bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning in the Detection of Dental Cyst, Tumor, and Abscess Lesions
Authors: Kumar Vyshiali Sivaram , R Pradeep Kumar. , Yadalam Pradeep Kumar , Anegundi Raghavendra Vamsi , Shrivastava Deepti , Alfurhud Ahmed Ata , Almaktoom Ibrahem T. , Alftaikhah Sultan Abdulkareem Ali , Alsharari Ahmed Hamoud L. , Srivast Kumar Chandan
Published: July 2023

Background and Objective:
Dental panoramic radiographs are utilized in computer-aided image analysis, which detects ab-normal tissue masses by analyzing the produced image capacity to recognize patterns of intensity fluctuations. This is done to reduce the need for invasive biopsies for arriving to a diagnosis. The aim of the current study was to examine and compare the accuracy of several texture analysis techniques, such as Grey Level Run Length Matrix (GLRLM), Grey Level Co-occurrence Matrix (GLCM), and wavelet analysis in recognizing dental cyst, tumor, and abscess lesions.
Materials & Methods
The current retrospective study retrieved a total of 172 dental panoramic radiographs with lesion including dental cysts, tumors, or abscess. Radiographs that failed to meet technical criteria for diagnostic quality (such as significant overlap of teeth, a diffuse image, or distortion) were excluded from the sample. The methodology adopted in the study comprised of five stages. At first, the radiographs are improved, and the area of interest was segmented manually. A variety of feature extraction techniques, such GLCM, GLRLM, and the wavelet analysis were used to gather information from the area of interest. Later, the lesions were classified as a cyst, tumor, abscess, or using a support vector machine (SVM) classifier. Eventually, the data was transferred into a Microsoft Excel spreadsheet and SPSS (version 21) was used to conduct the statistical analysis. Initially descriptive statistics were computed. For inferential analysis, statistical significance was determined by a p value < 0.05. The sensitivity, specificity, and accuracy were used to find the significant difference between assessed and actual diagnosis.
Results
The findings demonstrate that 98% accuracy was achieved using GLCM, 91% accuracy using Wavelet analysis & 95% accuracy using GLRLM in distinguishing between dental cyst, tumor, and abscess lesions. The AUC number indicates that GLCM achieves a high degree of accuracy. The results achieved excellent accuracy (98%) using GLCM.
Conclusion
The GLCM features can be used for further research. After improving the performance and training, it can support routine histological diagnosis and can assist the clinicians in arriving at accurate and spontaneous treatment plans.
Rock slope stability assessment based on the critical failure state curve for the Generalized Hoek‒Brown criterion
Authors: Zhang Wenlian , Sun Xiaoyun , Yuan Wei , Liu Ting , Jin Shenyi
Published: July 2023

The strength reduction method (SRM) based on the Generalized Hoek‒Brown (GHB) criterion has become an important and popular means to analyse the stability of rock slopes. Various reduction strategies have been proposed and applied by civil engineering. This paper proposed a new SRM for rock slopes with the GHB criterion based on the critical failure state curve (CFSC). The existence of the CFSC has been proven by theoretical analysis, and the explicit expression of the CFSCs for different parameters mi and slope angles β, considering the influence of disturbance factor D, has been obtained by curve fitting based on a great deal of simulation data. The new SRM provides a graphic method to determine the parameters at the critical failure state from the initial state and proposes a definition of the factor of safety (FOS) based on the parameters of the two states. This method was applied to 8 slope examples to verify its validity and accuracy. The relative errors between the critical state parameters obtained from the graphic method and that from the simulation analysis are less than 10%, which proves the accuracy of the CFSCs. The FOSs obtained by the proposed definition are compared with that obtained by the Bishop simplified method and the local linearization method (LLM), and the results are very close. The relative error is less than ± 5% compared with the LLM, and the stability state predicted is perfectly accurate. However, the calculation procedure is largely simplified, and the calculation speed is largely improved.
Changes of B cell subsets in different types of diabetes and its effect on the progression of Latent Autoimmune Diabetes in Adults
Authors: Wu Peihao , Song Yingxiang , Chen Zhuo , Xia Jun , Zhou Yu
Published: July 2023

Purpose
Developmental abnormalities in B cells is one of the key players in autoimmune diabetes, but little is known about its role in latent autoimmune diabetes in adults (LADA). This study aimed to investigate the distribution of B cell subsets in different types of diabetes and to analyze their correlations with other biochemical parameters.
Methods
A total of 140 participants were prospectively enrolled from January 2021 to December 2022. Diabetes-related autoantibodies and laboratory indicators were tested. Flow cytometry was used to analyze the percentage of circulating B cell subsets and T follicular cells. The correlation of B cell subsets with different indicators was assessed by Spearman’s correlation method.
Results
We observed that the Naïve phenotype cells tended to be less frequent in patients with diabetes than in healthy controls. The frequency of plasmablasts (PB) and Breg cell-related phenotype (B10) were significantly higher in LADA. Notably, the percentage of PB was positively associated with levels of islet cell antibody (ICA) and insulin autoantibody (IAA), but inversely associated with fasting C-peptide (FCP), further indicating that PB may promote the destruction of β-cell in patients with diabetes.
Conclusions
This study showed that patients with LADA had a significantly altered B cell repertoires, especially exhibiting a naive to memory phenotype shift. Our study provided valuable information on the distribution characteristics of B cell subsets in LADA and suggested the feasibility of B-cell targeted therapy in LADA patients.
Crystal Crafting: Controlling Crystallites Orientation and Facet Exposure for Enhanced Electrochemical Properties of Polycrystalline MoO3 Films
Authors: Trzciński Konrad , Zarach Zuzanna , Szkoda Mariusz , Nowak Andrzej P. , Sawczak Mirosław
Published: July 2023

This study focuses on the development and optimization of MoO3 films on commercially available FTO substrates using the pulsed laser deposition (PLD) technique. By carefully selecting deposition conditions and implementing post-treatment procedures, precise control over crystallite orientation relative to the substrate is achieved. Deposition at 450°C in O2 atmosphere results in random crystallite arrangement, while introducing argon instead of oxygen to the PLD chamber during the initial stage of sputtering exposes the (102) and (011) facets. On the other hand, room temperature deposition leads to the formation of amorphous film, but after appropriate post-annealing treatment, the (00k) facets were exposed. The deposited films are studied using SEM and XRD techniques. Moreover, electrochemical properties of FTO/MoO3 electrodes immersed in 1 M AlCl3 aqueous solution are evaluated using cyclic voltammetry and electrochemical impedance spectroscopy. The results demonstrate that different electrochemical processes are promoted based on the orientation of crystallites. When the (102) and (011) facets are exposed, the Al3+ ions intercalation induced by polarization is facilitated, while the (00k) planes exposure leads to the diminished hydrogen evolution reaction overpotential.
A risk-based subgroup analysis of the effect of adjuvant S-1 in estrogen receptor-positive, HER2-negative early breast cancer
Authors: Takada Masahiro , Imoto Shigeru , Ishida Takanori , Ito Yoshinori , Iwata Hiroji , Masuda Norikazu , Mukai Hirofumi , Saji Shigehira , Ikeda Takafumi , Haga Hironori , Saeki Toshiaki , Aogi Kenjiro , Sugie Tomoharu , Ueno Takayuki , Ohno Shinji , Ishiguro Hiroshi , Kanbayashi Chizuko , Miyamoto Takeshi , Hagiwara Yasuhiro , Toi Masakazu
Published: July 2023

PURPOSE: The Phase III POTENT trial demonstrated the efficacy of adding S-1 to adjuvant endocrine therapy for estrogen receptor-positive, HER2-negative early breast cancer. We investigated the efficacy of S-1 across different recurrence risk subgroups.
METHODS: This was a post-hoc exploratory analysis of the POTENT trial. Patients in the endocrine-therapy-only arm were divided into three groups based on composite risk values calculated from multiple prognostic factors. The effects of S-1 were estimated using the Cox model in each risk group. The treatment effects of S-1 in patients meeting the eligibility criteria of the monarchE trial were also estimated.
RESULTS: A total of 1,897 patients were divided into three groups: group 1 (≤ lower quartile of the composite values) (N = 677), group 2 (interquartile range) (N = 767), and group 3 (> upper quartile) (N = 453). The addition of S-1 to endocrine therapy resulted in 49% (HR: 0.51, 95% CI: 0.33–0.78) and 29% (HR: 0.71, 95% CI 0.49–1.02) reductions in invasive disease-free survival (iDFS) events in groups 2 and 3, respectively. We could not identify any benefit from the addition of S-1 in group 1. The addition of S-1 showed an improvement in iDFS in patients with one to three positive nodes meeting the monarchE cohort 1 criteria (N = 290) (HR: 0.47, 95% CI: 0.29–0.74).
CONCLUSIONS: The benefit of adding adjuvant S-1 was particularly marked in group 2. Further investigations are warranted to explore the optimal usage of adjuvant S-1.
Clinical trial registration: jRCTs051180057/CRB5180002
Association of Diet, Lifestyle, and Chronotype with Metabolic Health in Ukrainian Adults: A cross-sectional study
Authors: Romanenko Mariana , Schuster Julius , Piven Liubov , Synieok Liudmyla , Dubiley Tetyana , Bogomaz Liudmyla , Hahn Andreas , Mueller Mattea
Published: July 2023

Morning chronotypes are associated with healthier metabolic profiles and lifestyles compared to evening chronotypes. However, limited research examined the relationship between chronotype, dietary intake, and metabolic health using accurate measures such as food records. This cross-sectional study aimed to investigate the association between chronotype, dietary intake, and metabolic health markers in a cohort of Ukrainian individuals.
Chronotypes were determined using the Morningness-Eveningness Questionnaire (MEQ) in 110 healthy to obese individuals (30-75 years) without type 2 diabetes. Dietary intake was derived from weighed seven days food diaries, anthropometrics and blood markers of glucose and lipid metabolism were measured.
Morning chronotypes were significantly older and exhibited distinct dietary patterns, including lower intake of fat and animal protein and higher intake of carbohydrates when compared to evening chronotypes (p<0.01). Higher MEQ scores were associated with lower BMI, waist circumference, fasting triglyceride, and glucose (p<0.05). Further, being of morning chronotype predicted better overall metabolic health. These associations remained significant after adjusting for confounders.
The findings suggest that morning chronotypes have a different dietary pattern characterized by a more balanced diet and favorable metabolic profile. These results suggest that aligning daily activities with morning preferences may have positive effects on metabolic health.
Reference Ranges of Serum Pepsinogens on Two Platforms in the Chinese Population
Authors: Huang Yuan , Yang Hong , Ding Rui , Wang Li , Li Ji , Li Wenbo , Qin Xuzhen , Xu Yingchun , Qian Jiaming
Published: July 2023

Objective
The objective of this study was to establish the reference ranges of serum pepsinogen-I (PG-I), PG-II, and the PG-I/II ratio (PGR) in the Chinese population by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) and to explore the consistency between the two methods.
Methods
2904 individuals were enrolled from six regions in China as part of the Chinese Adult Digestive Diseases Surveillance (2016) program. The individuals completed questionnaires and volunteered to undergo examinations, including gastroscopy, urea breath test, abdominal ultrasound examination and routine serologic tests. Serum was collected to measure PGs (including PG-I, PG-II and PGR) by CLIA and ELISA. The reference ranges of PGs obtained by the two methods were established according to document CLSI-EP28-A3, with covariates of sex, age, and region. Spearman correlation analysis, linear regression analysis and allowable total error (ATE) zone analysis were used to assess the consistency between the two methods.
Results
Participants who were found obvious abnormalities or absent from the examinations were excluded. Ultimately, 747 healthy individuals were enrolled in this study. Data from the 747 individuals were analyzed for PGs reference ranges. Reference ranges of PGs by CLIA and ELISA platforms were obtained with stratification by age group and sex. The region was not an influencing factor on the PGs results, except in the PG-I findings by ELISA. ATE zone analysis showed the consistency between the two methods was poor, and the two methods could not be substituted for each other.
Conclusion
This study established and compared the reference ranges of PGs on two platforms by strict and intact enrollment standard. The findings are valuable for clinical application and laboratory interpretation.
ROCK1 orchestrates B cell differentiation in response to PAMPs and heme by controlling the heme-regulated proteins Bach2 and HRI
Authors: Rivera-Correa Juan , Gupta Sanjay , Ricker Edd , Flores-Castro Danny , Jenkins Daniel , Vulcano Stephen , Pannellini Tania , Miele Matthew , Li Zhuoning , Zamponi Nahuel , Kim Young , Giannopoulou Eugenia , Cerchietti Leandro , Pernis Alessandra
Published: July 2023

Protective humoral responses require that B cells successfully complete their differentiation programs even when exposed to hostile environments generated during severe infections, like the massive hemolysis triggered by malaria. The mechanisms utilized by differentiating B cells to withstand damaging conditions replete in PAMPs and DAMPs are poorly understood. Here we demonstrate that the serine-threonine kinase ROCK1 enables B cells to execute their differentiation programs upon exposure to PAMPs and high levels of heme, a critical DAMP, by controlling two key heme-regulated molecules, Bach2 and HRI. ROCK1 restrains plasma cell differentiation by phosphorylating Bach2. As B cells differentiate in the presence of PAMPs and heme, furthermore, ROCK1 limits the proinflammatory potential of B cells and restrains mTORC1 activity by controlling the assembly of multimolecular complexes that contain the adaptor p62, raptor, ripoptosome components, and molecules involved in RNA metabolism and proteostasis. ROCK1 regulates formation of these complexes by controlling the interplay between HSPs and the stress kinase HRI. Thus, ROCK1 helps B cells cope with intense pathogen-driven destruction by coordinating the activity and localization of key molecules that mediate cell-fate decisions, effector functions, and RNA and protein homeostasis. These ROCK1-dependent mechanisms may be widely employed by cells to handle severe environmental stresses and these findings may be broadly relevant for infections, vaccine development, and immune-mediated diseases marked by chronic tissue damage like autoimmune disorders.
An evidence-informed policymaking (EIPM) competency profile for the Brazilian Health System developed through consensus: process and outcomes
Authors: Barreto Jorge Otávio Maia , Romão Davi Mamblona Marques , Setti Cecília , Machado Maria Lúcia Teixeira , Riera Rachel , Gomes Romeu , Machado Daienne Amaral , Abreu João , de Andrade Keitty Regina Cordeiro , Boeira Laura dos Santos , Pozza Letícia , Souza Nathan Mendes , Logullo Patrícia , Silva Roberta Borges , de Oliveira Sandra Maria do Valle Leone , Mota Sara Emanuela de Carvalho , Dias Tamille Sales , Toma Tereza Setsuko , Silva Silvio Fernandes da
Published: July 2023

Background: Evidence-informed policymaking (EIPM) requires a set of individual and organizational knowledge, skills and attitudes that should be articulated with background factors and needs. In this regard, the development of an EIPM competency profile is important to support the diagnosis, planning and implementation of EIPM.
Purpose: To present the process and outcomes of the development of an EIPM competency profile by an expert committee, to be applied in different contexts of the Brazilian Health System.
Methods: A committee of experts in EIPM shared different views, experiences and opinions to develop an EIPM competency profile for Brazil. In six consensus workshops mediated by facilitators, the committee defined from macro problems to key actions and performances essential for the competency profile. The development steps consisted of: 1) Constitution of the committee, including researchers, professionals with practical experience, managers, and educators; 2) Development of a rapid review on EIPM competency profiles; 3) Agreement on commitments and responsibilities in the processes; 4) Identification and definition of macro problems relating to the scope of the competency profile; and 5) Outlining of general and specific capacities, to be incorporated into the competency profile, categorized by key actions.
Results: The development of the EIPM competency profile was guided by the following macro problems: 1) lack of systematic and transparent decision-making processes in health policy management; 2) underdeveloped institutional capacity for knowledge management and translation; and 3) incipient use of scientific evidence in the formulation and implementation of health policies. A general framework of key actions and performances of the EIPM Competency Profile for Brazil was developed, including 42 specific and general key actions distributed by area of activity (Health Management, Scientific Research, Civil Society, Knowledge Translation, and Cross-sectional areas).
Final considerations: The competency profile presented in this article can be used in different contexts as a key tool for the institutionalization of EIPM.
Validation of Adult Asthma Case Definitions for Primary Care Sentinel Surveillance
Authors: Moloney Max , Morra Alison , Morkem Rachael , Queenan John A. , Gupta Samir , To Teresa , Digby Geneviève , Barber David , Lougheed M Diane
Published: July 2023

Background
Most asthma diagnoses and patient care take place in primary care settings. Electronic medical records (EMRs) offer an opportunity to utilize technology to improve asthma diagnosis and care. The purpose of this study was to create and validate separate case definitions for suspected and confirmed asthma in primary care EMRs, to enable surveillance, benchmarking, and quality improvement in primary care settings.
Objective
To develop a case definition for suspected and confirmed asthma for use in a primary care sentinel surveillance system.
Methods
A single chart abstractor conducted a manual audit of 776 randomly selected patient charts from an academic primary care practice EMR in Kingston, Ontario. Following the single chart abstractor classification, a consensus on chart classification as “not asthma”, “suspected asthma”, or “confirmed asthma” was achieved between the abstractor, a family physician, and a respirologist using Canadian Thoracic Society (CTS) criteria. Case definition algorithms based on billing codes, clinical data elements and medications were applied to the site’s Canadian Primary Care Sentinel Surveillance Network (CPCSSN) data for the same charts and compared to abstractor classifications to determine each algorithm’s measurement properties.
Results
The prevalence of suspected and confirmed asthma were 7.3% (n = 54) and 2.4% (n = 18), respectively. None of the proposed case definitions could differentiate between suspected and confirmed asthma. One algorithm consisting of billing, clinical, and medication elements had the highest Youden’s Index for either suspected or confirmed asthma. The algorithm had a sensitivity of 81%, a specificity of 96%, positive predictive value of 71%, negative predictive value of 98%, and a Youden’s Index of 0.77 for combined suspected or confirmed asthma cases.
Conclusion
An EMR case definition for suspected or confirmed adult asthma has been validated for use in CPCSSN. Implementation of this case definition will enable the development of a surveillance electronic tool (eTool) for adult asthma that can foster quality improvement.
Factors Impacting Clinician Reluctance to Defer Prostate Biopsy in Men with Negative Magnetic Resonance Imaging
Authors: Alwis Samith Minu , Hanna Daniel , Martorana Danielle , Sathiananden Niranjan , Niall Owen , Satasivam Prassannah
Published: July 2023

Purpose: Multiparametric magnetic resonance imaging (mpMRI) enables clinicians to omit prostate biopsy in men with negative (Prostate Imaging-Reporting and Data System v2, PI-RADS ≤ 2) mpMRI. We evaluate one-year outcomes in clinically significant prostate cancer (csPCa) detection following recommendation to defer biopsy in men with negative mpMRI, and assess the relationship between factors influencing adherence to this recommendation and csPCa detection.Methods: Retrospective data including demographics and clinical characteristics were collected for patients who underwent cognitively-targeted transrectal ultrasound-guided biopsy at our institution over July 2017 -June 2020 (Pre-Medicare rebate, Post-Medicare/pre-recommendation and post-recommendation years respectively). Primary endpoint was to determine whether a unit recommendation to only perform biopsy in men with PI-RADS > 2 on mpMRI improved csPCa detection (International Society of Urological Pathology Grade Group, ISUP GG ≥ 2). Secondary endpoint was to assess factors influencing adherence to this recommendation.Results: 130 patients underwent biopsy over the period, with 19 on active surveillance. The recommendation was not adopted and therefore did not improve csPCa detection rate (41% vs 44% pre-recommendation). 52 men proceeded to biopsy despite negative mpMRI, a greater number than pre-recommendation (n = 35, 37%). Eight men with a negative mpMRI had csPCa, with two reporting high-grade disease (ISUP GG ≥ 4). On multivariable analysis, age, prostate-specific antigen, prostate volume, number of cores, abnormal digital rectal examination and family history were not associated with csPCa detection in men with negative mpMRI.Conclusion: The recommendation to defer biopsy in men with negative MRI was not adopted by clinicians. Although patient and clinical factors were commonly quoted reasons to biopsy, none were found to be accurate predictors of csPCa.
The Prediction through Artificial Intelligence Approach and Geographic Information Systems (GIS) of the Soil Temperature in Kastamonu Province, Turkey
Authors: Gürdal Mehmet
Published: July 2023

In the present work, the average soil temperature of Kastamonu province was predicted by artificial neural networks approach employing data gained from five various meteorological measurement districts located in provincial borders. Twenty-two years of (2000–2021) monthly average atmosphere temperature data achieved from soil depths (5, 10, 20, 50, and 100 cm) have been utilized for artificial intelligence structure. It has been compared monthly average soil temperature for Cide, Devrekani, İnebolu, Kastamonu City Center, and Tosya stations. Measured and estimated soil temperature values have been exceedingly related to the Correlation Coefficient values (R2), Mean Absolute Error (MAE), Mean Square Error (MSE), and Average Relative Deviation (ARD). As a result, the estimated soil temperature findings were in the acceptable range with the measured data with average R2 values of 0.9851, 0.9456, 0.9712, 0.9691, and 0.9586 for Cide, Devrekani, İnebolu, Kastamonu CC, and Tosya, the respectively. MAE of 0.6808°C to 0.6848°C, ARD of 0.010–10.674% and MSE of 0.144 and 4.109 at all measurement districts where insignificant error tendency is very clear.
Analysis of the characteristics, efficiency, and influencing factors of third-party mediation mechanisms for resolving medical disputes in public hospitals in China using 5,948 cases
Authors: Shen Yanfei , Li Gaiyun , Tang Zhiguo , Wang Qi , Zhang Zurong , Hao Xiangyong , Han Xuemei
Published: July 2023

Background:
Medical disputes, which are prevalent in China, are a growing global public health problem. The Chinese government has proposed third-party mediation (TPM) to resolve this issue. However, the characteristics, efficiency, and influencing factors of TPM in resolving medical disputes in public hospitals in China have yet to be determined.
Methods:
We conducted a systematic study using TPM records from medical disputes in Gansu Province in China from 2014 to 2019. A χ2 test was used to compare differences between groups, and binary logistic analysis was performed to determine the factors influencing the choice of TPM for resolving medical disputes.
Results:
We analyzed 5,948 TPM records of medical disputes in Gansu Province in China. The number of medical disputes and the amount of compensation awarded in public hospitals in the Gansu Province increased annually from 2014 to 2019, with most of the disputes occurring in secondary and tertiary hospitals. Approximately 89.01% of the medical disputes were handled by TPM; the average compensation amount with TPM was Chinese Yuan (CNY) 48,688.73, significantly less than that awarded via court judgment and judicial mediation. Moreover, compensation amounts, non-fatal outcomes, and no-fault liability determinations influence the choice of TPM for settling medical disputes.
Conclusion:
Our findings demonstrate that TPM mechanisms play a positive role in efficiently reducing compensation amounts and increasing medical dispute resolution rates.
Multi-ancestry epigenome-wide analyses identify methylated sites associated with aortic augmentation index in TOPMed MESA
Authors: Manichaikul Ani , Hu Xiaowei , Logan Jeongok , Kwon Younghoon , Lima Joao , Jacobs David , Duprez Daniel , Brumback Lyndia , Taylor Kent , Durda Peter , Johnson Craig , Cornell Elaine , Guo Xiuqing , Liu Yongmei , Tracy Russell , Blackwell Thomas , Papanicolaou George , Mitchell Gary , Rich Stephen , Rotter Jerome , Berg David Van Den , Chirinos Julio , Hughes Timothy , Garrett-Bakelman Francine
Published: July 2023

Despite the prognostic value of arterial stiffness (AS) and pulsatile hemodynamics (PH) for cardiovascular morbidity and mortality, epigenetic modifications that contribute to AS/PH remain unknown. To gain a better understanding of the link between epigenetics (DNA methylation) and AS/PH, we examined the relationship of eight measures of AS/PH with CpG sites and co-methylated regions using multi-ancestry participants from Trans-Omics for Precision Medicine (TOPMed) Multi-Ethnic Study of Atherosclerosis (MESA) with sample sizes ranging from 438 to 874. Epigenome-wide association analysis identified one genome-wide significant CpG (cg20711926-CYP1B1) associated with aortic augmentation index (AIx). Follow-up analyses, including gene set enrichment analysis, expression quantitative trait methylation analysis, and functional enrichment analysis on differentially methylated positions and regions, further prioritized three CpGs and their annotated genes (cg23800023-ETS1, cg08426368-TGFB3, and cg17350632-HLA-DPB1) for AIx. Among these, ETS1 and TGFB3 have been previously prioritized as candidate genes. Furthermore, both ETS1 and HLA-DPB1 have significant tissue correlations between Whole Blood and Aorta in GTEx, which suggests ETS1 and HLA-DPB1 could be potential biomarkers in understanding pathophysiology of AS/PH. Overall, our findings support the possible role of epigenetic regulation via DNA methylation of specific genes associated with AIx as well as identifying potential targets for regulation of AS/PH.
Oxidative photocatalysis on membranes triggers non-canonical pyroptosis
Authors: Kwon Tae-Hyuk , Lee Chaiheon , Park Mingyu , Wijesinghe W.C. Bhashini , Lee Chae Gyu , Hwang Eunhye , Yoon Gwangsu , Lee Jeong Kyeong , Roh Deok-Ho , Kwon Yoon Hee , Yang Jihyeon , Hughes Sebastian A. , Vince James , Seo Jeong Kon , Min Duyoung
Published: July 2023

Intracellular membranes composing organelles of eukaryotes include membrane proteins playing crucial roles in physiological functions. However, a comprehensive understanding of the cellular responses triggered by intracellular membrane-targeted oxidative stress remains elusive. Herein, we developed an amphiphilic photocatalyst localised in intracellular membranes to damage membrane proteins oxidatively, resulting in non-canonical pyroptosis. Our developed photocatalysis generated hydroxyl radicals and hydrogen peroxides via water oxidation, which was accelerated under hypoxia. Single-molecule magnetic tweezers revealed that photocatalysis-induced oxidation markedly destabilised membrane protein folding. In cell environment, label-free quantification revealed that oxidative damage occurred primarily in membrane proteins related to protein quality control, thereby aggravating mitochondrial and endoplasmic reticulum stress and inducing lytic cell death. Notably, the photocatalysis activated non-canonical inflammasome caspases, resulting in gasdermin D cleavage to its pore-forming fragment and subsequent pyroptosis. These findings suggest that the oxidation of intracellular membrane proteins triggers non-canonical pyroptosis.
Antcin-B, a phytosterol-like compound from Taiwanofungus camphoratus inhibits SARS-CoV-2 3-chymotrypsin-like protease (3CL Pro ) activity in-silico and in vitro
Authors: Dakpa Gyaltsen , Kumar K. J. Senthil , Nelen Jochem , Pérez-Sánchez Horacio , Wang Sheng-Yang
Published: July 2023

Antcins obtained from the fruiting bodies of Taiwanofungus camphoratus, have been traditionally used to treat infections, whereas their role in the SARS-CoV-2 3-chymotrypsin-like protease (3CLPro) remains unclear. We employed both in vitro and in silico approaches to understand the underlying chemical mechanism comprehensively. Our finding revealed that various antcins (A, B, C, H, I, and M) and non-antcins (citronellol and limonene) exhibited lower toxicity to cells than GC376, along with favorable drug-likeness based MTT assay and ADMET prediction. Molecular docking analysis predicted that antcin-B possessed the lowest binding affinity energy and interacts with key residues such as Glu169, Gln189, His41, Leu141, Asn142, Glu16, and His165 employing hydrophobic interaction, hydrogen bonding, and salt bridge. These interactions were further confirmed by molecular dynamics (MD) simulation, which demonstrated the formation of hydrogen bonds with Asn142 and Gly143 and bridge with Glu166 for approximately 40% and 70% of the simulation time, respectively. Indeed, in vitro, 3CLPro activity analysis supports the above notion that antcin-B significantly (96.39%) inhibits 3CLPro activity, which is highly comparable with a known antiviral drug GC367 (96.72%). Consequently, antcin-B could be considered for developing a potential drug candidate for inhibiting 3CLPro activity, thereby impeding reducing the severity of COVID-19 in patients.
BRCA1 and BRCA2 gene mutation spectrum and high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India.
Authors: Chapla Aaron , John Ajoy , Singh Ashish , Yadav Pratibha , Joel Anjana , Thumaty Divya , K Fibi , Georgy Josh , Cherian Anish , Thomas Shawn , Thomas Anitha , Thomas Vinotha , Peedicayil Abraham , Varghese Deny , R Parthiban , Ravichandran Lavanya , Johnson Jabasteen , Thomas Nihal , Yadav Bijesh , S Patricia , B Selvamani , Abraham Deepak , Paul M , Titus Raju
Published: July 2023

In a developing country like India, genomic data sets for even the most clinically relevant genes like BRCA1 and BRCA2 are relatively scarce. There is also a need to identify and screen population specific BRCA hotspot mutations to pave the way for affordable genetic testing strategies in clinical practice. We have carried out an ambispective study to evaluate Next-generations Sequencing (NGS) based approach to identify pathogenic variants in BRCA1 and BRCA2 genes among 772 breast and ovarian cancer patients. The target enrichment was carried out using the in-house designed Multiplex-PCR for BRCA1 and BRCA2, followed by targeted NGS on Ion Torrent Personal Genome Machine. Additionally, allele-specific PCR (ASPCR) based genotyping of BRCA1 c.68_69delAG also known as 185delAG, was carried out in 149 patients. We identified 181 BRCA1 and BRCA2 variants, and based on ACMG 2015 guidelines, these variants were classified as 111 pathogenic or likely pathogenic and 70 VUS (Variant with uncertain significance). The 185delAG was identified as a recurrent mutation in the Southern Indian population accounting for 25.21% of the pathogenic variants. In addition, a family history of cancers of the breast, ovary, pancreas, or prostate (BOPP) was found to be associated with a higher risk of identifying a deleterious BRCA1/2 variant [OR=2.15 (95%CI 1.46-3.2) p≤0.0001]. These results suggest that Multiplex PCR coupled NGS is a sensitive and specific strategy for BRCA testing. However, ASPCR-based genotyping of 185delAG followed by targeted NGS would be cost-effective in South Indian patients.
Path analysis of influencing factors for hoarding among college Students
Authors: Li Wangyue , Liu Na , Pei Tao , Chen Haocheng , Xie Minyao , Song Shasha , Zhang Xuedi , Jiang wenjing , Hong Can , Zhang Ning
Published: July 2023

Background: Hoarding may affect an individual’s daily life and mental health, moreover, it can gradually attract social attention and become a public health problem. Therefore, we explored the hoarding phenomenon and its influencing factors among college students in China to better understand the current status quo and how it is related to mental health issues. In addition, we describe appropriate interventions that could reduce the impact of hoarding.
Methods: This cross-sectional study (N=3958) was conducted from September 2020 to December 2020. An online survey was used to collect demographic and psychological data about depression, compulsion and hoarding.
Results: Of the 3958 students who completed the survey, 178 (4.5%) exhibited hoarding behaviors, and the results of the path analysis showed that life events and neurotic personality traits can influence hoarding directly and indirectly through compulsions.
Conclusion: Obsessive-compulsive symptom plays a mediating role in the relationship between life events and neurotic personality traits.
Optimization Pilot Scale Study on Ammonia Nitrogen Removal by Bio Filter
Authors: Meng Junlong , Shen Songtao , Zhou Chuanhui , Zhang Tuodi , Xu Yingyi
Published: July 2023

In order to obtain the optimal conditions for ammonia nitrogen (AN) wastewater treatment by bio filter (BF), the effects of C/N, pH, and hydraulic load (HL) on the AN degradation were studied by Response Surface Methodology (RSM). Central Composite Design (CCD) experiments were conducted, and the response of the AN removal rates were fitted to a second-order polynomial model. The analysis of variance showed that the model was accurate and reliable. Through model fitting, the optimal condition for AN removal was: C/N of 18.95, pH of 7.78, and HL of 1.04 d-1. The maximum AN removal rate predicted by the model was 91.90%, accorded with the experimental verification value of 91.37% under the optimal condition. The research provided valuable demonstration for optimizing process parameters on AN removal in BF.
Spatiotemporal and Seasonal Transmission Dynamics of Schistosoma haematobium and Snail Infectivity in Ase River Catchment, Southern Nigeria
Authors: Ito Edore Edwin , Nduka F.O , Eze C.N
Published: July 2023

Bulinus are intermediate snail hosts of Schistosoma haematobium. Despite their vectorial role, the transmission dynamics and infectivity of these intermediate snail hosts remain understudied in the Ase River. This longitudinal study evaluated the geospatial and seasonal transmission patterns and infectivity of three S. haematobium vectors between November 2020 and October 2022 in the Ase River catchment, Delta State, Nigeria. Eleven (11) geospatial water contact coordinates were mapped for monthly spatiotemporal collection of Bulinus species along the Ase River and its catchment, for two years. Snail sampling was performed for 45 minutes at each study site using scooping/hand-picking techniques and subsequently counted, identified, and recorded. Snails of the Bulinus genus were individually placed in a beaker containing distilled water and exposed to light to shed cercariae which were identified to be human schistosome type. The number of infected snails for each month and the season was also counted and recorded to establish spatiotemporal and seasonal infectivity transmission dynamics and infectivity. A total of 41.45% of the 2345 Bulinus snails collected were infected with S. haematobium. The monthly infectivity of Bulinus snails varied significantly (P < 0.05) throughout the study period (P = < 0.0001; F = 23.11; df = 11). Further analysis showed a strong significant association (χ2 = 23.57; df = 11; p = 0.015) between the study years. The Principal Component Analysis (PCA) also indicates that Bulinus infectivity in the Ase River catchment was primarily driven by February and January. B. truncatus consistently had the highest transmission potential, followed by B. globosus and B. senegalensis. ANOVA confirms that the monthly/study site infectivity and transmission potential in B. truncates, B. globosus and S. senegalensis were statistically, significant (P < 0.05). These results demonstrated a clear distinction in the patterns and relationships between the different months in terms of snail infectivity and seasonal transmission potential. This understanding will help in the continuous monitoring and targeted interventions to control schistosomiasis transmission in Ase River.
Comparison of Laryngeal Mask Airway and Endotracheal Tube Placement in Neonates
Authors: Roberts Kari , Wanous Amanda , Brown Roland , Rudser Kyle
Published: July 2023

Objective
We hypothesize that the time, number of attempts and physiologic stability of placement of an LMA would be superior compared to ETT.
Study Design:
Videotape and physiologic parameters of LMA (n = 36) and ETT (n = 31) placement procedures for infants 28–36 weeks gestation were reviewed.
Results
Duration of attempts (32 vs 66 sec, p < 0.001) and mean total procedure time (88 vs 153 sec, p = 0.06) was shorter for LMA compared to ETT. Mean number of attempts for successful placement was fewer for LMA (1.5 vs 1.9, p = 0.11). Physiologic parameters remained near baseline in both groups despite very different degrees of premedication.
Conclusion
Placement of an LMA required less time and fewer number of attempts compared to ETT. Physiologic stability of an LMA was maintained without the use of an analgesic and muscle relaxant. Use of an LMA is a favorable alternative to ETT placement for surfactant delivery in neonates.
Trial Registration
NCT01116921
Development of a sports nutrition knowledge questionnaire for Sri Lankan athletes
Authors: Jayawardena Ranil , Weerasinghe Kalani , Trakman Gina , Madhujith Terrence , Hills Andrew P , Kalupahana Nishan Sudheera
Published: July 2023

Background:Satisfactory nutrition knowledge among athletes is important to encourage proper dietary habits to overcome deficiencies and enhance sports performance. Identifying knowledge gaps in sports nutrition is essential for improving athletes' understanding, ideally through a contemporary tool that evaluates both general nutrition knowledge (GNK) and sports nutrition knowledge (SNK). This study aims to develop the Athletic Sports Nutrition Knowledge Questionnaire (A-SNKQ) specifically for Sri Lankan track and field athletes.Methods:The development of the A-SNKQ followed an extensive step-wise approach. Firstly, a systematic literature review was conducted on existing SNK questionnaires for athletes. Secondly, sports nutrition guidelines were incorporated into the questionnaire. Thirdly, information from local literature was gathered to ensure contextual relevance. Lastly, a qualitative study involving key athletic stakeholders was conducted to gain cultural insights. Additional processes were implemented to format and translate the tool.Results:The final version of the questionnaire consists of 33 questions, categorized into 12 sub-sections under two main sections: GNK (n = 16) and SNK (n = 17). The GNK section covers topics such as macronutrients, micronutrients, energy balance, hydration, and weight management. The SNK section addresses specific areas related to sporting performance, including carbohydrate loading, pre-training meals, meals during training, post-training meals, sports supplements, supplement label reading, alcohol consumption, isotonic drinks, doping, and relative energy deficiency syndrome in sports (RED-S). The questionnaire utilizes two question formats, namely single-best response questions and multiple-choice questions. In addition, three sports supplement labels were included.Conclusions:The GNK section of the A-SNKQ addresses the fundamental nutritional concepts. Conversely, the SNK focuses on the knowledge associated with sporting performance among track and field athletes.
A 39 kb structural variant causing Lynch Syndrome detected by optical genome mapping and nanopore sequencing
Authors: Gilfillan Gregor , Bjørnstad Pål , Aaløkken Ragnhild , Åsheim June , Sundaram Arvind , Felde Caroline , Østby Gina , Dalland Marianne , Carrizosa Christian , Vigeland Magnus , Sorte Hanne , Sheng Ying , Ariansen Sarah , Grindedal Eli , Sjursen Wenche
Published: July 2023

Lynch Syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in one of the four mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. It is characterized by a significantly increased risk of multiple cancer types, particularly colorectal and endometrial cancer, with autosomal dominant inheritance. Access to precise and sensitive methods for genetic testing is important, as early detection and prevention of cancer is possible when the variant is known. We present here two unrelated Norwegian families with family histories strongly suggestive of LS, where immunohistochemical and microsatellite instability analyses indicated presence of a pathogenic variant in MSH2, but targeted exon sequencing and multiplex ligation-dependent probe amplification (MLPA) were negative. Using Bionano optical genome mapping, we detected a 39 kb insertion in the MSH2gene. Precise mapping of the insertion breakpoints and inserted sequence was performed by low-coverage whole-genome sequencing with an Oxford Nanopore MinION. The same variant was present in both families, and later found in other families from the same region of Norway, indicative of a founder event. To our knowledge, this is the first diagnosis of LS caused by a structural variant using these technologies. We suggest that structural variant detection be performed when LS is suspected but not confirmed with first-tier standard genetic testing.
Myocardial performance imaging for the early identification of cardiac dysfunction in neonates with sepsis
Authors: Sumbaraju Sudheshna Lalitha , Nayak Krishnananda , Prabhu Sridevi , Nayak Vidya , Prabhu K Prathiksha , Lewis Leslie Edward
Published: July 2023

Purpose:
The assessment of cardiac performance in septic new-borns is crucial for detecting hemodynamic instability and predicting outcome. The aim of the study is to assess myocardial performance in neonates with sepsis for the early identification of cardiac dysfunction
Material and methods:
A case control study was carried out from September 2022 to May 2023 at the NICU, KMC, Manipal. A total of 68 neonates were included in the study, with 33 female and 35 males. The study population was further subdivided into 3 groups namely preterm septic neonates (n=21), term septic neonates (n=10) and non-septic healthy controls (n=37). The cardiac structure and function were assessed using conventional method, Tissue Doppler imaging (Sm) and speckle tracking echocardiography (GLS)
The study was approved by the Institutional Ethics Committee, Kasturba Medical College, Manipal (approval number IEC: 90/2022). The CTRI registration number for the study is CTRI/2022/09/045437 and was approved on September 12, 2022. Prior to the neonate’s enrolment, informed consent was obtained from their mothers or legal guardians.
Results:
Out of the total 68 neonates, 31 were cases and 37 were controls which included 33 females and 35 males. LV systolic function was not statistically significant between cases and controls. E/A ratio of the mitral valve was significantly lower in septic newborns than in healthy neonates. preterm neonates showed significantly lower Lateral E’ and RV E’ velocities than term neonates. TAPSE was significantly lower in septic preterm neonates. No significant difference was noted in MPI between septic neonates and healthy neonates.LV GLS was slightly lower in preterm septic neonates than in term neonates with sepsis
Conclusion:
Septic newborns are associated with LV diastolic dysfunction, RV systolic dysfunction and substantially higher pulmonary systolic pressures.
DrugRep-HeSiaGraph: When heterogenous siamese neural network meets knowledge graphs for drug repurposing
Authors: Ghorbanali Zahra , Zare-Mirakabad Fatemeh , Salehi Najmeh , Akbari Mohammad , Masoudi-Nejad Ali
Published: July 2023

Background: The Drug repurposing is an approach that holds promise in identifying new therapeutic uses for existing drugs. Recently, knowledge graphs have emerged as significant tools for addressing the challenges of drug repurposing. However, there are still major issues in constructing and embedding knowledge graphs.
Results: This study proposes a two-step method called DrugRep-HeSiaGraph to address these challenges. The method integrates the drug-diseases knowledge graph with the application of a heterogeneous siamese neural network. In the first step, a drug-diseases knowledge graph named DDKG-V1 is constructed by defining new relationship types, and then numerical vector representations for the nodes are created using distributional learning method. In the second step, a heterogeneous siamese neural network called HeSiaNet is applied to enrich the embedding of drugs and diseases by bringing them closer in a new unified latent space. Then, it predicts potential drug candidates for diseases. DrugRep-HeSiaGraph achieves impressive performance metrics, including an AUC-ROC of 91.16%, an AUC-PR of 90.32%, an accuracy of 84.52%, a BS of 0.119, and an MCC of 69.12%.
Conclusion: We demonstrate the effectiveness of the proposed method in identifying potential drugs for COVID-19 as a case study. In addition, this study shows the role of dipeptidyl peptidase 4 (DPP-4) as a potential receptor for SARS-CoV-2 and the effectiveness of DPP-4 inhibitors in facing COVID-19. This highlights the practical application of the model in addressing real-world challenges in the field of drug repurposing.