote inclusive and sustainable economic growth, productive employment and decent work for all.

Design/methodology/approach

The study engages data from Wave 4 (2018/2019) of the Living Standards Measurement Study – Integrated Surveys on Agriculture (LSMS-ISA). The logit regression, the propensity score matching and the inverse probability weighted regression adjustment are used as the estimation techniques.

Findings

The study underscores that educational level, access to electricity, location, age and income are significant determinants of ICT adoption among the youth. The findings also show that the youth's average weekly engagement in agricultural activities is about 24 h. In addition, the result reveals that ICT adoption can increase youth agricultural employment by approximately 21%. The mean difference indicates that those with access to ICT participate in agricultural activities more than their counterparts without ICT access by 29.46%.

Research limitations/implications

One of the limitations of the study is that some of the variables such as insecurity, social protection/safety nets, that may have a significant influence on youth agricultural participation where not included in the model due to data constraint. As a recommendation for further studies, given data availability, such variables should be considered when examining youth-agricultural employment nexus.

Practical implications

Since ICT adoption has a significant impact on agricultural employment, this study proposes improved infrastructure facilities such as reliable power supply, lowering the cost of mobile and data subscriptions and better education facilities should be prioritised at all localities. This will enable the youth to embrace agriculture and help improve their socioeconomic welfare and livelihood.

Originality/value

Using Wave 4 of the LSMS-ISA, logit regression, propensity score matching and the inverse probability weighted regression adjustment, makes this study one of the very few to examine the impact of ICT adoption on agricultural employment among the youth in Nigeria. It implies that this study has provided empirical evidence and expanded the frontiers of knowledge on the extent to which ICT adoption influences youth agricultural employment in Nigeria.
Channel attention-based spatial-temporal graph neural networks for traffic prediction
Authors: Wang Bin , Gao Fanghong , Tong Le , Zhang Qian , Zhu Sulei
Published: May 2023

Purpose

Traffic flow prediction has always been a top priority of intelligent transportation systems. There are many mature methods for short-term traffic flow prediction. However, the existing methods are often insufficient in capturing long-term spatial-temporal dependencies. To predict long-term dependencies more accurately, in this paper, a new and more effective traffic flow prediction model is proposed.

Design/methodology/approach

This paper proposes a new and more effective traffic flow prediction model, named channel attention-based spatial-temporal graph neural networks. A graph convolutional network is used to extract local spatial-temporal correlations, a channel attention mechanism is used to enhance the influence of nearby spatial-temporal dependencies on decision-making and a transformer mechanism is used to capture long-term dependencies.

Findings

The proposed model is applied to two common highway datasets: METR-LA collected in Los Angeles and PEMS-BAY collected in the California Bay Area. This model outperforms the other five in terms of performance on three performance metrics a popular model.

Originality/value

(1) Based on the spatial-temporal synchronization graph convolution module, a spatial-temporal channel attention module is designed to increase the influence of proximity dependence on decision-making by enhancing or suppressing different channels. (2) To better capture long-term dependencies, the transformer module is introduced.
Using green and ESG assets to achieve post-COVID-19 environmental sustainability
Authors: Hasan Md. Bokhtiar , Rashid Md Mamunur , Hossain Md. Naiem , Rahman Mir Mahmudur , Amin Md. Ruhul
Published: May 2023

Purpose

This research explores the spillovers and portfolio implications for green bonds and environmental, social and governance (ESG) assets in the context of the rapidly expanding trend in green finance investments and the need for a green recovery in the post-COVID-19 era.

Design/methodology/approach

This study utilizes Diebold and Yilmaz’s (2014) spillover method and portfolio strategies (hedge ratio, optimal weights and hedging effectiveness) for the data starting from February 29, 2012, to March 14, 2022.

Findings

The study’s findings reveal that the lower volatility spillover is evidenced between the green bonds and ESG stocks during tranquil and turbulent periods (e.g. COVID-19 and Russia-Ukraine War). Furthermore, hedging costs are lower both in normal times and during economic slumps. Investing the bulk of the funds in green bonds makes it possible to achieve maximum hedging effectiveness between the S&P green bond (GB) and the S&P 500 ESG.

Practical implications

Both investors and policymakers may use these findings to make wise investment and policy choices to achieve post-COVID environmental sustainability.

Originality/value

Unlike previous research, this is the first to explore the interconnectedness among the major global and country-specific green bonds and ESG assets. The major findings of this study about the lower volatility spillovers and hedging costs between green bonds and ESG assets during the tranquil and turbulent periods may contribute to the post-COVID investment portfolio for environmental sustainability.
The influence of protean attitude for women in STEM careers: coping-self efficacy as foundational and strong career identity as outcome
Authors: Blaique Lama , Pinnington Ashly , Aldabbas Hazem
Published: May 2023

Purpose

The under-representation of women working in Science, Technology, Engineering and Mathematics (STEM) careers is a persistent problem worldwide. This dilemma is exacerbated by the fact that an insufficient number of women enroll in STEM studies, and a significant proportion of those who do join then opt out of their STEM careers at different points in their lives. The protean attitude emphasizes agentic individual control over one’s career, and thus offers women substantial potential for developing and enhancing career outcomes. Therefore, this study aims to investigate coping self-efficacy as an antecedent and career identity as a consequent of a protean attitude for women working in STEM.

Design/methodology/approach

Using a questionnaire survey, data were collected from 482 women working in STEM in the Middle East region. Multiple regression and bootstrapping methods were used in the analysis of the data.

Findings

The findings indicate that coping self-efficacy positively affects both protean attitude and career identity. The results also show that a protean attitude mediates the relationship between coping self-efficacy and career identity.

Practical implications

This research presents organizational management and government policy recommendations aimed at increasing the recruitment and retention of women in STEM careers.

Originality/value

The study addresses some of the main challenges related to identifying antecedents and outcomes of protean attitude.