bluuebunny/crossref_metadata_2025_split huggingface dataset:
It needs more than a myocardial infarction to start exercising: the CoLaus|PsyCoLaus prospective study
Authors: Flammer François , Paraschiv-Ionescu Anisoara , Marques-Vidal Pedro 
Published: February 2024

Abstract
Background
Increased physical activity (PA) is recommended after an acute coronary event to prevent recurrences. Whether patients with acute coronary event actually increase their PA has not been assessed using objective methods such as accelerometer. We aimed to assess the subjectively and objectively measured physical activity (PA) levels of patients before and after an acute coronary event.

Methods
Data from the three follow-up surveys of a prospective study conducted in Lausanne, Switzerland. Self-reported PA was assessed by questionnaire in the first (2009–2012) and second (2014–2017) follow-ups. Objective PA was assessed by a wrist-worn accelerometer in the second and third (2018–2021) follow-ups. Participants who developed an acute coronary event between each survey period were considered as eligible. PA levels were compared before and after the event, and changes in PA levels were also compared between participants who developed an acute event with three gender and age-matched healthy controls.

Results
For self-reported PA, data from 43 patients (12 women, 64 ± 9 years) were used. No differences were found for all PA levels expressed in minutes/day before and after the event: moderate PA, median and [interquartile range] 167 [104–250] vs. 153 [109–240]; light PA: 151 [77–259] vs. 166 [126–222], and sedentary behaviour: 513 [450–635] vs. 535 [465–642] minutes/day. Comparison with gender- and age-matched healthy controls showed no differences regarding trends in reported PA. For accelerometer-assessed PA, data from 32 patients (16 women, 66 ± 9 years) were used. No differences were found for all PA levels expressed in minutes/day before and after the event: moderate PA: 159 [113–189] vs. 141 [111–189]; light PA: 95.8 [79–113] vs. 95.9 [79–117], and sedentary behaviour: 610 [545–659] vs. 602 [540–624]. Regarding the comparison with gender- and age-matched healthy controls, controls had an increase in accelerometer-assessed sedentary behaviour as % of day: multivariable adjusted average standard error 2.7 ± 0.6, while no increase was found for cases: 0.1 ± 1.1; no differences were found for the other PA levels.

Conclusion
Patients do not seem to change their PA levels after a first coronary event. Our results should be confirmed in larger samples.
Coronary artery disease incidence, risk factors, awareness, and medication utilization in a 10-year cohort study
Authors: Sarebanhassanabadi Mohammadtaghi , Mirjalili Seyed Reza , Marques-Vidal Pedro , Kraemer Alexander , Namayandeh Seyedeh Mahdieh 
Published: February 2024

Abstract
Background
There is a substantial disparity in coronary artery disease (CAD) burden between Iran and other nations that place a strong emphasis on the assessment of CAD risk factors and individuals’ awareness and ability to control them.

Methods
Two thousand participants of a community-based Iranian population aged 20–74 years were investigated with a mean follow-up of 9.9 years (range: 7.6 to 12.2). An analysis of Cox regression was conducted to determine the association between CAD development and classic risk factors such as age, sex, smoking, physical activity, education, obesity, dyslipidemia, hypertension, and diabetes mellitus. Furthermore, we computed the population attributable fraction for these risk factors.

Results
After a follow-up period of nearly 10 years, 225 CAD events were reported, constituting 14.5% of the overall incidence. Nighty three percent of participants had more than one risk factor. Age was the most predictive risk factor, with a hazard ratio (HR) and confidence interval (CI) of 5.56 (3.87–7.97, p < 0.001) in men older than 45 and females older than 55 compared to lower ages. In comparison to females, males had an HR of 1.45 (CI: 1.11–1.90, p value = 0.006) for developing CAD. Nearly 80% of the patients had dyslipidemia, with a hazard ratio of 2.19 (CI: 1.40–3.44, p = 0.01). Among the participants, 28.9% had hypertension, and 52% had prehypertension, which had HRs of 4.1 (2.4–7.2, p < 0.001) and 2.4 (1.4–4.2, p < 0.001), respectively. Diabetes, with a prevalence of 17%, had an HR of 2.63 (CI: 2 -3.47, p < 0.001), but prediabetes was not significantly associated with CAD. Awareness of diabetes, dyslipidemia, and hypertension was 81%, 27.9%, and 48.1%, respectively. Regarding medication usage, the corresponding percentages were 51% for diabetes, 13.2% for dyslipidemia, and 41% for hypertension.

Conclusions
Compared to previous studies in Iran and neighboring countries, the current study found a higher incidence of CAD, more prevalent risk factors, and a lower awareness and ability to control these risk factors. Thus, an effective preventive strategy is needed to reduce the CAD burden in Iran.
Psychologists’ involvement in and experiences of treating patients with stress-related exhaustion in primary care
Authors: Ellbin Susanne , Lindegård Agneta , Jonsdottir Ingibjörg H. , Dahlborg Elisabeth 
Published: February 2024

Abstract
Background
Primary health care is the setting for most patients with stress-related mental health problems. Good care processes are important for patients with stress-related mental health problems and the complex needs of these patients has become a challenge for primary care settings which is traditionally designed to manage acute episodes of one illness. The care process of these patients is thus interesting to investigate. The aim of this study was to explore psychologists´ involvement and experiences regarding the organisation of the care process and treatment of patients seeking care for stress-related exhaustion.

Method
Fifteen psychologists (14 women and 1 man, age range 27–72 years)c from fifteen different primary health care centres in the western part of Sweden, located in both rural and urban areas were included. Qualitative content analysis of individual semi-structured interviews was conducted.

Results
The analysis resulted in eight subcategories within the two main categories studied illuminating psychologists’ involvement and experiences regarding the organisation of the care process and challenges regarding treatment of patients seeking care for stress-related exhaustion.

Conclusion
The care process of patients with stress-related exhaustion is perceived to be ineffective and not congruent with the needs of the patients. A lack of holistic overview of the care process, a lack of collaboration and poor utilization of the health care professionals’ competence leads to an unstructured process forcing the patients to be the carriers and coordinators of their own care.
Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples
Authors: Dehghani Ali , Khajepour Fardin , Dehghani Mohammad , Razmara Ehsan , Zangouey Mohammadreza , Abadi Maryam Fekri Soofi , Nezhad Reza Bahram Abadi , Dabiri Shahriar , Garshasbi Masoud 
Published: February 2024

AbstractBackgroundThe human papillomavirus (HPV) infection may affect the miRNA expression pattern during cervical cancer (CC) development. To demonstrate the association between high-risk HPVs and the development of cervix dysplasia, we examined the expression patterns of hsa-miR-194-5p and hsa-miR-195-5p in Pap smear samples from southeast Iranian women. We compared samples that were HPV-positive but showed no abnormality in the cytological examination to samples that were HPV-positive and had severe dysplasia.MethodsPap smear samples were obtained from 60 HPV-positive (HPV-16/18) patients with histologically confirmed severe dysplasia (cervical intra-epithelial neoplasia (CIN 3) or carcinoma in situ) and the normal cytology group. The expression of hsa-miR-194-5p and hsa-miR-195-5p was analyzed by real-time quantitative PCR, using specific stem-loop primers and U6 snRNA as the internal reference gene. Clinicopathological features were associated with miRNA expression levels. Furthermore, functional enrichment analysis was conducted using in silico tools. The Kaplan–Meier survival method was also obtained to discriminate survival-significant candidate miRNAs in CC, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value.ResultsCompared to HPV-positive cytologically normal Pap smear samples, hsa-miR-194-5p and hsa-miR-195-5p relative expression decreased significantly in HPV-positive patients with a severe dysplasia Pap smear. Kaplan–Meier analysis indicated a significant association between the miR-194 decrease and poor CC survival. In essence, ROC curve analysis showed that miR-194-5p and miR-195-5p could serve as valuable markers for the development of cervix dysplasia in individuals who are positive for high-risk HPVs.ConclusionsThis study revealed that hsa-miR-194-5p and hsa-miR-195-5p may possess tumor suppressor capabilities in the context of cervical dysplasia progression. However, it remains uncertain whether these microRNAs are implicated in the transition of patients with high dysplasia to cervical cancer. We also showed the potential capability of candidate miRNAs as novel diagnostic biomarkers related to cervical dysplasia progression.
In vivo PET of synaptic density as potential diagnostic marker for cognitive disorders: prospective comparison with current imaging markers for neuronal dysfunction and relation to symptomatology - study protocol
Authors: Vanderlinden Greet , Carron Charles , Vandenberghe Rik , Vandenbulcke Mathieu , Van Laere Koen 
Published: February 2024

Abstract
Background
18F-FDG brain PET is clinically used for differential diagnosis in cognitive dysfunction of unclear etiology and for exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. 18F-FDG PET measures regional glucose metabolism, which represents a combination of neuronal/synaptic activity but also astrocytic activity and neuroinflammation. Recently, imaging of synaptic vesicle protein 2 A (SV2A) has become available and was shown to be a proxy of synaptic density. This prospective study will investigate the use of 18F-SynVesT-1 for imaging SV2A and its discriminative power for differential diagnosis in cognitive disorders in a head-to-head comparison to 18F-FDG PET. In addition, simultaneous PET/MR allows an evaluation of contributing factors and the additional value of advanced MRI imaging to FDG/SV2A PET imaging will be investigated. In this work, the study design and protocol are depicted.

Methods
In this prospective, multimodal imaging study, 110 patients with uncertain diagnosis of cognitive impairment who are referred for 18F-FDG PET brain imaging in their diagnostic work-up in a tertiary memory clinic will be recruited. In addition, 40 healthy volunteers (HV) between 18 and 85 years (M/F) will be included. All study participants will undergo simultaneous 18F-SynVesT-1 PET/MR and an extensive neuropsychological evaluation. Amyloid status will be measured by PET using 18FNAV4694, in HV above 50 years of age. Structural T1-weighted and T2-weighted fluid-attenuated inversion recovery MR images, triple-tagging arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI) will be obtained. The study has been registered on ClinicalTrials.gov (NCT05384353) and is approved by the local Research Ethics Committee.

Discussion
The main endpoint of the study will be the comparison of the diagnostic accuracy between 18F-SynVesT-1 and 18F-FDG PET in cognitive disorders with uncertain etiology and in exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. The strength of the relationship between cognition and imaging data will be assessed, as well as the potential incremental diagnostic value of including MR volumetry, ASL perfusion and rs-fMRI.
Identification and characterization of stromal-like cells with CD207+/low CD1a+/low phenotype derived from histiocytic lesions – a perspective in vitro model for drug testing
Authors: Śmieszek Agnieszka , Marcinkowska Klaudia , Małas Zofia , Sikora Mateusz , Kępska Martyna , Nowakowska Beata A. , Deperas Marta , Smyk Marta , Rodriguez-Galindo Carlos , Raciborska Anna 
Published: February 2024

Abstract
Background
Histiocytoses are rare disorders manifested by increased proliferation of pathogenic myeloid cells sharing histological features with macrophages or dendritic cells and accumulating in various organs, i.a., bone and skin. Pre-clinical in vitro models that could be used to determine molecular pathways of the disease are limited, hence research on histiocytoses is challenging. The current study compares cytophysiological features of progenitor, stromal-like cells derived from histiocytic lesions (sl-pHCs) of three pediatric patients with different histiocytoses types and outcomes. The characterized cells may find potential applications in drug testing.

Methods
Molecular phenotype of the cells, i.e. expression of CD1a and CD207 (langerin), was determined using flow cytometry. Cytogenetic analysis included GTG-banded metaphases and microarray (aCGH) evaluation. Furthermore, the morphology and ultrastructure of cells were evaluated using a confocal and scanning electron microscope. The microphotographs from the confocal imaging were used to reconstruct the mitochondrial network and its morphology. Basic cytophysiological parameters, such as viability, mitochondrial activity, and proliferation, were analyzed using multiple cellular assays, including Annexin V/7-AAD staining, mitopotential analysis, BrdU test, clonogenicity analysis, and distribution of cells within the cell cycle. Biomarkers potentially associated with histiocytoses progression were determined using RT-qPCR at mRNA, miRNA and lncRNA levels. Intracellular accumulation of histiocytosis-specific proteins was detected with Western blot. Cytotoxicyty and IC50 of vemurafenib and trametinib were determined with MTS assay.

Results
Obtained cellular models, i.e. RAB-1, HAN-1, and CHR-1, are heterogenic in terms of molecular phenotype and morphology. The cells express CD1a/CD207 markers characteristic for dendritic cells, but also show intracellular accumulation of markers characteristic for cells of mesenchymal origin, i.e. vimentin (VIM) and osteopontin (OPN). In subsequent cultures, cells remain viable and metabolically active, and the mitochondrial network is well developed, with some distinctive morphotypes noted in each cell line. Cell-specific transcriptome profile was noted, providing information on potential new biomarkers (non-coding RNAs) with diagnostic and prognostic features. The cells showed different sensitivity to vemurafenib and trametinib.

Conclusion
Obtained and characterized cellular models of stromal-like cells derived from histiocytic lesions can be used for studies on histiocytosis biology and drug testing.
Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis
Authors: Taherifard Erfan , Bakhtiar Muhammad , Mahnoor Mahnoor , Ahmed Rabeea , Cavalcante Ludimila , Zhang Janie , Saeed Anwaar 
Published: February 2024

Abstract
Background
Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET.

Methods
Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs).

Results
A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities.

Conclusions
In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).

Graphical Abstract
High expression of TBRG4 in relation to unfavorable outcome and cell ferroptosis in hepatocellular carcinoma
Authors: Tao Shanchun , Cui Di , Cheng Huimin , Liu Xiaofei , Jiang Zhaobin , Chen Hongwei , Gao Yong 
Published: February 2024

Abstract
Background
Hepatocellular carcinoma (HCC) is the most common type of malignant liver tumor with poor prognosis. In this study, we investigated the expression of transforming growth factor beta regulator 4 (TBRG4) in HCC and its effects on the proliferation, invasion, and metastasis of HCC cells, and analyzed the possible molecular mechanisms.

Method
Downloading the expression and clinical information of HCC samples in the TCGA database, analyzing the expression differences of TBRG4 by bioinformatics methods, analyzing the clinical relevance and prognostic significance. Performing GO, KEGG and GSEA enrichment analysis on the TBRG4-related gene set in patient HCC tissues. Applying cell counting, scratch test and Transwell experiment to study the biological function of TBRG4 in HCC. Mitochondrial membrane potential, apoptosis and ROS levels were evaluated to assess cell iron death. Western blot, RT-PCR, laser confocal microscopy and co-immunoprecipitation were used to detect and analyze the downstream signaling pathways and interacting molecules of TBRG4.

Results
Bioinformatics analysis revealed that TBRG4 was abnormally highly expressed in HCC tumor tissues and was associated with poor prognosis and metastasis in HCC patients. GO and KEGG functional enrichment analysis showed that TBRG4 was related to oxidative stress and NADH dehydrogenase (ubiquinone) activity. GSEA enrichment analysis showed that TBRG4 was associated with Beta catenin independent wnt signaling and B cell receptor. Functional experiments confirmed that knocking down TBRG4 could inhibit the proliferation, migration, and invasion of HCC cells. Mechanistically, TBRG4 inhibited the function of HCC cells through the DDX56/p-AKT/GSK3β signaling pathway. In addition, interference with TBRG4 expression could reduce the mitochondrial membrane potential and accumulate ROS in HCC cells, leading to increased ferroptosis. Co-IP analysis showed that TBRG4 specifically bound to Beclin1.

Conclusion
TBRG4 is highly expressed in HCC tumor tissues and is associated with poor prognosis. It may regulate the proliferation, invasion, and metastasis of HCC cells through the DDX56/p-AKT/GSK3β signaling pathway. TBRG4 may interact with Beclin1 to regulate the ferroptosis of HCC cells.
Inflammatory markers predict survival in patients with postoperative urothelial carcinoma receiving tislelizumab (PD-1 inhibitor) adjuvant therapy
Authors: Yang Meng , Zhang Jingwen , Wei Dongqun , Yu Tianyi , Chen Zeyu , Liu Xin , Zhu Haitao 
Published: February 2024

Abstract
Background
In the management of urothelial carcinoma, patient selection for immunotherapy, particularly with immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1), is important for treatment efficacy. Inflammatory markers are useful for predicting treatment outcomes and immune-related adverse events (irAEs). This study aims to retrospectively explore the associations between inflammatory markers and outcomes in patients with postoperative urothelial carcinoma undergoing tislelizumab (PD-1 inhibitor) adjuvant therapy.

Methods
A retrospective analysis was conducted on 133 patients with postoperative urothelial carcinoma who received tislelizumab adjuvant therapy at the Affiliated Hospital of Xuzhou Medical University from April 2020 to August 2023. The prognostic effects of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) on disease-free survival (DFS) and overall survival (OS) were assessed using Cox regression models. The correlation between inflammatory markers and the onset of irAEs was analyzed using logistic regression models.

Results
NLR < 5 and MLR < 0.31 were significantly associated with better outcomes compared to NLR >5 and MLR >0.31, respectively. Multivariate analysis revealed that an NLR < 5 was independently associated with better DFS and OS. However, there was no significant effect on the DFS and OS between PLR < 135 and PLR >135. Patients who experienced irAEs had longer DFS and OS. Multivariate analysis demonstrated that irAEs were an independent prognostic risk factor for DFS and OS. There was no significant difference in the occurrence of irAEs among different NLR, PLR, and MLR groups.

Conclusion
In patients with postoperative urothelial carcinoma receiving tislelizumab adjuvant therapy, the assessment of NLR and MLR before treatment may serve as valuable predictive markers of clinical outcome.
Non-pharmacological interventions for delirium in the pediatric population: a systematic review with narrative synthesis
Authors: Kim Kyua , Jeong Ju Hee , Choi Eun Kyoung 
Published: February 2024

Abstract
Background
Delirium is a serious complication experienced by hospitalized children. Therefore, preventive management strategies are recommended for these patients. However, comprehensive analyses of delirium interventions in children remain insufficient. Specifically, this systematic review aimed to summarize non-pharmacological interventions for pediatric delirium, addressing the urgent need for a comprehensive understanding of effective strategies. We also explored frequently measured outcome variables to contribute evidence for future research on delirium outcomes in children.

Methods
This systematic review searched articles from PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Excerpta Medica databases. The eligibility criteria were formed under the population, intervention, comparator, outcome, and study design framework. Studies were included if they involved (1) children aged under 18 years receiving hospital care, (2) non-pharmacological delirium interventions, (3) comparators involving no intervention or pharmacological delirium interventions, and (4) outcomes measuring the effectiveness of non-pharmacological delirium interventions. Only peer-reviewed articles published in English were included.

Results
Overall, 16 studies were analyzed; of them, 9 assessed non-pharmacological interventions for emergence delirium and 7 assessed interventions for pediatric delirium. The intervention types were grouped as follows: educational (n = 5), multicomponent (n = 6), and technology-assisted (n = 5). Along with pediatric and emergence delirium, the most frequently measured outcome variables were pain, patient anxiety, parental anxiety, pediatric intensive care unit length of stay, agitation, analgesic consumption, and postoperative maladaptive behavior.

Conclusions
Non-pharmacological interventions for children are effective treatments without associated complications. However, determining the most effective non-pharmacological delirium intervention for hospitalized children based on current data remains challenging.