bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: A Novel Homozygous Frameshift Mutation of the SKIV2L Gene in a Trichohepatoenteric Syndrome Patient Presenting With Short Stature, Premature Ovarian Failure, and Osteoporosis
Authors: Yang Minyi , Jiang Yu , Shao Xinyu 
Published: April 2022

Background: Trichohepatoenteric syndrome (THES) is a rare Mendelian autosomal recessive genetic disease characterized by intractable diarrhea, woolly hair, facial abnormality, immune dysfunction, and intrauterine growth restriction. THES mutations are found in the TTC37 and SKIV2L genes, which encode two components of the human superkiller (SKI) complex.Methods and results: We report one case of a 32-year-old woman of Chinese descent with THES, who was born with a low weight (2000 g). She had intractable diarrhea during the neonatal period and was allergic to cow’s milk and condensed milk, but did not require total parenteral nutrition. She experienced menarche at age 12 and amenorrhea at age 28. In May 2019, the patient presented with a left fibular head fracture and was diagnosed with osteoporosis. Genetic testing showed a novel mutation in exon1 [p.E5Afs∗37 (c.12_13del)] of SKIV2L, which is composed of 28 exons. After the diagnosis, hormone replacement therapy was prescribed, in addition to the routine calcium and vitamin D supplements.Conclusion: This case expands the clinical characteristic and phenotype spectrum of THES, providing further understanding of SKIV2L and its autoimmune influence.
Neuromuscular Blocking Agents and Monitoring in China: A Cross-Sectional Survey of Current Management
Authors: Wu HaoTian , Lin ZengMao , Zhou RuiHao , Huang SuiSui , Chen LingJun , Su Yang , Cheng LuoNa , Zhang Huan 
Published: April 2022

BackgroundLittle is known about the recent use of neuromuscular blocking agents (NMBAs) and monitoring in China. This paper presents the results of a nationwide survey conducted to obtain information regarding the current management of NMBAs in China.MethodsA questionnaire was sent to Chinese anesthesiologists inviting them to participate in the study. The questionnaire was available through the wenjuanxing website, and the link was sent to 1,488 anesthesiologists using the Wechat mini app.ResultsThe web-based survey consisted of 28 questions, and data were collected using an online tool. Between May 19, 2021 and June 16, 2021, 637 responses were collected (response rate = 42.8%). Only 10.2% of anesthesiologists reported using neuromuscular function monitors, and 6.59% of respondents reported that they had the relevant monitors in the operating room.ConclusionAlthough PORC is a potential safety issue, the frequency of using reversal agents and monitors remains extremely low in China. Surveys such as this are important to understand the use and application customs of NMBAs in China.
A Pilot Study of the Efficacy and Economical Sustainability of Acute Coronavirus Disease 2019 Patient Management in an Outpatient Setting
Authors: De Lorenzo Rebecca , Montagna Marco , Bossi Eleonora , Vitali Giordano , Taino Alba , Cilla Marta , Pata Giulia , Lazorova Ludmilla , Pesenti Riccardo , Pomaranzi Chiara , Bussolari Cecilia , Martinenghi Sabina , Bordonaro Nicoletta , Di Napoli Davide , Rizzardini Giuliano , Cogliati Chiara , Morici Nuccia , Rovere-Querini Patrizia 
Published: April 2022

ObjectiveTo report a preliminary experience of outpatient management of patients with Coronavirus disease 2019 (COVID-19) through an innovative approach of healthcare delivery.Patients and MethodsPatients evaluated at the Mild-to-Moderate COVID-19 Outpatient clinics (MMCOs) of San Raffaele University Hospital and Luigi Sacco University Hospital in Milan, Italy, from 1 October 2020 to 31 October 2021 were included. Patients were referred by general practitioners (GPs), Emergency Department (ED) physicians or hospital specialists (HS) in case of moderate COVID-19. A classification and regression tree (CART) model predicting ED referral by MMCO physicians was developed to aid GPs identify those deserving immediate ED admission. Cost-effectiveness analysis was also performed.ResultsA total of 660 patients were included. The majority (70%) was referred by GPs, 21% by the ED and 9% by HS. Patients referred by GPs had more severe disease as assessed by peripheral oxygen saturation (SpO2), ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) levels and interstitial involvement at lung ultrasound. Among them, 18% were addressed to the ED following MMCO assessment. CART analysis identified three independent predictors, namely home-measured SpO2, age and body mass index (BMI), that robustly divide patients into risk groups of COVID-19 severity. Home-measured SpO2 &lt; 95% and BMI ≥ 33 Kg/m2 defined the high-risk group. The model yielded an accuracy (95% CI) of 83 (77–88)%. Outpatient management of COVID-19 patients allowed the national healthcare system to spare 1,490,422.05 € when compared with inpatient care.ConclusionMild-to-moderate COVID-19 outpatient clinics were effective and sustainable in managing COVID-19 patients and allowed to alleviate pressure on EDs and hospital wards, favoring effort redirection toward non-COVID-19 patients.
Generating Flight Illusions Using Galvanic Vestibular Stimulation in Virtual Reality Flight Simulations
Authors: Pradhan Gaurav N. , Galvan-Garza Raquel , Perez Alison M. , Bogle Jamie , Cevette Michael J. 
Published: April 2022

BackgroundVestibular flight illusions remain a significant source of concern for aviation training. Most fixed-based simulation training environments, including new virtual reality (VR) technology, lack the ability to recreate vestibular flight illusions as vestibular cues cannot be provided without stimulating the vestibular end organs. Galvanic vestibular stimulation (GVS) has long been used to create vestibular perception. The purpose of this study is to evaluate the ability of GVS to simulate common flight illusions by intentionally providing mismatched GVS during flight simulation scenarios in VR.MethodsNineteen participants performed two flight simulation tasks—take off and sustained turn—during two separate VR flight simulation sessions, with and without GVS (control). In the GVS session, specific multi-axis GVS stimulation (i.e., electric currents) was provided to induce approximate somatogravic and Coriolis illusions during the take-off and sustained turn tasks, respectively. The participants used the joystick to self-report their subjective motion perception. The angular joystick movement along the roll, yaw, and pitch axes was used to measure cumulative angular distance and peak angular velocity as continuous variables of motion perception across corresponding axes. Presence and Simulator Sickness Questionnaires were administered at the end of each session.ResultsThe magnitude and variability of perceived somatogravic illusion during take-off task in the form of cumulative angular distance (p &lt; 0.001) and peak velocity (p &lt; 0.001) along the pitch-up axis among participants were significantly larger in the GVS session than in the NO GVS session. Similarly, during the sustained turn task, perceived Coriolis illusion in the form of cumulative angular distances (roll: p = 0.005, yaw: p = 0.015, pitch: p = 0.007) and peak velocities (roll: p = 0.003, yaw: p = 0.01, pitch: p = 0.007) across all three axes were significantly larger in the GVS session than in the NO GVS session. Subjective nausea was low overall, but significantly higher in the GVS session than in the NO GVS session (p = 0.026).DiscussionOur findings demonstrated that intentionally mismatched GVS can significantly affect motion perception and create flight illusion perceptions during fixed-based VR flight simulation. This has the potential to enhance future training paradigms, providing pilots the ability to safely experience, identify, and learn to appropriately respond to flight illusions during ground training.
Dietary Habits and Self-Reported Health Measures Among Norwegian Adults Adhering to Plant-Based Diets
Authors: Groufh-Jacobsen Synne , Bahr Bugge Annechen , Morseth Marianne Sandsmark , Pedersen Julia Tsuruta , Henjum Sigrun 
Published: April 2022

BackgroundAs plant-based diets is increasing, we aimed to investigate dietary habits, dietary motivation and self-reported health of Norwegian adults who adhere to different types of plant-based diets.MethodsIn 2020, 808 subjects (530 women and 278 men) participated in an online survey, including vegans (8%), lacto-ovo vegetarians (16%), pescatarians (23%), and flexitarians (53%).ResultsHalf of the participants reported to consume fruits daily, three quarters consumed vegetables daily, and one quarter consumed whole grain products daily. Half of the participants reported weekly consumption of sweets and salted snacks, and 10% reported daily consumption of sugary drinks. Daily consumption of milk and dairy substitutes were reported by vegans (49%), lacto-ovo vegetarians (33%), pescatarians (32%), and flexitarians (25%). Daily consumption of meat replacement products was reported by vegans (3%), lacto-ovo vegetarians (5%), pescatarians (2%). Reported supplement use was highest among vegans (62%) and lowest among flexitarians (28%). Dietary motivations were driven by environmental (71%), health (64%), and animal welfare (49%) concerns, across all dietary groups. 75% reported their self-perceived health to be good or very good.ConclusionWe found that Norwegian adults adhering to plant-based diets consumed less fruit, vegetables, and whole grain products, together with more sugar than recommended in the Norwegian dietary guidelines. The participants reported their self-perceived health to be good or very good.
Number of Episodes Can Be Used as a Disease Activity Measure in Familial Mediterranean Fever
Authors: Piskin David , Arici Zehra Serap , Konukbay Dilek , Romano Micol , Makay Balahan , Ayaz Nuray , Bilginer Yelda , Berard Roberta A. , Poyrazoglu Hakan , Kasapcopur Ozgur , Laxer Ronald M. , Speechley Kathy , Demirkaya Erkan 
Published: April 2022

ObjectiveTo evaluate the number of episodes in the past 12 months as an indicator of the overall disease activity status in Familial Mediterranean fever (FMF).MethodsIn this cross-sectional study, patients were recruited from tertiary pediatric hospitals. Demographic data, main clinical symptoms of the episodes, treatment modalities, and genetic mutations were recorded. The patients were grouped as no episodes (Group 1), 1–4 episodes (Group 2), and more than 4 episodes (Group 3) according to the number of episodes in the past 12 months. The Pediatric Quality Life Inventory (PedsQL), the Children’s Depression Inventory (CDI), and the Wong-Baker FACES Pain Rating Scale (FACES) scores were compared between groups. Concurrent validity between the number of episodes and the patient-reported outcome measures (PROMs) was assessed using Spearman’s rank correlation coefficient (ρ).ResultsA total of 239 patients were included. There were 74 patients (31%) in Group 1, 99 (41.4%) in Group 2, and 66 (27.6%) in Group 3. Groups were similar according to age, age at diagnosis, gender, consanguinity, family history, history of amyloidosis, clinical symptoms, and in terms of allele frequency (p &gt; 0.05). According to PROMs completed by parents, moderate correlations were found between the number of episodes and the PedsQL score (ρ = −0.48; 95% CI = −0.58 to −0.35, p &lt; 0.001) and between the number of episodes and the Wong-Baker FACES score (ρ = 0.47, 95% CI = 0.35–0.57, p &lt; 0.001).ConclusionThe number of episodes was positively and moderately correlated with patient- and parent-reported outcomes in our cohort. The number of episodes in patients with FMF can be used as a single measure to assess disease activity.
Astragaloside IV Alleviates Intestinal Barrier Dysfunction via the AKT-GSK3β-β-Catenin Pathway in Peritoneal Dialysis
Authors: He Jiaqi , Wang Mengling , Yang Licai , Xin Hong , Bian Fan , Jiang Gengru , Zhang Xuemei 
Published: April 2022

Background and aims: Long-term peritoneal dialysis (PD) causes intestinal dysfunction, including constipation, diarrhea, or enteric peritonitis. However, the etiology and pathogenesis of these complications are still unclear and there are no specific drugs available in the clinic. This study aims to determine whether Astragaloside IV (AS IV) has therapeutic value on PD-induced intestinal epithelial barrier dysfunction in vivo and in vitro.Methods: We established two different long-term PD treatment mice models by intraperitoneally injecting 4.25% dextrose-containing peritoneal dialysis fluid (PDF) in uremia mice and normal mice, which were served as controls. In addition, PDF was applied to T84 cells in vitro. The therapeutic effects of AS IV on PD-induced intestinal dysfunction were then examined by histopathological staining, transmission electron microscopy, western blotting, and reverse transcription polymerase chain reaction. The protein levels of protein kinase B (AKT), glycogen synthase kinase 3β (GSK-3β) and β-catenin were examined after administration of AS IV.Results: In the present study, AS IV maintained the intestinal crypt, microvilli and desmosome structures in an orderly arrangement and improved intestinal epithelial permeability with the up-regulation of tight junction proteins in vivo. Furthermore, AS IV protected T84 cells from PD-induced damage by improving cell viability, promoting wound healing, and increasing the expression of tight junction proteins. Additionally, AS IV treatment significantly increased the levels of phosphorylation of AKT, inhibited the activity GSK-3β, and ultimately resulted in the nuclear translocation and accumulation of β-catenin.Conclusion: These findings provide novel insight into the AS IV-mediated protection of the intestinal epithelial barrier from damage via the AKT-GSK3β-β-catenin signal axis during peritoneal dialysis.
Immunophenotyping of Acute Inflammatory Exacerbations of Lung Injury Driven by Mutant Surfactant Protein-C: A Role for Inflammatory Eosinophils
Authors: Nguyen Jacklyn , Armstrong Brittnie S. , Cowman Sophie , Tomer Yaniv , Veerabhadraiah Shivakumar R. , Beers Michael F. , Venosa Alessandro 
Published: April 2022

Acute inflammatory exacerbations (AIEs) represent immune-driven deteriorations of many chronic lung conditions, including COPD, asthma, and pulmonary fibrosis (PF). The first line of therapy is represented by broad-spectrum immunomodulation. Among the several inflammatory populations mobilizing during AIEs, eosinophils have been identified as promising indicators of an active inflammatory exacerbation. To better study the eosinophil-parenchymal crosstalk during AIE-PF, this work leverages a clinically relevant model of inflammatory exacerbations triggered by inducible expression of a mutation in the alveolar epithelial type 2 cell Surfactant Protein-C gene [SP-CI73T]. Unbiased single-cell sequencing analysis of controls and SP-CI73T mutants at a time coordinated with peak eosinophilia (14 days) defined heightened inflammatory activation, chemotaxis, and survival signaling (IL-6, IL-4/13, STAT3, Glucocorticoid Receptor, mTOR, and MYC) in eosinophils. To study the impact of eosinophils in inflammatory exacerbations, the SP-CI73T line was crossed with eosinophil lineage deficient mice (GATA1Δdbl) to produce the SP-CI73TGATA1KO line. Time course analysis (7–42 days) demonstrated improved lung histology, survival, and reduced inflammation in SP-CI73TGATA1KO cohorts. Spectral flow cytometry of tissue digests confirmed eosinophil depletion in GATA1KO mice and the absence of a compensatory shift in neutrophils and immature monocyte recruitment. Eosinophil deletion resulted in progressive monocyte-derived macrophage accumulation (14 days post-injury), combined with declines in CD3+CD4+ lymphocyte and B220+ B cell abundance. Histochemical analysis revealed atypical inflammatory cell activation in SP-CI73TGATA1KO mice, with reduced numbers of Arg-1+ and iNOS+ cells, but increases in tgfb1 mRNA expression in bronchoalveolar lavage cells and tissue. Dexamethasone treatment (1 mg/kg daily, i.p.) was utilized to investigate corticosteroid efficacy in highly eosinophilic exacerbations induced by mutant SP-CI73T. Dexamethasone successfully reduced total and eosinophil (CD11b+SigF+CD11c−) counts at 14 days and was linked to reduced evidence of structural damage and perivascular infiltrate. Together, these results illustrate the deleterious role of eosinophils in inflammatory events preceding lung fibrosis and demonstrate the efficacy of corticosteroid treatment in highly eosinophilic exacerbations induced by mutant SP-CI73T.
Discovery of METTL3 Small Molecule Inhibitors by Virtual Screening of Natural Products
Authors: Du Yue , Yuan Yongliang , Xu Le , Zhao Fang , Wang Wenbin , Xu Yiping , Tian Xin 
Published: April 2022

N6-Methyladenosine (m6A) is the most prevalent mRNA modification in mammalian cells that is mainly catalyzed by the methyltransferase complex of methyltransferase-like 3 and methyltransferase-like 14 (METTL3-METTL14). Many lines of evidence suggest that METTL3 plays important roles in several diseases such as cancers and viral infection. In the present study, 1,042 natural products from commercially available sources were chosen to establish a screening library, and docking-based high-throughput screening was performed to discover potential METTL3 inhibitors. The selected compounds were then further validated by an in vitro methyltransferase inhibition assay in which m6A content was determined by LC-MS/MS. A cellular assay of the inhibition of m6A methylation was performed to determine the METTL3 inhibitory activity of the selected compound. CCK-8 assay was applied to evaluate the effects of the selected compound on tumor cell viability. Additionally, binding mode analysis, molecular dynamics (MD) simulation, and binding free energy analysis were performed to study the process and characteristics of inhibitor binding. Finally, quercetin was identified as a METTL3 inhibitor with an IC50 value of 2.73 μM. The cellular assay of m6A methylation inhibition showed that quercetin decreased m6A level in a dose-dependent manner in MIA PaCa-2 pancreatic cancer cells. CCK-8 assay showed quercetin efficiently inhibited the proliferation of MIA PaCa-2 and Huh7 tumor cells, with IC50 values 73.51 ± 11.22 μM and 99.97 ± 7.03 μM, respectively. Molecular docking studies revealed that quercetin filled the pocket of the adenosine moiety of SAM but not the pocket of the SAM methionine in the METTL3 protein, and hydrogen bonds, hydrophobic interactions, and pi-stacking were formed. The values of the root mean square deviation (RMSD), the root mean square fluctuations (RMSF), and binding free energy suggested that quercetin can efficiently bind to the pocket of the METTL3 protein and form a stable protein-ligand complex. The present study is the first to identify METTL3 inhibitors from natural products, thus providing a basis for subsequent research and facilitating the development of METTL3-targeting drugs for diseases.
Magnetically Guided Capsule Endoscopy and Magnetic Resonance Enterography in Children With Crohn’s Disease: Manifestations and the Value of Assessing Disease Activity
Authors: Li Jia , Zhao Xuesong , Su Wen , Shen Ruizhe , Xiao Yuan , Wang Xinqiong , Xu Xu , Xu Chundi , Li Na , Yu Yi 
Published: April 2022

Objective: To investigate the value of magnetically guided capsule endoscopy (MGCE) and magnetic resonance enterography (MRE) in assessing the activity of pediatric Crohn’s disease.Methods: Clinical data from 82 subjects with pediatric Crohn’s disease, who underwent MGCE and MRE from October 2018 to March 2021 were analyzed retrospectively. Pairwise comparisons of several indexes, including MaRIA, CECDAI, PCDAI, and SES-CD, were performed by Spearman’s rank correlation test and kappa consistency analysis. CECDAI and MaRIA values predicted whether patients were moderately or severely active (PCDAI ≥30) clinically by logistic regression analysis. The area under the receiver operating characteristic curve (AUC) quantified the evaluation value of moderate to severe activity of pediatric CD.Results: In judging the severity of CD in the small intestine, the correlation coefficient between CECDAI and MaRIA was 0.406 (p &lt; 0.05), and the kappa value of the consistency analysis was 0.299 (p &lt; 0.05). MaRIA was weakly correlated with PCDAI (r = 0.254, p &lt; 0.05), and they were weakly consistent in assessing the activity of Crohn’s disease (kappa = 0.135, p &lt; 0.05). For predicting clinically moderate to severe activity, the fitted AUC based on CECDAI and MarRIA was 0.917, which was higher than applying a single parameter (CECDAI = 0.725, MarRIA = 0.899, respectively). MaRIA and serum albumin were significantly and negatively correlated (r = −1.064, p &lt; 0.05). The consistency of the detection rate of gastric ulcers by MGCE and gastroscopy was moderate (kappa = 0.586, p &lt; 0.05), and the detection rate of ulcers in the terminal ileum between MGCE and colonoscopy showed high consistency (kappa = 0.609, p &lt; 0.05).Conclusions: MGCE and MRE are valuable, non-invasive methods for evaluating small bowel lesions in children with CD. The combined application of MGCE and MRE can better characterize the disease activity.
Sirtuins 1 and 2 in the Acute Period After Photothrombotic Stroke: Expression, Localization and Involvement in Apoptosis
Authors: Eid Moez , Dzreyan Valentina , Demyanenko Svetlana 
Published: April 2022

Sirtuins (SIRTs) are NAD+- dependent histone deacetylases. They are involved in a variety of biological pathways and are thought to be a promising target for treating several human disorders. Although evidence is piling up to support the neuroprotective role of SIRTs in ischemic stroke, the role of different sirtuin isoforms needs further investigation. We studied the effects of photothrombotic stroke (PTS) on the expression and localization of sirtuins SIRT1 and SIRT2 in neurons and astrocytes of the penumbra and tested the activity of their selective and non-selective inhibitors. SIRT1 levels significantly decreased in the penumbra cells nuclei and increased in their cytoplasm. This indicated a redistribution of SIRT1 from the nucleus to the cytoplasm after PTS. The expression and intracellular distribution of SIRT1 were also observed in astrocytes. Photothrombotic stroke caused a sharp increase in SIRT2 levels in the cytoplasmic fraction of the penumbra neurons. SIRT2 was not expressed in the penumbra astrocytes. SIRT1 and SIRT2 did not co-localize with TUNEL-positive apoptotic cells. Mice were injected with EX-527, a selective SIRT1 inhibitor; SirReal2, selective SIRT2 inhibitor or salermide, a nonspecific inhibitor of SIRT1 and SIRT2. These inhibitors did not demonstrate any change in the infarction volume or the apoptotic index, compared to the control samples. The studies presented indicate the involvement of these sirtuins in the response of brain cells to ischemia in the first 24 h, but the alterations in their expression and change in the localization of SIRT1 are not related to the regulation of penumbra cell apoptosis in the acute period after PTS.