bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat stress induced IPEC‐J2 cells barrier dysfunction through endoplasmic reticulum stress mediated apoptosis by p‐eif2α/CHOP pathway
Authors: Cui Yan‐jun , Chen Le‐yi , Zhou Xu , Tang Zhi‐ning , Wang Chong , Wang Hai‐feng 
Published: October 2021

AbstractHeat stress (HS) induced by high ambient temperatures compromises intestinal epithelial cell. However, the underlying mechanisms by which HS causes intestinal barrier dysfunction remain unclear. In this study, we established an in vitro acute‐HS‐induced intestinal damage using porcine small intestinal epithelial cell (IPEC‐J2) that exposed to the high temperatures (43°C) for 2 h. The cell proliferation, apoptosis, tight junction (TJ) barrier integrity and transcriptomic profiles were measured. The results showed that HS decreased cell viability while increased proapoptotic signaling evidenced by Bax/bcl2 ratio, cytochrome C release to cytosol and active‐caspase 3 increases (p < 0.01). HS led to decreased transepithelial electrical resistance, increased cell permeability, and downregulated TJ proteins including ZO1, occludin, and claudin 3 (p < 0.05). Transcriptome sequencing and KEGG pathway analysis revealed HS‐induced cell cycle arrest and activation of endoplasmic reticulum stress (ERS) response mediated by a critical transcript eif2α and proapoptotic molecule DDIT3 (known as CHOP). Furthermore, inhibition of ERS by 4‐phenylbutyrate (4‐PBA) administration and knockdown of eif2α and CHOP significantly attenuated IPEC‐J2 cells apoptosis (p < 0.05). Transmission electron microscopy analysis suggested that 4‐PBA inhibited HS‐induced increase in ER lumen diameter, indicating ultrastructural sign of ERS. In addition, HS‐induced impairment of TJs was significantly attenuated by 4‐PBA (p < 0.05). Collectively, HS induces ERS and activates the p‐eif2α/CHOP signaling pathway to impair epithelial barrier integrity through triggering the intestinal epithelial cell apoptosis.
Liver‐humanized mice: A translational strategy to study metabolic disorders
Authors: Luo Yonghong , Lu Haocheng , Peng Daoquan , Ruan Xiangbo , Eugene Chen Yuqing , Guo Yanhong 
Published: October 2021

AbstractThe liver is the metabolic core of the whole body. Tools commonly used to study the human liver metabolism include hepatocyte cell lines, primary human hepatocytes, and pluripotent stem cells‐derived hepatocytes in vitro, and liver genetically humanized mouse model in vivo. However, none of these systems can mimic the human liver in physiological and pathological states satisfactorily. Liver‐humanized mice, which are established by reconstituting mouse liver with human hepatocytes, have emerged as an attractive animal model to study drug metabolism and evaluate the therapeutic effect in “human liver” in vivo because the humanized livers greatly replicate enzymatic features of human hepatocytes. The application of liver‐humanized mice in studying metabolic disorders is relatively less common due to the largely uncertain replication of metabolic profiles compared to humans. Here, we summarize the metabolic characteristics and current application of liver‐humanized mouse models in metabolic disorders that have been reported in the literature, trying to evaluate the pros and cons of using liver‐humanized mice as novel mouse models to study metabolic disorders.
OGT upregulates myogenic IL‐6 by mediating O‐GlcNAcylation of p65 in mouse skeletal muscle under cold exposure
Authors: Hu Yajie , Liu Yang , Yang Yuying , Lv Hongming , Lian Shuai , Xu Bin , Li Shize 
Published: October 2021

AbstractCold exposure is an unavoidable and severe challenge for people and animals residing in cold regions of the world, and may lead to hypothermia, drastic changes in systemic metabolism, and inhibition of protein synthesis. O‐linked‐N‐acetylglucoseaminylation (O‐GlcNAcylation) directly regulates the activity and function of target proteins involved in multiple biological processes by acting as a stress receptor and nutrient sensor. Therefore, our study aimed to examine whether O‐GlcNAcylation affected myogenic IL‐6 expression, regulation of energy metabolism, and promotion of survival in mouse skeletal muscle under acute cold exposure conditions. Total protein was extracted from C2C12 cells that had been cultured at 32°C for 3, 6, 9, and 12 h. Western blot analysis showed that mild hypothermia enhanced O‐GlcNAc transferase (OGT) and O‐GlcNAcase (OGA) expression. Furthermore, global OGT‐dependent glycosylation and interleukin‐6 (IL‐6) levels peaked 3 h after induction of mild hypothermia. Enhanced activation of the NF‐κB pathway was also observed in response to mild hypothermia. Alloxan and Thiamet G were used to reduce and increase global OGT glycosylation levels in C2C12 cells, respectively. Increased O‐GlcNAcylation was associated with significant upregulation of IL‐6 expression, as well as enhanced activity and nuclear translocation of p65, while decreased O‐GlcNAcylation had the opposite effect. In addition, increased O‐GlcNAcylation was associated with significantly increased glucose metabolism, and OGT‐mediated O‐GlcNAcylation of p65. We generated skeletal muscle‐specific OGT knockout mice and exposed them to cold at 4°C for 3 h per day for 1 week. OGT deficiency attenuated the O‐GlcNAcylation, activity, and nuclear translocation of p65, resulting in downregulation of IL‐6 in mouse skeletal muscle of mice exposed to cold conditions. Taken together, our data suggested that O‐GlcNAcylation of p65 enhanced p65 activity and nuclear translocation leading to the upregulation of IL‐6, which maintained energy homeostasis and promotes cell survival in mouse skeletal muscle during cold exposure.
Computed tomography‐defined low skeletal muscle index and density in cancer patients: observations from a systematic review
Authors: McGovern Josh , Dolan Ross D. , Horgan Paul G. , Laird Barry J. , McMillan Donald C. 
Published: October 2021

AbstractBackgroundComputed tomography (CT) analysis of body composition has garnered interest as a potential prognostic tool in those with cancer. A range of pre‐defined thresholds currently exist within the literature to define low skeletal muscle mass and density. The aim of the present systematic review was to assess the prevalence of low skeletal muscle index (SMI) and density (SMD) within the literature, across a range of common solid tumours.MethodsA systematic search of PubMed was carried out to identify studies reporting CT analysis of SMI and SMD in patients with colorectal, oesophageal, gastric, hepatobiliary, pancreatic, breast, and lung cancer. The type of cancer, whether curative or non‐curative disease, the anthropomorphic parameter studied, threshold used to define low SMI and SMD, and the prevalence of these anthropomorphic measurements within the population were recorded.ResultsOf the 160 studies included, 156 reported an assessment of SMI and 35 reported assessment of SMD. The median prevalence of low SMI was 43% (30.1–57.1) and low SMD 49.4% (31.7–58.5) across the entire cohort. There was little variation in the prevalence of low SMI and SMD when studies were divided into curative and non‐curative cohorts—40.7% (27.5–51.3) vs. 48.4% (30.9–60.1) and 37.8% (32.2–52.2) vs. 55.3% (38.5–64.7) respectively. When divided into colorectal, oesophageal, gastric, hepatobiliary, pancreatic, breast and lung cancers, similar prevalence of low SMI (46.0% %, 49.8%, 35.7%, 41.1%, 32.3%, 34%, and 49.5%) and low SMD were also observed (52.1%, 54.3%, 71.2%, 56.8%, 55.3%, and 52.6%). This was maintained when studies were stratified into cohorts by threshold used—low SMI (Martin 48.9%, Prado 49.9%, and Others 36.0%) and low SMD (Martin 52.4% and Others 48.6%).ConclusionsLow SMI and SMD are endemic across a range of cancer types and disease stage, challenging pre‐existing dogma of the determinants of prevalence.
Transcranial color Doppler sonography as an alternative tool for evaluation of terminal internal carotid artery steno‐occlusion in moyamoya disease
Authors: Wang Jing‐Zhe , Zhang Sheng , Wei Xi , Zhang Dong , Zhao Ya‐Hui , Zhu Xun 
Published: October 2021

AbstractObjectiveTo investigate color Doppler ultrasonography criteria and its value in assessing the steno‐occlusion of the terminal internal carotid artery in moyamoya disease.MethodsAccording to the digital subtraction angiography findings, patients were divided into three groups: occlusion of the terminal internal carotid artery, >50% stenosis, and ≤50% stenosis. We measured the terminal and proximal internal carotid artery parameters of each group using transcranial and cervical color Doppler sonography.ResultsBlood flow signals in 12 terminal internal carotid arteries were absent, which were verified as occlusion by digital subtraction angiography. Parameters were obtained in the remaining 159 terminal/proximal internal carotid arteries to predict cutoffs for >50% stenosis and occlusion. For >50% stenosis, mean flow velocity >88.50 cm/s in the terminal internal carotid artery could achieved the highest receiver operating characteristic curve area of 0.776 with 62.50% sensitivity, 88.15% specificity, 48.39% positive predictive values, 92.97% negative predictive value, and 84.27% overall accuracy. For the occlusion, mean flow velocity <49.50 cm/s in the terminal internal carotid artery achieve the highest receiver operating characteristic curve area of 0.734 with 55.56% sensitivity, 83.81% specificity, 63.83% positive predictive values, 78.57% negative predictive value, and 74.21% overall accuracy. The area under receiver operating characteristic curve cutoffs for other parameters were less than 0.7.ConclusionMean flow velocity of terminal internal carotid artery provides useful diagnostic information for detecting steno‐occlusion in moyamoya disease. It may be used as an alternative tool to evaluate steno‐occlusion of the terminal internal carotid artery in moyamoya disease.
Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe‐host‐communication in vivo
Authors: Bittel Miriam , Reichert Patrick , Sarfati Ilann , Dressel Anja , Leikam Stefanie , Uderhardt Stefan , Stolzer Iris , Phu Tuan Anh , Ng Martin , Vu Ngan K. , Tenzer Stefan , Distler Ute , Wirtz Stefan , Rothhammer Veit , Neurath Markus F. , Raffai Robert L. , Günther Claudia , Momma Stefan 
Published: October 2021

AbstractThe intestinal microbiota influences mammalian host physiology in health and disease locally in the gut but also in organs devoid of direct contact with bacteria such as the liver and brain. Extracellular vesicles (EVs) or outer membrane vesicles (OMVs) released by microbes are increasingly recognized for their potential role as biological shuttle systems for inter‐kingdom communication. However, physiologically relevant evidence for the transfer of functional biomolecules from the intestinal microbiota to individual host cells by OMVs in vivo is scarce. By introducing Escherichia coli engineered to express Cre‐recombinase (E. coliCre) into mice with a Rosa26.tdTomato‐reporter background, we leveraged the Cre‐LoxP system to report the transfer of bacterial OMVs to recipient cells in vivo. Colonizing the intestine of these mice with E. coliCre, resulted in Cre‐recombinase induced fluorescent reporter gene‐expression in cells along the intestinal epithelium, including intestinal stem cells as well as mucosal immune cells such as macrophages. Furthermore, even far beyond the gut, bacterial‐derived Cre induced extended marker gene expression in a wide range of host tissues, including the heart, liver, kidney, spleen, and brain. Together, our findings provide a method and proof of principle that OMVs can serve as a biological shuttle system for the horizontal transfer of functional biomolecules between bacteria and mammalian host cells.
Acute toxicity and patient‐reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer
Authors: Iizumi Takashi , Ishikawa Hitoshi , Sekino Yuta , Tanaka Keiichi , Takizawa Daichi , Makishima Hirokazu , Numajiri Haruko , Mizumoto Masashi , Nakai Kei , Okumura Toshiyuki , Sakurai Hideyuki 
Published: October 2021

AbstractIntroductionTo confirm the feasibility of hypofractionated proton beam therapy (PBT), we compared the acute adverse event rates and International Prostate Symptom Score (IPSS) in prostate cancer patients treated with hypofractionated versus conventionally fractionated (2.0 Gy relative biological effectiveness (RBE)/fraction) PBT.MethodsWe reviewed 289 patients with prostate cancer, of whom 73, 100, and 116 patients were treated with 2.0, 2.5, and 3.0 Gy (RBE)/fraction, respectively. The endpoints were acute genitourinary and gastrointestinal toxicities and the IPSS, evaluated up to 6 months after PBT initiation.ResultsNo significant differences were found in acute toxicity rates or the IPSS among the fractionation schedules. Diabetes mellitus, age, and androgen deprivation therapy were not identified as factors associated with the IPSS.ConclusionThere were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.
Long COVID syndrome‐associated brain fog
Authors: Asadi‐Pooya Ali A. , Akbari Ali , Emami Amir , Lotfi Mehrzad , Rostamihosseinkhani Mahtab , Nemati Hamid , Barzegar Zohreh , Kabiri Maryam , Zeraatpisheh Zahra , Farjoud‐Kouhanjani Mohsen , Jafari Anahita , Sasannia Sarvin , Ashrafi Shayan , Nazeri Masoume , Nasiri Sara , Shahisavandi Mina 
Published: October 2021

AbstractWe investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease‐2019 (COVID‐19) who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog. Adult patients (18–55 years of age), who were referred to the healthcare facilities anywhere in Fars province from February 19, 2020 to November 20, 2020 were included. All patients had a confirmed COVID‐19 diagnosis. In a phone call, at least 3 months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection. In total, 2696 patients had the inclusion criteria; 1680 (62.3%) people reported long COVID syndrome (LCS). LCS‐associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio [OR]: 1.4), respiratory problems at the onset (OR: 1.9), and intensive care unit (ICU) admission (OR: 1.7) were significantly associated with reporting chronic post‐COVID “brain fog” by the patients. In this large population‐based study, we report that chronic post‐COVID “brain fog” has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).
Concerns on the multiple nomenclature systems for SARS‐CoV‐2
Authors: Li Xingguang 
Published: October 2021

AbstractThe multiple nomenclature systems of SARS‐CoV‐2 are confusing and have several issues. The emergence of variants of concern and variants of interest has posed an increased risk to global health. To assist with public discussion and communication with nonscientific audiences about significant mutations, and ultimately to inform the ongoing response to the COVID‐19 pandemic, we scientists need to develop easy‐to‐pronounce and nonstigmatizing labels for significant mutations.
Natural spring water gargle samples as an alternative to nasopharyngeal swabs for SARS‐CoV‐2 detection using a laboratory‐developed test
Authors: Gobeille Paré Sarah , Bestman‐Smith Julie , Fafard Judith , Doualla‐Bell Florence , Jacob‐Wagner Mariève , Lavallée Christian , Charest Hugues , Beauchemin Stéphanie , Coutlée François , Dumaresq Jeannot , Busque Lambert , St‐Hilaire Manon , Lépine Guylaine , Boucher Valérie , Desforges Marc , Goupil‐Sormany Isabelle , Labbé Annie‐Claude ,   G‐SPIT study group
Published: October 2021

AbstractThe objective of this study was to validate the use of spring water gargle (SWG) as an alternative to oral and nasopharyngeal swab (ONPS) for SARS‐CoV‐2 detection with a laboratory‐developed test. Healthcare workers and adults from the general population, presenting to one of two COVID‐19 screening clinics in Montréal and Québec City, were prospectively recruited to provide a gargle sample in addition to the standard ONPS. The paired specimens were analyzed using thermal lysis followed by a laboratory‐developed nucleic acid amplification test (LD‐NAAT) to detect SARS‐CoV‐2, and comparative performance analysis was performed. An individual was considered infected if a positive result was obtained on either sample. A total of 1297 adult participants were recruited. Invalid results (n = 18) were excluded from the analysis. SARS‐CoV‐2 was detected in 144/1279 (11.3%) participants: 126 from both samples, 15 only from ONPS, and 3 only from SWG. Overall, the sensitivity was 97.9% (95% CI: 93.7–99.3) for ONPS and 89.6% (95% CI: 83.4–93.6; p = 0.005) for SWG. The mean ONPS cycle threshold (Ct) value was significantly lower for the concordant paired samples as compared to discordant ones (22.9 vs. 32.1; p < 0.001). In conclusion, using an LD‐NAAT with thermal lysis, SWG is a less sensitive sampling method than the ONPS. However, the higher acceptability of SWG might enable a higher rate of detection from a population‐based perspective. Nonetheless, in patients with a high clinical suspicion of COVID‐19, a repeated analysis with ONPS should be considered. The sensitivity of SWG using NAAT preceded by chemical extraction should be evaluated.
Influence of the El Niño–Southern Oscillation and the sypnotic systems on the rainfall variability over the Brazilian Cerrado via Climate Hazard Group InfraRed Precipitation with Station data
Authors: Correia Filho Washington Luiz Félix , de Oliveira‐Júnior José Francisco , da Silva Junior Carlos Antonio , Santiago Dimas de Barros 
Published: October 2021

AbstractThe rainfall is essential to Brazil's hydrological cycle, agricultural development, and power generation, mainly Cerrado biome. Thus, the study assessed the influence of the El Niño–Southern Oscillation (ENSO) and synoptic systems on rainfall variability over the Brazilian Cerrado. To evaluate this variability, it used monthly rainfall data from the second version of the Climate Hazard Group InfraRed Precipitation with Station (CHIRPS) database (1981–2020), based on the annual densidrograms and thematic maps. In Annual terms, the average climatological was 1,417 mm·year−1. The highest precipitation values (>1,500 mm·year−1) occurred at the boundaries between Cerrado and Amazon, mainly in the states of the Maranhão, Mato Grosso, and Tocantins due to physiography (<500 m). The seasonal rainfall was more frequent in summer (on average, 48% of the annual total) distributed over the biome due to the South American monsoon system and South Atlantic convergence zone. The climatological dry period occurred between November and March (on average, 8% of the annual total) due to the Atmospheric Blocking called as Bolivia High that inhibit the passage of synoptic system transients in Central Brazil. In monthly terms, January (July) is the wetter month with 18% (drier month with 1%) of the annual total. The annual densidrograms appointed the following wetter (drier) years: 1985, 1989, and 2009 (1990, 1993, and 2012), influenced by ENSO events. The year 1985 appointed an increase of 19% in the mean annual rainfall, but in 1990 showed a reduction of 18% in climatology (1981–2020). In terms of seasonal anomalies, the summer of 1985 (1990) appointed an increase of 26% above (2.5% below) mean seasonal climatological, verified in the states of Maranhão, Piauí, and Tocantins (states of Mato Grosso). The La Niña (El Niño) events influenced positively (negatively) the annual rainfall anomalous pattern in Cerrado.Highlights
The rainiest period occurs during September and April months (>200 mm·month−1).
The driest period occurs during May and August months (<200 mm·month−1).
1985 (1990) year presents the most significant (smallest) annual rainfall average.
The border zone between Amazon and Cerrado presents the highest annual rainfall.
Climate and environmental history at Lake Levinson‐Lessing, Taymyr Peninsula, during the last 62 kyr
Authors: Lenz Matthias , Lenz Marlene M. , Andreev Andrei , Scheidt Stephanie , Gromig Raphael , Lebas Elodie , Fedorov Grigory , Krastel Sebastian , Melles Martin , Wagner Bernd 
Published: October 2021

ABSTRACTThe 45.95 m‐long sediment succession shown in core Co1401 from Lake Levinson‐Lessing allows the reconstruction of the largely unexplored environmental and climatic history of the Taymyr Peninsula of the past 62 kyr. The core was analysed with a multidisciplinary approach including lithological, granulometric, geochemical and pollen analyses. The proxy data indicate a relatively stable, herb‐dominated environment with only subtle changes between a cold/wet late Marine Isotope Stage (MIS) 4 and early MIS 3, mild/dry middle and late MIS 3 and a cold/dry MIS 2. The absence of pronounced climate fluctuations demonstrates that the Lake Levinson‐Lessing catchment was not covered by an ice sheet during this period. Changes in precipitation were likely caused by waxing and waning of the large Eurasian ice sheets outside of the Taymyr Peninsula, which changed the eastward moisture transport and atmospheric circulation patterns. MIS 1 at Lake Levinson‐Lessing was associated with overall warmer and wetter conditions and short‐term climate fluctuations during the Bølling–Allerød warming, Younger Dryas cooling and Preboreal transition, which indicates the influence of North Atlantic air masses.
Analysis of polysomnogram findings in children with concurrent obstructive and central sleep apnea
Authors: Hwang Chaewon , Ramagopal Maya , Kwong Kelvin 
Published: October 2021

AbstractObjectiveIncreasing evidence suggests overlap in mechanisms of obstructive and central sleep apnea. Our objective was to compare the patient characteristics and polysomnographic findings of children with concurrent obstructive and central sleep apnea (obstructive sleep apnea + central sleep apnea [OSA + CSA]), to those with OSA only.MethodsA retrospective case series of polysomnogram (PSG) from 30 June 2013 to 30 June 2018 of patients 18 years and younger was performed. PSG parameters were analyzed per standard protocol. There were two groups, OSA only group and OSA + CSA group. OSA + CSA was subdivided into groups of central apnea index (CAI) ≤5, and CAI >5. Differences in the age, sex, body mass index (BMI) percentile, prevalence of medical conditions, and PSG parameters between OSA only and OSA + CSA were assessed for statistical significance.ResultsThe mean age of the OSA only group was 8.2 years, significantly higher than that of the OSA + CSA group, 5.0 years, P < .00001. The proportion of underweight, normal weight, overweight, and obese patients according to BMI percentiles was not statistically significantly different between the two groups, P > .05. Most common comorbidity in the two groups was pulmonary conditions, which included asthma. Of the PSG parameters, arousals due to respiratory events and obstructive apnea hypopnea index of all OSA + CSA groups were significantly higher than those of the OSA only group, P < .05. Rapid eye movement (REM) sleep was significantly higher in total OSA + CSA group and OSA + CSA subgroup with CAI ≤5, P < .05, compared to OSA only.ConclusionChildren with concurrent OSA + CSA are younger, but there appears to be no difference in BMI percentiles between OSA only and OSA + CSA. Compared to OSA only group, children with concurrent OSA + CSA have significantly different sleep architecture—higher REM %—and experience significantly higher respiratory arousals and obstructive events, especially in the subgroup with CAI >5. There appears to be overlap in mechanisms of CSA and OSA in this cohort.Level of Evidence4.