bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant CD5 and CD6 Ectodomains Induce Antiparasitic and Immunomodulatory Effects in Secondary Cystic Echinococcosis
Authors: García‐Luna Joaquín , Rivero‐Osorio Florencia , González‐Porcile María Clara , Arbildi Paula , Miles Sebastián , Magnone Javier , Velasco‐De‐Andrés María , Dematteis Sylvia , Lozano Francisco , Mourglia‐Ettlin Gustavo 
Published: April 2024

ABSTRACTScavenger receptors participate in a wide range of biological functions after binding to multiple non‐self or altered self‐ligands. Among them, CD5 and CD6 are lymphocyte scavenger receptors known to interact with different microbial‐associated molecular patterns, and the administration of the recombinant soluble ectodomains of human CD5 (rshCD5) and/or CD6 (rshCD6) has shown therapeutic/prophylactic potential in experimental models of fungal, bacterial and echinococcal infections. The latter is a zoonosis caused by the larval stage of the cestode parasite Echinococcus granulosus sensu lato, which in humans can induce secondary cystic echinococcosis (CE) after the spillage of protoscoleces contained within fertile cysts, either spontaneously or during surgical removal of primary hydatid cysts. Herein, we have analysed the mechanisms behind the significant protection observed in the mouse model of secondary CE following prophylactic administration of rshCD5 or rshCD6. Our results show that both molecules exhibit intrinsic antiparasitic activities in vitro, as well as immunomodulatory functions during early secondary CE, mainly through Th1/Th17 cytokine bias and promotion of peritoneal polyreactive antibodies. These data support the relevance of the parasite components bound by rshCD5 and rshCD6, as well as the potential of their prophylactic administration as a useful strategy to reduce secondary CE in patients.
Deep learning‐based grain‐size decomposition model: A feasible solution for dealing with methodological uncertainty
Authors: Liu Yuming , Wang Ting , Wen Tao , Zhang Jianguang , Liu Bo , Li Yue , Zhang Hang , Rong Xiaoqing , Ma Long , Guo Fei , Liu Xingxing , Sun Youbin 
Published: April 2024

ABSTRACTTerrigenous clastic sediments cover a large area of the Earth's surface and provide valuable insights into the Earth's evolution and environmental change. Sediment grain‐size decomposition has been widely used as an effective approach to inferring changes in sediment sources, transport processes and depositional environments. Several algorithms, such as single sample unmixing, end‐member modelling analysis and the universal decomposition model, have been developed for grain‐size decomposition. The performance of these algorithms is highly dependent on parameter selections, introducing subjective uncertainty. This uncertainty could undermine the reliability of decomposition results, limit the application of grain‐size decomposition techniques and reduce comparability across different studies. To mitigate the methodological uncertainty, a novel deep learning‐based framework for grain‐size decomposition of terrigenous clastic sediments is proposed. First, an improved universal decomposition model is used to analyse the collected grain‐size data, in order to provide training sets for the end‐to‐end decomposers. To meet the data size requirements of supervised learning, generative adversarial networks are also trained for data augmentation. The performance of the new framework is then evaluated using a small‐scale dataset (73 393 samples from 18 sites) of three sedimentary types (loess, fluvial and lake delta deposits). The decomposed grain‐size results demonstrate high feasibility and great potential of the framework in constructing a robust grain‐size decomposition model. Finally, it is proposed that future grain‐size research should aim to establish guidelines for grain‐size data sharing and produce a big grain‐size database for deep learning.
NS7a of SADS-CoV promotes viral infection via inducing apoptosis to suppress type III interferon production
Authors: Wang Xiaowei , Qiu Wenjing , Hu Guangli , Diao Xiaoyuan , Li Yunfei , Li Yue , Li Peng , Liu Yufang , Feng Yongtong , Xue Chunyi , Cao Yongchang , Xu Zhichao 
Published: April 2024

ABSTRACT

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered swine coronavirus with potential cross-species transmission risk. Although SADS-CoV-induced host cell apoptosis and innate immunity antagonization has been revealed, underlying signaling pathways remain obscure. Here, we demonstrated that infection of SADS-CoV induced apoptosis
in vivo
and
in vitro
, and that viral protein NS7a is mainly responsible for SADS-CoV-induced apoptosis in host cells. Furthermore, we found that NS7a interacted with apoptosis-inducing factor mitochondria associated 1 (AIFM1) to activate caspase-3 via caspase-6 in SADS-CoV-infected cells, and enhanced SADS-CoV replication. Importantly, NS7a suppressed poly(I:C)-induced expression of type III interferon (IFN-λ) via activating caspase-3 to cleave interferon regulatory factor 3 (IRF3), and caspase-3 inhibitor protects piglets against SADS-CoV infection
in vivo
. These findings reveal how SADS-CoV induced apoptosis to inhibit innate immunity and provide a valuable clue to the development of effective drugs for the clinical control of SADS-CoV infection.

IMPORTANCE
Over the last 20 years, multiple animal-originated coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, have caused millions of deaths, seriously jeopardized human health, and hindered social development, indicating that the study of animal-originated coronaviruses with potential for cross-species transmission is particularly important. Bat-originated swine acute diarrhea syndrome coronavirus (SADS-CoV), discovered in 2017, can not only cause fatal diarrhea in piglets, but also infect multiple human cells, with a potential risk of cross-species transmission, but its pathogenesis is unclear. In this study, we demonstrated that NS7a of SADS-CoV suppresses IFN-λ production via apoptosis-inducing factor mitochondria associated 1 (AIFM1)-caspase-6-caspase-3-interferon regulatory factor 3 (IRF3) pathway, and caspase-3 inhibitor (Z-DEVD-FMK) can effectively inhibit SADS-CoV replication and protect infected piglets. Our findings in this study contribute to a better understanding of SADS-CoV-host interactions as a part of the coronaviruses pathogenesis and using apoptosis-inhibitor as a drug as potential therapeutic approaches for prevention and control of SADS-CoV infection.
Genes involved in the limited spread of SARS-CoV-2 in the lower respiratory airways of hamsters may be associated with adaptive evolution
Authors: Takada Kosuke , Orba Yasuko , Kida Yurie , Wu Jiaqi , Ono Chikako , Matsuura Yoshiharu , Nakagawa So , Sawa Hirofumi , Watanabe Tokiko 
Published: April 2024

ABSTRACT

Novel respiratory viruses can cause a pandemic and then evolve to coexist with humans. The Omicron strain of severe acute respiratory syndrome coronavirus 2 has spread worldwide since its emergence in late 2021, and its sub-lineages are now established in human society. Compared to previous strains, Omicron is markedly less invasive in the lungs and causes less severe disease. One reason for this is that humans are acquiring immunity through previous infection and vaccination, but the nature of the virus itself is also changing. Using our newly established low-volume inoculation system, which reflects natural human infection, we show that the Omicron strain spreads less efficiently into the lungs of hamsters compared with an earlier Wuhan strain. Furthermore, by characterizing chimeric viruses with the Omicron gene in the Wuhan strain genetic background and
vice versa
, we found that viral genes downstream of ORF3a, but not the S gene, were responsible for the limited spread of the Omicron strain in the lower airways of the virus-infected hamsters. Moreover, molecular evolutionary analysis of SARS-CoV-2 revealed a positive selection of genes downstream of ORF3a (M and E genes). Our findings provide insight into the adaptive evolution of the virus in humans during the pandemic convergence phase.

IMPORTANCE
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread worldwide since its emergence in late 2021, and its sub-lineages are established in human society. Compared to previous strains, the Omicron strain is less invasive in the lower respiratory tract, including the lungs, and causes less severe disease; however, the mechanistic basis for its restricted replication in the lower airways is poorly understood. In this study, using a newly established low-volume inoculation system that reflects natural human infection, we demonstrated that the Omicron strain spreads less efficiently into the lungs of hamsters compared with an earlier Wuhan strain and found that viral genes downstream of ORF3a are responsible for replication restriction in the lower respiratory tract of Omicron-infected hamsters. Furthermore, we detected a positive selection of genes downstream of ORF3a (especially the M and E genes) in SARS-CoV-2, suggesting that these genes may undergo adaptive changes in humans.
Differential stability of Gcn4p controls its cell-specific activity in differentiated yeast colonies
Authors: Váchová Libuše , Plocek Vítězslav , Maršíková Jana , Rešetárová Stanislava , Hatáková Ladislava , Palková Zdena 
Published: April 2024

ABSTRACT

Gcn4p belongs to conserved AP-1 transcription factors involved in many cellular processes, including cell proliferation, stress response, and nutrient availability in yeast and mammals. AP-1 activities are regulated at different levels, such as translational activation or protein degradation, which increases the variability of regulation under different conditions. Gcn4p activity in unstructured yeast liquid cultures increases upon amino acid deficiency and is rapidly eliminated upon amino acid excess. Gcn2p kinase is the major described regulator of Gcn4p that enables
GCN4
mRNA translation
via
the uORFs mechanism. Here, we show that Gcn4p is specifically active in U cells in the upper regions and inactive in L cells in the lower regions of differentiated colonies. Using
in situ
microscopy in combination with analysis of mutants and strains with GFP at different positions in the translational regulatory region of Gcn4p, we show that cell-specific Gcn4p activity is independent of Gcn2p or other translational or transcriptional regulation. Genetically, biochemically, and microscopically, we identified cell-specific proteasomal degradation as a key mechanism that diversifies Gcn4p function between U and L cells. The identified regulation leading to active Gcn4p in U cells with amino acids and efficient degradation in starved L cells differs from known regulations of Gcn4p in yeast but shows similarities to the activity of AP-1 ATF4 in mammals during insulin signaling. These findings may open new avenues for understanding the parallel activities of Gcn4p/ATF4 and reveal a novel biological role for cell type-specific regulation of proteasome-dependent degradation.

IMPORTANCE
In nature, microbes usually live in spatially structured communities and differentiate into precisely localized, functionally specialized cells. The coordinated interplay of cells and their response to environmental changes, such as starvation, followed by metabolic adaptation, is critical for the survival of the entire community. Transcription factor Gcn4p is responsible for yeast adaptation under amino acid starvation in liquid cultures, and its activity is regulated mainly at the level of translation involving Gcn2p kinase. Whether Gcn4p functions in structured communities was unknown. We show that translational regulation of Gcn4p plays no role in the development of colony subpopulations; the main regulation occurs at the level of stabilization of the Gcn4p molecule in the cells of one subpopulation and its proteasomal degradation in the other. This regulation ensures specific spatiotemporal activity of Gcn4p in the colony. Our work highlights differences in regulatory networks in unorganized populations and organized structures of yeast, which in many respects resemble multicellular organisms.
A little mica goes a long way: Impact of phyllosilicates on quartz deformation fabrics in naturally deformed rocks
Authors: Gottardi Raphaël , Casale Gabriele , Economou John , Morris Kristen 
Published: April 2024

Abstract
Quartz deformation fabrics reflect stress and strain conditions in mylonites, and their interpretation has become a mainstay of kinematic and structural analysis. Quantification of grain size and shape and interpretation of textures reflecting deformation mechanisms can provide estimates of flow stress, strain rate, kinematic vorticity, and deformation temperatures. Empirical calibration and determination of quartz flow laws is based on laboratory experiments of pure samples; however, pure quartzite mylonites are relatively uncommon. In particular, phyllosilicates may localize and partition strain that can inhibit or enhance different deformation mechanisms. Experimental results demonstrate that even minor phyllosilicate content (&lt;15 vol%) can dramatically alter the strain behavior of quartz; however, few field studies have demonstrated these effects in a natural setting.
To investigate the role of phyllosilicates on quartz strain fabrics, we quantify phyllosilicate content and distribution in quartzite mylonites from the Miocene Raft River detachment shear zone (NW Utah, USA). We use microstructural analysis and electron backscatter diffraction to quantify quartz deformation fabrics and muscovite spatial distribution, and X-ray computed tomography to quantify muscovite content in samples with varying amounts of muscovite collected across the detachment shear zone. Phyllosilicate content has a direct control on quartz deformation mechanisms, and application of piezometers and flow laws based on quartz deformation fabrics yield strain rates and flow stresses that vary by up to two orders of magnitude across our samples. These findings have important implications for the application of flow laws in quartzite mylonites and strain localization mechanisms in mid-crustal shear zones.
Emergency department discharge practices for children with acute wheeze and asthma: a survey of discharge practice and review of safety netting instructions in the UK and Ireland
Authors: Hannah Romanie , Chavasse Richard J P G , Paton James Y , Walton Emily , Roland Damian , Foster Steven , Lyttle Mark D 
Published: April 2024

ObjectiveRecovery from acute wheeze and asthma attacks should be supported with safety netting, including treatment advice. We evaluated emergency department (ED) discharge practices for acute childhood wheeze/asthma attacks to describe variation in safety netting and recovery bronchodilator dosing.DesignTwo-phase study between June 2020 and September 2021, comprising (1) Departmental discharge practice survey, and (2) Analysis of written discharge instructions for caregivers.SettingSecondary and tertiary EDs in rural and urban settings, from Paediatric Emergency Research in the UK and Ireland (PERUKI).Main outcome measuresDescribe practice and variation in discharge advice, treatment recommendations and safety netting provision.ResultsOf 66/71 (93%) participating sites, 62/66 (93.9%) reported providing written safety netting information. 52/66 (78.8%) ‘nearly always’ assessed inhaler/spacer technique; routine medication review (21/66; 31.8%) and adherence (16/66; 21.4%) were less frequent. In phase II, 61/66 (92.4%) submitted their discharge documents; 50/66 (81.9%) included bronchodilator plans. 11/66 (18.0%) provided Personalised Asthma Action Plans as sole discharge information. 45/50 (90%) provided ‘fixed’ bronchodilator dosing regimes; dose tapering was common (38/50; 76.0%). Median starting dose was 10 puffs 4 hourly (27/50, 54.0%); median duration was 4 days (29/50, 58.0%). 13/61 (21.3%) did not provide bronchodilator advice for acute deterioration; where provided, 42/48 (87.5%) recommended 10 puffs immediately. Subsequent dosages varied considerably. Common red flags included inability to speak (52/61, 85.2%), inhalers not lasting 4 hours (51/61, 83.6%) and respiratory distress (49/61, 80.3%).ConclusionsThere is variation in bronchodilator dosing and safety netting content for recovery following acute wheeze and asthma attacks. This reflects a lack of evidence, affirming need for further multicentre studies regarding bronchodilator recovery strategies and optimal safety netting advice.
Cardiovascular safety of evogliptin dual and triple therapy in patients with type 2 diabetes: a nationwide cohort study
Authors: Park Sohee , Jeong Han Eol , Oh In-Sun , Hong Sangmo , Yu Sung Hoon , Lee Chang Beom , Shin Ju-Young 
Published: April 2024

ObjectiveTo investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in routine clinical practice.DesignA retrospective cohort study.SettingKorean Health Insurance Review and Assessment database.ParticipantsPatients who initiated metformin-based dual therapy and metformin+sulfonylurea-based triple therapy in South Korea from 2014 to 2018.InterventionsInitiation of combination therapy with evogliptin.Primary and secondary outcome measuresHazards of cardiovascular events, a composite endpoint of myocardial infarction, heart failure and cerebrovascular events, and its individual components. Cox proportional hazards model with propensity score-based inverse probability of treatment weighting were used to estimate HRs and 95% CIs.ResultsFrom the dual and triple therapy cohorts, 5830 metformin+evogliptin users and 2198 metformin+sulfonylurea+evogliptin users were identified, respectively. Metformin+evogliptin users, as compared with metformin+non-DPP4i, had a 29% reduced risk of cardiovascular events (HR 0.71, 95% CI 0.62 to 0.82); HRs for individual outcomes were cerebrovascular events (0.71, 95% CI 0.53 to 0.95), heart failure (0.70, 95% CI 0.59 to 0.82), myocardial infarction (0.89, 95% CI 0.60 to 1.31). Metformin+sulfonylurea+evogliptin users, compared with metformin+sulfonylurea+non-DPP4i, had a 24% reduced risk of cardiovascular events (0.76, 95% CI 0.59 to 0.97); HRs for individual outcomes were myocardial infarction (0.57, 95% CI 0.27 to 1.19), heart failure (0.74, 95% CI 0.55 to 1.01), cerebrovascular events (0.96, 95% CI 0.61 to 1.51).ConclusionsThese findings suggest that dual or triple therapies of evogliptin for the management of type 2 diabetes in routine clinical practice present no cardiovascular harms, but could alternatively offer cardiovascular benefits in this patient population.
Professionals’ perspectives on interventions to reduce problematic alcohol use in older adults: a realist evaluation of working elements
Authors: van den Bulck Fieke A E , Knijff Rikste , Crutzen Rik , van de Mheen Dike , Bovens Rob H L M , Stutterheim Sarah E , Van de Goor Ien , Rozema Andrea D 
Published: April 2024

ObjectivesThis study set out to understand how (which elements), in what context and why (which mechanisms) interventions are successful in reducing (problematic) alcohol use among older adults, from the perspective of professionals providing these interventions.DesignGuided by a realist evaluation approach, an existing initial programme theory (IPT) on working elements in alcohol interventions was evaluated by conducting semistructured interviews with professionals.Setting and participantsThese professionals (N=20) provide interventions across several contexts: with or without practitioner involvement; in-person or not and in an individual or group setting. Data were coded and links between contexts, elements, mechanisms and outcomes were sought for to confirm, refute or refine the IPT.ResultsFrom the perspective of professionals, there are several general working elements in interventions for older adults: (1) pointing out risks and consequences of drinking behaviour; (2) paying attention to abstinence; (3) promoting contact with peers; (4) providing personalised content and (5) providing support. We also found context-specific working elements: (1) providing personalised conversations and motivational interviewing with practitioners; (2) ensuring safety, trust and a sense of connection and a location nearby home or a location that people are familiar with in person and (3) sharing experiences and tips in group interventions. Furthermore, the mechanisms awareness and accessible and low threshold participation were important contributors to positive intervention outcomes.ConclusionIn addition to the IPT, our findings emphasise the need for social contact and support, personalised content, and strong relationships (both between client and practitioner, and client and peers) in interventions for older adults.
Rationale and protocol for a prospective cohort study of respiratory viral infections in patients admitted from emergency departments of community hospitals: Effect of respiratory Virus infection on EmeRgencY admission (EVERY) study
Authors: Morimoto Takeshi , Morikawa Toru , Imura Haruki , Nezu Mari , Hamazaki Kenya , Sakuma Mio , Chaumont Agnès , Moitinho de Almeida Maria , Moreno Victor Preckler , Ho Yufan , Harrington Lauriane , Matsuki Taizo , Nakamura Tsukasa 
Published: April 2024

IntroductionRespiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms.Methods and analysisWe are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients’ hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions.Ethics and disseminationThe study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings.Trial registration numberNCT05913700.