bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Open‐Label Phase II Trial of Pembrolizumab, an Immune Checkpoint Inhibitor Alone or in Combination With Oral Azacitidine as Second‐Line Therapy for Advanced Head and Neck Squamous Cell Cancers
Authors: Ramani Vinod K. , Gayen Srimonta , Naik Radheshyam 
Published: January 2025

ABSTRACTBackground and AimsSensitivity to immune checkpoint inhibitor (ICI) therapy depends in part on the genetic and epigenetic makeup of cancer cells, and CD8 T‐lymphocytes that mediate immune responses. Epigenetics are heritable reversible changes in gene expression that occur without any changes in the nuclear DNA sequence or DNA copy number.Primary Objectivei. To determine if non‐cytotoxic oral azacytidine when combined with pembrolizumab can improve ORRs of ICI treatment in patients with recurrent/metastatic tumors of head and neck region.Secondary Objectivesi. To evaluate the clinical effectiveness endpoints and toxicity of oral azacytidine when combined with pembrolizumab. ii. To assess the induction of a T‐cell response among the study subjects. iii. To examine the hypotheses on the predictive biomarkers of response to pembrolizumab, and the mechanisms of resistance.MethodsOur trial is a Phase 2 randomized study of immunotherapy drug pembrolizumab given in combination with azacitidine (HMA). The intervention model includes “Parallel assignment,” with the primary purpose of the trial being treatment. The primary effectiveness endpoint is overall RECIST‐defined response. To accomplish this goal, 232 patients will be randomized 1:1 (116 in each arm), respectively, to azacitidine plus pembrolizumab or pembrolizumab only groups.ResultsIn this trial, molecular profiling of tumor and peripheral blood samples will be conducted which will enable in gaining biological insights for survival benefit. The expected primary outcome assessed at a time frame of 2 years includes the objective response rate of patients measured as per RECIST 1.1 criteria. The secondary outcomes assessed at 2 years include progression‐free survival, time to progression, overall survival, and incidence of treatment‐emergent adverse events.ConclusionThe findings of this trial will have translational implications, in terms of immune reprogramming induced by epigenetic therapy among a subset of advanced H & N cancer patients in a clinical setting.
The Impact of Audience Response System in Changing Students' Attitudes Towards Lectures During Training Courses; A Before‐After Study
Authors: Zareie Farzad , Baghaei Rahim , Sheykhi Naser , Rasouli Davood 
Published: January 2025

ABSTRACTBackground and AimsThe primary teaching approach known as “traditional lecture” has drawbacks, including being dull and reducing student participation, which has made students feel negatively about it. It seems that by implementing certain changes, active learning techniques like the “Audience Response System” could alter students' perceptions of lectures. The purpose of this study is to find out how employing “ARS” throughout a course has affected nursing students' perceptions of traditional lectures.MethodsIn present research, 44 nursing students participated in quasi‐experimental study (Pretest‐Posttest Design). A 5‐item, 5‐point Likert questionnaire and a pre‐test question regarding the degree of participation during lecture were used to gauge the students' attitudes towards lectures. Following that, a six‐session pharmacology course including “Lectures + ARS” was held. Following the completion of the course, the original questionnaire, a posttest question regarding attitudes, and four 3‐point Likert items regarding students' opinions regarding the use of ARS going forward were used to assess changes in the students' attitudes towards lectures. SPSS Ver. 26 was used for the data analysis. p < 0.05 was taken into consideration as the significance threshold.ResultsIn comparison to before the course, the students' attitudes towards lectures had changed in a positive and significant way, specifically in items such as learning quality improvement, decreasing boredom, increasing participation and class activity. However, in the domain of “decreasing the use of lecture,” the ARS had failed to change the students' attitudes. 79.6% of students stated that the ARS had changed their attitudes towards lectures. More than 90% of students agreed with continued use of ARS in the future.ConclusionLecturing could transform from a passive position to an active position by implementing ARS. Lecture + ARS could lead to improvement in students' class participation and activity, both of which are essential factors of an optimal education.
Practical Steps to Design Brucellosis Preventive Interventions: An Intervention Mapping Approach
Authors: Ziapour Arash , Rezaei Farshid , Jafarzadeh Mohammad , Mirzaei Nasim , Moradi‐Asl Eslam , Nejhaddadgar Nazila 
Published: January 2025

ABSTRACTBackground and AimsCommon diseases between humans and animals are one of the health problems of countries, which requires targeted intervention. The intervention mapping model provides guidance for choosing the most appropriate methods and applications. Since one of the most important challenges in the endemic areas of Iran is the control of brucellosis. Therefore, the aim of this research is to examine the intervention mapping model and its steps to design interventions to prevent this disease.MethodsIn this research, the practical steps of the Brucellosis prevention intervention were carried out with the intervention mapping approach in six steps from July 2023 to December 2023. In the first step, needs assessment was done through literature review, semi‐structured in‐depth interview and checklist. In the second step, the matrix of change objectives was designed. After selecting intervention methods based on theory and practical applications, and producing program components and materials, the intervention was implemented and evaluated.ResultsIntervention mapping helped us in designing and implementing the brucellosis control educational program with the participation of participants, specifying the definition of results, performance goals and determinants, theoretical methods, practical applications, intervention design, implementation and step‐by‐step evaluation.ConclusionThe intervention mapping approach ensures the transparency of all intervention components and it provides a useful approach for developing behavior change interventions.
Retrospective Analysis of Antibiotic Resistance Patterns of Uropathogenic Escherichia coli With Focus on Extended‐Spectrum β‐Lactamase at a Tertiary Central Hospital in Saudi Arabia
Authors: Alameer Khalid M. , Abuageelah Bandar M. , Alharbi Rena H. , Alfaifi Mona H. , Hurissi Eman , Haddad Moayad , Dhayhi Nabil , Jafar Abdulelah S. , Mobarki Mousa , Awashi Hassan , Musawi Shaqraa , Alameer Abdulaziz M. , Kariri Shatha H. , Alhazmi Abdulaziz H. 
Published: January 2025

ABSTRACTBackground and AimsUrinary tract infections (UTIs) are a prevalent bacterial infection that has substantial implications for healthcare on a global scale. Escherichia coli (E. coli) is a gram‐negative rod responsible for most UTI cases. ESBL‐producing E. coli is widely recognized as a significant contributor to antibiotic resistance. This study aims to evaluate the prevalence and antibiotic resistance trends of ESBL‐producing E. coli in patients with UTIs at a tertiary hospital in Jazan, Saudi Arabia.MethodsA retrospective cross‐sectional analysis was conducted on 347 urine specimens collected between January 2022 and March 2023.ResultsThe study found that 31% of E. coli specimens were positive for ESBL. Among patients with ESBL‐producing E. coli, 78.9% were females, and the majority of ESBL‐producing E. coli cases were observed in the outpatient clinic departments. Among all E. coli isolates, ampicillin exhibited the highest resistance rate at 69.3%, aztreonam at 66.7%, and colistin at the lowest resistance. ESBL‐producing E. coli strains exhibited higher resistance rates than non‐ESBL‐producing E. coli strains.ConclusionThe study agrees with others in the region and shows a higher prevalence of ESBL‐producing E. coli in the region, emphasizing the importance of antibiotic stewardship programs and infection control measures to mitigate the prevalence and spread of ESBL‐producing E. coli in our region.
Prevalence of Diarrhea Disease and Associated Factors Among Children Under 5 Years in Geshiyaro Project Implementation Sites in Ethiopia: A Cross‐Sectional Study
Authors: Alemu Zinabu Assefa , Girmay Aderajew Mekonnen , Teklu Kirubel Tesfaye , Adugna Ermias Alemayehu , Serte Melaku Gizaw , Alemayehu Tsigereda Assefa , Likasa Badasa Wagari , Collyer Benjamin , Mehari Zelalem , Salasibew Mihretab , Tollera Getachew , Tessema Masresha 
Published: January 2025

ABSTRACTBackgroundGlobally, infectious diseases such as pneumonia, diarrhea, and malaria are the leading causes of death for children under 5. Diarrheal disease is a significant public health concern and causes the death of approximately 525,000 children under the age of 5 every year. In Ethiopia, studies revealed that the prevalence of diarrhea among children under 5 years is alarming. However, there has been a shortage of studies regarding the predictors of diarrheal disease in Geshiyaro project implementation sites in Ethiopia. Therefore, this study aimed to fill this gap.MethodsA community‐based cross‐sectional study was conducted from June to July 2023. A total of 2937 participants were enrolled in this investigation. Descriptive and multivariate logistic regression analysis was performed using STATA version 16.ResultsThe 2‐week prevalence of diarrhea among children under 5 years was 11.8%. The following factors were significantly associated (p < 0.05) with the occurrence of childhood diarrhea: sex of the child (AOR: 1.6; 95% CI, 1.17–2.19), child age in a month (AOR: 0.5; 95% CI, 0.26–0.94), drinking water service (AOR: 2.6; 95% CI, 1.33–5.25), knowledge on diarrhea prevention (AOR: 1.4; 95% CI, 1.05–1.98), open defecation practice (AOR: 1.9; 95% CI, 1.33–2.74), and rotavirus vaccination (AOR: 1.8; 95% CI, 1.20–2.56).ConclusionsThis study identified several factors contributing to diarrhea. Besides, it also studied and showed a larger number of children who were not receiving basic vaccines. Therefore, the government and partner organizations should implement effective interventions to increase vaccine coverage and reduce diarrhea.
Knowledge, Attitude, and Practice Regarding High Salt Intake and Association With Hypertension Among Rural Women in Chandpur District of Bangladesh
Authors: Chandra Pradip , Islam Aminul , Robertson Shahara , Abu‐Al‐Rafe  , Sayed Md. Abu , Ahona Afra Anjum , Parvin Mst. Nadira , Gupta Pradip Sen 
Published: January 2025

ABSTRACTBackground and AimsThe human body requires a relatively little quantity of sodium to transmit nerve impulses, contract and relax muscles, and maintain appropriate water and mineral balance and which is typically added from diets. The study aimed to assess the level of knowledge, attitude, and practice regarding high salt intake and their association with hypertension among rural women of a selected community in Chandpur.MethodsA cross‐sectional study was adopted to collect data from 250 households of Chandpur district. The study was conducted during May 2022 to July 2022. The semi‐structured pretested WHO‐modified step‐wise approach to the non‐communicable disease risk factor surveillance (STEPS). Instrument version 3.1 module was used to administer the knowledge, attitude and practice questionnaire to assess the knowledge, attitude and practice of the participants. Binary logistic regression was performed to examine the factor related with knowledge, attitude, and practices.ResultsThe result gives evidence that participant who added always salt to their meals were three times more likely to be hypotensive (AOR: 2.99; CI: 1.40, 6.42). Besides, participants who avoid eating outside are significantly less likely (AOR: 0.19; C.I: 0.05 to 0.70) to be hypertensive.ConclusionFindings showed that daily salt consumption and “avoid eating out” were significantly associated with hypertension status. These findings imply that further educational intervention is needed to increase understanding of healthy dietary salt intake among rural women.
Perspective on Antibiotic Resistance in Bangladesh: A Critical Yet Overlooked Public Health Crisis
Authors: Hassan Md. Mahadi , Nohor Noushin 
Published: January 2025

ABSTRACTBackground and AimsThis article explores antibiotic resistance as a critical public health issue in Bangladesh, emphasizing its growing threat to the nation's healthcare system. As a developing country, Bangladesh faces unique challenges in managing this crisis, with antibiotic resistance posing significant risks due to its multidimensional problems to both individual health and the broader population.MethodsWe searched for relevant pieces of literature that discuss the antibiotic resistance problem both from a global and national perspective. Based on the importance and our objectives we selected the relevant articles. The perspective was written using the evidence and information available in those articles.ResultsKey factors contributing to the rise of antibiotic resistance include the irrational use and prescription of antibiotics in both healthcare settings and agriculture, incomplete doses of antibiotics, and insufficient public awareness. The article also discusses potential policy recommendations, such as the implementation of stricter antimicrobial stewardship programs, enhanced surveillance systems, and public education campaigns to reduce the misuse of antibiotics.ConclusionIn conclusion, antibiotic resistance in Bangladesh requires urgent attention and coordinated efforts from all sectors of society to prevent further deterioration of public health and safeguard future generations.
Mechanisms of enhancer‐driven oncogene activation
Authors: Vriend Joyce , Delwel Ruud , Pastoors Dorien 
Published: January 2025

AbstractAn aggressive subtype of acute myeloid leukemia (AML) is caused by enhancer hijacking resulting in MECOM overexpression. Several chromosomal rearrangements can lead to this: the most common (inv(3)/t(3;3)) results in a hijacked GATA2 enhancer, and there are several atypical MECOM rearrangements involving enhancers from other hematopoietic genes. The set of enhancers which can be hijacked by MECOM can also be hijacked by BCL11B. Enhancer deregulation is also a driver of oncogenesis in a range of other malignancies. The mechanisms of enhancer deregulation observed in other cancer types, including TAD boundary disruptions and the creation of de novo (super‐) enhancers, may explain overexpression of MECOM or other oncogenes in AML without enhancer hijacking upon translocation. Gaining mechanistic insight in both enhancer deregulation and super‐enhancer activity is critical to pave the way for new treatments for AML and other cancers that are the result of enhancer deregulation.
An AG‐RetinaNet for Embryonic Blastomeres Detection and Counting
Authors: Zhou Wenju , Talha Ouafa , Han Xiaofei , Liu Qiang , Xu Yuan , Zhang Zhenbo , Yuan Naitong 
Published: January 2025

ABSTRACTEmbryo morphology assessment is crucial for determining embryo viability in assisted reproductive technology. Traditional manual evaluation, while currently the primary method, is time‐consuming, resource‐intensive, and prone to inconsistencies due to the complex analysis of morphological parameters such as cell shape, size, and blastomere count. For rapid and accurate recognition and quantification of blastomeres in embryo images, Attention Gated‐RetinaNet (AG‐RetinaNet) model is proposed in this article. AG‐RetinaNet combines an attention block between the backbone network and the Feature Pyramid Network to overcome the difficulties posed by overlapping blastomeres and morphological changes in embryo shape. The proposed model, trained on a dataset of human embryo images at different cell stages, uses ResNet50 and ResNet101 as backbones for performance comparison. Experimental results demonstrate its competitive performance against state‐of‐the‐art detection models, achieving 95.8% average precision while balancing detection accuracy and computational efficiency. Specifically, the AG‐RetinaNet achieves 83.08% precision, 91.13% sensitivity, 90.91% specificity, and an F1‐score of 86.92% under optimized Intersection Over Union and confidence thresholds, effectively detecting and counting blastomeres across various grades. The comparison between these results and the manual annotations of embryologists confirms that our model has the potential to improve and streamline the workflow of embryologists in clinical practice.
CRYAB is upregulated and predicts clinical prognosis in kidney renal clear cell carcinoma
Authors: Ren Hao , Chen Xinyu , Ji Meiling , Song Wengang , Cao Lili , Guo Xiaohong 
Published: January 2025

AbstractClear cell renal cell carcinoma (KIRC) is the most prevalent subtype of renal cell carcinoma (RCC), accounting for 70% to 80% of all RCC cases. The CRYAB (αB‐crystallin) gene is broadly expressed across various human tissues, yet its role in KIRC progression remains unclear. This study aims to elucidate the function of CRYAB in KIRC progression and to assess its potential as a biomarker for early diagnosis, therapeutic targeting, and prognosis. In our report, we found that CRYAB was dramatically upregulated in KIRC, and its expression was associated with TNM stage, pathological stage, and age. Also, patients with higher CRYAB expression exhibited poor survival and prognosis. CRYAB overexpression led to enhanced tumor cell proliferation. Vice versa, CRYAB downregulation resulted in decreased cell proliferation in vitro. Mechanistically, Gene set enrichment analysis plots showed the enrichment of cell survival. Consistently, these effects were associated with increased AKT signaling and BCL‐2 expression. Furthermore, we also observed that CRYAB expression levels were negatively correlated with immunocyte infiltration. In conclusion, these findings suggested that CRYAB could be regarded as a latent biomarker for early diagnosis, therapeutic targeting, and prognosis.
Exchange Rates, Uncovered Interest Parity, and Time‐Varying Fama Regressions
Authors: Fu Bowen , Li Mengheng , Haque Qazi 
Published: January 2025

ABSTRACTThis paper studies the forward premium puzzle, which signals a violation of the uncovered interest parity (UIP) hypothesis. We test this hypothesis with Fama‐style regressions with time‐varying parameters (TVPs) and stochastic volatility (SV) on six major currencies relative to the US dollar on monthly samples from 1993 to 2018. TVP‐SV regressions are also employed to examine the opposing predictions of the forward premium and excess volatility puzzles often found in exchange rate risk premiums and interest rate differentials. Using Bayesian methods, we document that the riskiness of exchange rates explains the forward premium puzzle, while a liquidity premium reconciles the contrasting predictions of the forward premium and excess volatility puzzles.
Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease—A Review
Authors: Moradi Fatemeh , Mokhtari Tahmineh 
Published: January 2025

ABSTRACTThe coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro‐inflammatory cytokines and excessive oxidative stress in these regions. This aberrant microglial response also results in localized neuroinflammation in brain areas crucial for cognitive function. Additionally, CP as a persistent physiological and psychological stressor may be associated with hypothalamic‐pituitary‐adrenal (HPA) axis dysfunction, systemic inflammation, disruption of the blood–brain barrier (BBB), and neuroinflammation. These pathophysiological changes can cause morphological and functional impairments in brain regions responsible for cognition, memory, and neurotransmitter production, potentially contributing to the development and progression of CP‐associated AD. Resultant neuroinflammation can further promote amyloid‐beta (Aβ) plaque deposition, a hallmark of AD pathology. Potential therapeutic interventions targeting these neuroinflammatory pathways, particularly through the regulation of microglial NLRP3 activation, hold promise for improving outcomes in individuals with comorbid CP and AD. However, further research is required to fully elucidate the complex interplay between these conditions and develop effective treatment strategies.
Development of Synthetic Antimicrobial Peptides Based on Genomic Analysis of Streptococcus salivarius
Authors: Grover Vishakha , Jain Ashish , Bhardwaj Amit , Mehta Manjula , Arora Suraj , Algarni Youssef A. , Bavabeedu Shashit Shetty , Das Gotam , Ali Ahmed Babiker Mohamed , Ahmed Naseer , Heboyan Artak 
Published: January 2025

ABSTRACTBackgroundIn the oral environment, the production of bacteriocins or antimicrobial peptides (AMPs) plays a crucial role in maintaining ecological balance by impeding the proliferation of closely related microorganisms. This study aims to conduct in silico genome screening of Streptococcus salivarius to identify potential antimicrobial compounds existing as hypothetical peptides, with the goal of developing novel synthetic antimicrobial peptides.MethodsDraft genomes of various oral Streptococcus salivarius strains were obtained from the NCBI database and subjected to analysis using bioinformatic tools, viz. Expert Protein‐Analysis System (Expasy), UniProt Knowledgebase (UniProtKB), European Molecular Biology Open Software Suite (EMBOSS), Pepwheel, and PEP‐FOLD Peptide Structure Prediction Server. The antimicrobial potential of peptides was assessed through the Antimicrobial Peptide Database (AMP) and Bactibase. Two short peptides, viz. synthetic antimicrobial peptides (SAMPs), were designed based on current knowledge of hydrophobic and cationic residues, synthesized, and their efficacy against biofilm formation was evaluated with standard microbiological methods.ResultsThe synthesized short peptides reduced the growth and effectively inhibited biofilm formation by specific oral microbial strains, demonstrating their potential as antimicrobial peptides. Furthermore, the alignment of bacteriocin biosynthetic clusters among streptococcus strains revealed variations in putative bacteriocin amino acid sequences across different strains of the same organism.ConclusionStreptococcus salivarius emerges as a promising bioresource for the development of novel antimicrobial agents, particularly for combating biofilm‐associated oral infections.