bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance of serum-derived exosomal PD-L1 expression in patients with advanced pancreatic cancer
Authors: Park Se Jun , Park Ju Yeon , Shin Kabsoo , Hong Tae Ho , Lee MyungAh , Kim Younghoon , Kim In-Ho 
Published: May 2023

Abstract
Background
Interactions between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) lead to immune evasion in various tumors and are associated with poor prognosis in patients with pancreatic cancer; however, the roles of PD-L1-containing exosomes in pancreatic cancer is poorly understood. Here, we investigated the correlation between circulating exosomal PD-L1 (exoPD-L1) and PD-L1 expression in tumor tissue, and survival outcomes in patients with advanced PDAC.

Methods
Exosomes were derived from pre-treatment serum samples isolated using ExoQuick kit from 77 patients with advanced pancreatic cancer. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immunosorbent assay, and matched tumor tissues PD-L1 expression were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with receiver operating characteristic curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival (OS), and hazard ratio was estimated using a stratified Cox regression model.

Results
The median exoPD-L1 serum concentration was 0.16 pg/mg, with undetected levels in seven patients. ExoPD-L1 levels were significantly higher in patients with systemic disease than in those with locally advanced disease (p = 0.023). There was a significantly higher proportion of elevated exoPD-L1 levels in patients with positive PD-L1 expression compared to patients with negative PD-L1 expression (p = 0.001). Patients were classified into groups with low and high exoPD-L1 levels using ROC curve-derived cutoffs (0.165 pg/mg; area under the curve, 0.617; p = 0.078). At a median follow-up of 8.39 months, the median OS was 13.2 (95% CI, 8.17–18.3) and 6.36 months (95% CI, 3.27–9.45) in the low and high exoPD-L1 groups, respectively (HR = 0.61; 95% CI, 0.35–1.04; p = 0.059). ExoPD-L1 levels did not affect the proportion of CD8+CD69+ effector cytotoxic T cells in either of the groups (p = 0.166).

Conclusions
The serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Collectively, higher serum exoPD-L1 levels in patients with advanced pancreatic cancer suggested worse survival outcomes and may have clinical implications.
Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma
Authors: Liu Jianlan , Pei Shengbin , Zhang Pengpeng , Jiang Keyu , Luo Binlin , Hou Zuoqiong , Yao Gang , Tang Jian 
Published: May 2023

Abstract
Background
In recent years, there has been growing evidence indicating a relationship between liquid–liquid phase separation (LLPS) and cancer development. However, to date, the clinical significance of LLPS in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains to be elucidated. In the current study, the impact of LLPS-related genes on melanoma prognosis has been explored.

Methods
LLPS-related genes were retrieved from the DrLLPS database. The prognostic feature for LLPS in melanoma was developed in The Cancer Genome Atlas (TCGA) dataset and verified in the GSE65904 cohort. Based on risk scores, melanoma patients were categorized into high- and low-risk groups. Thereafter, the differences in clinicopathological correlation, functional enrichment, immune landscape, tumor mutational burden, and impact of immunotherapy between the two groups were investigated. Finally, the role of key gene TROAP in melanoma was validated by in vitro and in vivo experiments.

Results
The LLPS-related gene signature was developed based on MLKL, PARVA, PKP1, PSME1, RNF114, and TROAP. The risk score was a crucial independent prognostic factor for melanoma and patients with high-risk scores were related to a worse prognosis. Approximately, all immune-relevant characteristics, such as immune cell infiltration and immune scores, were extremely evident in patients with low-risk scores. The findings from the in vitro and in vivo experiments indicated that the viability, proliferation, and invasion ability of melanoma cells were drastically decreased after the knockdown of TROAP.

Conclusion
Our gene signature can independently predict the survival of melanoma patients. It provides a basis for the exploration of the relationship between LLPS and melanoma and can offer a fresh perspective on the clinical diagnosis and treatment of the disease.
Feasibility of implementing a supervised telehealth exercise intervention in frail survivors of hematopoietic cell transplantation: a pilot randomized trial
Authors: Lee Kyuwan , Shamunee Justin , Lindenfeld Lanie , Ross Elizabeth , Hageman Lindsey , Sedrak Mina S. , Wong F. Lennie , Nakamura Ryotaro , Forman Stephen J. , Bhatia Smita , Armenian Saro H. 
Published: May 2023

Abstract
Background
Patients undergoing hematopoietic cell transplantation (HCT) are at high risk of chronic health complications, including frailty and physical dysfunction. Conventional exercise programs have been shown to improve frailty in other cancer populations, but these have largely been based out of rehabilitation facilities that may act as geographic and logistical barriers. There is a paucity of information on the feasibility of implementing telehealth exercise interventions in long-term HCT survivors.

Methods
We conducted a pilot randomized trial to assess the feasibility of an 8-week telehealth exercise intervention in 20 pre-frail or frail HCT survivors. Participants were randomized to either a telehealth exercise (N = 10) or delayed control (N = 10). We administered a remote physical function assessment at baseline, followed by an 8-week telehealth exercise intervention (30-60 min/session, 3 sessions/week), and post-intervention. The primary endpoint was feasibility as determined by 1) > 70% of participants completing all remote physical functional assessments, and 2) > 70% of participants in the exercise group completing > 70% (17/24) of the prescribed exercise sessions. Exploratory outcomes included changes in gait speed, handgrip strength, and short physical performance battery.

Results
The mean [standard deviation] age at study enrollment was 64.7 [9.1] years old. Twelve had undergone allogenic and 8 had undergone autologous HCT at an average of 17 years from study enrollment. Both feasibility criteria were achieved. Nineteen patients (95%) completed all remote study outcome assessments at baseline and post-intervention, and nine participants in the exercise group completed > 70% of prescribed exercise sessions. Overall, no significant group x time interaction was observed on handgrip strength, fatigue, body mass index, and short physical performance battery test (P < 0.05). However, there were significant within-group improvements in four-meter gait speed (+ 13.9%; P = 0.004) and 5-minute gait speed (+ 25.4%; P = 0.04) in the exercise group whereas non-significant changes in four-meter gait speed (-3.8%) and 5-minute gait speed (-5.8%) were observed after 8 weeks.

Conclusion
Implementing an 8-week telehealth exercise intervention for long-term HCT survivors was feasible. Our findings set the stage for innovative delivery of supervised exercise intervention that reduces the burden of frailty in HCT survivors as well as other at-risk cancer survivors.

Trial registration
The protocol and informed consent were approved by the institutional IRB (IRB#20731) and registered (ClinicalTrials.gov NCT04968119; date of registration: 20/07/2021).
Heterologous effect of influenza vaccination on molluscum contagiosum infection; a case report of siblings
Authors: Lawson Michelle L. , Szari Sofia M. , Beachkofsky Thomas M. , Hrncir David E. 
Published: May 2023

Abstract
Background
Molluscum contagiosum virus (MCV) is a benign, common cutaneous infection predominantly affecting the younger pediatric population. Traditional treatments may be time consuming with variable efficacy. Time to spontaneous resolution is variable and treatment is often sought to shorten duration of infection, prevent further autoinoculation, prevent infectious spread to others and treat cosmetic intolerability.

Case presentation
We present the case of two patients with complete, simultaneous clearance of their molluscum contagiosum infections after receiving a routine 2018 quadrivalent influenza vaccination. Neither patient has had recurrence of molluscum contagiosum or permanent scarring. We review trials of intralesional immunotherapy in treatment of cutaneous infections to theorize the mechanism of MCV infection clearance post influenza vaccination.

Conclusion
We propose a delayed-type hypersensitivity reaction was induced as a heterologous effect of the influenza vaccination, similar to that seen in current immunotherapy treatments. This is the first reported case of MCV-directed immune reaction with infection clearance after influenza vaccination.
Association of parent-child relationship quality and problematic mobile phone use with non-suicidal self-injury among adolescents
Authors: Xu Huiqiong , Xiao Wan , Xie Yang , Xu Shaojun , Wan Yuhui , Tao Fangbiao 
Published: May 2023

Abstract
Background
Non-suicidal self-injury behavior (NSSI) is a common mental health threat among adolescents. Poor parent-child relationship (PCR) and problematic mobile phone use (PMPU) are risk factors for NSSI. We aimed to explore the impact of PCR quality, PMPU, and their interaction effects on NSSI among adolescents in China, as well as the sex difference.

Method
A survey was conducted among school students in 4 provinces in China between 2017 and 2018. The study included 14,500 valid participants. The students’ general demographic characteristics was collected, and further data on PCR quality, PMPU, and NSSI were obtained through self-rated questionnaire. Chi-square test, binomial logistic regression models, and the Andersson Excel were used for data analysis.

Results
The 12-month prevalence of NSSI was 27.3%. Lower PCR quality and PMPU were significantly associated with NSSI, respectively. The low PCR + yes PMPU group had the greatest association with NSSI, followed by the high PCR + yes PMPU group, low PCR + no PMPU group. Moreover, in low father-child relationship + yes PMPU group, females had a higher risk of NSSI than males; in high mother-child relationship + yes PMPU group, females had a higher risk of NSSI than males. Additive interaction analysis indicated that mother-child relationship quality and PMPU were associated with increased risks of NSSI, in the subgroup of males.

Conclusions
The findings underline the importance of simultaneously studying the quality of PCR and PMPU for a comprehensive understanding of NSSI behavior, and especially highlights the significance of maternal relationship quality.
Identifying dementia using medical data linkage in a longitudinal cohort study: Lothian Birth Cohort 1936
Authors: Mullin Donncha S. , Stirland Lucy E. , Buchanan Emily , Convery Catherine-Anne , Cox Simon R. , Deary Ian J. , Giuntoli Cinzia , Greer Holly , Page Danielle , Robertson Elizabeth , Shenkin Susan D. , Szalek Anna , Taylor Adele , Weatherdon Georgina , Wilkinson Tim , Russ Tom C. 
Published: May 2023

Abstract
Background
The Lothian Birth Cohort 1936 (LBC1936) is a longitudinal study of ageing with well-characterised assessments, but until now, it has relied on self-report or proxies for dementia such as cognitive tests. Our aims were twofold:
a) to describe a framework for identifying dementia in a cohort study.
b) to report the age-specific incidence and prevalence of all-cause dementia and dementia subtypes in 865 individuals in the LBC1936.

Methods
Electronic Health Records (EHR) of all participants were reviewed, and relevant information was extracted to form case vignettes for everyone with any record of cognitive dysfunction. The EHR data sources include hospital and clinic letters, general practitioner and hospital referrals, prescribed medications, imaging and laboratory results. Death certificate data were obtained separately. Clinician assessments were performed when there was concern about a participant's cognition. A diagnosis of probable dementia, possible dementia, or no dementia was agreed upon by a consensus diagnostic review board, comprised of a multidisciplinary team of clinical dementia experts who reviewed case vignettes and clinician assessment letters. For those with probable dementia, a subtype was also determined, where possible. We compared the agreement between our newly ascertained dementia diagnoses with the existing self-reported dementia diagnoses.

Results
Self-reported dementia diagnoses were positive in only 17.8% of ascertained dementia diagnoses. The EHR review identified 163/865 (18.8%) individuals as having cognitive dysfunction. At the consensus diagnostic review board, 118/163 were diagnosed with probable all-cause dementia, a prevalence of 13.6%. Age-specific dementia prevalence increased with age from 0.8% (65–74.9 years) to 9.93% (85–89.9 years). Prevalence rates for women were higher in nearly all age groups. The most common subtype was dementia due to Alzheimer disease (49.2%), followed by mixed Alzheimer and cerebrovascular disease (17.0%), dementia of unknown or unspecified cause (16.1%), and dementia due to vascular disease (8.5%).

Conclusions
We present a robust systematic framework and guide for other cohort teams wanting to ascertain dementia diagnoses. The newly ascertained dementia diagnosis provides vital data for further analyses of LBC1936 to allow exploration of lifecourse predictors of dementia.
The mediating role of psychological flexibility in the association of autistic-like traits with burnout and depression in medical students during clinical clerkships in Japan: a university-based cross-sectional study
Authors: Watanabe Takafumi , Akechi Tatsuo 
Published: May 2023

Abstract
Background
Burnout and depression among medical students is linked to serious problems that require appropriate solutions. Subthreshold autism traits or autistic-like traits (ALTs) may be possible factors associated with burnout and depression. The effectiveness of acceptance and commitment therapy (ACT) for burnout and depression has been widely reported. The treatment aims to improve psychological flexibility, a concept indicating engagement in personal value-based behaviors without avoiding uncomfortable private experiences. This study examined whether ALTs were associated with burnout or depression among medical students during clinical clerkships in Japan, and then investigated what psychological flexibility processes might mediate these associations.

Methods
A cross-sectional survey was administered to 284 medical students at Nagoya City University School of Medical Sciences who had been in clinical clerkships for 10 months or longer. Linear multiple regressions were performed with each burnout factor or depression as the outcome variable using validated tools measuring burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), ALT (Autism-Spectrum Quotient Japanese version-21), and psychological flexibility processes (Cognitive Fusion Questionnaire-7 and Valuing Questionnaire). Additionally, a mediation analysis was conducted using structural equation modeling.

Results
A linear multiple regression analysis that controlled for age and gender found that ALTs were significantly associated with lower personal accomplishment, a factor of burnout, and depression. Lower personal accomplishment was also associated with males and lower progress toward values of the psychological flexibility process. Depression was also associated with males and higher cognitive fusion, lower progress towards values, and higher obstruction to values of the psychological flexibility process. Surprisingly, emotional exhaustion and depersonalization were not significantly associated with ALTs. The mediation analysis revealed that the relationship between ALTs and personal accomplishment was partially mediated by a process of progress toward values, while the relationship between ALTs and depression was partially mediated by both processes of progress toward values and cognitive fusion.

Conclusions
ALTs were significantly associated with lower personal accomplishment of burnout and depression among medical students in clinical clerkships. Consideration should be given to the psychological flexibility processes that focus on interventions targeting psychological flexibility for medical students with ALTs to reduce burnout and depression.
Socio-economic inequalities in non-use of modern contraceptives among young and non-young married women in India
Authors: Srivastava Shobhit , Mohanty Parimala , Muhammad T. , Kumar Manish 
Published: May 2023

Abstract
Background
It is documented that married women do not utilize contraceptive methods, because of the fear of adverse effects, no or seldom sexual interaction; perception that they should not use contraception during breastfeeding, postpartum amenorrhea, or dissatisfaction with a specific method of contraception. The current study aimed to examine the socio-economic inequalities associated with the non-use of modern contraceptive methods among young (15-24 years) and non-young (25-49 years) married women and the contributing factors in those inequalities.

Methods
The present study utilized the cross-sectional data from the fourth round of the National Family Health Survey (NFHS-4) with a sample of 499,627 women who were currently married. The modern methods of family planning include sterilization, injectables, intrauterine devices (IUDs/PPIUDs), contraceptive pills, implants, the standard days method, condoms, diaphragm, foam/jelly, the lactational amenorrhea method, and emergency contraception. Multivariable logistic regression analysis was used to estimate the odds of non-use of modern contraceptive methods according to different age groups after controlling for various confounding factors. Additionally, concentration curve and Wagstaff decomposition method were used in the study.

Results
The prevalence of non-use of modern contraceptive use was higher among women from young category (79.0%) than non-young category (45.8%). The difference in prevalence was significant (33.2%; p < 0.001). Women from non-young age group had 39% significantly lower odds of non-use of modern contraceptive use than women from young age group (15–24 years) [AOR: 0.23; CI: 0.23, 0.23]. The value of concentration quintile was -0.022 for young and -0.058 for non-young age groups which also confirms that the non-use of modern contraceptives was more concentrated among women from poor socio-economic group and the inequality is higher among non-young women compared to young women. About 87.8 and 55.5% of the socio-economic inequality was explained by wealth quintile for modern contraceptive use in young and non-young women. A higher percent contribution of educational status (56.8%) in socio-economic inequality in non-use of modern contraceptive use was observed in non-young women compared to only -6.4% in young women. Further, the exposure to mass media was a major contributor to socio-economic inequality in young (35.8%) and non-young (43.2%) women.

Conclusion
Adverse socioeconomic and cultural factors like low levels of education, no exposure to mass media, lack of or limited knowledge about family planning, poor household wealth status, religion, and ethnicity remain impediments to the use of modern contraceptives. Thus, the current findings provide evidence to promote and enhance the use of modern contraceptives by reducing socioeconomic inequality.
Prevalence and associated factors of postoperative orthostatic intolerance at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2022: cross sectional study
Authors: Gobezie Negesse Zurbachew , Endalew Nigussie Simeneh , Tawuye Hailu Yimer , Aytolign Habtu Adane 
Published: May 2023

Abstract
Background
Postoperative orthostatic intolerance is an inability to maintain an upright position because of symptoms of cerebral hypoperfusion. It is a common problem in the early postoperative period and hinders early mobilization, however, there is limited information about factors associated with it. Thus, the main aim of this study was to determine the prevalence and identify factors associated with postoperative orthostatic intolerance.

Method
Hospital based cross-sectional study was conducted from April 08 to July 20, 2022, at University of Gondar comprehensive Specialized Hospital. A semi-structured questionnaire containing sociodemographic variables and perioperative factors related to anesthesia and surgery was used for data collection. The presence of postoperative orthostatic intolerance during the first ambulation was evaluated with a standardized symptom checklist which contains symptoms of orthostatic intolerance. Binary logistic regression analysis was performed to assess factors associated with postoperative orthostatic intolerance. In multivariable regression, variables with P-value < 0.05 were considered statistically significant.

Result
A total of 420 patients were included in this study with a response rate of 99.06%. Postoperative orthostatic intolerance was experienced in 254 (60.5%) participants. Being female (AOR = 2.27; 95% CI = 1.06–4.86), low BMI (AOR = 0.79; 95% CI = 0.71–0.95), ASA II and above (AOR = 3.34; 95% CI = 1.34–8.28), low diastolic blood pressure (AOR = 0.82; 95% CI = 0.88–0.99), general anesthesia (AOR = 3.26, 95% CI = 1.31–8.12), high intraoperative blood lose (AOR = 0.93, 95% CI = 0.88–0.99), high postoperative fluid intake (AOR = 2.09, 95% CI = 1.23–3.55), pain before ambulation (AOR = 1.99, 95% CI = 1.28–3.11) and pain during ambulation (AOR = 1.82, 95% CI = 1.23–2.69) were the significant factors associated with orthostatic intolerance.

Conclusion
Our study revealed that postoperative orthostatic intolerance was experienced in nearly two-thirds of participants. During the time of ambulation, assessing patients for the presence of orthostatic intolerance is necessary to reduce the adverse effects of postoperative OI. In addition, maintaining preoperative normotension, reducing intraoperative blood loss and optimizing postoperative pain control is recommended to reduce the risk of postoperative orthostatic intolerance.