bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRPA1/M8 agonists upregulate ciliary beating through the pannexin-1 channel in the human nasal mucosa
Authors: Nguyen Thi Nga , Koga Yuma , Wakasugi Tetsuro , Kitamura Takuro , Suzuki Hideaki 
Published: August 2022

Abstract
Background: Nasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by transient receptor potential (TRP) M8, a thermoreceptor for cool temperatures. We herein investigated the effect of the activation of thermosensitive TRPs for cool/cold temperatures on ciliary beating and searched for a compensatory mechanism that maintains ciliary beating against the fall of temperature in the human nasal mucosa. Methods and Results: Inferior turbinates were collected from patients with chronic hypertrophic rhinitis, and ex vivo ciliary beat frequency (CBF) was immediately measured using a high-speed digital video camera attached to a phase-contrast light microscope. The samples were also subjected to fluorescence immunohistochemistry and real-time RT-PCR for TRPA1/TRPM8. CBF was significantly increased by adding either cinnamaldehyde (TRPA1 agonist) or l-menthol (TRPM8 agonist), and this increase was inhibited by pannexin-1 blockers, carbenoxolone and probenecid. Immunohistochemistry detected TRPA1 and TRPM8 on the epithelial surface and in the submucosal nasal glands. Expressions of mRNAs for these receptors were confirmed by real-time RT-PCR. Conclusions: These results indicate the stimulatory effect of the activation of TRPA1/TRPM8 on ciliary beating in the nasal mucosa, which would be advantageous to maintain airway mucosal defense under normal nasal breathing. This stimulatory effect is likely to be mediated by pannexin-1. Understanding the regulatory mechanism of airway ciliary beating should aid in the development of new, effective treatments for intractable airway diseases. BackgroundNasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by transient receptor potential (TRP) M8, a thermoreceptor for cool temperatures. We herein investigated the effect of the activation of thermosensitive TRPs for cool/cold temperatures on ciliary beating and searched for a compensatory mechanism that maintains ciliary beating against the fall of temperature in the human nasal mucosa.
Gender-specific Association of Frailty, Polypharmacy, and the Five-year Mortality Risk: A Real-world Retrospective Study
Authors: Lin Shih-Yi , Chen Yi-Ming , Chou Yin-Yi , Lee Yu-Shan , Lin Chu-Sheng , Chen Jun-Peng , Kuo Fu-Hsuan , Lin Cheng-Fu 
Published: August 2022

Abstract
Background: With higher age, frailty escalates the risk of falls, unexpected physical dysfunction, hospitalization, and mortality. Polypharmacy in the older population is a major challenge that not only increases medical costs, but also may worsen the risk of hospitalization and death. This study aimed to investigate the sex difference in the association of polypharmacy and frailty with mortality.Methods: Participants older than 65 years who attended the geriatric outpatient clinic of the study center between January 2015 and July 2020 were invited to participate in this retrospective study. Comprehensive geriatric assessment (CGA) data were collected and the phenotype of frailty was determined by Fried’s criteria. Cox regression and the Kaplan–Meier curve were used to identify risk factors of 5-year survival along with intergroup differences in the risks.Results: Of the 2077 participants, 47.5% were female. The prevalence of frailty and the rate of polypharmacy were 44.7% and 60.6%, respectively. Higher age, male sex, low body mass index, low Mini-Mental State Examination scores, low activities of daily living, frailty status, polypharmacy, and a high Charlson Comorbidity Index score were significant risk factors that were associated with the 5-year all-cause mortality. Male patients with frailty exhibited the highest risks of mortality compared with male patients without frailty and female patients with or without frailty. Polypharmacy was significantly associated with a higher 5-year mortality rate in the frail male group compared with the non-frail male. Conclusions: Polypharmacy synergistically interacted with frailty and intensified the 5-year mortality risk in a gender-specific manner. To mitigate mortality risks, clinicians should prudently identify polypharmacy in the non-frail male older population.
MARS: Improved De Novo Peptide Candidate Selection for Non-Canonical Antigen Target Discovery in Cancer
Authors: Liao Hanqing , Barra Carolina , Peng Xu , Woodhouse Isaac , Tailor Arun , Parker Robert , Carré Alexia , Mallone Roberto , Hogan Michael , Paes Wayne , Eisenlohr Laurence , Nielsen Morten , Ternette Nicola 
Published: August 2022

Abstract
Cryptic Human Leukocyte Antigen (HLA)-presented peptide identification from unannotated genome sources is a priority for target antigen discovery for development of next generation immunotherapies in cancer. Current immunopeptidomic approaches utilize the integration of transcriptomics data to inform spectral interpretation, however, recent observations that tumour-associated antigen-encoding RNA levels are often low highlights limitations of such proteogenomic approaches1. We here employ a de novo sequencing approach with a refined, MHC-centric analysis strategy to detect non-canonical HLA-associated peptide sequences (HLAp) in cancer without integration of transcript sequence information. Our strategy integrates HLA binding prediction, peptide retention time prediction, and average local confidence scores culminating in the machine learning model MARS (MHC binding prediction, Average Local Confidence Score, and Retention time integration for improved de novo candidate Selection). We demonstrate increased HLA-I peptide identification sensitivity by benchmarking our model against de novo sequencing alone with a large synthetic HLA-I peptide library dataset. We further define the sensitivity of MARS by reanalysis of a published dataset of high-quality non-canonical HLAp identifications in human cancer cell line and tissue datasets and achieve almost 2-fold improvement of the full sequence recall (FSR) for high quality spectral assignments in comparison to de novo sequencing alone2. We minimize the false discovery rate (FDR) through a step-wise peptide sequence mapping strategy and are able to expand the reported non-canonical peptide space with an assignment accuracy above 85.7%. Finally, we utilize MARS to detect and validate lncRNA-derived peptides in human cervical tumour resections, demonstrating its suitability to discover novel, non-canonical peptide sequences in primary tumour tissue at reduced FDR, in the absence of transcriptomic sequencing data.
Cerebral small vessel disease: a bibliometric analysis
Authors: Ma Wei , Yang Yi-Bao , Xie Ting-Ting , Xu Yi , Liu Na , Mo Xueni 
Published: August 2022

Abstract
Background
Cerebral small vessel disease is a common neurological disease, and its incidence is increasing year by year worldwide. In recent years, research on cerebral small vessel disease has gained more and more attention. Our research aims to visualize publications to identify the hotspots and frontiers of cerebral small vessel disease research, and to provide reference and guidance for further research.
Methods
Publications related to cerebral small vessel disease were searched from the Web of Science Core Collection and screened according to inclusion criteria. Citespace 5.8.R3 was used to evaluate and visualize results, including generating web maps and analyzing annual publications, countries, institutions, bibliographic and co-cited references, and keywords, in this article, we use Citespace and VOSviewer for the 2012 Cerebral small vessel disease and bibliometric analysis from January 1, 2022 to April 30, 2022.
Results
A total of 3037 papers related to cerebral small vessel disease were retrieved, and the number of published papers showed a steady upward trend. Among them, Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration, the most symbolic references in the field of cerebral small vessel disease has been cited a total of 438 times.Stroke is the most active journal (227 articles) and Usa publishes up to 800 articles. Harvard Med SchUniv Edinburgh (133 papers) and Charidimou (85 papers), who are the institutions and authors who have made the most contributions in this field, respectively. Among the keywords, most of them are related to the pathogenesis of cerebral small vessel disease. After 2018,gut-brain axi and cortex are the keywords with the strongest number of cited outbreaks. There is increasing evidence that cerebral small vessel disease is a research frontier and may remain a research hotspot in the future.
The molecular mechanism of coronary spasm in iPSC-derived smooth muscle cells: Role of p122 RhoGAP/DLC-1 and phospholipase C-δ1
Authors: Tanaka Makoto , Osanai Tomohiro , Okumura Ken , Yoshioka Toshitada , Tomita Hirofumi 
Published: August 2022

Abstract
Background: We previously reported that the activity of phospholipase C-δ1 and the expression of p122RhoGTPase-activating protein (GAP)/deleted in liver cancer-1 (p122RhoGAP/DLC-1) were enhanced in skin fibroblasts obtained from patients with coronary spastic angina (CSA). Overexpression of p122RhoGAP/DLC-1 increased intracellular free calcium concentration ([Ca2+]i) in response to acetylcholine (ACh). We generated transgenic mice overexpressing vascular smooth muscle-specific p122RhoGAP/DLC-1 (p122-TG) and showed that coronary spasm was induced by ergometrine infusion.Methods: To examine Ca2+ signaling in coronary arteries, we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of CSA patients (n = 3) and control subjects (n = 3), and differentiated the iPSCs into vascular smooth muscle cells (VSMCs). Results: We identified the molecular mechanism for enhanced Ca2+ signaling involved in the pathogenesis of CSA using iPSC-derived VSMCs. The concentration of [Ca2+]i after ACh stimulation at 10-4 M was 53 ± 10 nM in the control iPSC-derived VSMCs and 129 ± 24 nM in the CSA iPSC-derived VSMCs (P < 0.05). Diltiazem hydrochloride (voltage gated Ca2+ channel blocker) or xestospongin C [inositol-1,4,5-trisphosphate receptor (IP3R) antagonist] blocked the ACh-induced increase of [Ca2+]i in CSA iPSC-derived VSMCs. Western blot analysis revealed that p122RhoGAP/DLC-1 and IP3R1 protein levels were increased by 2.53 ± 0.88 and 7.53 ± 3.78 times, respectively, in CSA iPSC-derived VSMCs compared with control iPSC-derived VSMCs (all P < 0.05). PLC-δ1 activity in the whole cell was significantly higher (3.12 ± 1.28 times) in CSA iPSC-derived VSMCs compared with control iPSC-derived VSMCs (P < 0.05). Conclusions: Enhanced PLC-δ1 activity contributes to increased [Ca2+]i in response to ACh in CSA patients concomitantly with enhanced p122RhoGAP/DLC-1 and IP3R1 protein expression.
Inference of cell type-specific gene regulatory networks on cell lineages from single cell omic datasets
Authors: Zhang Shilu , Pyne Saptarshi , Pietrzak Stefan , Siahpirani Alireza , Sridha Rupa , Roy Sushmita 
Published: August 2022

Abstract
Cell type-specific gene expression patterns are outputs of transcriptional gene regulatory networks (GRNs) that connect transcription factors and signaling proteins to target genes. These networks reconfigure during dynamic processes such as cell fate specification to drive diverse cellular states. Single-cell transcriptomic technologies, such as single cell RNA-sequencing (scRNA-seq) and single cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), can examine the transcriptional state of individual cells, allowing the study of cell-type specific gene regulation at unprecedented detail. However, current approaches to infer cell type-specific gene regulatory networks from these datasets are limited in their ability to integrate scRNA-seq and scATAC-seq measurements and to model network dynamics on a cell lineage. To address this challenge, we have developed single-cell Multi-Task Network Inference (scMTNI), a multi-task learning framework to infer the gene regulatory network for each cell type on a lineage from scRNA-seq and scATAC-seq data. Using simulated, published and newly collected single cell omic datasets, we show that scMTNI is able to accurately infer gene regulatory networks and captures meaningful network dynamics that identify GRN components associated with cell type transitions. Application of our method to mouse cellular reprogramming identified key regulators associated with cell populations that reprogram versus those that are stalled. Taken together, scMTNI is a powerful framework to infer cell type-specific gene regulatory networks and their dynamics from scRNA-seq and scATAC-seq datasets.
Body mass index and cancer risk: An umbrella review of meta-analyses of observational studies
Authors: Chen Junhao , Ke Kaimin , Liu Zhenghuan , Peng Zhufeng , Yang Luchen , Wang Linchun , Zhou Jing , Dong Qiang 
Published: August 2022

Abstract
Background: Increasing evidence indicates that obesity is a risk factor for various tumors. We aimed to clarify the evidence for association between body mass index (BMI) and cancer risk based on existing systematic review and meta-analyses.Methods: PubMed, Embase and Web of science were systematically searched to obtain systematic review and meta-analyses reporting association between BMI and cancer incidence. The methodological quality and strength of evidence of each meta-analysis were assessed by AMSTAR and GRADE respectively. We also assessed the heterogeneity and publication bias of all included meta-analyses.Results: Finally, 43 meta-analyses with 19 cancers were identified by this umbrella review. The result revealed that underweight was inversely associated with the incidence of brain tumors while was positively related to the risk of esophageal and lung cancer. Overweight would enhance the incidence of brain tumors, kidney cancer, endometrial cancer, ovarian cancer, multiple myeloma, bladder cancer and liver cancer. Obesity was related to the increased incidence of brain tumors, cervical cancer, kidney cancer, endometrial cancer, esophageal cancer, gastric cancer, ovarian cancer, multiple myeloma, gallbladder cancer, bladder cancer, colorectal cancer, liver cancer, thyroid cancer and Hodgkin’s lymphoma. What’s more, dose-response analysis was conducted by 10 studies and the results demonstrated that per 5Kg/m2 increment of BMI was associated with 1.01 to 1.13 fold increased risk of general brain tumors, multiple myeloma, bladder cancer, pancreatic cancer, breast cancer, Non-Hodgkin’s lymphoma. And every 1Kg/m2 increment of BMI was linked to 6% and 4% increment in the risk of kidney cancer and gallbladder cancer respectively.Conclusions: The evidence presented in this umbrella review showed that overweight and obesity were associated with increased risk of most cancers. We recommend that it is better to maintain BMI within the normal range to prevent the occurrence of tumors. However, prospective studies with high quality are needed to further investigate the association between BMI and various cancer risk.
Resolving colistin resistance and heteroresistance in Enterobacter species
Authors: Doijad Swapnil , Gisch Nicolas , Frantz Renate , Kumbhar Bajarang , Falgenhauer Jane , Imirzalioglu Can , Falgenhauer Linda , Mischnik Alexander , Rupp Jan , Behnke Michael , Buhl Michael , Eisenbeis Simone , Gastmeier Petra , Gölz Hanna , Häcker Georg , Käding Nadja , Kern Winfried , Kola Axel , Kramme Evelyn , Peter Silke , Rohde Anna , Seifert Harald , Tacconelli Evelina , Vehreschild Maria , Walker Sarah , Zweigner Janine , Schwudke Dominik , Chakraborty Trinad 
Published: August 2022

Abstract
Enterobacter cloacae complex (ECC) represent globally important nosocomial pathogens. A three-year study of ECC in Germany identified Enterobacter xiangfangensis as the most common species (65.5%) detected, a result replicated by examining a global pool of 3246 isolates. Antibiotic resistance profiling revealed widespread resistance and heteroresistance to the antibiotic colistin and detected the mobile colistin resistance (mcr)-9 gene in 19.2% of all isolates. We show that resistance and heteroresistance properties depend on the chromosomal arnBCADTEF gene cassette whose products catalyze transfer of L-Ara4N to lipid A. Using comparative genomics, mutational analysis, and quantitative lipid A profiling we demonstrate that intrinsic lipid A modification levels are genospecies-dependent and governed by allelic variations in phoPQ and mgrB, that encode a two-component sensor-activator system and specific inhibitor peptide. By generating phoPQ chimeras and combining them with mgrB alleles, we show that interactions at the pH-sensing interface of the sensory histidine kinase phoQ dictate arnBCADTEF expression levels. To minimize therapeutic failures, we developed an assay that accurately detects colistin resistance levels for any ECC isolate.
Baseline gut microbiota composition is associated with oral mucositis and tumour recurrence in patients with head and neck cancer: a pilot study
Authors: Al-Qadami Ghanyah , Bowen Joanne , Sebille Ysabella Van , Secombe Kate , Dorraki Mohsen , Verjans Johan , Wardill Hannah , Le Hien 
Published: August 2022

Abstract
Purpose
Mounting evidence suggests the gut microbiome influences radiotherapy efficacy and toxicity by modulating immune signalling. However, its contribution to radiotherapy outcomes in head and neck cancer (HNC) is yet to be investigated. This study, therefore, aimed to uncover associations between an individual’s pre-therapy gut microbiota and i) severity of radiotherapy-induced oral mucositis (OM), and ii) recurrence risk in patients with HNC.
Methods
In this prospective pilot study, 20 patients with HNC scheduled to receive radiotherapy or chemoradiotherapy were recruited. Stool samples were collected before treatment and microbial composition was analysed using 16S rRNA gene sequencing. OM severity was assessed using the NCI-CTCAE scoring system. Patients were also followed for 12 months of treatment completion to assess tumour recurrence.
Results
Overall, 80% of the patients were male with a median age of 65.5 years. 53% experienced mild/moderate OM while 47% developed severe OM. Further, 18% experienced tumour relapse within 1 year of treatment completion. A pre-treatment microbiota enriched of Eubacterium, Victivallis, and Ruminococcus was associated with severe OM. Conversely, a higher relative abundance of immunomodulatory microbes Faecalibacterium, Prevotella, and Phascolarctobacterium was associated with a lower risk of tumour recurrence.
Conclusion
Our results indicate that a patient’s gut microbiota composition at the start of treatment is linked to OM severity and recurrence risk. We now seek to validate these findings to determine their ability to predict treatment outcomes in HNC, with the goal of using this data to inform second-generation microbial therapeutics to optimise treatment outcomes for patients with HNC.
Heterogeneous interface catalysts with electron local exchange towards highly selective oxidation of biomass platform compounds
Authors: Ren Zhen , Yang Yusen , Wang Si , Niu Yiming , Wang Lei , Yu Jun , Song Yingjie , Zhang Xin , Zhang Bingsen , Wei Min 
Published: August 2022

Abstract
Catalytic oxidation conversion of biomass-derived compounds to high value-added products has aroused intensive research interest. Herein, we report a Co3O4/Co2MnO4 metal oxides composite catalyst (denoted as CoMn-MOCs) prepared from layered double hydroxide (CoMn-LDHs) precursors, which is featured by uniformly inter-dispersed two-phase heterogeneous interface. This sample exhibits extraordinary catalytic performance for selective oxidation reaction of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid (yield: 98%; formation rate: 488.0 μmol gMn−1 h−1), which is the highest level in the state-of-the-art catalysts. The combination study including HR-TEM, XAFS, XPS and Raman confirms that a strong electron local exchange interaction occurs at the Co3O4/Co2MnO4 heterogeneous interface with electron transfer from Mn in spinel to Co in oxide. Both experimental investigations (quasi in situ XPS, in situ FT-IR and in situ Raman) and theoretical calculations substantiate that the interfacial metal-oxygen bridge (Co2+−O−Mn4+) serves as intrinsic active site in determining reaction pathway: C=O group in reactant experiences activation adsorption at Mn4+, followed by the escape of interfacial lattice oxygen and the oxidation of aldehyde group to carboxylic acid; subsequently, O2 molecule undergoes dissociation at the in situ-generated oxygen vacancies. This electron local exchange interaction facilitates the mobility of interfacial lattice oxygen, whose universality is demonstrated in catalytic oxidation of other eleven biomass-derived furanoids to corresponding carboxylic acids.
Black Men’s Awareness of Peripheral Artery Disease and Acceptability of Screening in Barbershops: A Qualitative Analysis
Authors: Coy Tyler , Brinza Ellen , DeLozier Sarah , Gornik Heather L. , Webel Allison R. , Longenecker Christopher T , White-Solaru Khendi 
Published: August 2022

Abstract
IntroductionPeripheral artery disease (PAD) disproportionately burdens Black Americans, particularly Black men. Despite the significant prevalence and high rate of associated morbidity and mortality, awareness of and treatment initiation for PAD remains low in this demographic group. To improve awareness, early detection, and treatment initiation of PAD among Black men, barbershops may be ideal settings for screening and education. MethodsA qualitative study involving 1:1 participant interviews in Cleveland, Ohio assessed perspectives of Black men about barbershop-based screening and education about PAD. Inductive thematic analysis was performed to derive themes directly from the data to reflect perceived PAD awareness and acceptability of screening in a barbershop setting. Results 28 African American/Black, non-Hispanic men completed a qualitative interview for this analysis. Mean age was 59.3±11.2 years and 93% of participants resided in socioeconomically disadvantaged zip codes. Several themes emerged indicating increased awareness of PAD and acceptability of barbershop-based screenings for PAD, advocacy for systemic changes to improve the health of the community, and a desire among participants to increase knowledge about cardiovascular disease.ConclusionsParticipants were overwhelmingly accepting of PAD screenings and reported increased awareness of PAD and propensity to seek healthcare due to engagement in the study. Participants provided insight into barriers and facilitators of health and healthcare-seeking behavior, as well as into the community and the barbershop as an institution. Additional research is needed to explore the perspectives of additional stakeholders and to translate community-based screenings into treatment initiation.