bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Trial of Nivolumab in Metastatic Rare Cancer with dMMR or MSI-H and Relation with Immune Phenotypic Analysis (the ROCK Trial)
Authors: Okuma Hitomi S. , Watanabe Keisuke , Tsuchihashi Kenji , Machida Ryunosuke , Sadachi Ryo , Hirakawa Akihiro , Ariyama Hiroshi , Kanai Masashi , Kamikura Masahisa , Anjo Kenta , Hiramitsu Akari , Sekine Shigeki , Okita Natsuko , Mano Hiroyuki , Nishikawa Hiroyoshi , Nakamura Kenichi , Yonemori Kan 
Published: October 2023

Abstract

Purpose:
Mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) are positive predictive markers for immune checkpoint inhibitors. However, data on the activity of nivolumab in advanced dMMR/MSI-H rare cancers and more accurate biomarkers are worth exploring.

Patients and Methods:
We conducted a multicenter phase II, open-label, single-arm clinical trial to explore the effectiveness and safety of nivolumab monotherapy in patients with advanced rare cancers with dMMR/MSI-H, in parallel with immune phenotype analysis, to explore new biomarkers. A Bayesian adaptive design was applied. Characterization of peripheral blood mononuclear cells (PBMC) was characterized by multicolor flow cytometric analysis and CyTOF using samples collected before and after the intervention. The dMMR was identified by the complete loss of MLH1/MSH2/MSH6/PMS2.

Results:
From May 2018 to March 2021, 242 patients were screened, and 11 patients were enrolled, of whom 10 were included in the full analysis. Median follow-up was 24.7 months (interquartile range, 12.4–31.5). Objective response rate was 60% [95% confidence interval (CI), 26.2–87.8] by central assessment and 70% (95% CI, 34.8–93.3) by local investigators. Median progression-free survival was 10.1 months (95% CI, 0.9–11.1). No treatment-related adverse events of grade 3 or higher were observed. Patients with a tumor mutation burden of ≥10/Mb showed a 100% response rate (95% CI, 47.8–100). Responders had increased T-bet+ PD-1+ CD4+ T cells in PBMC compared with nonresponders (P &lt; 0.05).

Conclusions:
The trial met its primary endpoint with nivolumab, demonstrating clinical benefit in advanced dMMR/MSI-H rare solid cancers. Besides, the proportion of T-bet+ PD-1+ CD4+ T-cells may serve as a novel predictive biomarker.
A Large-Scale Field Experiment to Reduce Non-Payments for Water: From Diagnosis to Treatment
Authors: Rockenbach Bettina , Tonke Sebastian , Weiss Arne R. 
Published: October 2023

Abstract
In a field experiment among 9,823 customers of the Namibian water utility, we implement interventions to reduce non-payments. The interventions are based on diagnostic surveys to identify key obstacles to payments. They address informational frictions and apply psychological commitment techniques to narrow the gap between customers' willingness to pay and actual payments. Initially, payments increase by 29% to 55%, making the interventions highly cost-effective. While removing informational frictions has a lasting impact, the commitment techniques produce only short-term effects. We demonstrate the effectiveness and limitations of behavioral interventions in settings where heavy-handed tools, e.g., disconnecting non-payers, are difficult to implement.
Factors impacting the demonstration of relational autonomy in medical decision-making: A meta-synthesis
Authors: Le Thi Dung , Lin Shih-Chun , Huang Mei-Chih , Fan Sheng-Yu , Kao Chi-Yin 
Published: October 2023

Background Relational autonomy is an alternative concept of autonomy in which an individual is recognized as embedded into society and influenced by relational factors. Social context, including social location, political structure, and social forces, significantly influence an agent to develop and exercise autonomy skills. The relational approach has been applied in clinical practice to identify relational factors impacting patient autonomy and decision-making, yet there is a knowledge gap in how these factors influence the demonstration of relational autonomy in the context of medical decisions of adults. Objective The present study targeted the existing knowledge of what and how relational factors impact individuals making medical decisions using the theoretical framework of relational autonomy. Methods A meta-synthesis study was utilized. Four electronic databases, including Embase, OVID Medline, CINAHL, and PubMed, were searched, along with gray literature and reference lists, to identify relevant studies. Results 23 studies reporting 21 qualitative and two mixed-method studies were reviewed. Four themes emerged from the qualitative findings: (1) supportive relationships facilitate an individual’s relational autonomy; (2) obtaining comprehensive information from broader sources helps individuals exercise relational autonomy; (3) undue family pressure impedes the exercising of patient relational autonomy; and (4) healthcare providers’ dominant voice hampers the demonstration of relational autonomy. Conclusions Applying relational autonomy to assist adults in making well-considered decisions is essential. The meta-synthesis suggests establishing a supportive relationship between individuals, healthcare providers, and family. A supportive relationship will allow healthcare providers to make judgments in line with an individual’s values and wishes with the aim of promoting relational autonomy. Advance care planning was proposed as the effective solution to obtain a consensus between individuals and their families while respecting an individual’s values and preferences. Furthermore, it is considered crucial for healthcare providers to appreciate an individual's values and incorporate their preferences into recommendations.
Anti-Aging of the Nervous System and Related Neurodegenerative Diseases With Chinese Herbal Medicine
Authors: Du Xiaohui , Lou Nanbin , Hu Sinan , Xiao Ruopeng , Chu Chu , Huang Qiankai , Lu Lin , Li Shanshan , Yang Jing 
Published: October 2023

Human beings have always pursued a prolonged lifespan, while the aging of the nervous system is associated with a large variety of diseases. Pathological aging of the nervous system results in a series of neurodegenerative diseases and can cause disability and death in the elderly. Therefore, there is an urgent need for the prevention and treatment of nervous system aging. Chinese herbal medicines have a long history, featuring rich and safe ingredients, and have great potential for the development of anti-aging treatment. We searched the publications on PubMed with key words “anti-aging of the nervous system” and “Chinese herbal medicine” in recent 10 years, and found sixteen Chinese herbal medicines. Then by comparing their popularity of use as well as active components based on the research articles, five common Chinese herbal medicines namely Ginseng Radix, Lycii Fructus, Astragali Radix, Coptidis Rhizoma and Ginkgo Folium, were confirmed to be the most related to anti-nervous system aging and neural degenerative diseases. At the same time, the active ingredients, research models, action mechanisms and curative effects of these five common Chinese herbal medicines were reviewed. From the five common Chinese herbal medicines reviewed in this paper, many encouraging effects of Chinese herbal medicines on treating nervous system aging and related diseases were revealed and more potent herbs would be explored with the help of the proposed possible mechanisms.
A new method for the detection of Mycobacterium tuberculosis based on the CRISPR/Cas system
Authors: Zhang Xiaoyu , He Xiaoying , Zhang Yubo , Chen Lei , Pan Zhaobao , Huang Yueying , Li Heng 
Published: October 2023

Abstract
Object
Mycobacterium tuberculosis (MTB) is a bacterium that can cause zoonoses by aerosol transmission. Tuberculosis (TB) caused by MTB heavily burdens world public health security. Developing efficient, specific, convenient, and inexpensive MTB assays are essential for preventing and controlling TB.

Methods
In this study, we established a specific detection method for MTB using the Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) system, combined with recombinase mediated isothermal nucleic acid amplification (RAA) to improve the sensitivity of the detection system and achieve “two-level” amplification of the detection signal. The sensitivity and specificity of RAA combined with the CRISPR/Cas system were analyzed. Using BACTEC 960 culture as the gold standard for detecting MTB, we established the TB-CRISPR technique by testing 504 samples from patients with suspected TB.

Results
MTB H37Ra could be seen as low as 3.13 CFU/mL by the CRISPR-Cas12a system targeting IS6110. With BACTEC960 culture (120 positives and 384 negatives) as the gold standard, the sensitivity of the TB-CRISPR technique was 0.883 (0.809–0.932), and the specificity was 0.940 (0.910–0.961). According to the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) reached 0.944 (0.914–0.975) within 95% CI. The positive likelihood ratio (PLR) was 14.747 (9.870-22.035), and the negative likelihood ratio (NLR) was 0.124 (0.076–0.203). The positive predictive value (PPV) was 0.822 (0.742–0.881), and the negative predictive value (NPV) was 0.963 (0.937–0.979).

Conclusion
TB-CRISPR plays an essential role in the molecular diagnosis of TB. The whole detection time is less than 1.5 h. It is easy to operate and does not need complex instruments. It is of great significance for the rapid detection of MTB and the clinical diagnosis of TB.
Chronic disease prevention literacy and its influence on behavior and lifestyle: a cross-sectional study in Xinjiang, China
Authors: Abudireyimu Alimire , Su Yinxia , Hu Conghui , Li Yuanyuan , Yao Hua 
Published: October 2023

Abstract
Objective
To understand the status and influencing factors of Kyrgyz chronic disease prevention literacy, and to explore the impact of chronic disease prevention literacy on behavior and living habits.

Method
Using stratified sampling method, Kyrgyz residents aged ≥ 18 years in Artush City, Aheqi County and Ucha County were surveyed by questionnaire.

Results
A total of 10,468 subjects were investigated, and the literacy rate of chronic disease prevention in Kyrgyz was 11.2%. The results of Logistic regression analysis showed that the literacy rate of chronic disease prevention was low among people with low education level, herdsmen, low income, urban and chronic disease (P < 0.05). Residents with chronic disease prevention literacy were more inclined to not smoke, not drink alcohol, drink milk every day, eat soy products every month, eat whole grains every day (P < 0.05).

Conclusion
The literacy level of chronic disease prevention of Kyrgyz residents in Kezhou has been improved, but it is still at a low level compared with another subcategories. The behavioral lifestyle is related to the literacy level of chronic disease prevention. Therefore, local health promotion strategies should be developed to improve the literacy level of chronic disease prevention and promote the formation of good behavioral and living habits.
Exploring the interest of medical students in global health in South Korea: Does taking a global health course matter?
Authors: Park Jayoung , Hwang Jongnam , Lim Yeji , Heo Jongho , Kim Woong-Han 
Published: October 2023

Abstract
Background
Prioritizing global health is important for positive health outcomes. Doctors play a pivotal role in addressing health issues that they need to recognize the importance of global health practice. However, medical education in global health is still in its early stages in many countries, including South Korea.

Methods
This study is a quantitative cross-sectional study. Medical students were recruited from all 40 Korean medical schools and data collection was conducted in 2021. Stratified proportional quota sampling was employed as the sampling method. The study examined medical students’ interest in global health as the dependent variable. Independent variables included whether individuals had taken global health courses as part of their medical curriculum, while covariates included student background and institutional factors. Logistic regression was used to determine if taking a global health class was associated with global health interests.

Results
The study included 2450 participants and almost 32% of medical students (n = 781) were interested in global health. Taking global health classes in school was associated with a higher likelihood of developing an interest in global health (OR: 1.29, 95% CI: 1.00-1.67). The likelihood of being interested in global health decreased across the academic year (OR: 0.70, 95% CI: 0.53–0.94). Individuals in graduate entry programs were associated with an interest in global health (OR: 1.32, 95% CI: 1.01–1.72).

Conclusion
This study provides the first comprehensive nationwide assessment of medical students’ perspectives on global health education in South Korea. The findings underscore the importance of early and sustained exposure to global health topics in medical education in fostering interest in global health. These results can serve as valuable evidence for medical educators seeking to integrate global health education into their curricula.
Implementation determinants of physical activity interventions in primary health care settings using the TICD framework: a systematic review
Authors: Silva Catarina Santos , Godinho Cristina , Encantado Jorge , Rodrigues Bruno , Carraça Eliana V. , Teixeira Pedro J. , Silva Marlene Nunes 
Published: October 2023

Abstract
Background
Translation into practice of effective physical activity interventions in primary care is difficult, due to a complex interaction of implementation determinants. We aimed to identify implementation barriers and facilitators of four primary care interventions: physical activity assessment, counselling, prescription, and referral.

Methods
A systematic review of qualitative, quantitative and mixed-methods studies published since 2016 was conducted. The “Tailored Implementation for Chronic Diseases” (TICD) framework was adapted to extract and synthesize barriers and facilitators.

Results
Sixty-two studies met the inclusion criteria. Barriers (n = 56) and facilitators (n = 55) were identified across seven domains, related to characteristics of the intervention, individual factors of the implementers and receivers, organizational factors, and political and social determinants. The five most frequently reported determinants were: professionals’ knowledge and skills; intervention feasibility/compatibility with primary health care routine; interventions’ cost and financial incentives; tools and materials; and professionals’ cognitions and attitudes. “Social, political and legal factors” domain was the least reported. Physical activity counselling, prescription, and referral were influenced by determinants belonging to all the seven domains.

Conclusion
The implementation of physical activity interventions in primary care is influenced by a broader range of determinants. Barriers and facilitators related with health professionals, intervention characteristics, and available resources were the most frequently reported. A deep understanding of the local context, with particularly emphasis on these determinants, should be considered when preparing an intervention implementation, in order to contribute for designing tailored implementation strategies and optimize the interventions’ effectiveness.
Clinical efficacy analysis of percutaneous “tripod” combined with radiofrequency ablation and bone cement filling in the treatment of periacetabular metastases
Authors: Lan Yun , Li Ruoyu , Jiang Linheng , Zhou Nannan , He Mincon , Fang Bin , Yi Chunzhi 
Published: October 2023

Abstract
Background
To investigate the clinical efficacy of a percutaneous “tripod” combined with radiofrequency ablation and bone cement filling surgery in treating acetabular bone metastases.

Methods
We retrospectively analyzed 11 patients who underwent percutaneous “tripod” combined with radiofrequency ablation and bone cement filling for acetabular bone metastases at a tertiary care hospital from February 2021 to December 2022.

Results
11 cases with 13 hips underwent this procedure, including two female patients who underwent both sides, and the rest were unilateral. All cases were followed up for 3–24 months, with a mean of 12 months and a median follow-up time of 11 months. Two of the 11 patients died by the final follow-up, and nine survived. One died 7 months after surgery, and one died 8 months after surgery; the survival of the deceased patients was 7.5 months (range: 7–8 months), with a median survival time of 7.5 months. All 11 patients completed the surgery successfully, and the average unilateral operation time was 167.4 min (148–193). The amelioration of postoperative pain, concomitant with improved quality of life, was observed significantly, ultimately resulting in a prolonged and sustained effect.

Conclusions
The combination of percutaneous “tripod”, radiofrequency ablation, and bone cement filling can effectively relieve pain without delaying the patient's systemic anti-tumor therapy and is a minimally invasive, safe, and effective procedure for the treatment of periacetabular metastases.
Validation of the Cantonese version of the Traditional Chinese Medicine (TCM) Body constitution Questionnaire in elderly people
Authors: Wong Yiu Lin , Zhang Jialing , Wu Xingyao , Wong Suet Yee , Wang Zheng , Zhong Linda L. D. , Bian Zhaoxiang 
Published: October 2023

Abstract
Background
The Traditional Chinese Medicine (TCM) Body Constitution Questionnaire (For Elderly People) (TCMECQ) is a patient-reported outcome questionnaire developed in Mandarin in 2013 to differentiate the body constitutions of the elderly aged 65 and above. Considering the cultural and linguistic differences between Mainland China and Hong Kong (HK) Special Administrative Region, the TCMECQ was translated into Cantonese following “back translation” policy and validated in proper process.

Methods
Ten Chinese Medicine Practitioners (CMPs) and 30 senior citizens aged 65 or above were recruited to evaluate the first version of the Traditional Chinese Medicine Body Constitution Questionnaire (For Elderly People) (Cantonese version) (TCMECQ-C). Based on their comments, the second version was developed and discussed in the panel meeting to form the third version, validated the third version on 270 recruited seniors. Based on the validation results, a panel of 5 experts finalized the Questionnaire as the final version. The TCMECQ-C developers finalized the Questionnaire as the validated endorsed third version (i.e. final version).

Results
The item-level content validity index of most items of the TCMECQ-C (First Version) were ranging from 0.80 to 1.00 in terms of clarity, relevance and appropriateness. Factor loadings of Qi-deficiency Constitution ranging from 0.37 to 0.71, Yang-deficiency Constitution ranging from 0.36 to 0.65, Yin-deficiency Constitution ranging from 0.36 to 0.65, and Stagnant Qi Constitution ranging from 0.68 to 0.82. The chi-squared degree-of-freedom ratio was 2.13 (928.63/436), Goodness-of-Fit Index (0.83), Adjusted Goodness-of-Fit Index (0.79), Normed Fit Index (0.66), Comparative Fit Index (0.78), Incremental Fit Index (0.78), Relative Fit Index (0.61) and Tucker–Lewis Index (0.75), and Root Mean Square Error of Approximation (0.07) and Standardized Root Mean Square Residual (0.07), implied acceptable Confirmatory Factor Analysis model fit of the overall scale. A Pearson correlation coefficient (r) showed the sufficient convergent validity for excessive subscales (Phlegm-dampness Constitution and Dampness-heat Constitution with r = 0.35, p < 0.01). Cronbach’s alpha coefficient ranged from 0.56 to 0.89, including Qi-deficiency Constitution (0.67), Yang-deficiency Constitution (0.84), Yin-deficiency Constitution (0.59), Stagnant Blood Constitution (0.56), Stagnant Qi Constitution (0.89), Inherited Special Constitution (0.76) and Balanced Constitution (0.73), indicating acceptable internal consistency for subscales. The intra-class correlation coefficients of the TCMECQ-C ranged from 0.70 to 0.87 (p < 0.001), indicating moderate to good test–retest reliability.

Conclusion
TCMECQ-C is a valid and reliable questionnaire for assessing the body constitution in Cantonese elderly.
Long-term benefits of physical activity in adult patients with late onset Pompe disease: a retrospective cohort study with 10 years of follow-up
Authors: Ismailova Gamida , Wagenmakers Margreet A. E. M. , Brusse Esther , van der Ploeg Ans T. , Favejee Marein M. , van der Beek Nadine A. M. E. , van den Berg Linda E. M. 
Published: October 2023

Abstract
Background
In 2011 a 12 weeks personalized exercise training program in 23 mildly affected adult late onset Pompe patients (age 19.6–70.5 years) improved endurance, muscle strength and function. Data on long-term effects of this program or of other physical activity in Pompe disease are absent. This retrospective cohort study aimed to explore effects of long-term healthy physical activity according to the WHO norm and the former exercise training program on the disease course.

Results
A total of 29 adult late onset Pompe patients were included: 19 former exercise training program participants and 10 comparable control patients. Patients, who based on interviews, met the 2010 WHO healthy physical activity norm (active, n = 16) performed better on endurance (maximal cardiopulmonary exercise test), muscle strength and function compared to patients not meeting this norm (inactive, n = 13) (p < 0.05). Majority of the outcomes, including endurance and manually tested muscle strength, tended to be higher in the active patients of the 2011 training cohort who continued the program compared to active control patients (p > 0.05).

Conclusion
In Pompe disease long-term healthy physical activity according to the 2010 WHO norm leads to physical benefits and a personalized exercise training program may have additional favorable effects and both should be recommended as standard of care.
A pilot study: handgrip as a predictor in the disease progression of SCA3
Authors: Chiu Chungmin , Cheng Wenling , Lin Yongshiou , Lin Tatsung , Chang Huiju , Chang Yujun , Lee Chiaju , Chang Henhong , Liu Chinsan 
Published: October 2023

Abstract
Background
Spinocerebellar ataxia type 3 (SCA3) is an inherited, autosomal, and rare neurodegenerative disease. Serum/plasma biomarkers or functional magnetic resonance imaging used to assess progression, except for neurological examinations, is either inconvenient or expensive. Handgrip strength (HGS) may be considered as a biomarker to predict the progress of SCA3 and align with the alteration of plasma neurofilament light chain (NfL) and Scale for the Assessment and Rating of Ataxia (SARA).

Methods
Patients with SCA3 and healthy subjects were recruited from Changhua Christian Hospital. SARA, body mass index (BMI), and NfL were obtained for both groups. HGS was measured using a Jamar Plus + hand dynamometer.

Results
This study recruited 31 patients and 36 controls. HGS in the SCA3 group revealed a profound decrease (P < 0.001) compared with normal subjects. HGS also had a negative correlation with SARA (r =  − 0.548, P = 0.001), NfL (r =  − 0.359, P = 0.048), and a positive correlation with BMI (r = 0.680, P < 0.001). Moreover, HGS/BMI ratio correlated with SARA (r =  − 0.441, P = 0.013). Controlling for gender and age, HGS still correlated with the above clinical items. The initial hypothesis was also proved in SCA3 84Q transgenic mice, showing grip strength weakness compared to normal mice.

Conclusions
HGS can be an alternative tool to assess the clinical severity of SCA3. Further research is needed to investigate the underlying mechanisms.