bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-sitosterol: a new antiviral agent produced by Streptomyces misakiensis and its potential activity against Newcastle disease virus
Authors: Abdelaziz Rewan , Tartor Yasmine H. , Barakat Ahmed B. , EL-Didamony Gamal , Gado Marwa M. , Zaki Mohamed Samir A. , Eid Refaat A. , El-Samadony Hanaa A. 
Published: February 2024

Abstract
Background
Newcastle Disease Virus (NDV) causes severe economic losses in the poultry industry worldwide. Hence, this study aimed to discover a novel bioactive antiviral agent for controlling NDV. Streptomyces misakiensis was isolated from Egyptian soil and its secondary metabolites were identified using infrared spectroscopy (IR), gas chromatography–mass spectrometry (GC–MS), and nuclear magnetic resonance (NMR) spectroscopy. The inhibitory activity of bioactive metabolite against NDV were examined. Three experimental groups of 10-day-old specific pathogen-free embryonated chicken eggs (SPF-ECEs), including the bioactive metabolite control group, NDV control positive group, and α-sitosterol and NDV mixture-treated group were inoculated.

Results
α-sitosterol (Ethyl-6-methylheptan-2-yl]-10,13-dimethyl-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol), a secondary metabolite of S. misakiensis, completely inhibited hemagglutination (HA) activity of the NDV strain. The HA activity of the NDV strain was 8 log2 and 9 log2 for 0.5 and 0.75% RBCs, respectively. The NDV HA activity for the two concentrations of RBCs was significantly (P < 0.0001) inhibited after α-sitosterol treatment. There was a significant (P < 0.0001) decrease in the log 2 of HA activity, with values of − 0.500 (75%, chicken RBCs) before inoculation in SPF-ECEs and − 1.161 (50%, RBCs) and − 1.403 (75%, RBCs) following SPF-ECE inoculation. Compared to ECEs inoculated with NDV alone, the α-sitosterol-treated group showed improvement in histological lesion ratings for chorioallantoic membranes (CAM) and hepatic tissues. The CAM of the α-sitosterol- inoculated SPF-ECEs was preserved. The epithelial and stromal layers were noticeably thicker with extensive hemorrhages, clogged vasculatures, and certain inflammatory cells in the stroma layer in the NDV group. However, mild edema and inflammatory cell infiltration were observed in the CAM of the treated group. ECEs inoculated with α-sitosterol alone showed normal histology of the hepatic acini, central veins, and portal triads. Severe degenerative alterations, including steatosis, clogged sinusoids, and central veins, were observed in ECEs inoculated with NDV. Mild hepatic degenerative alterations, with perivascular round cell infiltration, were observed in the treated group.

Conclusion
To the best of our knowledge, this is the first study to highlight that the potentially bioactive secondary metabolite, α-sitosterol, belonging to the terpene family, has the potential to be a biological weapon against virulent NDV. It could be used for the development of innovative antiviral drugs to control NDV after further clinical investigation.
Food sufficiency status and sleep outcomes in older adults: the National Health and Aging Trends Study (NHATS)
Authors: Flores Ashley C. , Sarpong Christopher , Dou Nan , Na Muzi 
Published: February 2024

Abstract
Background
Studies investigating the relationship between food insecurity and sleep among older populations are limited. This study aimed to cross-sectionally examine the associations between food sufficiency status and sleep outcomes in a nationally representative sample of older adults.

Methods
Our study included 1,665 older adults (≥ 65 years), using data from the 2013 and 2014 National Health and Aging Trends Study (NHATS). Food insufficiency was determined via participants’ experience and utilization of food assistance programs (FAP). Sleep outcomes, including nighttime and total sleep hours, sleep latency, and sleep quality, were derived from self-reported data. Multivariable linear regression and logistic regression models were used to estimate the associations between food sufficiency status and sleep outcomes.

Results
In 2013–2014, 86.1% of older adults were classified as food sufficient without FAP, 9.85% as food sufficient with FAP, and 4.08% as food insufficient. Adjusting for sociodemographic characteristics, food sufficient older adults with FAP reported more total sleep hours (𝛽 = 0.31, 95% CI: -0.02, 0.64) than those participants who are food sufficient without FAP. Further adjusting for health factors, food sufficient participants with FAP had more nighttime sleep hours and greater total sleep hours compared to those participants food sufficient without FAP. Compared to those deemed as food sufficient without FAP, food sufficient participants with FAP had lower odds of having longer sleep latency (OR = 0.50, 95% CI: 0.28, 0.89), after further adjusting for physical function performance.

Conclusions
Among older adults, food sufficiency with FAP is associated with greater total sleep hours, greater nighttime sleep hours, and lower odds of longer sleep latency. Our findings may help inform nutrition food assistance programs targeting older populations.
Diversity of astroviruses in wild animals in Yunnan province, China
Authors: Huang Xingyu , Hou Junjie , Le Xiang , Hou Yutong , Yang Lingsi , Li Qian , Wang Binghui , Xia Xueshan 
Published: February 2024

Abstract
Background
Astroviruses (AstVs) are single-stranded RNA viruses that have been detected in a wide range of mammals and birds. They are associated with numerous interspecies transmissions and viral recombination events, posing a threat to human and animal health.

Methods
We collected 1,333 samples from wild animals, including bats, rodents, wild boars, and birds, from various states and cities in the Yunnan Province, China, between 2020 and 2023 to investigate the presence of AstVs. AstVs were detected using a polymerase chain reaction targeting the RdRp gene. Finally, the Molecular Evolutionary Genetics Analysis software was used to construct the phylogenetic tree.

Results
The overall positivity rate for AstVs was 7.12% in four species, indicating their widespread occurrence in the region. High genetic diversity among AstVs was observed in different animal species, suggesting the potential for interspecies transmission, particularly among rodents and birds. Additionally, we identified a novel AstV strain and, for the first time, provided information on the presence of bastroviruses in Yunnan, China.

Conclusions
The widespread distribution and high genetic diversity of AstVs, along with the observed potential for interspecies transmission, highlight the importance of further investigation and surveillance in the region. The findings emphasize the need for increased attention to AstVs and their potential impact on human and animal health in Yunnan and other regions.
Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles
Authors: Janssen Lisa MF , Lemaire Frauke , Marain Nora Fopke , Ronsmans Steven , Heylen Natasja , Vanstapel Arno , Velde Greetje Vande , Vanoirbeek Jeroen AJ , Pollard Kenneth Michael , Ghosh Manosij , Hoet Peter HM 
Published: February 2024

AbstractBackgroundInhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization.ResultsThe findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains.ConclusionMouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.
Evidence on the impact of community health workers in the prevention, identification, and management of undernutrition amongst children under the age of five in conflict-affected or fragile settings: a systematic literature review
Authors: Bridge Rachel , Lin Tracy Kuo 
Published: February 2024

Abstract
Background
Malnutrition, specifically undernutrition, is a significant global challenge that contributes to nearly half of deaths in children under the age of five. The burden of undernutrition is disproportionately borne by conflict-affected, fragile settings (CAFS); children living in a conflict zone being more than twice as likely to suffer from malnourishment. Community health worker (CHW) models have been employed in CAFS to improve healthcare coverage and identify and treat illnesses. However, there lacks systematic evidence on the impact of CHW models in preventing, identifying, and managing child undernutrition in CAFS. We conducted this review to systematically evaluate evidence of CHW models in preventing, identifying, and managing undernutrition in children under the age of five in CAFS.

Methodology
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards. The search strategy was developed using the Population-Intervention-Comparisons-Outcomes-Setting framework as a guide. Searches were performed using Ovid online database search platform, searching the databases of Ovid MEDLINE(R), COCHRANE, Embase Classic, Embase, Econlit, Global Health, SCOPUS, and Social Policy and Practice. Peer-reviewed publications were eligible for inclusion if they evaluated an intervention using a CHW model that aims to prevent, identify, or manage some form of undernutrition in children under five in a CAFS.

Results
We identified 25 studies—spanning 10 countries—that were included in the systematic review. CHW models were implemented alongside a variety of interventions, including behaviour change communication, supplementary foods, nutrition counselling, and integrated community health programmes. Key barriers in implementing successful CHW models include disruption of programmes due to active conflict, states of emergency, militancy, or political unrest; weak links between the community-based interventions and public health system; weak health system capacity that impeded referral and follow-ups; and cost of care and care-seeking. Key facilitators include CHWs’ connection to the community, close proximity of programmes to the community, supervision, and investment in high quality training and tools.

Conclusions
The findings suggest that CHW models may be effective, cost-effective, acceptable, feasible, and scalable in the prevention, identification, and management child undernutrition in CAFS. The study findings also confirmed a need for greater evidence in the field. These findings may inform policymaking, programme implementation, and design to strengthen best practices for CHW models addressing child undernutrition in CAFS.
Tumor-derived exosomal ADAM17 promotes pre-metastatic niche formation by enhancing vascular permeability in colorectal cancer
Authors: Li Keyu , Xue Wenhua , Lu Zhihua , Wang Suo , Zheng Jiayao , Lu Kuangyi , Li Ming , Zong Yang , Xu Feng , Dai Jiamin , Yang Yang , Sun Jinbing 
Published: February 2024

Abstract
Background
Hematological metastasis has been recognized as a crucial factor contributing to the high rates of metastasis and mortality observed in colorectal cancer (CRC). Notably, exosomes derived from cancer cells participate in the formation of CRC pre-metastatic niches; however, the mechanisms underlying their effects are largely unknown. While our preliminary research revealed the role of exosome-derived disintegrin and metalloproteinase 17 (ADAM17) in the early stages of CRC metastasis, the role of exosomal ADAM17 in CRC hematogenous metastasis remains unclear.

Methods
In the present study, we isolated and purified exosomes using ultracentrifugation and identified exosomal proteins through quantitative mass spectrometry. In vitro, co-culture assays were conducted to evaluate the impact of exosomal ADAM17 on the permeability of the blood vessel endothelium. Vascular endothelial cell resistance, the cell index, membrane protein separation, flow cytometry, and immunofluorescence were employed to investigate the mechanisms underlying exosomal ADAM17-induced vascular permeability. Additionally, a mouse model was established to elucidate the role of exosomal ADAM17 in the modulation of blood vessel permeability and pre-metastatic niche formation in vivo.

Results
Our clinical data indicated that ADAM17 derived from the circulating exosomes of patients with CRC could serve as a blood-based biomarker for predicting metastasis. The CRC-derived exosomal ADAM17 targeted vascular endothelial cells, thus enhancing vascular permeability by influencing vascular endothelial cadherin cell membrane localization. Moreover, exosomal ADAM17 mediated the formation of a pre-metastatic niche in nude mice by inducing vascular leakage, thereby promoting CRC metastasis. Nonetheless, ADAM17 selective inhibitors effectively reduced CRC metastasis in vivo.

Conclusions
Our results suggest that exosomal ADAM17 plays a pivotal role in the hematogenous metastasis of CRC. Thus, this protein may serve as a valuable blood-based biomarker and potential drug target for CRC metastasis intervention.
Use of Remdesivir in children with COVID-19: report of an Italian multicenter study
Authors: Romani Lorenza , Roversi Marco , Bernardi Stefania , Venturini Elisabetta , Garazzino Silvia , Donà Daniele , Krzysztofiak Andrzej , Montagnani Carlotta , Funiciello Elisa , Calò Carducci Francesca Ippolita , Marabotto Caterina , Castagnola Elio , Salvini Filippo , Lancella Laura , Lo Vecchio Andrea , Galli Luisa , Castelli Gattinara Guido ,   Italian Society of Pediatric Infectious Diseases (SITIP)
Published: February 2024

Abstract
Background
COVID-19 is generally milder in children than in adults, however severe infection has been described in some patients. Few data are available on use of Remdesivir (RDV) in children, as most clinical trials focused on adult patients. We report a multicenter study conducted in 10 Italian Hospitals to investigate the safety of RDV in children affected by COVID-19.

Methods
We collected the clinical data of children with COVID-19 treated with RDV between March 2020 and February 2022 in 10 Italian hospitals. Clinical data were compared according to a duration of RDV therapy more or less than 5 days. Linear regression model was used to determine the association of significant variables from the bivariate analysis to the duration of RDV therapy.

Results
A total of 50 patients were included, with a median age of 12.8 years. Many patients had at least one comorbidity (78%), mostly obesity. Symptoms were fever (88%), cough (74%) and dyspnea (68%). Most patients were diagnosed with pneumonia of either viral and/or bacterial etiology. Blood test showed leukopenia in 66% and increased C-reactive protein (CRP) levels in 63% of cases. Thirty-six patients received RDV for 5 days, nine patients up to 10 days. Most children who received RDV longer were admitted to the PICU (67%). Treatment with RDV was well tolerated with rare side effects: bradycardia was recorded in 6% of cases, solved in less than 24 h after discontinuation. A mild elevation of transaminases was observed in 26% of cases, however for the 8%, it was still detected before the RDV administration. Therefore, in these cases, we could not establish if it was caused by COVID-19, RDV o both. Patients who received RDV for more than 5 days waited longer for its administration after pneumonia diagnosis. The presence of comorbidities and the duration of O2 administration significantly correlated with the duration of RDV therapy at the linear regression analysis.

Conclusion
Our experience indicates that RDV against SARS-CoV-2 is safe and well-tolerated in pediatric populations at high risk of developing severe COVID-19. Our data suggest that delaying RDV therapy after diagnosis of pneumonia may be associated with a longer duration of antiviral therapy, especially in patients with comorbidities.
Effectiveness and cost-effectiveness of a transdiagnostic intervention for alcohol misuse and psychological distress in humanitarian settings: study protocol for a randomised controlled trial in Uganda
Authors: van der Boor Catharina F. , Taban Dalili , Tol Wietse A. , Akellot Josephine , Neuman Melissa , Weiss Helen A. , Greco Giulia , Vassall Anna , May Carl , Nadkarni Abhijit , Kinyanda Eugene , Roberts Bayard , Fuhr Daniela C. 
Published: February 2024

Abstract

Background
The war in South Sudan has displaced more than four million people, with Uganda hosting the largest number of South Sudanese refugees. Research in Uganda has shown elevated levels of alcohol misuse and psychological distress among these refugees. The World Health Organization (WHO) has developed a trans-diagnostic scalable psychological intervention called Problem Management Plus (PM +) to reduce psychological distress among populations exposed to adversities. Our study aims to evaluate the effectiveness and cost-effectiveness of the CHANGE intervention, which builds on PM + , to also address alcohol misuse through problem-solving therapy and selected behavioural strategies for dealing with alcohol use disorders. We hypothesise that the CHANGE intervention together with enhanced usual care (EUC) will be superior to EUC alone in increasing the percentage of days abstinent.

Methods
A parallel-arm individually randomised controlled trial will be conducted in the Rhino Camp and Imvepi settlements in Uganda. Five hundred adult male South Sudanese refugees with (i) elevated levels of alcohol use (between 8 and 20 on the Alcohol Use Disorder Identification Test [AUDIT]); and (ii) psychological distress (> 16 on the Kessler Psychological Distress Scale) will be randomly assigned 1:1 to EUC or CHANGE and EUC. CHANGE will be delivered by lay healthcare providers over 6 weeks. Outcomes will be assessed at 3 and 12 months post-randomisation. The primary outcome is the percentage of days abstinent, measured by the timeline follow-back measure at 3 months. Secondary outcomes include percentage of days abstinent at 12 months and alcohol misuse (measured by the AUDIT), psychological distress (i.e. depression, anxiety, posttraumatic stress disorder), functional disability, perpetration of intimate partner violence, and health economic indicators at 3 and 12 months. A mixed-methods process evaluation will investigate competency, dose, fidelity, feasibility, and acceptability. Primary analyses will be intention-to-treat.

Discussion
CHANGE aims to address alcohol misuse and psychological distress with male refugees in a humanitarian setting. If it is proven to be effective, it can help fill an important under-researched gap in humanitarian service delivery.

Trial registration
ISRCTN ISRCTN10360385. Registered on 30 January 2023.
Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age
Authors: Shorey-Kendrick Lyndsey E. , McEvoy Cindy T. , Milner Kristin , Harris Julia , Brownsberger Julie , Tepper Robert S. , Park Byung , Gao Lina , Vu Annette , Morris Cynthia D. , Spindel Eliot R. 
Published: February 2024

Abstract
Background
We previously reported in the “Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function” randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for airway epithelium, is associated with vitamin C supplementation, improved lung function, and decreased occurrence of wheeze.

Methods
We conducted epigenome-wide association studies (EWAS) using Infinium MethylationEPIC arrays and buccal DNAm from 158 subjects (80 placebo; 78 vitamin C) with pulmonary function testing (PFT) performed at the 5-year visit. EWAS were performed on (1) vitamin C treatment, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25–75), and (3) offspring wheeze. Models were adjusted for sex, race, study site, gestational age at randomization (≤ OR > 18 weeks), proportion of epithelial cells, and latent covariates in addition to child length at PFT in EWAS for FEF25–75. We considered FDR p < 0.05 as genome-wide significant and nominal p < 0.001 as candidates for downstream analyses. Buccal DNAm measured in a subset of subjects at birth and near 1 year of age was used to determine whether DNAm signatures originated in utero, or emerged with age.

Results
Vitamin C treatment was associated with 457 FDR significant (q < 0.05) differentially methylated CpGs (DMCs; 236 hypermethylated; 221 hypomethylated) and 53 differentially methylated regions (DMRs; 26 hyper; 27 hypo) at 5 years of age. FEF25–75 was associated with one FDR significant DMC (cg05814800), 1,468 candidate DMCs (p < 0.001), and 44 DMRs. Current wheeze was associated with 0 FDR-DMCs, 782 candidate DMCs, and 19 DMRs (p < 0.001). In 365/457 vitamin C FDR significant DMCs at 5 years of age, there was no significant interaction between time and treatment.

Conclusions
Vitamin C supplementation to pregnant smokers is associated with buccal DNA methylation in offspring at 5 years of age, and most methylation signatures appear to be persistent from the prenatal period. Buccal methylation at 5 years was also associated with current lung function and occurrence of wheeze, and these functionally associated loci are enriched for vitamin C associated loci.
Clinical trial registration ClinicalTrials.gov, NCT01723696 and NCT03203603.