bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual anticancer activity of Aspergillus nidulans pigment and Ionizing γ-Radiation on human larynx carcinoma cell line
Authors: Ahmed Hanaa Y. , Gazzar Eman M. El , Safwat Nesreen , Badawy Monda M. M. 
Published: September 2023

Abstract
Background
Fungi are a readily available source of naturally generated colored compounds. These compounds might be used as radiosensitizers for treating cancer cells.

Methods
Aspergillus nidulans was examined for its color-producing ability in Potato dextrose agar (PDA) broth medium. The pigment was characterized by Ultraviolet (UV) spectrophotometer and Gas Chromatography Mass Spectrometry (GC/MS). Pigment extracts from A. nidulans were studied for their cytotoxic effects on the growth of human larynx carcinoma cell line (HEp-2) with or without exposure to γ-radiation at three different doses (5, 10, and 15 Gy). A. nidulans pigment cytotoxic activity was tested against normal Vero cells. Cell apoptosis was studied using flow cytometry. Gene expression of P53, Caspase 3 and Bcl-2 were quantified.

Results
Ultraviolet spectrum and GC/MS revealed the ability of Aspergillus nidulans to produce Rhodopin pigment. HEp-2 cells treated with A. nidulans pigment only give IC50 about 208 µg/ml. In contrast, when treated with the pigment +10 Gy γ-radiation, it give about 115 µg/ml. However, for normal cells, lower cytotoxic activity was detected. Treatment with pigment (208 g/mL) caused about 50% ± 1.0 total apoptosis level and gene expression of P53: 2.3 fold and Caspase 3: 1.84 fold in respect to untreated HEp-2), while Bcl-2 was decreased (Bcl-2: 0.63 fold in respect to untreated HEp-2). Furthermore, treated with pigment (115 µg/mL) + 10Gy caused about 47.41% ± 1.7 total apoptosis level and P53: 2.53 fold and Caspase 3: 2.0 fold in respect to untreated HEp-2, while Bcl-2 was downregulated (Bcl-2: 0.61 fold in respect to untreated HEp-2).

Conclusion
This study concluded that the anti-cancer activity of Aspergillus nidulans pigment was enhanced by ionizing radiation at 10 Gy, as well as its low cytotoxic activity against normal Vero cells.
Analysis of different gamification-based teaching resources for physiotherapy students: a comparative study
Authors: Sandoval-Hernández Irene , Molina-Torres Guadalupe , León-Morillas Felipe , Ropero-Padilla Carmen , González-Sánchez Manuel , Martínez-Cal Jesús 
Published: September 2023

AbstractBackgroundFor health professionals, gamification is a new teaching method that has achieved an important role in recent years, with excellent results in learning and knowledge acquisition. Thus, the objective of this study was to analyze the gaming experience through different gamification resources in the classroom with physiotherapy students.MethodsA comparative study on gamification-based teaching resources was carried out during the first semester of the 2021–2022 academic year. A total of 33 physiotherapy students participated in this study. After the theoretical topics were taught, the participants were invited to participate in different gamification resources such as Kahoot!, Physiotherapy Party and Escape Room. The gaming experience with the different gamification resources was measured with the GAMEX scale.ResultsThe Physiotherapy Party showed a higher score in relation to the enjoyment dimension compared to the Kahoot! and Escape Room (p = 0.004). The Escape Room presented higher scores in absorption, creative thinking, activation and dominance compared to Kahoot! and Physiotherapy Party (p < 0.005).ConclusionsGamification resources promote enjoyment and creativity in the students in the classroom. The use of new teaching methods based on gamification, such as Escape Room as Physiotherapy Party should be considered as first choice in the use of gamification resources due to the benefits they bring to students.
Determining the frequency of burn wound dressing for clinically competent nursing students: establishing standards based on learning curves
Authors: Alizadeh-Taghiabad Batoul , Mazloum Seyyed Reza , Miri Kheizaran , Namazinia Mohammad 
Published: September 2023

AbstractBackgroundThe primary objective of clinical practice in nursing education is to achieve mastery of clinical skills through repetitive practice. Therefore, there exists a correlation between the frequency of skill demonstration and clinical competency. This study aimed to address the following question: How many times should a nursing student perform burn wound dressing to attain clinical competency?MethodsThis time series study was conducted on 41 junior nursing students who were selected through a census sampling method at Neyshabur School of Nursing from spring 2015 to summer 2021. The data collection tool was a researcher-made competency evaluation checklist (CEV). The competency score of each student for each skill demonstraion episode was evaluated using the Competency Evaluation Checklist (CEV) and recorded on the learning curve until a plateau was reached. SPSS16 and repeated measures analysis of variance (ANOVA) were used.ResultsThe mean competency score of burn wound dressing was 67.5 ± 11.0 (out of 100) during the first attempt, which increased to 95.9 ± 4.3 by the ninth attempt. The learning curve for the burn wound dressing skill reached a plateau after five attempts. Additionally, by the fifth attempt of dressing the burn wound, all students could accurately identify the depth, extent, and severity of the wound.ConclusionsEstablishing a standardized frequency for clinical skill performance and ensuring ample practice opportunities can have significant benefits in nursing education systems. These benefits include long-lasting learning, reduced costs, and improved effectiveness. As a result, nurse managers and lecturers should consider the resources available in their educational systems and strive to provide students with adequate opportunities and a supportive environment to practice their skills.
Combining unsupervised, supervised and rule-based learning: the case of detecting patient allergies in electronic health records
Authors: Berge Geir Thore , Granmo Ole-Christoffer , Tveit Tor Oddbjørn , Ruthjersen Anna Linda , Sharma Jivitesh 
Published: September 2023

Abstract
Background
Data mining of electronic health records (EHRs) has a huge potential for improving clinical decision support and to help healthcare deliver precision medicine. Unfortunately, the rule-based and machine learning-based approaches used for natural language processing (NLP) in healthcare today all struggle with various shortcomings related to performance, efficiency, or transparency.

Methods
In this paper, we address these issues by presenting a novel method for NLP that implements unsupervised learning of word embeddings, semi-supervised learning for simplified and accelerated clinical vocabulary and concept building, and deterministic rules for fine-grained control of information extraction. The clinical language is automatically learnt, and vocabulary, concepts, and rules supporting a variety of NLP downstream tasks can further be built with only minimal manual feature engineering and tagging required from clinical experts. Together, these steps create an open processing pipeline that gradually refines the data in a transparent way, which greatly improves the interpretable nature of our method. Data transformations are thus made transparent and predictions interpretable, which is imperative for healthcare. The combined method also has other advantages, like potentially being language independent, demanding few domain resources for maintenance, and able to cover misspellings, abbreviations, and acronyms. To test and evaluate the combined method, we have developed a clinical decision support system (CDSS) named Information System for Clinical Concept Searching (ICCS) that implements the method for clinical concept tagging, extraction, and classification.

Results
In empirical studies the method shows high performance (recall 92.6%, precision 88.8%, F-measure 90.7%), and has demonstrated its value to clinical practice. Here we employ a real-life EHR-derived dataset to evaluate the method’s performance on the task of classification (i.e., detecting patient allergies) against a range of common supervised learning algorithms. The combined method achieves state-of-the-art performance compared to the alternative methods we evaluate. We also perform a qualitative analysis of common word embedding methods on the task of word similarity to examine their potential for supporting automatic feature engineering for clinical NLP tasks.

Conclusions
Based on the promising results, we suggest more research should be aimed at exploiting the inherent synergies between unsupervised, supervised, and rule-based paradigms for clinical NLP.
Clinician consensus on “Inappropriate” presentations to the Emergency Department in the Better Data, Better Planning (BDBP) census: a cross-sectional multi-centre study of emergency department utilisation in Ireland
Authors: Cummins Niamh M , Barry Louise A , Garavan Carrie , Devlin Collette , Corey Gillian , Cummins Fergal , Ryan Damien , Wallace Emma , Deasy Conor , Flynn Mary , McCarthy Gerard ,   BDBP Team, Barry Tomas , Boyd Martin , Fitzgerald Des , Hayes Peter , Lane Gerry , McMahon Geraldine , McNamara Rosa , McNamee Lisa , Moore Anna , O’Hare Darragh , O’Regan Andrew , Reynolds Lorraine , Galvin Rose 
Published: September 2023

Abstract
Background
Utilisation of the Emergency Department (ED) for non-urgent care increases demand for services, therefore reducing inappropriate or avoidable attendances is an important area for intervention in prevention of ED crowding. This study aims to develop a consensus between clinicians across care settings about the “appropriateness” of attendances to the ED in Ireland.

Methods
The Better Data, Better Planning study was a multi-centre, cross-sectional study investigating factors influencing ED utilisation in Ireland. Data was compiled in patient summary files which were assessed for measures of appropriateness by an academic General Practitioner (GP) and academic Emergency Medicine Consultant (EMC) National Panel. In cases where consensus was not reached charts were assessed by an Independent Review Panel (IRP). At each site all files were autonomously assessed by local GP-EMC panels.

Results
The National Panel determined that 11% (GP) to 38% (EMC) of n = 306 lower acuity presentations could be treated by a GP within 24-48 h (k = 0.259; p < 0.001) and that 18% (GP) to 35% (EMC) of attendances could be considered “inappropriate” (k = 0.341; p < 0.001). For attendances deemed “appropriate” the admission rate was 47% compared to 0% for “inappropriate” attendees. There was no consensus on 45% of charts (n = 136). Subset analysis by the IRP determined that consensus for appropriate attendances ranged from 0 to 59% and for inappropriate attendances ranged from 0 to 29%. For the Local Panel review (n = 306) consensus on appropriateness ranged from 40 to 76% across ED sites.

Conclusions
Multidisciplinary clinicians agree that “inappropriate” use of the ED in Ireland is an issue. However, obtaining consensus on appropriateness of attendance is challenging and there was a significant cohort of complex heterogenous presentations where agreement could not be reached by clinicians in this study. This research again demonstrates the complexity of ED crowding, the introduction of evidence-based care pathways targeting avoidable presentations may serve to alleviate the problem in our EDs.
Addressing housing-related social needs for Medicaid beneficiaries: a qualitative assessment of Maryland’s Medicaid §1115 waiver program
Authors: DeGrazia Robert , Abdullahi Abdikarin , Mood MaryAnn , Diehl Christin , Stockwell Ian , Pollack Craig Evan 
Published: September 2023

Abstract
Background
While health care payers are increasingly considering approaches that help support stable and affordable housing for their beneficiaries, experience with these initiatives is limited. Through its §1115 HealthChoice waiver, Maryland Medicaid has begun experimenting with programs designed to pay for housing and tenancy support/case management services. This study investigates barriers and facilitators to the success of Maryland’s pilot program initiative — Assistance in Community Integration Services (ACIS).

Methods
The study focused on key stakeholders employed by the four Lead Entities that currently participate in the ACIS program. The stakeholders included members of each Lead Entity’s administration, direct service providers, state and local government officials, and case managers from local hospitals. The convenience sample was selected through an initial list of stakeholders and was supplemented using snowball sampling methods. Interviews were audio recorded and turned into transcripts via Otter.ai and then analyzed using NVivo by two independent reviewers.

Results
A total of 23 interviews were conducted between February 2022 and May 2022, representing a broad range of stakeholders across different Maryland geographies. A total of 4 themes were identified through the course of the interviews. Stakeholders identified difficulty finding housing for the target population in a tight housing market, challenges with communication within the program and with its clients, and problems with non-healthcare providers documenting services for reimbursement. At the same time, ACIS was seen as creating opportunities for organizations to work together across siloes in meeting client needs.

Conclusions
The findings of this study helps to highlight Medicaid §1115 waivers as a novel approach to using Medicaid funds to support tenancy-based services, such as ACIS and to improve the lives of individuals while reducing healthcare costs. Implementation of the ACIS program in Maryland has been a resounding success in helping individuals obtain and sustain stable housing. However, continued efforts to align capacity with demand, streamline billing and reimbursement and improve communication with clients and across partners will need to be prioritized. The program also highlights the growing need to address root causes of housing insecurity including the limited supply of affordable housing.
COL5A2 is a prognostic-related biomarker and correlated with immune infiltrates in gastric cancer based on transcriptomics and single-cell RNA sequencing
Authors: Chen Meiru , Zhu Xinying , Zhang Lixian , Zhao Dongqiang 
Published: September 2023

Abstract
Background
There is still a therapeutic challenge in treating gastric cancer (GC) due to its high incidence and poor prognosis. Collagen type V alpha 2 (COL5A2) is increased in various cancers, yet it remains unclear how it contributes to the prognosis and immunity of GC.

Methods
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to download transcriptome profiling (TCGA-STAD; GSE84437), single-cell RNA sequencing (scRNA-seq) data (GSE167297) and clinical information. COL5A2 expression and its relationship with clinicopathological factors were analyzed. We conducted survival analysis and Cox regression analysis to evaluate the prognosis and independent factors of GC. Co-expressed analysis was also performed. To identify the underlying mechanism, we conducted analyses of differentially expressed genes (DEGs) and functional enrichment. The correlations between COL5A2 expression and immune cell infiltration levels and immune infiltrate gene marker sets were further explored. Additionally, we analyzed the association of COL5A2 expression with immunological checkpoint molecules. Furthermore, the relationship between COL5A2 expression and immunotherapy sensitivity was also investigated.

Results
COL5A2 expression was elevated in GC. More than this, the scRNA-seq analysis revealed that COL5A2 expression had a spatial gradient. The upregulated COL5A2 was associated with worse overall survival. A significant correlation was found between COL5A2 overexpression and age, T classification and clinical stage in GC. COL5A2 was found to be an independent factor for the unfortunate outcome in Cox regression analysis. The co-expressed genes of COL5A2 were associated with tumor stage or poor survival. Enrichment analysis revealed that the DEGs were mainly associated with extracellular matrix (ECM)-related processes, PI3K-AKT signaling pathway, and focal adhesion. GSEA analyses revealed that COL5A2 was associated with tumor progression-related pathways. Meanwhile, COL5A2 expression was correlated with tumor-infiltrating immune cells. Moreover, immunophenoscore (IPS) analysis and PRJEB25780 cohorts showed that patients with low COL5A2 expression were highly sensitive to immunotherapy.

Conclusions
COL5A2 might act as a prognostic biomarker of GC prognosis and immune infiltration and may provide a therapeutic intervention strategy.
Changes in the triglyceride glucose-body mass index estimate the risk of stroke in middle-aged and older Chinese adults: a nationwide prospective cohort study
Authors: Huo Rong-Rui , Zhai Lu , Liao Qian , You Xue-Mei 
Published: September 2023

Abstract
Background
Stroke was reported to be highly correlated with the triglyceride glucose-body mass index (TyG-BMI). Nevertheless, literature exploring the association between changes in the TyG-BMI and stroke incidence is scant, with most studies focusing on individual values of the TyG-BMI. We aimed to investigate whether changes in the TyG-BMI were associated with stroke incidence.

Methods
Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. The exposures were changes in the TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in the TyG-BMI were classified using K-means clustering analysis, and the cumulative TyG-BMI was calculated as follows: (TyG-BMI2012 + TyG-BMI2015)/2 × time (2015–2012). Logistic regressions were used to determine the association between different TyG-BMI change classes and stroke incidence. Meanwhile, restricted cubic spline regression was applied to examine the potential nonlinear association of the cumulative TyG-BMI and stroke incidence. Weighted quantile sum regression was used to provide a comprehensive explanation of the TyG-BMI by calculating the weights of FBG, triglyceride-glucose (TG), and BMI.

Results
Of the 4583 participants (mean [SD] age at baseline, 58.68 [9.51] years), 2026 (44.9%) were men. During the 3 years of follow-up, 277 (6.0%) incident stroke cases were identified. After adjusting for potential confounders, compared to the participants with a consistently low TyG-BMI, the OR for a moderate TyG-BMI with a slow rising trend was 1.01 (95% CI 0.65–1.57), the OR for a high TyG-BMI with a slow rising trend was 1.62 (95% CI 1.11–2.32), and the OR for the highest TyG-BMI with a slow declining trend was 1.71 (95% CI 1.01–2.89). The association between the cumulative TyG-BMI and stroke risk was nonlinear (Passociation = 0.017; Pnonlinearity = 0.012). TG emerged as the primary contributor when the weights were assigned to the constituent elements of the TyG-BMI (weight2012 = 0.466; weight2015 = 0.530).

Conclusions
Substantial changes in the TyG-BMI are independently associated with the risk of stroke in middle-aged and older adults. Monitoring long-term changes in the TyG-BMI may assist with the early identification of individuals at high risk of stroke.
Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition
Authors: Han Rui , Ling Changquan , Wang Yuqian , Lu Lingeng 
Published: September 2023

AbstractHepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality but lacks effective treatments thus far. Although the emergence of immune checkpoint inhibitors in recent years has shed light on the treatment of HCC, a considerable number of patients are still unable to achieve durable and ideal clinical benefits. Therefore, refining the combination of immune checkpoint inhibitors (ICIs) to enhance the therapeutic effect has become a global research hotspot. Several histone deacetylase 2 inhibitors have shown advantages in ICIs in many solid cancers, except for HCC. Additionally, the latest evidence has shown that histone deacetylase 2 inhibition can regulate PD-L1 acetylation, thereby blocking the nuclear translocation of PD-L1 and consequently enhancing the efficacy of PD-1/PD-L1 inhibitors and improving anti-cancer immunity. Moreover, our team has recently discovered a novel HDAC2 inhibitor (HDAC2i), valetric acid (VA), that possesses great potential in HCC treatment as a monotherapy. Thus, a new combination strategy, combining HDAC2 inhibitors with ICIs, has emerged with significant development value. This perspective aims to ignite enthusiasm for exploring the application of ideal HDAC2 inhibitors with solid anti-tumor efficacy in combination with immunotherapy for HCC.
HER3 functions as an effective therapeutic target in triple negative breast cancer to potentiate the antitumor activity of gefitinib and paclitaxel
Authors: Lyu Hui , Shen Fei , Ruan Sanbao , Tan Congcong , Zhou Jundong , Thor Ann D. , Liu Bolin 
Published: September 2023

Abstract
Background
Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease.

Methods
Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. Specific shRNA was used to knockdown HER3 expression. IncuCyte system was utilized to monitor cell growth and migration. LIVE/DEAD Cell Imaging was to detect live and dead cells. HER3 recognition by our anti-HER3 monoclonal antibody (mAb) 4A7 was verified by ELISA, flow cytometry, and co-immunoprecipitation assays. Orthotopic tumor models were established in nude mice to determine the capability of TNBC cells forming tumors and to test if our mAb 4A7 could potentiate the antitumor activity of paclitaxel in vivo.

Results
Elevated expression of HER3 was observed in approximately half of the TNBC specimens and cell lines tested. Analyses of TCGA databases found that the TNBC patients with high HER3 mRNA expression in the tumors showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with low HER3 expression. Specific knockdown of HER3 markedly inhibited TNBC cell proliferation and mammosphere formation in vitro and tumor growth in vivo. Our mAb 4A7 abrogated heregulin (a ligand for HER3), but not SDF-1 (a ligand for CXCR4)-induced enhancement of TNBC cell migration. Combinations of 4A7 and the EGFR-tyrosine kinase inhibitor (TKI) gefitinib dramatically decreased the levels of phosphorylated HER3, EGFR, Akt, and ERK1/2 in TNBC cells and potently induced growth inhibition and cell death. Moreover, 4A7 in combination with paclitaxel exerted significant antitumor activity against TNBC in vitro and in vivo.

Conclusions
Our data demonstrate that increased HER3 is an effective therapeutic target for TNBC and our anti-HER3 mAb (4A7) may enhance the efficacy of gefitinib or paclitaxel in TNBC.