bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and initial validation of a modified LTT assay in patients with DRESS and AGEP
Authors: Weir Chris , LI Jamma , Fulton Richard , Fernando Suran
Published: August 2022

BackgroundThe lymphocyte transformation test (LTT) is an in vitro assay used to diagnose drug induced hypersensitivity reactions by detecting the activation and expansion of drug-specific memory T cells to the suspected implicated drug. Traditionally radiolabelled thymidine (3H-thymidine) has been used but requires the handling and disposal of radioactive materials.ObjectiveTo examine safe alternatives to 3H-thymidine, test assay modifications for improved assay sensitivity and validate the modified LTT in patients with DRESS and AGEP.MethodsFour proliferation detection assays (BRDU, CyQUANT™, MTT and XTT) were screened for LTT sensitivity. XTT the most sensitive and practical was selected for further validation. Modifications like autologous serum (AS) and regulatory T cell depletion (T-REG) were evaluated for improved assay sensitivity. Finally, an initial validation of the XTT-LTT was performed in 8 patients with DRESS and 2 with AGEP including cytokine testing.ResultsOf the non-radioactive alternatives we tested, XTT a colorimetric assay was the most sensitive and practical to move to validation. The addition of AS increased background signal. Depletion of T-REGs improved sensitivity but cell sorting time and risk of contamination limited benefit.Of eight patients diagnosed with DRESS and 2 with AGEP tested with XTT-LTT assay results showed our assay matched clinical findings of implicated drugs in 8/10 patients when using a stimulation index (SI) ≥2 and 8/10 with analysis by ANOVA. All ten patients were correctly diagnosed by either analysisConclusionXTT appears to be a safe, viable alternative to 3H-thymidine, with high sensitivity and allowing direct cytokine quantification on specific patient cells.
ATP6AP2 is robustly expressed in pancreatic β cells and neuroendocrine tumors, and plays a role in maintaining cellular viability
Authors: Taguchi Tomomi , Hoshiyama Ayako , Masaki Tsuguto , Inoue Mitsuko , Kato Yukiko , Takano Koji , Miyatsuka Takeshi
Published: August 2022

ATP6AP2, also known as (pro)renin receptor, has been shown to be expressed in several tissues including pancreatic β cells. Whereas ATP6AP2 plays an important role in regulating insulin secretion in mouse pancreatic β cells, the expression profiles and roles of ATP6AP2 in human pancreatic endocrine cells and neuroendocrine tumor cells remain unclear. Here in this study, we investigated the expression profiles of ATP6AP2 in pancreatic endocrine cells, and found that ATP6AP2 is robustly expressed in pancreatic insulinoma cells as well as in normal β cells. Although ATP6AP2 was also expressed in low-grade neuroendocrine tumors, it was not or faintly detected in intermediate- and high-grade neuroendocrine tumors. Knockdown experiments of the Atp6ap2 gene in rat insulinoma-derived INS-1 cells demonstrated decreased cell viability accompanied by a significant increase in apoptotic cells. Taken together, these findings suggest that ATP6AP2 plays a role in maintaining cellular homeostasis in insulinoma cells, which could lead to possible therapeutic approaches for endocrine tumors.
Craniofacial Anthropometric Differences Among the β-Thalassemia Major Patients and Healthy Subjects: A Cross-Sectional Study
Authors: Genç Çiğdem Çetin , Genç Celal , Yenigürbüz Fatma Demir
Published: August 2022

ObjectiveThe present study aims to compare β-thalassemia major patients and healthy individuals in terms of anthropometric characteristics and changes in craniofacial profile.Subjects and MethodCraniofacial anthropometric measurements were performed on a total of 422 subjects (199 β-thalassemia major patients and 223 healthy individuals) by using a millimetric caliper on 19 anthropometric parameters (8 horizontal, 10 vertical, and 1 head circumference) in cranial, facial, nasal, orolabial, and orbital zones.ResultsThe difference between the orbital, nasal, and orolabial zone parameters of healthy subjects and β-Thalassemia patients was found to be statistically significant (p < 0.05). There was no statistically significant difference between the groups in terms of head circumference in the cranial zone and total facial height in facial zone (n-gn) values (p˃0.05). In intragroup comparison between females and males with β-Thalassemia, statistically significant differences were found in forehead width (ft-ft), forehead height (tr-gl), right eye width (R ex-ex), and upper lip height (sn-stm) (p < 0.05).ConclusionUnderstanding the craniofacial profile changes in β-thalassemia major patients and increasing our knowledge about the relationship between the course and severity of disease and the level of these changes would contribute to the advancements in diagnoses to be made in facial and jaw zones of these patients and in the treatment plans.Clinical RelevanceWe believe that the analysis and results of the craniofacial anthropometric data obtained in the study will contribute to the diagnosis and treatment processes of patients with beta-thalassemia in areas of expertise such as craniofacial surgery, orthodontics, and hemato-oncology.
The frequency of defective genomes in Omicron differs from that of the Alpha, Beta and Delta variants
Authors: Campos Carolina , Colomer-Castell Sergi , Garcia-Cehic Damir , Gregori Josep , Andrés Cristina , Piñana Maria , González-Sánchez Alejandra , Borràs Blanca , Parés-Badell Oleguer , Adombi Caroline Melanie , Ibañez Marta , Esperalba Juliana , Codina Maria Gema , Rando Ariadna , Saubí Narcis , Esteban Juan Ignacio , Rodriguez-Frías Francisco , Pumarola Tomàs , Antón Andrés , Quer Josep
Published: August 2022

The SARS-CoV-2 Omicron variant emerged showing higher transmissibility and possibly higher resistance to current COVID-19 vaccines than other variants dominating the global pandemic. In a March 2020 study performed in clinical samples, we found that a portion of genomes in the SARS-CoV-2 viral population accumulated deletions at the S1/S2 cleavage site (PRRAR/S) of the spike gene, generating a frameshift and appearance of a premature stop codon. The main aim of this study was to determine the frequency of defective deletions in prevalent variants from the first to sixth pandemic waves in our setting and discuss whether the differences observed might support epidemiological proposals.The complete SARS-CoV-2 spike gene was deeply studied by next-generation sequencing using the MiSeq platform. More than 90 million reads were obtained from respiratory swab specimens of 78 COVID-19 patients with mild infection caused by the predominant variants circulating in the Barcelona city area during the six pandemic waves: B.1.5, B.1.1, B.1.177, Alpha, Beta, Delta, and Omicron.The frequency of defective genomes found in variants dominating the first and second waves was similar to that seen in Omicron, but differed from the frequencies seen in the Alpha, Beta and Delta variants.Our results support the notion cited in epidemiological reports that Omicron did not emerge from continuous evolution of the Alpha, Beta or Delta variant.
Bone Marrow Derived Cells Mediated Regulation of Schwann Cells Proliferation and Migration In Vitro
Authors: Wang Xiaopan , Zhao Peishuai , Chen Xiaotian , Yan Jun , Wu Min
Published: August 2022

Schwann cells (SCs) are the unique glial cells in the peripheral nerve. After peripheral nerve injury, SCs change their morphology, function, and play a new role as repair cells, through this process, factors that enhance SCs proliferation and promote SCs migration will benefit nerve regeneration and functional recovery. Bone marrow-derived cells (BMDCs), which has been proved to offer several regenerative benefits for tissue and organ injuries. However, whether BMDCs support nerve regeneration by affect the proliferation and migration of SCs, remains unclear. Here, we taken BMDCs co-cultured with nerve segments, and then investigated the proliferation and migration of SCs in vitro. Results demonstrated that BMDCs can enhance the proliferation of SCs, and then promoted SCs migration, forming Bungner’s brand-liked structure in vitro. These finding provide a potential new method for repair of injured peripheral nerves in clinical.
Exploring the Predictors of Physical Inactivity in a University Setting
Authors: Ndupu Lawrence Bismarck , Faghy Mark , Staples Vicki , Lipka Sigrid , Bussell Chris
Published: August 2022

Background: Changes in lifestyle patterns and the dependence on technology have contributed to an increase in prevalence of inactivity. To address this there is a need to identify the predictors of physical inactivity using the Theoretical Domains Framework (TDF). Methods: One hundred and twenty-one university administrative staff and 114 PhD students completed a survey. Physical activity (PA) levels were assessed using the Global Physical Activity Questionnaire (GPAQ), with participants scoring below 600 MET-minutes/week of total PA regarded as inactive. The predictors of physical inactivity were assessed using the Determinants of Physical Activity Questionnaire (DPAQ). Multiple regression analyses were used to identify which domains of the TDF predicted physical inactivity in the study samples.Results: The results indicated that 64% of administrative staff (Mean= 411.3 ± 118.3 MET-minutes/week of total PA) and 62% of PhD students (Mean= 405.8 ± 111.0 MET-minutes/week of total PA) did not achieve the recommended PA levels. The physical skills domain (t 106 = 2.198, p=0.030) was the significant predictor of physical inactivity amongst the administrative staff. Knowledge (t 99 = 2.018, p=.046) and intentions (t 99 = 4.240), p=0.001) domains were the significant predictors of physical inactivity amongst PhD students. Conclusions: The results of this study should be used as a theoretical starting point in carrying out behavioural diagnosis, which could inform the design of effective interventions to increase PA levels in universities and other settings.
A stable class of finite difference scheme for time-fractional partial differential equation
Authors: PATEL VIJAY
Published: August 2022

In this article, a numerical study is introduced for solving the fractional partial differential equation (FPDE) arising from electromagnetic waves in dielectric media (EMWDM) by using an efficient class of finite difference methods. The proposed numerical finite difference scheme is based on the Hermite formula. The Caputo's fractional derivatives in time are discretized by a finite difference scheme of order O(k(3-α) ) and O(k(3-β) ), 1<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
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

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

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

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

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

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

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

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

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

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

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

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.
Time Trends in Episiotomy and Severe Perineal Tears in Portugal: A Nationwide Register-based Study
Authors: Teixeira Cristina , Lorthe Elsa , Barros Henrique
Published: August 2022

Introduction: Rates of episiotomy and severe perineal tears (SPT) are indicators of the quality of obstetric care. Time-trends in the reported occurrence of episiotomy and SPT can contribute to understand both, changes in care and in the frequency of risk factors. Therefore, the aim of this research was to estimate time trends in the frequency of SPT in Portugal and its relationship with episiotomy. Methods: Nationwide register-based study by using data on singleton vaginal deliveries from the national inpatient database of all Portuguese public hospitals between 2000 and 2015. Time-trend analysis using joinpoint regression models was performed to identify trends (joinpoints) and compare time changes in the prevalence of SPT and risk factors expressed as annual percentage change (APC) with 95% Confidence Interval (95% CI). Poisson regression models were fitted to know whether time-trends in SPT rates were explained by changes in risk factors and to assess the association between episiotomy and SPT. Adjusted relative risk (RR) and respective 95% CI were obtained.Results: From 908 999 singleton vaginal deliveries, 20.6% were instrumental deliveries, 76.7% with episiotomy and 0.56% were complicated by SPT. SPT decreased among women with non-instrumental deliveries and no episiotomy from 2009 onwards (1.3% to 0.7%), whereas SPT kept increasing in women with episiotomy for both non-instrumental (0.1% in 2000 to 0.4% in 2015) and instrumental deliveries (0.7% in 2005 to 2.3% in 2015). Episiotomy was associated with a decrease in SPT with adjusted RR varying between 2000 and 2015 from 0.18 (95%CI:0.13-0.25) to 0.59 (95%CI:0.44-0.79) for non-instrumental deliveries and from 0.45 (95%CI:0.25-0.81) to 0.50 (95%CI:0.40-0.72) for instrumental deliveries. Conclusions: Episiotomy rate could safely further decrease as the main factor driving SPT rates seems to be an increase in awareness and reporting of SPT particularly among women who underwent an episiotomy.
Sleep Movements and Respiratory Coupling as a Biobehavioral Marker for Early Alzheimer’s Disease in Independently Dwelling Adults
Authors: Khosroazad Somayeh , Gilbert Christopher , Aronis Jessica A. , Daigle Katrina M. , Esfahani Masoumeh , Almaghasilah Ahmed , Elias Merrill F. , Meuser Thomas M. , Kaye Lenard , Singer Clifford M. , Abedi Ali , Hayes Marie J. , Ahmed Fayeza S.
Published: August 2022

INTRODUCTION: Sleep disorder is often the first symptom of age-related cognitive decline in Mild Cognitive Impairment (MCI), or early Alzheimer’s disease. Patient or family sleep complaints in primary care do not reliably lead to screening for sleep or cognitive loss. In this study, poor sleep and arousability were examined using movement arousals, a novel biobehavioral marker of cumulative sleep loss, identified by periodic (circa 4 min) sleep movements (SM). We report that SM events trigger respiratory upregulation (RR) in healthy, but not in MCI-related, sleep. Time latency (TL) between SM-RR events is proposed as a marker of sleep loss and potentially of neurodegeneration associated with cognitive loss in MCI.METHOD. Community-dwelling older adults (N=95; 62-90 years) were tested in the home bed for two days on an “under the sheets” mattress overlay with high sensitivity for respiration and all movement, including micro-movements of SM. Wrist actigraphy (7 days) and standard sleep self-reports were collected as well. A suite of neurocognitive testing identified three groups: Normal Cognition (NC; n=45); clinic diagnosed MCI (MCI-DX; n= 17); and MCI-Consensus determined by an expert panel (MCI-CON; n=33 consensus or pre-clinical MCI) groups.RESULTS: In adjusted cohort analyses, sleep fragmentation (SF) and WASO predicted poorer memory performance selectively. Actigraphy revealed greater sleep latency (SL; p<.008), sleep duration (p<.01) and SF (p=.008) in MCI-DX compared to NC groups. Longer SL and poor sleep were associated with depression which was more prevalent in both MCI groups than NC. Neural Networks AI methods were applied to discriminate MCI and NC cases using the TL metric between SM-RR coupling events. ROC diagnostics were applied which identified MCI vs. NC cases with 87% sensitivity; 89% specificity; and 88% positive predictive value. DISCUSSION: MCI cognitive phenotype was detected with a novel sleep biomarker TL, associated with the tight gap between SM-RR coupling, which is proposed as a corollary of sleep quality/loss that affects the autonomic regulation of respiration during sleep. Movement arousals are less effective in initiating respiratory upregulation in MCI which suggests a potential mechanism for neurodegenerative changes and cognitive loss in early MCI.
Chronic heart failure hampers regulatory T cell homeostasis which is not restored by cardiac resynchronization therapy
Authors: Martins Silvia , António Natália , Carvalheiro Tiago , Laranjeira Paula , Rodrigues Ricardo , Gonçalves Lino , Tomaz Cândida , Paiva Artur
Published: August 2022

Background: T cells have been implicated in the development and progression of inflammatory process in chronic heart failure (CHF). Cardiac resynchronization therapy (CRT) has beneficial effects on symptoms and cardiac remodeling in CHF. However, its impact on the inflammatory immune response remains controversial. We aimed to study the impact of CRT on T cells in heart failure patients (HFP). Methods: Thirty-nine HFP were evaluated before CRT (T0) and 6 months later (T6). Quantification of T cells, their subsets, and their functional characterization, after in vitro stimulation, were evaluated by flow cytometry. Results: T regulatory (Treg) cells were decreased in CHF patients (healthy group (HG): 1.08±0.50 versus HFP-T0: 0.69±0.40, P=0.022) and remaining diminished after CRT (HFP-T6: 0.61±0.29, P=0.003). Responders (R) to CRT presented a higher frequency of T cytotoxic (Tc) cells producing IL-2 at T0 compared with non-responders (NR) (R: 36.52±12.55 versus NR: 24.71±11.66, P=0.006). After CRT, HFP presented a higher percentage of Tc cells expressing TNF-α and IFN-γ (HG: 44.50±16.62 versus R: 61.47±20.54, P=0.014; and HG: 40.62±15.36 versus R: 52.39±18.66, P=0.049, respectively). Conclusion: The dynamic of different functional T cell subpopulations is significantly altered in CHF, which results in an exacerbated pro-inflammatory response, which could be due, at least in part, to the inability of CRT to restore Treg cells levels or inhibit Tc1 cell-mediated pro-inflammatory pathway.Trial registration: Retrospectively registered.
A Focus Module based Lightweight End-to-End CNN framework for Voiceprint Recognition
Authors: Velayuthapandian Karthikeyan , S Suja Priyadharsini
Published: August 2022

Speaker identification is a recognition problem that entails identifying a spokesperson from a set of consecutive time-series information. Because voice is a continuous one-dimensional time-stream, the majority of recent experimental techniques use convolutional neural networks (CNNs) or deep neural networks (DNNs). Because of the spectrogram in audio, the spatial attributes of utterances (which correlates to the speech spectra) and CNN are appropriate for spatial characteristic extraction. Simultaneously, the signal is time-series data, and DNN can better capture extended speeches than deep models. This work presents a DNN model for speaker identification using a jump-connected one-dimensional convolutional neural network (1-D CNN) with a focus module (FM). The 1-D convolutional layer integrated with FM is employed in the presented model for speaker characteristic extraction and lessens heterogeneity in the temporal and spatial domains, allowing for quicker layer processing. Furthermore, the layered CNN hopping interconnection is employed to overcome the connectivity glitches, and a solution based on softmax loss and smooth L1-norm combined regulation is presented to increase efficiency. The ELSDSR, TIMIT, NIST, 16000PCM, and experimental audio datasets were used to test the suggested network model. The Equal Error Rate (EER) of end-to-end CNN for voiceprint identification is enhanced by 9.02% when assessed to baseline approaches, according to the experimental data. Our proposed DNN model, which we term the deep FM-1D CNN, had a high recognition accuracy of 99.21 percent in the experiments. At the same time, the observations show that the suggested network model outperforms other models in terms of robustness. This method could be used for other types of research, such as language modelling, with further optimization.
The Localization, development and validation of a survey instrument to assess attitudes toward professionalism based on the opinions of clinical teachers
Authors: hosseinizadeh Adeleh , Shakour Mahsa , Afshar Leila
Published: August 2022

Background: This study examined the validation of a survey instrument to assess attitudes toward professionalism based on the opinions of clinical teachers in Iran and localized it.Methods: The research is applied-descriptive, that is conducted in two stages: qualitative and quantitative. Fifteen expert professors in the field of professionalism from Iranian universities of medical sciences participated in qualitative stage by Delphi. sampling method was purposive. In the quantitative stage, using simple and quota sampling method, 82 samples were collected from all clinical professors of first ranked universities of medical sciences. We used “The Penn State College of Medicine Professionalism Questionnaire” as a basic questionnaire. Its validity assessed by Delphi and survey. Some items changed, deleted and added. Then it confirmed by confirmatory factor analysis.Data analysis was performed using one-sample t-test and SmartPLS software. Results: 7 dimensions and 48 final indicators were approved and all 7 dimensions were in good condition. Among the approved dimensions, “the enrichment” with a factor load of 0.238, was the biggest factor in measuring the variable of professionalism. The dimensions of “respect”, “responsibility”, “altruism”, “duty”, “honor, honesty and justice”, “respectively” with factor loads of 0.215, 0.212, 0.163, 0.146, 0.106 and 0.047 are ranked in order.
Indian Ocean influence on the ENSO-monsoon teleconnection is mostly apparent
Authors: Bódai Tamás , Aneesh Sundaresan , Lee June-Yi , Lee Sun-Seon
Published: August 2022

“Decadal influence” on the El Nino–Southern Oscillation-Indian summer monsoon (ENSO-ISM) teleconnection has been much studied but with plurality and ambiguity about the concept of influence. Here we provide formal definitions of the apparent influence of a specific factor which enable us to test them as null-hypotheses. Using the recently released Community Earth System Model v2 (CESM2) Large Ensemble (LE) data, we show that a 50% chance for the detection of the apparent Indian Ocean (IO) influence under stationary conditions might take 2000 years of data. However, we find that this influence is mostly apparent indeed, as it originates from fluctuations of the decadal apparent – as opposed to climatological – ENSO variability, which causally influences an IO dipole-like apparent mean state. We also show that no unattributed so-called “decadal influence”, reflected in a deviation from a linear regression model of the teleconnection as a null-hypothesis, can be detected in 20th c. observations even regionally. However, as a new insight, we find our new influence concept to be possibly consistent with such a null-hypothesis.
Size-specific Dose Estimate for Lower-limb CT
Authors: Kobayashi Masanao , Nishihara Yusei , Haba Tomonobu , Matsunaga Yuta , Asada Yasuki , Kobayashi Shigeki
Published: August 2022

The Computed Tomography Dose Index (CTDI) is an indicator for dose management in computed tomography (CT), but has limited use for patient dosimetry. To evaluate the patient dose, the size-specific dose estimate (SSDE), reported by the American Association of Physics in Medicine task groups 204, 220, and 293, must be calculated by the CTDIvol(z) displayed on the CT console and the conversion factor f(D(z)) from the effective diameter (DEff) or water equivalent diameter (Dw). However, no reports have verified the appropriateness of using the 320-mm diameter phantom for dose assessment in CT examinations involving the lower limbs. Therefore, we validated a new method for evaluating the SSDE(z) of the lower limbs, using two 160-mm diameter phantoms instead of the 320-mm diameter phantom. The CTDIvol(z) obtained from Monte Carlo (MC) simulation study was reliable because they were almost the same as obtained in a dosimetry study. The conversion factor f (D (zl.l.)) for the lower limbs was evaluated based on the CTDIvol(z) obtained by MC simulation performed using two polymethyl methacrylate cylinder phantoms of 160-mm diameter. The MC simulation was performed by the International Commission on Radiological Protection publication 135 reference adult phantom and was used to evaluate the absorbed dose of the pelvis, lower limbs, knees, and ankles. The dose showing the greatest difference was the lower limbs, which was 8.3 mGy (16%) lower than the absorbed dose. Thus, the SSDE (zl.l.) could be estimated from the \({\text{C}\text{T}\text{D}\text{I}}_{\text{v}\text{o}\text{l}}^{320}\left(\text{z}\right)\) displayed on the CT scanner console.