bluuebunny/crossref_metadata_2025_split huggingface dataset:
A non-negative spike-and-slab lasso generalized linear stacking prediction modeling method for high-dimensional omics data
Authors: Shen Junjie , Wang Shuo , Dong Yongfei , Sun Hao , Wang Xichao , Tang Zaixiang 
Published: March 2024

Abstract
Background
High-dimensional omics data are increasingly utilized in clinical and public health research for disease risk prediction. Many previous sparse methods have been proposed that using prior knowledge, e.g., biological group structure information, to guide the model-building process. However, these methods are still based on a single model, offen leading to overconfident inferences and inferior generalization.

Results
We proposed a novel stacking strategy based on a non-negative spike-and-slab Lasso (nsslasso) generalized linear model (GLM) for disease risk prediction in the context of high-dimensional omics data. Briefly, we used prior biological knowledge to segment omics data into a set of sub-data. Each sub-model was trained separately using the features from the group via a proper base learner. Then, the predictions of sub-models were ensembled by a super learner using nsslasso GLM. The proposed method was compared to several competitors, such as the Lasso, grlasso, and gsslasso, using simulated data and two open-access breast cancer data. As a result, the proposed method showed robustly superior prediction performance to the optimal single-model method in high-noise simulated data and real-world data. Furthermore, compared to the traditional stacking method, the proposed nsslasso stacking method can efficiently handle redundant sub-models and identify important sub-models.

Conclusions
The proposed nsslasso method demonstrated favorable predictive accuracy, stability, and biological interpretability. Additionally, the proposed method can also be used to detect new biomarkers and key group structures.
The mediating effect of nutrition on oral frailty and fall risk in community-dwelling elderly people
Authors: Song Huizi , Wei Yulian , Wang Yan , Zhang Jiahui 
Published: March 2024

Abstract
Background
Population aging is accelerating, particularly in Asian countries. Falls are the leading cause of unintentional injuries in the elderly over 60 years old in China. Hence, it is crucial to anticipate the risk factors associated with fall risk. We aimed to explore whether oral frailty and fall risk were reciprocally related and whether nutrition mediated their association.

Methods
From October 2022 to March 2023, a total of 409 elderly individuals from the Yangzhou community were selected using the convenience sampling method. Cross-sectional data on older adults’ oral frailty, nutrition, and fall risk were collected using questionnaires. Data analysis was performed using SPSS 27.0 and PROCESS macro.

Results
The fall risk score was 1.0 (ranging from 0 to 4.0), with 107 cases (26.2%) identified as being at risk of falling. Spearman correlation analysis revealed a positive correlation between oral frailty and the risk of falls (rs = 0.430, P < 0.01). Nutrition was found to have a negative correlation with both oral frailty and fall risk (rs=-0.519、-0.457, P < 0.01). When controlling for covariates, it was observed that nutrition mediated the relationship between oral frailty and falls. The mediating effect value accounted for 48.8% of the total effect (P < 0.01).

Conclusions
Oral frailty was significantly associated with fall risk, and nutrition might be a mediating factor for adverse effects of oral frailty and fall risk. Enhancing the nutrition of older individuals is a vital approach to mitigating fall risk among those with oral frailty.
Comparing the efficacy of fluconazole and cryotherapy Versus cryotherapy alone on treating cutaneous leishmaniasis: a triple-blind randomized clinical trial
Authors: Parhizkar Ahmad Reza , Sharafi Mehdi , Mansuri Susan , Hadibarhaghtalab Maryam , Afrashteh Sima , Fatemian Hossein , Chijan Mahsa Rostami 
Published: March 2024

Abstract
Objective
Cutaneous Leishmaniasis (CL) is one of the highly prevalent endemic diseases in the Middle East. The disease is a complex skin infection imposing a heavy burden on many developing countries. This study aimed to evaluate the impact of adding oral fluconazole to topical cryotherapy on the treatment efficacy and time to achieve complete recovery of CL lesions.

Method
This triple-blind randomized clinical trial included 52 participants with CL. Participants were allocated to receive either weekly cryotherapy with liquid nitrogen and oral fluconazole at a dose of 6 mg/kg daily at a maximum of 400 mg for 6 weeks as the interventional arm or weekly cryotherapy with liquid nitrogen plus the placebo for the same period of 6 weeks as the control arm.

Results
Fifty-two eligible participants enrolled the study, with a CL lesion count of 1 to 8 (mean 1.96), and served as the interventional (n = 28) and control (n = 24) arms. The trend of the mean surface area of the lesions was significantly decreasing in both arms (P < 0.001), with no statistically significant difference between arms (P = 0.133) or all assessed time point pairwise comparisons (P > 0.05). There was no significant difference between the treatment arms in terms of the end-point recovery status (P = 0.491) or the frequency of post-treatment secretion (P = 0.437). No adverse effect was observed.

Conclusion
Despite a slightly higher reduction in the lesion surface in the cryotherapy and fluconazole treatment arm, the addition of fluconazole did not provide statistically significant therapeutic value to cryotherapy in the treatment of CL. However, with adjustment for the initial lesion size, the efficacy of the regimen in the interventional arm was more pronounced, though it was still insignificant.
Improving dengue fever predictions in Taiwan based on feature selection and random forests
Authors: Kuo Chao-Yang , Yang Wei-Wen , Su Emily Chia-Yu 
Published: March 2024

Abstract
Background
Dengue fever is a well-studied vector-borne disease in tropical and subtropical areas of the world. Several methods for predicting the occurrence of dengue fever in Taiwan have been proposed. However, to the best of our knowledge, no study has investigated the relationship between air quality indices (AQIs) and dengue fever in Taiwan.

Results
This study aimed to develop a dengue fever prediction model in which meteorological factors, a vector index, and AQIs were incorporated into different machine learning algorithms. A total of 805 meteorological records from 2013 to 2015 were collected from government open-source data after preprocessing. In addition to well-known dengue-related factors, we investigated the effects of novel variables, including particulate matter with an aerodynamic diameter < 10 µm (PM10), PM2.5, and an ultraviolet index, for predicting dengue fever occurrence. The collected dataset was randomly divided into an 80% training set and a 20% test set. The experimental results showed that the random forests achieved an area under the receiver operating characteristic curve of 0.9547 for the test set, which was the best compared with the other machine learning algorithms. In addition, the temperature was the most important factor in our variable importance analysis, and it showed a positive effect on dengue fever at < 30 °C but had less of an effect at > 30 °C. The AQIs were not as important as temperature, but one was selected in the process of filtering the variables and showed a certain influence on the final results.

Conclusions
Our study is the first to demonstrate that AQI negatively affects dengue fever occurrence in Taiwan. The proposed prediction model can be used as an early warning system for public health to prevent dengue fever outbreaks.
A new classification allowing assessment of instrumental vaginal-birth practices
Authors: Schaeffer Marine , Faisant Marie-Caroline , Buisson Alexandre , Vanneaux Manon , Hoffmann Pascale , Riethmuller Didier 
Published: March 2024

Abstract
Background
Instrumental vaginal birth, a very common intervention in obstetrics, concerns nearly one in eight women in France. Instrumentally assisted vaginal childbirth can be for maternal and/or fetal indications. Although it reduces recourse to caesarean section, it is subject to risks. Practices concerning instrumental birth are disparate, varying among different practitioners, maternity units and countries, and it is essential to be able to evaluate them. Our objective was to create a classification tool of women requiring instrumental birth to facilitate the analysis of practices within our maternity unit as well as to enable temporal and geographical comparisons.

Materials and methods
We propose a simple and robust classification based on the same principles as Robson's classification. It is made up of seven totally inclusive and mutually exclusive groups. Our classification was refined and validated using the Delphi method by a panel of 14 experts from throughout France, and tested in our maternity unit using data from throughout 2021.

Results
The seven clinically relevant groups are based on five obstetric criteria (multiplicity, presentation, gestational age, previous type of birth, induction of labor). To classify each woman in a group, five successive questions are posed in a predefined order. The classification has been validated by the experts with highly satisfactory overall agreement.

Conclusion
In order to improve the quality of care, we propose a tool to standardize the evaluation of instrumental vaginal birth practice (called the “Isère classification”, after the county where we work in south-eastern France). It will also facilitate the comparison the practices among different maternity units in a network, a country or even among different countries.
Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer
Authors: Jo Jung Hyun , Park Soo Been , Chung Joowon , Oh Taeyun , Lee Hee Seung , Chung Moon Jae , Park Jeong Youp , Bang Seungmin , Park Seung Woo , Jung Dawoon E. , Song Si Young 
Published: March 2024

Abstract
Background
Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC.

Methods
TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application.

Results
Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001).

Conclusion
TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure.
Tumor burden score and carcinoembryonic antigen predict outcomes in patients with intrahepatic cholangiocarcinoma following liver resection: a multi‑institutional analysis
Authors: Fu Jun , Zheng Lifang , Tang Shicuan , Lin Kongying , Zheng Shuguo , Bi Xinyu , Wang Jianming , Guo Wei , Li Fuyu , Wang Jian , Wang Kui , Li Haitao , Zeng Yongyi 
Published: March 2024

Abstract
Background
The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients.

Methods
Patients who underwent curative − intent resection of ICC between 2011 and 2019 were identified from a large multi − institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence − free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage.

Results
A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 − year survival (both p < 0.001). As expected, patients with low CTC grade (i.e., low TBS/low CEA) were associated with the best OS as well as RFS, while high CTC grade (i.e., high TBS/high CEA) correlated to the worst outcomes. The model exhibited well performance in both the derivation cohort (area under the curve of 0.694) and the validation cohort (0.664). The predictive efficacy of the CTC grade system remains consistently stable across TNM stages I and III/IV.

Conclusion
The CTC grade, a composite parameter derived from the combination of TBS and CEA levels, served as an easy − to − use tool and performed well in stratifying patients with ICC relative to OS and RFS.
Cost-related medication nonadherence in adults with COPD in the United States 2013–2020
Authors: Wen Xin , Qiu Hongbin , Yu Bo , Bi Jinfeng , Gu Xia , Zhang Yiying , Wang Shanjie 
Published: March 2024

Abstract
Background
Cost-related medication nonadherence (CRN) is associated with poor prognosis among patients with chronic obstructive pulmonary disease (COPD), a population that requires long-term treatment for secondary prevention. In this study, we aimed to estimate the prevalence and sociodemographic characteristics of CRN in individuals with COPD in the US.

Methods
In a nationally representative survey of US adults in the National Health Interview Survey (2013–2020), we identified individuals aged ≥18 years with a self-reported history of COPD. Cross-sectional study.

Results
Of the 15,928 surveyed individuals, a weighted 18.56% (2.39 million) reported experiencing CRN, including 12.50% (1.61 million) missing doses, 13.30% (1.72 million) taking lower than prescribed doses, and 15.74% (2.03 million) delaying filling prescriptions to save costs. Factors including age < 65 years, female sex, low family income, lack of health insurance, and multimorbidity were associated with CRN.

Conclusions
In the US, one in six adults with COPD reported CRN. The influencing factors of CRN are multifaceted and necessitating more rigorous research. Targeted interventions based on the identified influencing factors in this study are recommended to enhance medication adherence among COPD patients.
Development of an integrated milestone assessment tool across multiple early-adopter programs for breaking bad news: a pilot project
Authors: Turner Anisha , Gopakumar Sricharan , Minard Charles , Guffey Danielle , Allen Nathan , Kuo Dick , Poszywak Kelly , Pillow M. Tyson 
Published: March 2024

Abstract
Background
The transition of the Accreditation Council for Graduate Medical Education (ACGME) to milestone assessment creates opportunities for collaboration and shared assessments across graduate medical programs. Breaking bad news is an essential communication skill that is a common milestone across almost every medical specialty. The purpose of this study was to develop and pilot an integrated milestone assessment (IMA) tool for breaking bad news using ACGME milestone criteria and to compare the IMA tool with the existing SPIKES protocol.

Methods
The IMA tool was created using sub-anchors in professionalism and interpersonal communication skills that are applicable to every specialty and to the ability to break bad news. Two cases of breaking bad news, designed to be “easy” and “intermediate” in difficulty, were used to assess basic skills in breaking bad news in first-year medical residents from six residency specialties. Eight standardized patients were trained to portray the cases in sessions held in November 2013 and May 2014. Standardized patients completed an assessment checklist to evaluate each resident’s performance in breaking bad news based on their use of the SPIKES protocol and IMA tool. Residents answered post-encounter questions about their training and comfort in breaking bad news. The association between SPIKES and IMA scores was investigated by simple linear regression models and Spearman rank correlations.

Results
There were 136 eligible medical residents: 108 (79.4%) participated in the first session and 97 (71.3%) participated in the second session, with 96 (70.6%) residents participating in both sessions. Overall, we were able to identify residents that performed at both extremes of the assessment criteria using the integrated milestone assessment (IMA) and the SPIKES protocol. Interestingly, residents rated themselves below “comfortable” on average.

Conclusion
We developed an integrated milestone assessment (IMA) that was better than the SPIKES protocol at assessing the skill of breaking bad news. This collaborative assessment tool can be used as supplement tool in the era of milestone transformation. We aim assess our tool in other specialties and institutions, as well as assess other shared milestones across specialties.
Development, implementation, and evaluation of an undergraduate family medicine program in the United Arab Emirates
Authors: Sulaiman Nabil , Shorbagi Sarra , Guraya Salman Yousuf 
Published: March 2024

Abstract
Background
Healthcare systems rely on well-trained family medicine physicians who can offer continuous quality services to their communities and beyond. The American Academy of Family Physicians and the World Organization of Family Doctors recommend that medical curricula should have adequately supervised education and training of the learners in family medicine during their preclinical and clinical placements. However, some medical schools don’t have a comprehensive family medicine program to prepare graduates who can meet the community needs. This work aims to report the essential steps for the development, implementation, and evaluation of the family medicine program at the College of Medicine at the University of Sharjah in United Arab Emirates.

Methods
We used the Kern’s 6-step model to describe the development, implementation, and evaluation of the family medicine program. This includes problem identification, needs assessment, goals setting, educational strategies, implementation, and evaluation. During 2014–2022, we longitudinally collected essential information about the family medicine program from different stakeholders including the feedback of clinical coordinators, adjunct clinical faculty, and medical students at the end-of-clerkship. All responses were analysed to determine the effective implementation and evaluation of the family medicine program.

Results
Over the course of 8 academic years, 804 medical students, 49 adjunct clinical faculty and three College of Medicine faculty participated in the evaluation of the family medicine program. The majority of respondents were satisfied with various aspects of the family medicine program, including the skills gained, the organisation of program, and the variety of clinical encounters. The medical students and adjunct clinical faculty suggested the inclusion of e-clinics, faculty development program, and the expansion of more clinical sites for the effectiveness of the family medicine program.

Conclusions
We report a successful development, implementation, and evaluation of the family medicine program in United Arab Emirates with a positive and impactful learning experience. More attention should be paid towards a suitable representation of family medicine program in the medical curriculum with focused and targeted educational plans for medical students.
Increasing pediatric radiation oncology capacity in sub-saharan Africa using technology: a pilot of a pediatric radiation oncology virtual training course
Authors: Joseph Adedayo O. , Akinsete Adeseye M. , Ajose Azeezat O. , Oladipo Aishat T. , Maliki Adeola , Akindele Korede , Mangongolo Michelle , Adeneye Samuel , Ngwa Wilfred 
Published: March 2024

Abstract
Background
The shortage of skilled healthcare professionals in pediatric oncology and the limited access to training programs remain significant challenges in Nigeria and sub-Saharan Africa. The the Pediatric Radiation Oncology (Virtual) Course, ‘PedROC’ project aims to contribute to improving pediatric cancer outcomes in Nigeria by increasing the capacity of radiation oncology professionals. To address the gap in access to pediatric radiation oncology professional development, the PedROC project was created, harnessing technology to improve radiation oncology training via a curriculum delivered through web-conferencing. This study aimed to evaluate the effectiveness of the PedROC pilot in enhancing the capacity, confidence, and skill of radiation oncologists in decision-making, prescribing, and treatment planning of radiotherapy for children diagnosed with cancer.

Methods
A multidisciplinary faculty of specialists in radiation oncology, pediatric oncology, oncology nursing, radiation therapy technology, and medical physics collaborated to identify the key learning needs in pediatric radiation oncology in the country. The team collaborated to develop a comprehensive curriculum covering the most common pediatric cancers in sub-Saharan Africa for the training program. The training course was conducted over two days, delivering twenty-four half-hour sessions for a total of 12 h, from July 31 to August 01, 2021.

Results
Analysis of pre and post - training surveys showed a significant increase in self-reported confidence measures across all domains among radiation oncologists. The program successfully improved participants’ knowledge and confidence levels in managing common pediatric cancers using radiotherapy, particularly addressing radiotherapy-specific issues such as appropriate dose, target volume delineation, treatment planning, dose constraints, and plan evaluation.

Conclusion
The PedROC pilot showed the efficacy of this model in enhancing the capacity and confidence of radiation oncology professionals involved in the treatment of pediatric cancer. The findings indicate that technology holds significant potential to increase pediatric radiation oncology capacity in Africa, ensuring improved access to proper treatment and ultimately improving pediatric cancer outcomes.