bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health problems among disaster responders to the 2023 Turkey-Syria earthquake: a cross-sectional study
Authors: Hugelius Karin , Murphy Jason , Blomberg Karin 
Published: December 2024

Abstract
Objective
The aim of this study was to describe perceived health problems among disaster responders after the earthquake in eastern Turkey/Syria in February 2023.

Methods
A non-probability cross-sectional study was conducted using an online survey.

Results
A total of 525 local (18%) and international disaster responders (81%) participated in the study. Of these responders, 46% reported physical or mental health problems during or after their deployment, 15% required medical care during the mission, and 7% required medical evacuation. The most common health problems during the field mission were feeling scared or unsafe, sleeping problems, and headache. After the mission, fatigue, sleeping problems, and feeling depressed were the most frequently reported health problems. The local responders perceived significantly more health problems than did the international responders. Approximately 11% of the participants could not return to their ordinary work after deployment because of infections or mental health issues.

Conclusions
Physical and mental health problems are commonly perceived by disaster responders and may reduce the effectiveness of disaster response. Raising awareness of health risks among disaster response workers and employers is essential to ensure proper duty of care and should include reparations and medical support during and after disaster response operations.
The feasibility of integrating an alcohol screening clinical decision support tool into primary care clinical software: a review and Australian key stakeholder study
Authors: Canaway Rachel , Dai Libby , Hallinan Christine , Caddy Cassandra , Hegarty Kelsey , Boyle Douglas 
Published: December 2024

Abstract
Background
This study explored the feasibility of integrating a clinical decision support tool into general practice clinical management software in Australia to prompt for alcohol screening among patients who are pregnant or planning a pregnancy. The study aimed to increase understanding of what is an appropriate and acceptable clinical decision support tool, the circumstances when a prompt to use such a screening tool should occur, and the barriers and enablers of successful implementation.

Methods
This feasibility study employed a mixed methods approach and purposive sampling to identify key stakeholders to interview. Participants included vendors of clinical software used in Australian general practice, clinicians in general practice, and relevant others. Data from a literature review and 23 interviews were analysed leading to recommendations which were ‘sense-tested’ by an additional 22 stakeholders.

Results
Although there are at least 18 clinical software packages used in Australian general practice, it is feasible to integrate an alcohol screening tool for pregnancy into software for the majority of general practices in Australia. The AUDIT-C alcohol screening tool for pregnancy was widely accepted as suitable for such a purpose. Clinicians suggested the greatest barriers to screening were lack of time within antenatal consultations and insufficient remuneration for longer consultations. Many clinicians saw opportunity for introducing a multifunctional antenatal tool that could incorporate screening and clinical decision support for alcohol, tobacco and other substance use, mental health, domestic and family violence and potentially other areas informing healthy pregnancy. It could also be used opportunistically for preconception screening and counselling. Deployment of the tool could be supported by an education campaign from professional associations.

Conclusion
The integration of a tool for screening for alcohol use among women who are pregnant or planning pregnancy into general practice clinical software is feasible; however, a multifunctional antenatal screening tool, incorporating other psychosocial elements, was considered more useful than a stand-alone alcohol screening tool. Codesign is needed with vendors and end-users to develop an acceptable tool that can be widely implemented. Issues with GP renumeration need also to be addressed to encourage alcohol screening pre-pregnancy and in the early months of pregnancy.
Prognostic effect of immunohistochemically determined molecular subtypes in gastric cancer
Authors: Brodkin Jefim , Kaprio Tuomas , Hagström Jaana , Leppä Alli , Kokkola Arto , Haglund Caj , Böckelman Camilla 
Published: December 2024

Abstract
Introduction
Gastric cancer is the fifth most common cancer worldwide and the fourth most common cause of cancer-related death. Two molecular subtyping classifications were recently introduced: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications.

Methods
We classified a cohort of 283 gastric cancer patients undergoing surgery at Helsinki University Hospital between 2000 and 2009. We constructed a tumour tissue microarray immunostained for the following markers: microsatellite instability (MSI) markers MSH2, MSH6, MLH1, and PMS2; p53; E-cadherin; and EBERISH.

Results
In the univariate survival analysis for disease-specific survival, the Epstein–Barr virus (EBV) -positive subtype exhibited the worst prognosis with a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.19–5.25, p = 0.016) compared with the most benign subtype, chromosomal instability (CIN). Using TCGA’s classification, the genetically stable (GS) and MSI subtypes exhibited a worse survival compared with CIN (HR 1.73 [95% CI 1.15–2.60], p = 0.009 and HR 1.74 [95% CI 1.06–2.84], p = 0.027, respectively). Using the ACRG classification, the p53 aberrant subtype exhibited the best prognosis, whereas wild-type p53, MSI, and the epithelial–mesenchymal transition (EMT) subtypes exhibited poorer prognoses (EMT: HR 1.90 [95% CI 1.30–2.77], p < 0.001) when compared with aberrant p53.

Conclusions
Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. However, our study did not find that either molecular subtyping performed better than the other classification. Thus, further development of the most optimal grouping of different molecular subtypes is still needed.
What is it all about? An explorative study of patients’ experiences with medication free treatment
Authors: Reitan Elisabeth C. Klæbo , Riley Henriette , Iversen Valentina C. , Høye Anne 
Published: December 2024

Abstract
Background
As a response to the political decision by the Norwegian Ministry of Health and Care Services to establish some kind of “medication free treatment” for patients with severe mental illness throughout the country, a 6-bed ward unit dedicated to offer such treatment was in 2017 established in Tromsø, Norway by the North Norway Health Care Region. The aim of the present study was to explore the experiences of patients admitted to this ward unit.

Method
Semi-structured interviews were conducted with 19 persons who had received treatment from the ward during the period January 2017 to October 2021. Analysis was done in line with Systematic Text Condensation and interviews were recorded, transcribed and analyzed using software NVivo.

Results
The importance of engaging in a dialogue about the possibilities of living a life without medication was unanimously validated, along with a focus on empowerment, motivation, activity and flexibility. Not everyone reported fulfillment of their own wishes or the ward’s goal of tapering down, and reflected upon emotions such as ambivalence or fear. Three core concepts were identified to describe the participants’ experiences: 1) Tapering off, 2) Relations, and 3) Frames and content. A fourth concept overarches the process formed by these concepts; 4) Processes across categories.

Conclusion
The study contributes to a deeper understanding of what "medication free" truly means, going beyond simply taking or not taking medications. It adds nuance to the debate surrounding medication free treatment. The ability to taper off medications is linked to intrapersonal factors, such as readiness and personal commitment, as well as the therapeutic environment, including the frames and values present on the ward. "Medication free" is more complex than it may initially appear, as many participants continue to use some form of psychotropic drugs. The sense of being part of something new and "exclusive" can be understood in light of what participants felt was lacking in previous treatment. It appears to be a need of rediscovering the significance of empowerment and empathic relationships in treatment of severe mental illness, in order to foster a sense of coherence and meaning.
All-cancer incidence and mortality in Pakistanis, Bangladeshis, and their descendants in England and Wales
Authors: Harrison Joseph , Sullivan Frank , Keenan Katherine , Kulu Hill 
Published: December 2024

Abstract
Background
This paper identifies differences in all-cancer incidence and mortality between Pakistani-born (PB), Bangladeshi-born (BB), their descendants, and the White British (WB) in England and Wales. Pakistanis and Bangladeshis are the most marginalised and disadvantaged groups in England and Wales yet, are found to have low cancer mortality and low all-cause mortality. Previous studies though have not looked at generational differences, applied individual-level data nor separated Pakistanis and Bangladeshis from each other and other Asian groups.

Methods
We use the Office for National Statistics Longitudinal Study of England and Wales which is a 1% representative sample of the population. We apply event history analysis on a study period from 1971 to 2016, following individuals from age 20 until a first cancer incidence, censoring at emigration or death. We observe 10,885,500 person-years and 71,926 cancer incidences for WB; 125,700 person-years and 295 events for PB; 53,900 person-years and 113 events for BB and 26,900 person-years and 24 events for descendants. Following incidence, we study a maximum of ten years until a death from cancer, or censoring. In this second analysis on mortality our sample has 329,700 person-years and 31,689 cancer deaths for WB; 1,200 person-years and 104 events for PB; 400 person-years and 50 events for BB and 100 person-years and 10 events for descendants.

Results
Results from the fully adjusted models show that the risk of cancer incidence is lower for PB, BB and descendants compared to the WB native group. Estimated hazard ratio (HR) equals 0.42 for PB (95% confidence interval (CI): 0.38–0.47), for BB HR is 0.38 (CI: 0.32–0.46) and, for descendants HR is 0.36 (CI: 0.24–0.54). Results for cancer mortality after incidence show HR for PB is 0.93 (CI: 0.76–1.12), for BB it is 0.95 (CI: 0.72–1.25) and for descendants HR equals 1.62 (CI: 0.87–3.02 - significant at 90%).

Conclusions
Using high quality representative data, we show that lower incidence of cancer and not better survival is the driver of the low cancer mortality previously found. This advantage persists across immigrant generations, but all-cancer mortality following incidence may be elevated for descendants.
Measuring domestic violence against Egyptian women and its consequent cost using a latent variable model
Authors: Hafez Mai Sherif , Mounir Carolin Sherif , El Zeini Laila Othman 
Published: December 2024

Abstract
Background
Domestic Violence is a threatening worldwide problem. Its consequences against women can be dramatic, as it negatively affects women’s quality of life reflected in their general wellbeing including physical, mental, emotional and sexual health, in addition to the economic cost. Both domestic violence and its cost are multidimensional constructs that cannot be directly measured.

Methodology
In this study, a latent trait model is used by applying item response theory to measure both domestic violence and its consequent cost via thirty-five observed variables. Accordingly, the study fills a gap in the literature since it is the first attempt to examine the relationship between domestic violence and its consequent cost in Egypt using latent variable modelling rather than simple descriptive statistics. Each construct is considered as a multidimensional latent variable. The overall latent trait model also estimates the relationship between domestic violence and its consequent cost. The effect of a number of socioeconomic covariates on domestic violence is examined within the model. The proposed model is fitted to data from the 2015 Egypt Economic Cost of Gender-Based Violence Survey (ECGBVS) using Mplus software.

Results
The study shows that psychological violence is equally important in measuring domestic violence, as physical violence. The cost resulting from domestic violence relies in its measurement both on the reduced quality of life and the monetary cost endured by the violated woman and children. For socioeconomic covariates, it is shown that domestic violence is affected by women’s and husband’s age, educational level, and husband’s occupational status.

Conclusion
Domestic violence is measured by summarizing four forms of violence: physical, psychological, sexual and economic violence, in a single continuous latent variable measuring “Domestic Violence”. Similarly, Cost is measured by summarizing three forms of consequent cost of violence: economic cost, cost on children and cost on women’s quality of life, in another a single continuous latent variable “Cost”. Each of these dimensions is measured by a number of aspects, reflecting the multidimensional nature of the variables. The fitted latent trait model ensured the positive relationship between Domestic Violence and its consequent multidimensional cost.
Identification of critical residues at the C-terminal tip of ACKR4 regulating chemokine internalization and βarrestin involvement
Authors: Gerken Oliver J. , Catone Nicola , Legler Daniel F. 
Published: December 2024

Abstract
Background
Atypical chemokine receptors (ACKRs) play an important role in regulating the availability of chemokines and are responsible for the formation of chemokine gradients required for the directed migration of immune cells in health and disease. ACKR4 shapes gradients of the chemokines CCL19 and CCL21, which are essential for guiding leukocyte homing to lymphoid organs where they initiate an adaptive immune response against invading pathogens. How ACKRs internalize and scavenge chemokines on the molecular level remains poorly understood. Current state-of the art methods to study βarrestin recruitment, signaling and trafficking of ACKRs - and G-protein-coupled receptors in general - rely heavily on C-terminally tagged receptors with unknown consequences for receptor functions.

Methods
Fluorescently labelled CCL19 was used to quantify chemokine internalization by native and tagged receptors as assessed by flow cytometry and live cell confocal microscopy. Steady-state interaction and chemokine-driven recruitment of βarrestins was determined by NanoBiT bystander assays. βarrestin-dependency for CCL19 internalization was determined in wild-type versus βarrestin1/2-double deficient cell lines. Statistical significance was determined by unpaired t-test or one-way ANOVA with Dunnett’s or Tukey’s multiple comparison tests.

Results
Addition of a C-terminal tag selectively affected the function of ACKR4, but not other ACKRs. Fusing a short peptide tag or a fluorescent protein to ACKR4 significantly augmented its ability to internalize its cognate ligand CCL19. In comparison to native ACKR4, its C-terminal tagging provoked an elevated pre-association of βarrestins with the plasma membrane, yet a reduction in chemokine-driven βarrestin recruitment. Furthermore, the addition of a C-terminal tag led to a shift from a βarrestin-dependent towards a βarrestin-independent endocytosis pathway. Similar results on chemokine uptake and on βarrestin-dependency were obtained with ACKR4 variants, in which a putative class II PDZ-binding domain located at the C-terminal tip of the receptor was mutated.

Conclusion
This study identifies that the integrity of the C-terminus of ACKR4 is critical for receptor function. The addition of a C-terminal tag to ACKR4 enhances chemokine uptake and alters the involvement of βarrestins in receptor trafficking.
Clinical spectrum and molecular basis in 19 Chinese patients with 46, XY disorder of sexual development caused by NR5A1 mutations
Authors: Xu Yue , Liu Xuemeng , Liu Yang , Zhu Hui , Wu Jing , Han Bing , Ling Shiying , Cao Ren , Yao Haijun , Chen Yan , Liu Yu , Rao Yamin , Liu Xiaoyu , Zhao Shuangxia , Song Huaidong , Qiao Jie 
Published: December 2024

Abstract
Background
Nuclear receptor subfamily 5 group A member 1 (NR5A1) plays pivotal roles in steroidogenesis and gonadal development. 46, XY disorder of sexual development (DSD) caused by NR5A1 mutations is a rare genetic condition. This study aimed to provide a comprehensive analysis of the clinical characteristics and molecular defects observed in 19 Chinese patients with NR5A1 variants, including assessing the deleterious effects of novel variants in vitro and evaluating their functional impact on the gonad and adrenal glands in vivo.

Materials and methods
Subjects with NR5A1 variants were identified from 223 Chinese 46, XY DSD patients via next-generation sequencing. In-silico analysis and functional assays were performed to evaluate the transcriptional activity, expression levels and nuclear localization of novel NR5A1 variants. The histological structure of the gonads was evaluated via immunohistochemistry (IHC).

Results
Patients with NR5A1 gene variants presented with serious conditions, including micropenis, cryptorchidism, azoospermia, and radiological abnormalities of the spleen. Five novel NR5A1 variants were identified, including heterozygous p.Y5*, p.Q42E and p.L359_L363del, as well as copy number variation (CNV) of chr9:127213317–127570245_del and an exon 6 duplication. A total of 63.2% (12/19) of patients harbored additional variants other than NR5A1. Defective transcriptional regulatory activities and abnormal protein expression levels were observed in NR5A1 variants. The reduced levels of DHEA-S and 11-oxygenated steroids indicate a mild impairment in adrenal function among certain patients. The IHC analysis of the testis revealed intact expression levels of SOX9 in Sertoli cells, while significant differences were observed in the expression pattern of CYP17A1 in Leydig cells among patients. The preserved maturation of adult Leydig cells in the patients may trigger spontaneous puberty.

Conclusions
Patients with NR5A1 mutations exhibit complex phenotypes. The observed clinical heterogeneity may be attributed to oligogenic mutations, dysregulated Leydig cell function, as well as the impaired ability to modulate the transcription of target genes.
Use of mesoglycan in the acute phase of hemorrhoidal disease (the CHORMES study): study protocol for a double-blind, randomized controlled trial
Authors: Gallo Gaetano , Picciariello Arcangelo , Realis Luc Alberto , Salvatore Antonella , Di Vittori Angelo , Rinaldi Marcella , Trompetto Mario 
Published: December 2024

Abstract
Background
Hemorrhoidal disease (HD) is associated with substantial economic burden and negative effects on health-related quality of life (HRQoL). The aCute HaemORrhoids treatment with MESoglycan (CHORMES) study aims to evaluate the effects of orally administered mesoglycan, a natural preparation of glycosaminoglycans with antithrombotic and profibrinolytic properties, as an acute treatment in patients with HD.

Methods
CHORMES is a phase 2, double-blind, randomized controlled trial being conducted at two centers in Italy. Adults aged 18–75 years with Grade I–III HD according to Goligher classification or external thrombosed hemorrhoids, and a Hemorrhoidal Disease Symptom Score (HDSS) of ≥ 5, will be randomly allocated in a 1:1 ratio to mesoglycan or placebo and will be treated for 40 days (two capsules for the first 5 days and one capsule for the subsequent 35 days twice daily [after breakfast and dinner], equivalent to 200 mg in the first 5 days and 100 mg subsequently). Concomitant use of analgesics is permitted in both treatment groups. The trial aims to enroll 50 patients, with 25 patients in each treatment group. The primary objective of the trial is to evaluate the efficacy of mesoglycan in reducing symptoms of HD, assessed via change in HDSS from baseline (day 0) to day 40 in the intention-to-treat population. Secondary objectives include changes in HRQoL from baseline to day 40 using the Short Health Scale for Hemorrhoidal Disease, safety (adverse effects, physical assessments, vital signs and laboratory parameters in the safety population), fecal continence assessed using the Vaizey score, bleeding assessed using the Bleeding score, the amount and type of analgesic taken, and pain. Patient enrolment began on 11 December 2023, and trial completion is expected by December 2024.

Discussion
The CHORMES trial will evaluate the efficacy and safety of mesoglycan, in addition to its impact on HRQoL, analgesic use and pain, in patients with HD. The results of the trial will assist clinicians in determining the most effective treatment for patients with HD.

Trial registration
ClinicalTrials.gov NCT06101992. Prospectively registered on 26 October 2023 at https://clinicaltrials.gov/ct2/show/NCT06101992.
Relations between daily stressful events, exertion, heart rate variability, and thoracolumbar fascia deformability: a case report
Authors: Brandl Andreas , Engel Raimund , Egner Christoph , Schleip Robert , Schubert Christian 
Published: December 2024

Abstract
Background
The posture of performance-oriented sport climbers adapts in a way that likely promotes the development of low back pain. The thoracolumbar fascia, while also contributing to performance, seems to be involved in that process. Furthermore, there has been evidence of the stiffening of the fascial structures in disorders associated with negative affectivity. The study aims to investigate the relationship between the autonomic nervous system and the deformability of the thoracolumbar fascia in a sport climber in a natural setting.

Case presentation
Over a 30 day period, a 50-year-old German male reported daily morning resting heart rate variability and daily inventory of stressful events. The thoracolumbar fascia deformation was measured daily using ultrasound in a manual therapy clinic. A time series analysis was performed to detect possible time-delayed relationships between the variables.
A cluster analyses revealed two distinguishable heart rate variability clusters (heart rate variability clusters 1 and 2). Both clusters were correlated with thoracolumbar fascia deformation and daily inventory of stressful events. Higher heart rate variability cluster 1 immediately caused lower thoracolumbar fascia deformation. Heart rate variability cluster 1 parameters mediated the effect of daily inventory of stressful events on a decrease in thoracolumbar fascia deformation with a 2-day delay. One heart rate variability cluster 2 parameter mediated the effect of daily inventory of stressful events on an increase in thoracolumbar fascia deformation with a 7-day delay.

Conclusion
Heart rate variability cluster 1 values, which probably indicate sympathetic nervous system activity, are directly related to thoracolumbar fascia. Presumably, the sympathetic nervous system mediated the effect of daily inventory of stressful events on a lower thoracolumbar fascia deformation with a 2-day delay, followed by a supercompensation, most likely parasympathetically mediated. Coaches and trainers should be aware of these mechanisms and consider monitoring during training to minimize potential additional risk factors for impaired performance and health.