bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of the SF-6D utility score from Lung cancer FACT-L: a mapping study in China
Authors: Yang Qing , Jiang Long Lin , Li Yin Feng , Huang Deyu 
Published: November 2023

Abstract
Objective
To develop a mapping algorithm for generating the Short Form Six-Dimension (SF-6D) utility score based on the Functional Assessment of Cancer Therapy-Lung (FACT-L) of lung cancer patients.

Methods
Data were collected from 625 lung cancer patients in mainland China. The Spearman rank correlation coefficient and principal component analysis were used to evaluate the conceptual overlap between the FACT-L and SF-6D. Five model specifications and four statistical techniques were used to derive mapping algorithms, including ordinary least squares (OLS), Tobit and beta-mixture regression models, which were used to directly estimate health utility, and ordered probit regression was used to predict the response level. The prediction performance was evaluated using the correlations between the root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), Akaike information criterion (AIC) and Bayesian information criterion (BIC) and the observed and predicted SF-6D scores. A five-fold cross-validation method was used to test the universality of each model and select the best model.

Results
The average FACT-L score was 103.024. The average SF-6D score was 0.774. A strong correlation was found between FACT-L and SF-6D scores (ρ = 0.797). The ordered probit regression model with the total score of each dimension and its square term, as well as age and sex as covariates, was most suitable for mapping FACT-L to SF-6D scores (5-fold cross-validation: RMSE = 0.0854; MAE = 0.0655; CCC = 0.8197; AEs > 0.1 (%) = 53.44; AEs > 0.05 (%) = 21.76), followed by beta-mixture regression for direct mapping. The Bland‒Altman plots showed that the ordered probit regression M5 had the lowest proportion of prediction scores outside the 95% agreement limit (-0.166, 0.163) at 4.96%.

Conclusions
The algorithm reported in this paper enables lung cancer data from the FACT-L to be mapped to the utility of the SF-6D. The algorithm allows the calculation of quality-adjusted life years for cost-utility analyses of lung cancer.
Developing and validating a multi-criteria decision analytic tool to assess the value of cancer clinical trials: evaluating cancer clinical trial value
Authors: Gillett Piers , Mahar Robert K , Tran Nancy R , Rosenthal Mark , IJzerman Maarten 
Published: November 2023

Abstract
Background
Demonstrating safety and efficacy of new medical treatments requires clinical trials but clinical trials are costly and may not provide value proportionate to their costs. As most health systems have limited resources, it is therefore important to identify the trials with the highest value. Tools exist to assess elements of a clinical trial such as statistical validity but are not wholistic in their valuation of a clinical trial. This study aims to develop a measure of clinical trials value and provide an online tool for clinical trial prioritisation.

Methods
A search of the academic and grey literature and stakeholder consultation was undertaken to identify a set of criteria to aid clinical trial valuation using multi-criteria decision analysis. Swing weighting and ranking exercises were used to calculate appropriate weights of each of the included criteria and to estimate the partial-value function for each underlying metric. The set of criteria and their respective weights were applied to the results of six different clinical trials to calculate their value.

Results
Seven criteria were identified: ‘unmet need’, ‘size of target population’, ‘eligible participants can access the trial’, ‘patient outcomes’, ‘total trial cost’, ‘academic impact’ and ‘use of trial results’. The survey had 80 complete sets of responses (51% response rate). A trial designed to address an ‘Unmet Need’ was most commonly ranked as the most important with a weight of 24.4%, followed by trials demonstrating improved ‘Patient Outcomes’ with a weight of 21.2%. The value calculated for each trial allowed for their clear delineation and thus a final value ranking for each of the six trials.

Conclusion
We confirmed that the use of the decision tool for valuing clinical trials is feasible and that the results are face valid based on the evaluation of six trials. A proof-of-concept applying this tool to a larger set of trials with an external validation is currently underway.
Insights into the regulatory role of RNA methylation modifications in glioma
Authors: Long Shengrong , Yan Yu , Xu Hongyu , Wang Lesheng , Jiang Jiazhi , Xu Ziyue , Liu Runming , Zhou Qiangqiang , Huang Xiaopeng , Chen Jincao , Li Zhiqiang , Wei Wei , Li Xiang 
Published: November 2023

AbstractEpitranscriptomic abnormalities, which are highly prevalent in primary central nervous system malignancies, have been identified as crucial contributors to the development and progression of gliomas. RNA epitranscriptomic modifications, particularly the reversible modification methylation, have been observed throughout the RNA cycle. Epitranscriptomic modifications, which regulate RNA transcription and translation, have profound biological implications. These modifications are associated with the development of several cancer types. Notably, three main protein types—writers, erasers, and readers, in conjunction with other related proteins, mediate these epitranscriptomic changes. This review primarily focuses on the role of recently identified RNA methylation modifications in gliomas, such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), and N1-methyladenosine (m1A). We delved into their corresponding writers, erasers, readers, and related binding proteins to propose new approaches and prognostic indicators for patients with glioma.
Deletion of voltage-gated calcium channels in astrocytes decreases neuroinflammation and demyelination in a murine model of multiple sclerosis
Authors: Denaroso G. E. , Smith Z. , Angeliu C. G. , Cheli V. T. , Wang C. , Paez P. M. 
Published: November 2023

AbstractThe experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis was used in combination with a Cav1.2 conditional knock-out mouse (Cav1.2KO) to study the role of astrocytic voltage-gated Ca++ channels in autoimmune CNS inflammation and demyelination. Cav1.2 channels were specifically ablated in Glast-1-positive astrocytes by means of the Cre-lox system before EAE induction. After immunization, motor activity was assessed daily, and a clinical score was given based on the severity of EAE symptoms. Cav1.2 deletion in astrocytes significantly reduced the severity of the disease. While no changes were found in the day of onset and peak disease severity, EAE mean clinical score was lower in Cav1.2KO animals during the chronic phase of the disease. This corresponded to better performance on the rotarod and increased motor activity in Cav1.2KO mice. Furthermore, decreased numbers of reactive astrocytes, activated microglia, and infiltrating lymphocytes were found in the lumbar section of the spinal cord of Cav1.2KO mice 40 days after immunization. The degree of myelin protein loss and size of demyelinated lesions were also attenuated in Cav1.2KO spinal cords. Similar results were found in EAE animals treated with nimodipine, a Cav1.2 Ca++ channel inhibitor with high affinity to the CNS. Mice injected with nimodipine during the acute and chronic phases of the disease exhibited lower numbers of reactive astrocytes, activated microglial, and infiltrating immune cells, as well as fewer demyelinated lesions in the spinal cord. These changes were correlated with improved clinical scores and motor performance. In summary, these data suggest that antagonizing Cav1.2 channels in astrocytes during EAE alleviates neuroinflammation and protects the spinal cord from autoimmune demyelination.
“Sex without fear”: exploring the psychosocial impact of oral HIV pre-exposure prophylaxis on gay men in England
Authors: Hayes Rosalie , Nutland Will , Rayment Michael , Wayal Sonali , Apea Vanesa , Clarke Amanda , McOwan Alan , Sullivan Ann , Desai Monica , Jajja Andrew , Rice Brian , Horne Rob , McCormack Sheena , Gafos Mitzy 
Published: November 2023

AbstractGay, bisexual, and other men who have sex with men (GBMSM) experience a high prevalence of psychosocial health problems, such as harmful substance use and depression, as well as being disproportionately affected by HIV. HIV Pre-Exposure Prophylaxis (PrEP) may provide psychosocial benefits beyond its intended purpose of reducing HIV infection. We explore the psychosocial impact of oral PrEP use on gay men in England using qualitative data from the PROUD study. From February 2014 to January 2016, semi-structured in-depth interviews were conducted with 40 gay men and one trans woman. Participants were purposively recruited based on trial arm allocation, adherence, and sexual risk behaviours. By removing HIV risk from sex, PrEP improves users’ wellbeing by reducing HIV-related anxiety and internalised stigma and increasing HIV prevention self-efficacy, sexual pleasure, and intimacy. In turn, these psychological changes may influence behaviour in the form of greater sexual freedom, reduced harmful drug use, and more protective sexual health behaviours. However, PrEP may create internal conflict for some gay men, due to its disruption of social norms around condom use and its perceived influence on their sexual behaviour leading to reduced condom self-efficacy. These findings provide a baseline of PrEP’s psychosocial impact amongst some of the first PrEP users in England and supports calls to consider the psychosocial impact of PrEP in prescribing guidelines.
Maintaining quality of life after major lung resection for carcinoid tumor
Authors: Abdel Jalil Riad , Abdallah Farah A. , Obeid Zeinab , Abou Chaar Mohamad K. , Harb Ahmad Khaled , Shannies Tariq Bassam , El-Edwan Ahed , Haddad Hussam , Ghraibeh Azza , Abu-Shanab Ahmad 
Published: November 2023

Abstract
Background
Pulmonary carcinoid is a rare diagnosis with surgery remaining the standard treatment of choice. However, resection may impact patients’ daily activities due to decreased lung volume reserve and postoperative pain. Our study aims to compare the impact of different types of surgical resection on the post-operative quality of life with the application of a strict peri-operative pulmonary care program.

Methods
Patients who underwent surgery for bronchopulmonary carcinoid tumors in a tertiary cancer center between August, 2017 and March, 2020 were identified and demographic data was collected. Patients were contacted via phone for the qualitative and quantitative assessment of pain and quality of life, utilizing the Arabic version of Short-form McGill Pain Questionnaire and Activity of Daily Living (ADL) instrument respectively. Lung reserve was assessed before and after surgery. Statistical analysis used Chi-Square for categorical variables and ANOVA for continuous variables.

Results
A total of 16 patients underwent different type of resection. The majority were male (n = 10; 63%) with a mean age of 44 years (19–81). Most common clinical stage was stage I (n = 12, 75%) with typical carcinoid features recorded in more than half of the cases (n = 11, 69%). Almost all patients underwent surgical excision (n = 15, 94%) with negative resection margin and no major post-operative complications. Bilobectomy was the most frequent procedure (n = 6, 40%) and video-assisted thoracoscopic surgery (VATS) was utilized in 8 patients (50%). Expected changes were recorded in pre- and postoperative pulmonary function test with an average drop of 10 in FEV1 and 14 mL/min/mmHg in DLCO. The majority of patients (n = 15, 94%) were totally independent doing daily activities. Mild intermittent pain was found in 7 patients (44%) who scored an average intensity of 1.6 out of 10.

Conclusions
Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors with little to no effect on patients’ lung function and quality of life in regard to performance status and post-operative pain when a good peri-operative pulmonary, physical rehabilitation, and pain management programs are adopted and strictly implemented.
Formation of an invasion-permissive matrix requires TGFβ/SNAIL1-regulated alternative splicing of fibronectin
Authors: Franco-Valls Héctor , Tusquets-Uxó Elsa , Sala Laura , Val Maria , Peña Raúl , Iaconcig Alessandra , Villarino Álvaro , Jiménez-Arriola Martín , Massó Pere , Trincado Juan L. , Eyras Eduardo , Muro Andrés F. , Otero Jorge , García de Herreros Antonio , Baulida Josep 
Published: November 2023

Abstract
Background
As in most solid cancers, the emergence of cells with oncogenic mutations in the mammary epithelium alters the tissue homeostasis. Some soluble factors, such as TGFβ, potently modify the behavior of healthy stromal cells. A subpopulation of cancer-associated fibroblasts expressing a TGFβ target, the SNAIL1 transcription factor, display myofibroblastic abilities that rearrange the stromal architecture. Breast tumors with the presence of SNAIL1 in the stromal compartment, and with aligned extracellular fiber, are associated with poor survival prognoses.

Methods
We used deep RNA sequencing and biochemical techniques to study alternative splicing and human tumor databases to test for associations (correlation t-test) between SNAIL1 and fibronectin isoforms. Three-dimensional extracellular matrices generated from fibroblasts were used to study the mechanical properties and actions of the extracellular matrices on tumor cell and fibroblast behaviors. A metastatic mouse model of breast cancer was used to test the action of fibronectin isoforms on lung metastasis.

Results
In silico studies showed that SNAIL1 correlates with the expression of the extra domain A (EDA)-containing (EDA+) fibronectin in advanced human breast cancer and other types of epithelial cancers. In TGFβ-activated fibroblasts, alternative splicing of fibronectin as well as of 500 other genes was modified by eliminating SNAIL1. Biochemical analyses demonstrated that SNAIL1 favors the inclusion of the EDA exon by modulating the activity of the SRSF1 splicing factor. Similar to Snai1 knockout fibroblasts, EDA- fibronectin fibroblasts produce an extracellular matrix that does not sustain TGFβ-induced fiber organization, rigidity, fibroblast activation, or tumor cell invasion. The presence of EDA+ fibronectin changes the action of metalloproteinases on fibronectin fibers. Critically, in an mouse orthotopic breast cancer model, the absence of the fibronectin EDA domain completely prevents lung metastasis.

Conclusions
Our results support the requirement of EDA+ fibronectin in the generation of a metastasis permissive stromal architecture in breast cancers and its molecular control by SNAIL1. From a pharmacological point of view, specifically blocking EDA+ fibronectin deposition could be included in studies to reduce the formation of a pro-metastatic environment.
ACSM5 inhibits ligamentum flavum hypertrophy by regulating lipid accumulation mediated by FABP4/PPAR signaling pathway
Authors: Cao Yanlin , Li Jianjun , Qiu Sujun , Ni Songjia , Duan Yang 
Published: November 2023

Abstract
Background
Ligamentum flavum (LF) hypertrophy is the main cause of lumbar spinal canal stenosis (LSCS). Previous studies have shown that LF hypertrophy tissue exhibits abnormal lipid accumulation, but the regulatory mechanism remains unclear. The objective of this study was to explore the function and potential mechanism of ACSM5 in LF lipid accumulation.

Methods
To assess the ACSM5 expression levels, lipid accumulation and triglyceride (TG) level in LF hypertrophy and normal tissue, we utilized RT-qPCR, western blot, oil red O staining, and TG assay kit. The pearson correlation coefficient assay was used to analyze the correlation between ACSM5 levels and lipid accumulation or TG levels in LF hypertrophy tissue. The role of ACSM5 in free fatty acids (FFA)-induced lipid accumulation in LF cells was assessed in vitro, and the role of ACSM5 in LF hypertrophy in mice was verified in vivo. To investigate the underlying mechanisms of ACSM5 regulating lipid accumulation in LF, we conducted the mRNA sequencing, bioinformatics analysis, and rescue experiments.

Results
In this study, we found that ACSM5, which was significantly down-regulated in LF tissues, correlated with lipid accumulation. In vitro cell experiments demonstrated that overexpression of ACSM5 significantly inhibited FFA-induced lipid accumulation and fibrosis in LF cells. In vivo animal experiments further confirmed that overexpression of ACSM5 inhibited LF thickening, lipid accumulation, and fibrosis. Mechanistically, ACSM5 inhibited lipid accumulation of LF cells by inhibiting FABP4-mediated PPARγ signaling pathway, thereby improving hypertrophy and fibrosis of LF.

Conclusions
our findings elucidated the important role of ACSM5 in the regulation of LF lipid accumulation and provide insight into potential therapeutic interventions for the treatment of LF hypertrophy. This study further suggested that therapeutic strategies targeting lipid deposition may be an effective potential approach to treat LF hypertrophy-induced LSCS.
Effect of the telemedicine-supported multicomponent exercise therapy in patients with knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Feng Yuan , Wu Yan , Liu Huizhen , Bao Tianjie , Wang Chongyang , Wang Zezhang , Huang Jielei , Jiang Yiwei , He Chengqi , Zhu Siyi 
Published: November 2023

Abstract
Introduction
The rising prevalence of knee osteoarthritis is placing a considerable strain on the global healthcare system. To address this issue, telemedicine-supported multicomponent exercise therapy has emerged as a promising approach. This therapy combines exercise, patient education, and health coaching to empower knee osteoarthritis patients to manage their condition from the comfort of their homes. Nevertheless, there are some existing limitations in the current research on this approach, including challenges related to patient compliance and the absence of objective evaluation methods.

Methods and analysis
Patients diagnosed with knee osteoarthritis, who have not undergone knee surgery in the past year, will be recruited for a randomized controlled trial. The trial will include an intervention group and a control group. The intervention group will receive an mHealth app-based multicomponent exercise therapy, consisting of exercise therapy, patient education, and health coaching. Meanwhile, the control group will receive usual care, involving drug therapy and patient education. The primary outcome of the trial will be the measurement of pain intensity, assessed using a visual analog scale at baseline and at 4, 8, and 12 weeks of the post-intervention. To analyze the data, a two-factor, four-level repeated measures ANOVA will be used if the assumptions of homogeneity of variance and sphericity are met. If not, a mixed effects model will be employed.

Discussion
The aim of the study is to evaluate the effectiveness of multicomponent exercise therapy aimed at enhancing pain self-management for knee osteoarthritis patients in the comfort of their own homes. The intervention incorporate wearable devices equipped with advanced deep learning systems to monitor patients' adherence to the prescribed at-home exercise regimen, as well as to track changes in outcomes before and after the exercise sessions. The findings from this trial have the potential to enhance both the accessibility and quality of care provided to knee osteoarthritis patients, offering valuable insights for future improvements in their treatment and management.

Trial registration
Chinese Clinical Trials Registry, ChiCTR2300073688. Registered on 19 July 2023, https://www.chictr.org.cn/bin/project/edit?pid=199707. World Health Organization International Clinical Trials Registry Platform, https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300073688.
Multiple cardiometabolic diseases enhance the adverse effects of hypoalbuminemia on mortality among centenarians in China: a cohort study
Authors: Li Haowei , Wang Shengshu , Yang Shanshan , Liu Shaohua , Song Yang , Chen Shimin , Li Xuehang , Li Zhiqiang , Li Rongrong , Zhao Yali , Zhu Qiao , Ning Chaoxue , Liu Miao , He Yao 
Published: November 2023

Abstract
Background
Although hypoalbuminemia was associated with high risk of mortality in community-dwelling older adults, as well as in the hospitalized older adults, little is known among centenarians. And there are limited data on whether having cardiometabolic diseases (CMDs) is associated with additive effects.

Methods
Baseline examinations including a determination of albumin levels were performed in 1002 Chinese centenarians from January 2014 through to December 2016, and the survival status was subsequently ascertained until 31 May 2021. Cox proportional risk model was performed to assess the risk of all-cause mortality associated with albumin levels and hypoalbuminemia combined with CMDs.

Results
Of 1002 participants included in the analysis, the mean level of albumin was 38.5 g/L (± standard deviation, 4.0 g/L), and 174 (17.4%) had hypoalbuminemia (albumin < 35 g/L). The multivariable analyses showed that albumin level was negatively associated with all-cause mortality (Ptrend < 0.05). Compared to normoalbuminemia, hypoalbuminemia was associated with an increased mortality risk in the overall participants (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.22–1.97). Furthermore, the HR (95% CI) of hypoalbuminemia combined with multiple CMDs was 2.15 (1.14–4.07). There was evidence of an additive deleterious dose effect of an increasing number of CMDs (Ptrend = 0.001).

Conclusions
Hypoalbuminemia is associated with an increased risk of all-cause mortality in Chinese centenarians, and this risk is more pronounced among centenarians with multiple cardiometabolic diseases. Our findings suggest that older adults with hypoalbuminemia, especially comorbid multiple CMDs warrant early identification and management.
Do cool shirts make a difference? The effects of upper body garments on health, fluid balance and performance during exercise in the heat
Authors: Engeroff L. , Niederer D. , Groneberg D. , Vogt L. , Engeroff Tobias 
Published: November 2023

Abstract
Objectives
Due to climate change and major sport events in hot climate, temperature regulation during exercise is gaining relevance in professional and amateur sports. This study compares the effects of an upper body garment with water-soaked inlays, of a synthetic- and of a cotton shirt on health, fluid balance and performance during a high intensity exercise session in the heat.

Methods
32 healthy participants (age 25 ± 4 years; 15 women) were assigned to one of three upper body garments (cotton-shirt, synthetic-fiber-shirt, cooling-vest with water-soaked inlays) and underwent a high intensity steady state ergometer exercise test (Temperature 30.5 °C, frontal airflow 20 km/h, relative air-humidity 43 ± 13%). Time to exhaustion, physiologic parameters (inner ear temperature, heart rate, relative oxygen uptake, body weight, garment weight) and subjective data (perceived exertion, thermal sensation, skin wettedness, clothing humidity, feeling scale) were assessed. Time to exhaustion was analyzed using a survival time analysis. Other outcomes were evaluated using Kruskal-Wallis Tests and 95%-confidence-intervals.

Results
Time to exhaustion was not different between groups. Cooling-vests were heavier and led to lower inner ear temperature, lower thermal- and higher clothing-humidity-sensation at the start of exercise. Physiologic and subjective parameters showed no group differences at exercise termination.

Conclusions
In a realistic setting including frontal airflow, synthetic and cotton-fiber shirts reach comparable effects on health and thermoregulation and are perceived as equally comfortable. Although inducing a small pre-exercise cooling effect, a water-soaked garment induces a weight penalty and creates a less comfortable situation.