bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting participation in remote digital health studies: An expert interview study
Authors: Daniore Paola , Nittas Vasileios , Gille Felix , von Wyl Viktor 
Published: November 2023

Background Remote digital health studies are on the rise and promise to reduce the operational inefficiencies of in-person research. However, they encounter specific challenges in maintaining participation (enrollment and retention) due to their exclusive reliance on technology across all study phases. Objective The goal of this study was to collect experts’ opinions on how to facilitate participation in remote digital health studies. Method We conducted 13 semi-structured interviews with principal investigators, researchers, and software developers who had recent experiences with remote digital health studies. Informed by the Unified Theory of Acceptance and Use of Technology (UTAUT) framework, we performed a thematic analysis and mapped various approaches to successful study participation. Results Our analyses revealed four themes: (1) study planning to increase participation, where experts suggest that remote digital health studies should be planned based on adequate knowledge of what motivates, engages, and disengages a target population; (2) participant enrollment, highlighting that enrollment strategies should be selected carefully, attached to adequate support, and focused on inclusivity; (3) participant retention, with strategies that minimize the effort and complexity of study tasks and ensure that technology is adapted and responsive to participant needs, and (4) requirements for study planning focused on the development of relevant guidelines to foster participation in future studies. Conclusions Our findings highlight the significant requirements for seamless technology and researcher involvement in enabling high remote digital health study participation. Future studies can benefit from collected experiences and the development of guidelines to inform planning that balances participant and scientific requirements.
Identification of exosome protein panels as predictive biomarkers for non-small cell lung cancer
Authors: Luo Bin , Que Zujun , Lu Xinyi , Qi Dan , Qiao Zhi , Yang Yun , Qian Fangfang , Jiang Yi , Li Yan , Ke Ronghu , Shen Xiaoyun , Xiao Hua , Li Hegen , Wu Erxi , Tian Jianhui 
Published: November 2023

Abstract
Background
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes.

Methods
Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes.

Results
Our study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients.

Conclusions
These findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.
Study methodology and insights from the palovarotene clinical development program in fibrodysplasia ossificans progressiva
Authors: Pignolo Robert J. , Al Mukaddam Mona , Baujat Geneviève , Brown Matthew A. , De Cunto Carmen , Hsiao Edward C. , Keen Richard , Le Quan Sang Kim-Hanh , Grogan Donna R. , Marino Rose , Strahs Andrew R. , Kaplan Frederick S. 
Published: November 2023

Abstract
Background
The design of clinical trials in rare diseases is often complicated by a lack of real-world translational knowledge. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by skeletal malformations and progressive heterotopic ossification (HO). Palovarotene is a selective retinoic acid receptor gamma agonist. Here, we describe the methodology of three studies in the palovarotene clinical development program in FOP and discuss insights that could inform future research, including endpoint suitability and the impact of trial design.

Methods
PVO-1A-001 (NCT02322255) was a prospective, protocol-specified, longitudinal FOP natural history study (NHS). PVO-1A-201 (NCT02190747) was a randomized, double-blind, placebo-controlled phase II trial; PVO-1A-202 (NCT02279095) was its open-label extension. Trial designs, including treatment regimens and imaging assessments, were refined between PVO-1A-201 and PVO-‍1A-202, and within PVO-1A-202, based on emerging data as the studies progressed. Palovarotene doses were administered using a flare-up treatment regimen (higher dose for 2/4 weeks, followed by lower dose for 4/≥8 weeks; from flare-up onset), with or without accompanying chronic (daily) treatment. Flare-up and disease progression outcomes were assessed, including incidence and volume of new HO during flare-ups and/or annually, as well as other clinical, patient-reported, and exploratory outcomes. Safety was monitored throughout all studies.

Results
Overall, 114 and 58 individuals with FOP were enrolled in the NHS and phase II trials, respectively. Results of the NHS and PVO-1A-201 were published in 2022; complete results of PVO-1A-202 will be publicly available in due course. Together the studies yielded important information on endpoint suitability, including that low-dose whole-body computed tomography was the optimum imaging modality for assessing HO progression annually and that long study durations are needed to detect substantial changes in functional and patient-reported outcomes.

Conclusions
A flexible clinical development program is necessary for underexplored rare diseases to overcome the many challenges faced. Here, the NHS provided a longitudinal evaluation of FOP progression and interventional trials were based on emerging data. The studies described informed the design and endpoints implemented in the phase III MOVE trial (NCT03312634) and provide a foundation for future clinical trial development.

Trial registration
NCT02322255 (registered 23/12/2014); NCT02190747 (registered 15/07/2014); NCT02279095 (registered 30/10/2014).
Knowledge and practice attitudes regarding the relationship between diabetes and periodontitis: a survey among Swiss endocrinologists and general physicians
Authors: Chatzaki Natalia , Zekeridou Alkisti , Paroz Elsa , Gastaldi Giacomo , Giannopoulou Catherine 
Published: November 2023

Abstract
Background
The objective of the present survey is to assess the knowledge about the relationship between oral health and diabetes and to identify the practice behaviors of Swiss endocrinologists and general practitioners regarding oral health in diabetic patients.

Methods
A thirty- item questionnaire was mailed to 428 internists and 99 endocrinologists working in the French speaking part of Switzerland. Participants were asked about their awareness of the relationship between diabetes and periodontal disease, their practice behaviors as well as their willingness for an interdisciplinary education and collaboration with oral health professionals. The questions were answered according to a three-point or five-point Likert scale.

Results
The response rate was 23%. All participants were aware of the inflammatory and infectious nature of periodontal disease. They all agreed that good periodontal health is important for overall health. However, most of the practitioners responded that only rarely received information during their education curricula on the link between systemic and oral health or concerning periodontal problems in diabetic patients (60.9% for endocrinologists and 54.1% for general physicians); thus, only a minority of health practitioners addresses oral health care to their patients (13% and 15.3%, respectively). Both endocrinologists and general health physicians agreed that an oral health screening could be included in their practice (79% for both groups).

Conclusions
An interdisciplinary education and collaboration among medical and dental health providers should be established to effectively prevent, manage, and control both diabetes and periodontal disease in diabetic patients.
Establishment of a prognostic signature based on fatty acid metabolism genes in HCC associated with hepatitis B
Authors: Yan Ping , Luo Yunhai , Huang Zuotian , Mou Tong , Yang Hang , Peng Dadi , Wu Zhongjun 
Published: November 2023

Abstract
Background
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is one of the most common and deadly cancer and often accompanied by varying degrees of liver damage, leading to the dysfunction of fatty acid metabolism (FAM). This study aimed to investigate the relationship between FAM and HBV-associated HCC and identify FAM biomarkers for predicting the prognosis of HBV-associated HCC.

Methods
Gene Set Enrichment Analysis (GSEA) was used to analyze the difference of FAM pathway between paired tumor and adjacent normal tissue samples in 58 HBV-associated HCC patients from the Gene Expression Omnibus (GEO) database. Next, 117 HBV-associated HCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to establish a prognostic signature based on 42 FAM genes. Then, the prognostic signature was validated in an external cohort consisting of 30 HBV-associated HCC patients. Finally, immune infiltration analysis was performed to evaluate the FAM-related immune cells in HBV-associated HCC.

Results
As a result, FAM pathway was clearly downregulated in tumor tissue of HBV-associated HCC, and survival analysis demonstrated that 12 FAM genes were associated with the prognosis of HBV-associated HCC. Lasso-penalized Cox regression analysis identified and established a five-gene signature (ACADVL, ACAT1, ACSL3, ADH4 and ECI1), which showed effective discrimination and prediction for the prognosis of HBV-associated HCC both in the TCGA cohort and the validation cohort. Immune infiltration analysis showed that the high-risk group, identified by FAM signature, of HBV-associated HCC had a higher ratio of Tregs, which was associated with the prognosis.

Conclusions
Collectively, these findings suggest that there is a strong connection between FAM and HBV-associated HCC, indicating a potential therapeutic strategy targeting FAM to block the accumulation of Tregs into the tumor microenvironment of HBV-associated HCC.
Cost-effectiveness analysis of antiretroviral drugs for treatment-naive HIV infection in China
Authors: Li Min , Cao Yuxin , Huang Hao , Qin Gang , Chu Minjie , Zou Meiyin , Zhuang Xun 
Published: November 2023

Abstract
Introduction
Dolutegravir (DTG)-based regimen was included in the expanded formulary of China's National Free Antiretroviral Treatment Program at the end of 2021. Yet high price of DTG and lack of health economic evaluation in China present barriers for implementation of the regimen. The study aims to investigate the lifetime cost-effectiveness of DTG-based regimen for treatment-naive HIV infection in China.

Methods
A decision-analytic Markov model was used to obtain the costs and effectiveness of four regimens: Arm A, efavirenz (EFV)-based regimen; Arm B, DTG-based regimen; Arm C, elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/c/FTC/TAF) regimen; Arm D, abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) regimen. The potential impact of national centralized drug procurement policy was assessed in scenario analysis. The results were further validated through sensitivity analysis.

Results
Compared with other three regimens, DTG-based regimen led to the fewest cumulative adverse reactions, opportunistic infections and deaths. Compared with EFV-based regimen, the base-case ICERs for DTG-based regimen were 13,357 (USD/QALY) and 13,424 (USD/QALY) from the healthcare system and societal perspective respectively. In the policy scenario analysis with the procurement price of DTG equal to that of LPV/r, DTG-based regimen would be dominant. The model results remained robust in sensitivity analyses.

Conclusions
DTG-based regimen for treatment-naive patients is likely to be cost-effective and deserve wider implementation in China. This study strongly suggests the centralized procurement of DTG to minimize cost and maximize cost-effectiveness.
Associations between overactive bladder and sleep patterns: a cross-sectional study based on 2007–2014 NHANES
Authors: Lu Zechao , Zhang Jiahao , Lin Shihao , Fan Zhongxi , He Zhaohui , Tang Fucai 
Published: November 2023

Abstract
Objectives
To determine whether relationship exists between overactive bladder (OAB) and sleep patterns through the cross-sectional study.

Patients and methods
Patients from the National Health and Nutrition Examination Survey (NHANES) 2007–2014 were included in this study. Data were extracted through questionnaires, including demographics, dietary and health-related behaviors, body measurements and disease information. Three sleep factors were included to aggregate overall sleep scores, ranging from 0 to 3. A sleep score of 0 to 1, 2 or 3 was expressed as a bad, intermediate or healthy sleep pattern, respectively. The Overactive Bladder Symptom Score (OABSS) scale was applied to quantify the severity of OAB for each participant. Weighted logistic regression models were used to investigate the associations between sleep and OAB.

Results
A total of 16,978 participants were enrolled in this study. The relationship between OAB and sleep patterns was statistically significant. After fully adjusting for confounding factors, the OAB risk of patients with intermediate and poor sleep patterns obviously increased by 26% and 38%, respectively, and mild (OR = 1.21, 95% CI [1.03,1.42]), moderate (OR = 1.45, 95% CI [1.27,1.66]) and severe (OR = 1.57, 95% CI [1.18,2.09]) OAB were significantly associated with sleep pattern grouping. The prevalence of OAB is significantly higher in patients with bad sleep patterns, and vice versa.

Conclusion
This study indicated that there is a positive relationship between OAB and worse sleep-related issues.
Orthodontic patients and the information found on the web: a cross-sectional study
Authors: Crispino Roberta , Mannocci Alice , Dilena Irene Alfonsa , Sides Jackson , Forchini Federico , Asif Alherawi Wael Mohammad , Frazier-Bowers Sylvia A. , Grippaudo Cristina 
Published: November 2023

Abstract
Background
In recent years, the Web has become a source of medical information for patients, even though the information available online may be incorrect or qualitatively inadequate. Younger generations, immersed in a digital environment since a very tender age, are more likely to get informed online. This study aims to understand the relevance of online information for prospective orthodontic patients and to investigate the effects of digital research on patients’ decision-making process, and it also aims to investigate potential generational differences between digital natives and digital immigrants.

Materials and methods
An anonymous questionnaire was developed to investigate patients’ orthodontic-themed Web searches as well as the effects digital material had on their decision-making process. Before submitting the newly designed survey to patients, it was validated in a pilot study. Univariate analysis was applied to analyze the relationship between the demographic characteristics of respondents and their answers on the use of digital research for the decision-making process.

Results
64.6% of the study population searched the Web for orthodontic information prior to their visit. Google was the most used platform regardless of patients’ age. The perceived reliability of online sources varied significantly with age. Men displayed more trusting behavior towards their doctor than women. Prospective patients’ satisfaction with affected patients’ decision-making processes, and the perceived reliability of online sources of information had repercussions on the doctor-patient relationship.

Conclusions
Orthodontists should be aware that the majority of patients use the Internet as a source for orthodontic information, and that patients who are digital immigrants are more prone to trust the information found online. Patients who perceive the information found on the Web as either useful or reliable don’t easily discard it, even if it is inconsistent with the orthodontist’s opinion.
Are committee experiences of minoritized family medicine faculty part of the minority tax? a qualitative study
Authors: Campbell Kendall M , Ogbeide Stacy A. , Echiverri Angela , Guillaume Gina , Henderson Johnathan E , Jackson Nicole , Marquez Crystal M , Miranda Carolina , Montoya Melissa , Oni Keyona , Pierre Grant , Semenya Afi Mansa , Scott LaTraia , Udezi Victoria , Flattes Valerie J , Rodríguez José E , Washington Judy C 
Published: November 2023

Abstract
Background and Objectives
Because much of the work in academic medicine is done by committee, early career URiM faculty, are often asked to serve on multiple committees, including diversity work that may not be recognized as important. They may also be asked to serve on committees to satisfy a diversity “check box,” and may be asked more often than their non-URiM peers to serve in this capacity. We sought to describe the committee experiences of early career URiM faculty, hypothesizing that they may see committee service as a minority tax.

Methods
Participants in the Leadership through Scholarship Fellowship (LTSF) were asked to share their experiences with committee service in their careers after participating in a faculty development discussion. Their responses were analyzed and reported using qualitative, open, axial, and abductive reasoning methods.

Results
Four themes, with eight sub-themes (in parenthesis), emerged from the content analysis of the LTSF fellows responses to the prompt: Time commitment (Timing of committee work and lack of protected time for research and scholarship), URiM Committee service (Expectation that URiM person will serve on committees and consequences for not serving), Mentoring issues (no mentoring regarding committee service, faculty involvement is lacking and the conflicting nature of committee work) and Voice (Lack of voice or acknowledgement).

Conclusions
Early career URiM faculty reported an expectation of serving on committees and consequences for not serving related to their identity, but other areas of committee service they shared were not connected to their URiM identity. Because most of the experiences were not connected to the LTSF fellows’ URiM identity, this group has identified areas of committee service that may affect all early career faculty. More research is necessary to determine how committee service affects URiM and non-URiM faculty in academic family medicine.
The effect of gamification-based training on the knowledge, attitudes, and academic achievement of male adolescents in preventing substance and internet addiction
Authors: Taghipour Esmaeel , Vizeshfar Fatemeh , Zarifsanaiey Nahid 
Published: November 2023

Abstract
Background
Preventing addiction through training takes precedence over treatment and plays a crucial role in enhancing the well-being of adolescents. Utilizing inclusive and participatory methods can significantly enhance the effectiveness of education. Numerous studies have demonstrated that gamification, as an interactive and comprehensive approach, has the potential to boost teenagers’ motivation to engage in learning and contributes to better comprehension.

Aim
This study aimed to assess the impact of gamification-based training to prevent substance and internet addiction on the knowledge and attitudes of male adolescents. Additionally, the study examined this educational program’s effects on male adolescents’ academic achievement.

Methods
This study employed a quasi-experimental design with a control group. One hundred fourteen male adolescents were randomly assigned to the intervention or control groups. They completed a pre-intervention questionnaire assessing addiction-related knowledge, attitudes, and academic achievement. Subsequently, the intervention group received the gamification-based drug and internet addiction prevention training. Post-tests were conducted immediately after the training and again one month later for both groups.

Results
Before the intervention, there were no significant differences in knowledge of substance and internet addiction, attitudes toward substances and the Internet, and academic achievement between the intervention and control groups (P > 0.05). However, after the intervention, the intervention group demonstrated significantly higher scores in knowledge of substance and internet addiction, attitudes toward substances and the Internet, and academic achievement compared to the control group (P < 0.001).

Conclusion
The current study highlights the positive impact of gamification-based training on enhancing male adolescents’ knowledge, attitudes, and academic achievement.