bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in genetic abnormalities, epigenetic reprogramming, and immune landscape of intracranial germ cell tumors
Authors: Zhang Yi , Zhong Chengyi , Ke Xindi , Liu Jifang , Ye Zhang , Lu Lin , Deng Kan , Zhu Huijuan , Yao Yong 
Published: November 2023

AbstractIntracranial germ cell tumors (IGCTs) are a rare subtype of central nervous system neoplasms that predominantly affect young individuals and exhibit a higher incidence in East Asia. IGCTs can be pathologically divided into two main categories: germinomas and non-germinomatous germ cell tumors (NGGCTs). Despite the scarcity of this disease, recent advancements in molecular biology techniques have facilitated the discovery of the inherent genetic and molecular characteristics of IGCTs. Somatic mutations that result in the activation of the KIT/RAS/MAPK and PI3K/AKT/mTOR pathways, chromosomal instability leading to characteristic changes in chromosomal fragments (notably 12p gain), and potentially diagnostic miRNAs (such as miR-371a-3p) may provide valuable insights for the efficient diagnosis, targeted therapy, and prognosis evaluation of IGCTs. Additionally, transcriptomic and methylomic analyses have provided new perspectives on the intrinsic development of IGCTs, further elucidating their equivalence with GCTs at other sites. The evaluation of the tumor immune landscape may guide prognosis prediction and immunotherapy for IGCT patients. Nevertheless, current research still faces challenges such as the absence of basic laboratory research systems, a single source of large sample research data, and a limited overall volume of research. The incorporation of larger sample sizes, the implementation of more innovative evaluation systems, and the employment of novel experimental methods are urgently required to become the focus of future research.
The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies
Authors: Hartinger Stefanie , Hammersen Jakob , Leistner Niklas A. , Lawson McLean Anna , Risse Clemens , Senft Christian , Schütze Stefanie , Heiling Bianka , Schwab Matthias , Mäurer Irina 
Published: November 2023

AbstractA relevant number of cancer patients who receive potentially neurotoxic cytostatic agents develop a chemotherapy-induced peripheral neuropathy over time. Moreover, the increasing use of immunotherapies and targeted agents leads to a raising awareness of treatment-associated peripheral neurotoxicity, e.g., axonal and demyelinating neuropathies such as Guillain–Barré-like syndromes. To date, the differentiation of these phenomena from concurrent neurological co-morbidities or (para-)neoplastic nerve affection as well as their longitudinal monitoring remain challenging. Neuromuscular ultrasound (NMUS) is an established diagnostic tool for peripheral neuropathies. Performed by specialized neurologists, it completes clinical and neurophysiological diagnostics especially in differentiation of axonal and demyelinating neuropathies. No generally approved biomarkers of treatment-induced peripheral neurotoxicity have been established so far. NMUS might significantly extend the repertoire of diagnostic and neuromonitoring methods in this growing patient group in short term. In this article, we present enlargements of the dorsal roots both in cytostatic and in immunotherapy-induced neurotoxicity for the first time. We discuss related literature regarding new integrative applications of NMUS for cancer patients by reference to two representative case studies. Moreover, we demonstrate the integration of NMUS in a diagnostic algorithm for suspected peripheral neurotoxicity independently of a certain cancer treatment regimen emphasizing the emerging potential of NMUS for clinical routine in this interdisciplinary field and prospective clinical trials.
Mild heat treatment in vitro potentiates human adipose stem cells: delayed aging and improved quality for long term culture
Authors: Ryu Chiseon , Lee Minseo , Lee Jae Young 
Published: November 2023

Abstract

Background
Mesenchymal stem cells (MSCs) have gained significant attention for diverse biomedical applications, including cell-based therapy. Hence, in vitro expansion of MSCs is critical; however, in vitro MSC culture, especially long-term culture, inevitably leads to significant loss of stemness, growth, and differentiation potential.

Method
Effects of mild heat treatment (HT) conditions (temperature, duration, and repetition) on the characteristics of adipose tissue-derived MSCs in vitro were systematically investigated. Characteristics of the MSCs subjected to the predetermined HT conditions (41 or 44ºC, 1 h, and 2X HT) were first analyzed in a single passage using various assays. In addition, the feasibility of HT for long-term MSC culture was studied. The RNA sequencing analyses were performed to elucidate the mechanism of HT effects on MSCs.

Results
A comprehensive exploration of various HT conditions revealed that specific mild HT at 41ºC or 44ºC for 1 h upregulated the expression of heat shock proteins and stemness markers and enhanced differentiation potentials. Furthermore, periodic mild HT extended the maintenance of growth rate and stemness of MSCs up to an additional 10 passages, which substantially retarded their spontaneous aging during subsequent in vitro culture. RNA sequencing analyses unveiled that HT downregulated genes associated with aging and apoptosis.

Conclusion
Our study successfully demonstrated that mild HT of MSCs has positive effects on their application in various biomedical fields, enhancing their capabilities and slowing down the aging process.

Graphical Abstract
An evaluation of Mp1p antigen screening for talaromycosis in HIV-infected antiretroviral therapy-naïve population in Guangdong, China
Authors: Gong Dandan , Lin Weiyin , Zhang Huihua , Ou Xu , Li Liya , Guo Pengle , He Yaozu , Liu Cong , Cai Weiping , Tang Xiaoping , Li Linghua 
Published: November 2023

Background
Talaromycosis is one of the most common opportunistic infections in human immunodeficiency virus (HIV) infected patients. However, few researches have explored the prevalence in Southern China and fully assessed the value of the Mp1p antigen screening for the diagnosis of talaromycosis.

Methodology/Principal findings
We performed a cross-sectional study of HIV-infected antiretroviral therapy (ART)-naïve adult patients who were seen in 2018 at Guangzhou Eighth People’s Hospital, Guangzhou Medical University. Serum samples collected from all the 784 enrolled patients were tested for Mp1p antigen using double-antibody sandwich enzyme-linked immunosorbent assay. A culture of pathogen was conducted in 350 clinically suspected patients to confirm talaromycosis. The overall prevalence of talaromycosis based on the Mp1p antigen detection was 11.4% (89/784) and peaked at 32.2% (75/233) in patients with CD4+ ≤50 Nr/μl. Logistic regression analysis found Mp1p antigen positive rate decreased with the increase in CD4+ counts (OR 0.982, 95% CI 0.977–0.987, P<0.01). The optimal cut-off point of the CD4+ count was 50 Nr/μl or less. Among the 350 patients received both fungal culture and Mp1p antigen detection, 95/350 (27.1%) patients were culture-positive for a Talaromyces marneffei, 75/350 (21.4%) patients were Mp1p antigen positive. The Mp1p antigen assay showed a good agreement to the culture of pathogen, and the sensitivity, specificity, positive predictive value, negative predictive value and kappa value was 71.6% (68/95), 97.3% (248/255), 90.7% (68/75), 90.2% (248/275), and 0.737, respectively. The screening accuracy of the Mp1p antigen assay in patients with CD4+ counts of ≤50 Nr/μl was superior to that in those with higher CD4+ counts.

Conclusions/Significance
Mp1p antigen screening can be an effective tool for more efficient diagnosis of Talaromycosis, especially in HIV/AIDS patients with low CD4+ counts. Future validation studies are needed.
The role of direct contact in forming peace-oriented international relations of a divided country: Focusing on the division of the Korean Peninsula
Authors: Shin Hye Cho , Lee Gi-Eun , Choi Seo-Yun , Lee Jang-Han 
Published: November 2023

Background
The division of the Korean peninsula involved many neighbouring countries in the Korean War. The relations with those countries have since been reorganised due to active exchange. This study examined how the quantity and quality of contact with traditional alliance (US and Japan) and strategic partner (China and Russia) countries affected their national images.

Methods
To this end, this study analyzed the relation with the national image by measuring the quantity and quality of contact of an individual with each country. The quantity of contact included an evaluation of the individual’s subjective amount of contact, contact path, and contact status, and the quality of contact was measured as an evaluation for the pleasure, competitiveness, intimacy, spontaneity, and necessity when contacting each country’s culture. A total of 387 participants were divided into two groups based on the presence of direct contact and the quantity and quality of their contact and national images were examined. The participants were followed by a completion of the self-questionnaires including the Culture Experience Questionnaire, National Image Questionnaire, and demographic information questionnaire.

Results
The results of this study are as follow: first, regardless of the type of country, the national image was highly correlated with the degree of subjective contact evaluated by individuals, but there was a weak tendency with contact quality. Second, there was no significant interaction between the country type and contact status for national image, however, different national images for each country were detected. In other word, for contact quantity, contact groups showed more positive national images compared to non-contact groups in Russia, but not Japan, China, and the US. For contact quality, the positive contact experience group showed more positive national images compared to the negative contact experience group, but only in traditional alliance countries.

Conclusion
This study highlights the importance of implementing different strategies for countries to maintain peaceful international relations.
Preloaded combination nicotine replacement therapy for smoking cessation in Kazakhstan: A randomized controlled trial study protocol
Authors: Purushothama Chethan , Crape Byron Lawrence , Stolyarov Valentina , Jaxybayeva Altynshash , la Fleur Philip , Olickal Jeby Jose 
Published: November 2023

Background
Tobacco use is a major cause of premature death and disease in Kazakhstan, with over 22,500 deaths per year. Although efforts have been made to control tobacco use, smoking-related deaths have continued to increase. One strategy to help smokers quit is to use nicotine replacement therapy (NRT), with combination NRT resulting in higher long-term quit rates than a single form of NRT. A study aims to determine the effectiveness of preloaded combination NRT on smoking cessation, the change in health-related quality of life due to smoking cessation, and explore treatment adherence perceptions.

Methods and analysis
The study will be conducted as a randomized, single-blind superiority trial, with 100 participants in each arm. The trial will be carried out at the National Research Cardiac Surgery Center, Astana, Kazakhstan, and will recruit current smokers aged 18 years and above with a motivation to quit. Participants will be randomly allocated to either the intervention group or the control group. The former will receive preloaded combination NRT, while the latter will receive fast-acting NRT alone. The primary outcome measure will be sustained abstinence from smoking after six months. Secondary outcome measures will include health-related quality of life and adherence to the treatment.

Discussion
The study may gather further evidence that a combination NRT is more efficient than a fast-acting NRT alone. The findings of this study may help to improve tobacco cessation strategies in Kazakhstan and other countries with high smoking prevalence rates.

Trial registration number
NCT05484505.
Delivery of a novel intervention to facilitate liberation from mechanical ventilation in paediatric intensive care: A process evaluation
Authors: Jordan Joanne , Tume Lyvonne , Clarke Mike , McAuley Danny , McDowell Cliona , McIlmurray Lisa , Morris Kevin , Peters Mark , Walsh Timothy , Blackwood Bronagh 
Published: November 2023

Background
Prolonged mechanical ventilation increases the risk of mortality and morbidity. Optimising sedation and early testing for possible liberation from invasive mechanical ventilation (IMV) has been shown to reduce time on the ventilator. Alongside a multicentre trial of sedation and ventilation weaning, we conducted a mixed method process evaluation to understand how the intervention content and delivery was linked to trial outcomes.

Methods
10,495 children admitted to 18 paediatric intensive care units (ICUs) in the United Kingdom participated in a stepped-wedge, cluster randomised controlled trial, with 1955 clinical staff trained to deliver the intervention. The intervention comprised assessment and optimisation of sedation levels, and bedside screening of respiratory parameters to indicate readiness for a spontaneous breathing trial prior to liberation from ventilation. 193 clinical staff were interviewed towards the end of the trial. Interview data were thematically analysed, and quantitative adherence data were analysed using descriptive statistics.

Results
The intervention led to a reduced duration of IMV (adjusted median difference– 7.1 hours, 95% CI -9.6 to -5.3, p = 0.01). Overall intervention adherence was 75% (range 59–85%). Ease and flexibility of the intervention promoted it use; designated responsibilities, explicit pathways of decision-making and a shared language for communication fostered proactivity and consistency towards extubation. Delivery of the intervention was hindered by established hospital and unit organisational and patient care routines, clinician preference and absence of clinical leadership.

Conclusions
The SANDWICH trial showed a significant, although small, reduction in duration of IMV. Findings suggest that greater direction in decision-making pathways, robust embedment of new practice in unit routine, and capitalising on the skills of Advanced Nurse Practitioners and physiotherapists would have contributed to greater intervention effect.

Trial registration
isrctn.org Identifier: ISRCTN16998143.
Economic burden of Thalassemia treatment: An analysis from the Vietnam Social Security perspective
Authors: Nhac-Vu Hoang-Thy , Tran Van Thi-Ngoc , Nguyen Trong-Duy-Thuc , Pham Vu-Thanh , Le Tho 
Published: November 2023

Objectives
Thalassemia is a genetic disorder that significantly impacts the health and well-being of individuals in Vietnam. This study aimed to assess the economic burden of Thalassemia treatment in Lam-Dong Province from the perspective of the Vietnam Social Security and to develop a model to forecast these costs.

Methods
This study analyzed the medical records of all 288 health-insured Thalassemia patients who received treatment in Lam-Dong Province from 2019–2021. The annual economic burden was calculated as the total direct medical cost of treatment per patient over one year. Bayesian Model Averaging (BMA) was utilized to forecast economic burdens. The best fit model was selected based on evaluation criteria including the R2 value, the Bayesian information criterion (BIC), and posterior model probabilities.

Results
The study found that the average annual economic burden of Thalassemia treatment was VND 9,947,000 (±6,854,000), equivalent to approximately USD 426.7 (±294.0), with blood transfusions being the main contributor to costs (63%). Using BMA, the best fit model to forecast economic burdens included variables including patient age, sex, and length of hospitalization, with age being the key factor with the greatest impact on the increase in economic burden.

Conclusion
These findings provided important information for policymakers in Vietnam, as they highlighted the significant economic burden of Thalassemia treatment in the country. By developing a model to forecast these costs, policymakers can make informed decisions on how to allocate resources and support individuals with Thalassemia and their families.
Real world treatment sequences and outcomes for metastatic renal cell carcinoma
Authors: Lai Gu-Shun , Li Jian-Ri , Wang Shian-Shiang , Chen Chuan-Shu , Yang Chun-Kuang , Lin Chia-Yen , Hung Sheng-Chun , Chiu Kun-Yuan , Yang Shun-Fa 
Published: November 2023

Objectives
The treatment landscape for metastatic renal cell carcinoma changed a lot in the last few years. This study aimed to assess the treatment sequences and outcomes for metastatic renal cell carcinoma in a real-world setting.

Materials and methods
We enrolled patients with metastatic renal cell carcinomawho received first-line systemic treatment with tyrosin kinase inhibitors monotherapy, ipilimumab plus nivolumab, or pembrolizumab plus axitinibbetween January2009 and May 2023 on the database of TriNetX network. Overall survival, time on treatment and time to next treatment were evaluated using Kaplan-Meiermethod.

Results
Totally, 4183 received tyrosine kinase inhibitor monotherapy, 1555 received ipilimumab plus nivolumab, and 559 received axitinib plus pembrolizumab. Median time on treatment was 2.5 months for the tyrosine kinase inhibitor monotherapy cohort, 5.4 months for the ipilimumab plus nivolumab cohort, and 8.3 months for the pembrolizumab plus axitinib cohort. Median time to next treatment was 16.6 months for both the tyrosine kinase inhibitor monotherapy and ipilimumab plus nivolumab cohorts, and 22.1 months for the pembrolizumab plus axitinib cohort. Median overall survival was 42.2 months for the tyrosine kinase inhibitor monotherapy cohort, 39.7monthsfor the ipilimumab plus nivolumab cohort, and not reached for the pembrolizumab plus axitinib cohort. In comparison with the tyrosine kinase inhibitor monotherapy cohort, patients in the pembrolizumab plus axitinib cohort showed survival benefit (log-rank p = 0.0168) in overall survival, but not the case in the ipilimumab plus nivolumab cohort.

Conclusion
There was a trend toward using first-line immuno-oncology based therapy for patients with metastatic renal cell carcinoma in a real-world practice. Axitinib plus pembrolizumuab cohort had survival benefits over tyrosine kinase inhibitor and ipilimumab plus nivolumab cohorts, while patients in the ipilimumab plus nivolumab cohort had more distant metastases and comorbidities.
12-month substance use disorders among first-year university students in Kenya
Authors: Jaguga Florence , Mathai Muthoni , Ayuya Caroline , Francisca Ongecha , Musyoka Catherine Mawia , Shah Jasmit , Atwoli Lukoye 
Published: November 2023

Objectives
The period of entry into university represents one of vulnerability to substance use for university students. The goal of this study is to document the 12-month prevalence of substance use disorders among first year university students in Kenya, and to test whether there is an association between substance use disorders and mental disorders.

Methods
This was a cross-sectional online survey conducted in 2019 and 2020 as part of the World Health Organization’s World Mental Health International College Student (WMH-ICS) survey initiative. A total of 334 university students completed the survey. Descriptive statistics were used to summarize the demographic characteristics of the participants. Multivariate logistic regression was used to assess the association between substance use disorder and mental disorders after adjusting for age and gender.

Results
The 12-month prevalence for alcohol use disorder was 3.3%, while the 12-month prevalence for other substance use disorder was 6.9%. Adjusting for age and gender, there was an association between any substance use disorder and major depression, generalized anxiety disorder, bipolar 1 disorder, intermittent explosive disorder, social anxiety disorder, suicidal ideation, suicide attempt, and non-suicidal self-injury.

Conclusion
These findings highlight the need to institute policies and interventions in universities in Kenya that address substance use disorders and comorbid mental disorders among first-year students.
Comparing adverse maternal and perinatal outcomes in primary caesarean delivery during first versus second-stage of labour in Kenya: An institution-based cohort study
Authors: Omwodo Kimbley Asaso , Were Edwin 
Published: November 2023

Background
As caesarean delivery rates continue to increase globally, so are the number of second-stage caesarean deliveries. Second-stage caesareans may carry additional risk of complications for both the mother and fetus owing to fetal head impaction into the maternal pelvis and manipulations required for delivery. So far, data on this procedure’s outcomes from low resource countries are limited.

Objectives
To compare adverse maternal and perinatal outcomes between second-stage and first-stage of labour intrapartum primary caesarean deliveries over 12 months at a tertiary referral obstetric hospital in Kenya.

Methods
In a hospital-based cohort study, 222 women with singleton, cephalic presenting fetuses at term gestation who had intrapartum primary caesarean delivery during active labour were recruited post-partum. Second-stage caesarean deliveries (73) were compared to 149 first-stage caesarean deliveries. The proportion of caesarean deliveries in the second-stage of labour was estimated and the adverse maternal and perinatal outcomes were compared. The study was conducted from August 2021 to July 2022 at the Moi Teaching and Referral Hospital, Eldoret.

Results
The proportion of second-stage caesarean deliveries among intrapartum primary caesarean deliveries was 4.3% [95% CI: 2.9% - 4.7%]. Compared to first-stage caesarean deliveries, second-stage caesarean deliveries had a significantly higher risk of adverse maternal outcomes (RR 3.272, 95% CI 2.28–4.71, P < 0.001), including intraoperative trauma, atony, blood transfusion, and a postoperative hospital stay of more than three days. Additionally, there was a higher risk of adverse perinatal outcomes (RR 2.748, 95% CI 2.45–4.50, P < 0.001), including increased risk of a 5-min APGAR ≤3, admission to NBU, and neonatal death.

Conclusions
An increased risk of adverse maternal and perinatal outcomes is associated with primary second-stage caesarean deliveries compared to primary first-stage caesarean deliveries.