bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can the SARS-CoV-2 Spike Protein Bind Integrins Independent of the RGD Sequence?
Authors: Beaudoin Christopher A. , Hamaia Samir W. , Huang Christopher L.-H. , Blundell Tom L. , Jackson Antony P. 
Published: November 2021

The RGD motif in the Severe Acute Syndrome Coronavirus 2 (SARS-CoV-2) spike protein has been predicted to bind RGD-recognizing integrins. Recent studies have shown that the spike protein does, indeed, interact with αVβ3 and α5β1 integrins, both of which bind to RGD-containing ligands. However, computational studies have suggested that binding between the spike RGD motif and integrins is not favourable, even when unfolding occurs after conformational changes induced by binding to the canonical host entry receptor, angiotensin-converting enzyme 2 (ACE2). Furthermore, non-RGD-binding integrins, such as αx, have been suggested to interact with the SARS-CoV-2 spike protein. Other viral pathogens, such as rotaviruses, have been recorded to bind integrins in an RGD-independent manner to initiate host cell entry. Thus, in order to consider the potential for the SARS-CoV-2 spike protein to bind integrins independent of the RGD sequence, we investigate several factors related to the involvement of integrins in SARS-CoV-2 infection. First, we review changes in integrin expression during SARS-CoV-2 infection to identify which integrins might be of interest. Then, all known non-RGD integrin-binding motifs are collected and mapped to the spike protein receptor-binding domain and analyzed for their 3D availability. Several integrin-binding motifs are shown to exhibit high sequence similarity with solvent accessible regions of the spike receptor-binding domain. Comparisons of these motifs with other betacoronavirus spike proteins, such as SARS-CoV and RaTG13, reveal that some have recently evolved while others are more conserved throughout phylogenetically similar betacoronaviruses. Interestingly, all of the potential integrin-binding motifs, including the RGD sequence, are conserved in one of the known pangolin coronavirus strains. Of note, the most recently recorded mutations in the spike protein receptor-binding domain were found outside of the putative integrin-binding sequences, although several mutations formed inside and close to one motif, in particular, may potentially enhance binding. These data suggest that the SARS-CoV-2 spike protein may interact with integrins independent of the RGD sequence and may help further explain how SARS-CoV-2 and other viruses can evolve to bind to integrins.
Body Roundness Index Is a Superior Obesity Index in Predicting Diabetes Risk Among Hypertensive Patients: A Prospective Cohort Study in China
Authors: Liu Yingshan , Liu Xiaocong , Guan Haixia , Zhang Shuting , Zhu Qibo , Fu Xiaoying , Chen Hongmei , Tang Songtao , Feng Yingqing , Kuang Jian 
Published: November 2021

Objective: Individuals with both hypertension and diabetes have been confirmed to significantly increase the risk of cardiovascular disease morbidity and mortality compared with those with only hypertension or diabetes. This study aimed to evaluate the potential of different anthropometric indices for predicting diabetes risk among hypertensive patients.Methods: The study group consisted of 6,990 hypertensive adults without diabetes who were recruited in China. Demographic and clinical assessment, physical examinations, laboratory tests, and anthropometric measurements, including body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and novel indices (ABSI, AVI, BAI, BRI, CI, WWI, and WHHR), were performed at baseline and during the (median) 3-year follow-up. Cox regression analyses were conducted to estimate effects from these indices for the onset of diabetes. Receiver operator characteristic (ROC) analyses were conducted to assess the predictive capacities of the anthropometric indices and determine the optimal cut-points.Results: A total of 816 (11.7%) developed diabetes during our prospective study. Multivariate Cox regression analyses revealed weight, WC, WHR, WHtR, BAI, BRI, and WWI as the independent risk factor for diabetes among hypertensive patients, regardless of whether it was treated as a continuous or categorical variable (P &lt; 0.05). Further Cox analyses combining BMI and different central obesity indices showed that elevated WC, WHR, WHtR, AVI, BRI, CI, regardless of the general obesity status, were found to be each independently associated with increased diabetes risk (P &lt; 0.05). Dynamic increases of BRI &lt; 5.24 to BRI ≥ 5.24 were associated with increased risk (HR = 1.29; 95% CI, 1.02, 1.64), and its reversal was associated with reduced risk (HR = 1.56; 95% CI, 1.23, 1.98) compared with the others (HR = 1.95; 95% CI, 1.63, 2.32). ROC analysis indicated that the areas under the ROC curves (AUC) of the anthropometric indices ranged from 0.531 to 0.63, with BRI (cut-off value = 4.62) and WHtR having the largest area.Conclusions: Based on this novel study, BRI was the most superior predictor and independent determinant for diabetes onset among the hypertensive population. Hypertensive patients with BRI &gt; 4.62, regardless of general obesity status, were at high risk of diabetes. Thus, the prompt screening and diagnosis of diabetes should be carried out among these patients for timely integrated intervention.
Big Steps, Little Change: A Case Study in French University Teachers’ Cognitions in the Context of Pedagogical Innovation
Authors: Lami Raphaël , Gastineau Sylvie , Flom Haley , Desdevises Yves 
Published: November 2021

The rate of failure of French students during their first years at university is substantial, with only 42% graduating in the expected three or 4 years. As a result, French universities have called for a “pedagogical transformation” encouraging innovative teaching practices to improve undergraduate students’ academic success, notably the introduction of blended learning methods. In 2015, teachers from the three marine stations of Sorbonne Université created the online blended learning platform e-marin’lab for their marine science programs. In this paper, we investigated the participating teachers’ cognitions with regard to teaching and learning. Despite the success of the project that relied on their substantial voluntary commitment, the teachers demonstrated an adhesion to more traditional views (i.e., directive teacher-student transmission of knowledge is more efficient for students’ learning). Perhaps more paradoxically, our data reveal that the same teachers saw themselves as teaching in a student-oriented way, and that their students’ lack of engagement in class was due to their poor study skills and intrinsic motivation. Among other factors that will be discussed, we believe that these results are influenced by a context that does not provide many teacher training opportunities and that places little importance on teaching in university professors’ career recognition. Finally, the importance of the e-marin’lab platform in the context of the SARS-CoV-2 pandemic situation from 2020 and the massive use of distance teaching in marine sciences during national lockdown periods is discussed.
Drug Repositioning For Allosteric Modulation of VIP and PACAP Receptors
Authors: Langer Ingrid , Latek Dorota 
Published: November 2021

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two neuropeptides that contribute to the regulation of intestinal motility and secretion, exocrine and endocrine secretions, and homeostasis of the immune system. Their biological effects are mediated by three receptors named VPAC1, VPAC2 and PAC1 that belong to class B GPCRs. VIP and PACAP receptors have been identified as potential therapeutic targets for the treatment of chronic inflammation, neurodegenerative diseases and cancer. However, pharmacological use of endogenous ligands for these receptors is limited by their lack of specificity (PACAP binds with high affinity to VPAC1, VPAC2 and PAC1 receptors while VIP recognizes both VPAC1 and VPAC2 receptors), their poor oral bioavailability (VIP and PACAP are 27- to 38-amino acid peptides) and their short half-life. Therefore, the development of non-peptidic small molecules or specific stabilized peptidic ligands is of high interest. Structural similarities between VIP and PACAP receptors are major causes of difficulties in the design of efficient and selective compounds that could be used as therapeutics. In this study we performed structure-based virtual screening against the subset of the ZINC15 drug library. This drug repositioning screen provided new applications for a known drug: ticagrelor, a P2Y12 purinergic receptor antagonist. Ticagrelor inhibits both VPAC1 and VPAC2 receptors which was confirmed in VIP-binding and calcium mobilization assays. A following analysis of detailed ticagrelor binding modes to all three VIP and PACAP receptors with molecular dynamics revealed its allosteric mechanism of action. Using a validated homology model of inactive VPAC1 and a recently released cryo-EM structure of active VPAC1 we described how ticagrelor could block conformational changes in the region of ‘tyrosine toggle switch’ required for the receptor activation. We also discuss possible modifications of ticagrelor comparing other P2Y12 antagonist – cangrelor, closely related to ticagrelor but not active for VPAC1/VPAC2. This comparison with inactive cangrelor could lead to further improvement of the ticagrelor activity and selectivity for VIP and PACAP receptor sub-types.
Identification of Potential Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis
Authors: Peng Yajie , Zhu Hui , Han Bing , Xu Yue , Liu Xuemeng , Song Huaidong , Qiao Jie 
Published: November 2021

BackgroundAndrogen insensitivity syndrome (AIS) is a rare X-linked genetic disease and one of the causes of 46,XY disorder of sexual development. The unstraightforward diagnosis of AIS and the gender assignment dilemma still make a plague for this disorder due to the overlapping clinical phenotypes.MethodsPeripheral blood mononuclear cells (PBMCs) of partial AIS (PAIS) patients and healthy controls were separated, and RNA-seq was performed to investigate transcriptome variance. Then, tissue-specific gene expression, functional enrichment, and protein–protein interaction (PPI) network analyses were performed; and the key modules were identified. Finally, the RNA expression of differentially expressed genes (DEGs) of interest was validated by quantitative real-time PCR (qRT-PCR).ResultsIn our dataset, a total of 725 DEGs were captured, with functionally enriched reproduction and immune-related pathways and Gene Ontology (GO) functions. The most highly specific systems centered on hematologic/immune and reproductive/endocrine systems. We finally filtered out CCR1, PPBP, PF4, CLU, KMT2D, GP6, and SPARC by the key gene clusters of the PPI network and manual screening of tissue-specific gene expression. These genes provide novel insight into the pathogenesis of AIS in the immune system or metabolism and bring forward possible molecular markers for clinical screening. The qRT-PCR results showed a consistent trend in the expression levels of related genes between PAIS patients and healthy controls.ConclusionThe present study sheds light on the molecular mechanisms underlying the pathogenesis and progression of AIS, providing potential targets for diagnosis and future investigation.
Effects of Proton Pump Inhibitor Therapy, H. pylori Infection and Gastric Preneoplastic Pathology on Fasting Serum Gastrin Concentrations
Authors: Veysey-Smith Reuben , Moore Andrew R. , Murugesan Senthil V. , Tiszlavicz Laszlo , Dockray Graham J. , Varro Andrea , Pritchard D. Mark 
Published: November 2021

BackgroundHypergastrinaemia occasionally indicates the presence of a gastrinoma. However it is much more commonly associated with various benign causes including proton pump inhibitor (PPI) use, Helicobacter pylori infection and/or atrophic gastritis. The extent to which these factors interact to influence fasting serum gastrin concentrations remains incompletely understood.Materials and MethodsFasting serum gastrin concentrations were measured by radioimmunoassay in 1,400 patients attending for diagnostic oesophagogastro-duodenoscopy. After exclusions, 982 patients were divided into four groups and their results analysed. We compared gastrin concentrations in normal patients (no H. pylori infection, no PPI use and no histological evidence of gastric preneoplasia (n=233)), with those in patients who were taking regular PPIs (H. pylori negative with no gastric preneoplasia (n=301)), patients who had active H. pylori infection but no gastric preneoplasia (n=164) and patients with histologically confirmed gastric preneoplasia (n=284).ResultsMedian fasting gastrin concentration in the normal group was 20pM and was significantly increased in PPI users (46pM, p&lt;0.0001), patients with active H. pylori infection (27pM, p&lt;0.0001), and patients with antral (25pM, p&lt;0.01) or corpus (48pM, p&lt;0.0001) gastric preneoplasia. PPI use resulted in further significant increases in fasting serum gastrin concentrations in patients who were infected with H. pylori (50pM, n=56) or who had antral gastric preneoplasia (53pM, n=87), but did not significantly alter serum gastrin concentrations in patients with corpus preneoplasia (90pM, n=66).ConclusionsPPI use, H. pylori infection and atrophic gastritis all caused significant elevations of median fasting gastrin concentrations. However, several patients who had potential risk factors for hypergastrinaemia still demonstrated fasting serum gastrin concentrations within the normal range.
NILs of Cold Tolerant Japonica Cultivar Exhibited New QTLs for Mineral Elements in Rice
Authors: Ali Muhammad Kazim , Sun Zheng-Hai , Yang Xiao-Meng , Pu Xiao-Ying , Duan Cheng-Li , Li Xia , Wang Lu-Xiang , Yang Jia-Zhen , Zeng Ya-Wen 
Published: November 2021

Chilling stress at booting stage can cause floret deterioration and sterility by limiting the supply of food chain and the accumulation of essential mineral elements resulting in reduction of yield and grain quality attributes in rice. Genomic selection of chilling tolerant rice with reference to the accumulation of mineral elements will have great potential to cope with malnutrition and food security in times of climate change. Therefore, a study was conducted to explore the genomic determinants of cold tolerance and mineral elements content in near-isogenic lines (NILs) of japonica rice subjected to chilling stress at flowering stage. Detailed morphological analysis followed by quantitative analysis of 17 mineral elements revealed that the content of phosphorus (P, 3,253 mg/kg) and potassium (K, 2,485 mg/kg) were highest while strontium (Sr, 0.26 mg/kg) and boron (B, 0.34 mg/kg) were lowest among the mineral elements. The correlation analysis revealed extremely positive correlation of phosphorus (P) and copper (Cu) with most of the cold tolerance traits. Among all the effective ear and the second leaf length correlation was significant with half of the mineral elements. As a result of comparative analysis, some QTLs (qBRCC-1, qBRCIC-2, qBRZC-6, qBRCHC-6, qBRMC-6, qBRCIC-6a, qBRCIC-6b, qBRCHC-6, and qBRMC-6) identified for calcium (Ca), zinc (Zn), chromium (Cr) and magnesium (Mg) on chromosome number 1, 2, and 6 while, a novel QTL (qBCPC-1) was identified on chromosome number 1 for P element only. These findings provided bases for the identification of candidate genes involved in mineral accumulation and cold tolerance in rice at booting stage.
Circadian Variation in the Median Effective Dose of Epidural Ropivacaine for Labor Analgesia
Authors: Deng Jiali , Wei Changna , Liu Lin , Qian Jing , Xiao Fei , Chen Xinzhong 
Published: November 2021

Background: Labor pain perception has been demonstrated to exhibit a circadian rhythm with lower pain scores during the day compared with the night. This study aimed to determine and compare the median effective dose (ED50) of ropivacaine in parturients having epidural labor analgesia during the day vs. during the night.Methods: The study group consisted of 60 nulliparous healthy parturients who were assigned to one of two groups according to the time they requested labor analgesia: Day Group (7:01 am to 7:00 pm) and Night Group (7:01 pm to 7:00 am). A bolus of.15% ropivacaine was administered epidurally and effective analgesia was defined as the attainment of a visual analog scale (VAS) pain score ≤ 10 mm within 30 min. The dose of ropivacaine for the first parturient in each group was 18 mg. The dose for each subsequent parturient was varied with increments or decrements of 3 mg based on the response of the previous subject. The ED50 was calculated using up-down sequential analysis. Probit regression was used to estimate the relative mean potency of ropivacaine between groups.Results: The ED50 (mean [95% CI]) of ropivacaine was lower in the Day Group (17.9 [16.5–19.4] mg) than in the Night Group (20.9 [19.2–22.7] mg) (P = 0.003). The estimate of relative potency for ropivacaine for the Night Group vs. the Day Group was 0.85 (95% CI:0.56–0.98).Conclusions: Under the conditions of this study, the dose requirement for epidural ropivacaine for labor analgesia was ~ 15% greater during the night than during the day.Clinical Trials Registration: Chinese Clinical Trial Registry (No.: ChiCTR1900025269. http://www.chictr.org.cn/showprojen.aspx?proj=36993).
Plasma C-C Chemokine Concentrations in Intermediate Age-Related Macular Degeneration
Authors: Palestine Alan G. , Wagner Brandie D. , Patnaik Jennifer L. , Baldermann Rebecca , Mathias Marc T. , Mandava Naresh , Lynch Anne M. 
Published: November 2021

Purpose: To determine the relationship between plasma concentrations of the C-C chemokines CCL2, CCL3, CCL4, and CCL5 and intermediate age-related macular degeneration (iAMD) patients compared with control inidividuals to further define the inflammatory pathways associated with age-related macular degeneration.Methods: The concentrations of CCL2, CCL3, CCL4, and CCL5 were measured using multiplex assays in plasma collected from 210 patients with iAMD and 102 control individuals with no macular degeneration as defined by multi-modal imaging. Non-inflammatory data included in the analysis were: age, sex, family history of AMD, history of smoking, body mass index, presence of reticular pseudo-drusen and cardiovascular disease. Median concentrations as well as a cutoff value for each chemokine were compared between the two groups.Results: The median concentrations of CCL2 and CCL4 did not differ between control and iAMD groups, however, CCL2 was elevated in iAMD when a cutoff comparison was used (p &lt; 0.05). Median CCL3 and CCL5 concentrations were significantly decreased in the macular degeneration group compared with controls (p &lt; 0.001) as well as when a cutoff value comparison was used. CCL3 and CCL5 were negatively correlated in cases and positively correlated in controls.Conclusions: Plasma CCL3 and CCL5 concentrations were significantly decreased and CCL2 concentrations were increased in patients with iAMD compared with controls, suggesting a role for C-C chemokines in the systemic inflammatory processes associated with disease development.
Rate of Cornea Endothelial Cell Loss and Biomechanical Properties in Fuchs' Endothelial Corneal Dystrophy
Authors: Reinprayoon Usanee , Jermjutitham Monthira , Kasetsuwan Ngamjit 
Published: November 2021

Background: Our study aimed to determine the correlation between the clinical staging of Fuchs' endothelial corneal dystrophy (FECD), rate of endothelial cell loss, and corneal biomechanical properties.Methods: This study combined a longitudinal retrospective/prospective analysis of corneal endothelial cell loss and a prospective cross-sectional analysis of corneal biomechanics of Fuchs' endothelial dystrophy. The trial was registered at the Thai Clinical Trials Registry as TCTR 20160927004. FECD was diagnosed by the presence of corneal guttata detected by slit lamp microscopy; the disease severity was classified into four stages using the modified Stocker's classification. In vivo confocal microscopy, Scheimpflug imaging, and Corneal Visualization Scheimpflug Technology were performed to evaluate endothelial cell count, central corneal thickness, and corneal biomechanical properties. Linear mixed modeling analyses were used to estimate the endothelial cell densities in a 4-year period. The corneal biomechanics were compared among the stages using Corvis ST parameters.Results: Eighty eyes from eighty subjects were enrolled (42, 26, 12, and none in stages 1, 2, 3, and 4, respectively). The mean endothelial cell density was 1228.35 cells/mm2. The year-by-year reduction rate was 94.3 cells/mm2 (μEMM = −94.3, 95% CI: −115.4 to −73.2, p &lt; 0.001). Corneal endothelial cell losses in Fuchs' endothelial dystrophy were estimated to be 7.7, 7.8, and 8.4% per year for stages 1, 2, and 3, respectively. The mean corneal thicknesses of stages 1, 2, and 3 were 556 ± 32, 623 ± 33, and 648 ± 50 mm, respectively. For the corneal biomechanical parameters, the A1-length and A1-time were significantly different between stages 1 and 3 (A1-length: mean diffstage1vs.3 = 0.10, 95% CI: &lt; 0.001–0.15, p &lt; 0.001, A1-time: mean diffstage1vs.3 = −0.24, 95% CI: −0.41 to −0.07, respectively).Conclusions: In the advanced stage, corneas significantly changed their biomechanical viscoelastic behavior by decreasing resistance, as measured by a longer A1-length and shorter A1-time.