bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between neighbourhood income and youth mental health service use differs by immigration experience: analysis of population-based data in British Columbia, Canada
Authors: Kaoser Ridhwana , Thakore Padmini , Peterson Sandra , Wiedmeyer Mei-ling , Sierra-Heredia Cecilia , Goldenberg Shira , Machado Stefanie , Hagos Selamawit , Tayyar Elmira , Bozorgi Yasmin , Lavergne M. Ruth 
Published: December 2024

Abstract
Background
We investigated the relationship between neighbourhood income quintile and mental health service use by immigration experience among youth and explored changes during the COVID-19 pandemic.

Method
We used administrative data to examine mental health service use among youth aged 10 to 24 in British Columbia, Canada, between April 1, 2019, and March 31, 2022. We compared rates of community-based mental health service use, emergency department visits, and hospitalizations and the proportion of involuntary admissions by neighbourhood income quintile and immigration. We used models stratified by immigration to estimate the relationship with income.

Results
Non-immigrant youth used substantially more services than immigrant youth. Service use increased following the pandemic’s start and peaked between January and March 2021. We observed a clear income gradient for community-based service use among both immigrant and non-immigrant youth, but the direction of the gradient was reversed. Service use was highest among non-immigrant youth in lower-income neighbourhoods and lowest for immigrant youth in lower-income neighbourhoods. We observed similar patterns of income gradient for non-immigrant youth for emergency department visits and hospitalization. The proportion of involuntary admissions was higher for immigrant youth.

Conclusions
Mental health service use was substantially lower among immigrant youth than non-immigrant youth, but higher proportions of immigrant youth were hospitalized involuntarily. The reverse income gradient patterns observed for community-mental health service use are noteworthy and suggest significant barriers to accessing preventable care among immigrant youth, particularly those living in lower-income neighbourhoods.
Predictors of quality of life among caregivers of patients with moderate to severe kidney disease: an Australian cross-sectional study
Authors: Zimbudzi Edward , Blessan Asha , Fraginal Denise , Gute Lelise , Wang Qiumian , Ziganay Shari 
Published: December 2024

Abstract
Background
Little is known about the quality of life (QoL) of caregivers of patients with chronic kidney disease (CKD) along the disease continuum. We investigated factors associated with low QoL among caregivers of patients with CKD including those on dialysis. We also examined the relationship between kidney disease severity and the QoL of caregivers.

Methods
We recruited caregivers of patients with CKD (stage 3 to 5) attending renal outpatient clinics as well as dialysis units of a tertiary hospital and patients from January 2018 to November 2023. Quality of life was assessed using a valid and reliable tool, the Adult Carer Quality of Life Questionnaire. Logistic regression analyses were performed to determine factors associated with low QoL among caregivers.

Results
A total of 278 dyads of caregivers and patients were studied with a mean age of 56.6 ± 15.2 and 63.7 ± 15.3 years respectively. The proportion of caregivers reporting low to mid-range QoL scores ranged from 37 to 73.3% across the eight domains, with 48% having low to mid-range overall QoL scores. The severity of CKD had no impact on overall QoL of caregivers in the personal growth and carer satisfaction domains where caregivers of patients on dialysis reported worse scores compared to caregivers of predialysis patients. Female gender of caregivers and patients, longer caregiving time, diagnosis of diabetes and lower socioeconomic status of patients were all associated with lower scores in one or more domains.

Conclusion
This study identified several factors associated with low QoL among caregivers of patients with CKD. An understanding of these factors provides insight into the development of targeted interventions to improve the QoL of caregivers.
Platelet-derived extracellular vesicles induced through different activation pathways drive melanoma progression by functional and transcriptional changes
Authors: Tavukcuoglu Zeynep , Butt Umar , Faria Alessandra V. S. , Oesterreicher Johannes , Holnthoner Wolfgang , Laitinen Saara , Palviainen Mari , Siljander Pia R-M 
Published: December 2024

Abstract
Background
Beyond their conventional roles in hemostasis and wound healing, platelets have been shown to facilitate hematogenous metastasis by interacting with cancer cells. Depending on the activation route, platelets also generate different platelet-derived extracellular vesicles (PEVs) that may educate cancer cells in the circulation or within the tumor microenvironment. We engaged different platelet-activating receptors, including glycoprotein VI and C-type lectin-like receptor 2, to generate a spectrum of PEV types. This allowed us to investigate the differential capacity of PEVs to alter cancer hallmark functions such as proliferation, invasion, and pro-angiogenic potential using melanoma as a model. Additionally, we analyzed changes in the cell transcriptomes and cancer EV profiles.

Methods
Two human melanoma cell lines (MV3 and A2058) with differential metastatic potential were studied in the 3D spheroid cultures. Human platelets were activated with collagen related peptide (CRP), fucoidan from Fucus vesiculosus (FFV), thrombin & collagen co-stimulus and Ca2+ ionophore, and PEVs were isolated by size-exclusion chromatography followed by ultrafiltration. Spheroids or cells were treated with PEVs and used in functional assays of proliferation, invasion, and endothelial tube formation as well as for the analysis of cancer EV production and their tetraspanin profiles. Differentially expressed genes and enriched signaling pathways in the PEV-treated spheroids were analyzed at 6 h and 24 h by RNA sequencing.

Results
Among the studied PEVs, those generated by CRP and FFV exhibited the most pronounced effects on altering cancer hallmark functions. Specifically, CRP and FFV PEVs increased proliferation in both MV3 and A2058 spheroids. Distinct tetraspanin signatures of melanoma EVs were induced by all PEV types. While the PI3K-Akt and MAPK signaling pathways were activated by both CRP and FFV PEVs, they differently upregulated the immunomodulatory TGF-β and type-I interferon signaling pathways, respectively.

Conclusions
Our study revealed both shared and distinct, cancer-promoting functions of PEVs, which contributed to the transcriptome and metastatic capabilities of the melanoma spheroids. Inhibiting the platelet receptors that modulate the PEVs’ cancer-promoting properties may open up new strategies for identifying promising treatment targets for cancer therapy.
The effectiveness of digital physical activity interventions in older adults: a systematic umbrella review and meta-meta-analysis
Authors: Alley Stephanie J. , Waters Kim M. , Parker Felix , Peiris D. L. I. H. K. , Fien Samantha , Rebar Amanda L. , Vandelanotte Corneel 
Published: December 2024

Abstract
Background
Physical activity is important for healthy ageing, however most older adults are inactive. Numerous reviews with a range of inclusion criteria have been conducted on digital interventions to promote physical activity in older adults, and a synthesis of these is needed. Therefore, the objective of this study is to conduct an umbrella review and meta-meta-analysis on the effectiveness of digital interventions to promote physical activity in older adults.

Methods
Nine databases were searched from January 2010 to December 2023. Systematic reviews and meta-analyses of primary studies using digital physical activity interventions to target healthy older adults or clinical populations of older adults with a self-reported or device measured physical activity outcome were eligible for inclusion.

Results
In total, 22 systematic reviews and meta-analyses covering 185 primary research papers were eligible for inclusion. The total number of participants across all primary studies was 28,198. Most (21, 95%) reviews and meta-analyses were rated as having a low or critically low AMSTAR-2 confidence rating. Of the 22 included systematic reviews, 13 (59%) conducted a meta-analysis and 10 (45%) conducted a narrative synthesis. Most systematic reviews with a narrative synthesis found strong evidence for a positive effect or moderate evidence for a positive effect for physical activity outcomes (7/9, 78%) and steps (3/3, 100%). The meta-meta-analysis of primary papers included in meta-analyses demonstrated a significant moderate effect for steps and a significant small effect for total PA and MVPA. The strength of effect did not vary by intervention components (activity tracker, app-based, SMS/phone, web-based, and face-to-face), population (primary or secondary prevention), control group (none, other digital intervention, or non-digital intervention), or outcome measurement (self-reported or device measured). Only 3 (14%) reviews included longer term follow up outcomes after the end of the intervention, with mixed results.

Conclusions
Evidence from 22 reviews and meta-analyses suggests that digital physical activity interventions are effective at increasing physical activity in older adults. Further primary research is needed in adults 65 years and over exclusively, and with longer-term follow up of physical activity outcomes. Future reviews should include a published protocol and interpret results according to risk-of-bias.
Systems analysis and improvement to optimize opioid use disorder care quality and continuity for patients exiting jail (SAIA-MOUD)
Authors: Gimbel Sarah , Basu Anirban , Callen Emily , Flaxman Abraham D. , Heidari Omeid , Hood Julia E. , Kellogg Anna , Kern Eli , Tsui Judith I. , Turley Ericka , Sherr Kenneth 
Published: December 2024

Abstract
Background
Between 2012–2022 opioid-related overdose deaths in the United States, including Washington State, have risen dramatically. Opioid use disorder (OUD) is a complex, chronic, and criminalized illness with biological, environmental, and social causes. One-fifth of people with OUD have recent criminal-legal system involvement; > 50% pass through WA jails annually.
Medications for Opioid Use Disorder (MOUD) can effectively treat OUD. WA has prioritized improving access to MOUD, including for those in jails. As patients in jail settings are systematically marginalized due to incarceration, it is critical to foster connections to MOUD services upon release, an acknowledged period of high overdose risk. Currently, there is insufficient focus on developing strategies to foster linkages between jail-based MOUD and referral services.
The Systems Analysis and Improvement Approach (SAIA), an evidence-based implementation strategy, may optimize complex care cascades like MOUD provision and improve linkages between jail- and community-based providers. SAIA bundles systems engineering tools into an iterative process to guide care teams to visualize cascade drop-offs and prioritize steps for improvement; identify modifiable organization-level bottlenecks; and propose, implement, and evaluate modifications to overall cascade performance. The SAIA-MOUD study aims to strengthen the quality and continuity of MOUD care across jail and referral clinics in King County, WA, and ultimately reduce recidivism and mortality.

Methods
We will conduct a quasi-experimental evaluation of SAIA effectiveness on improving MOUD care cascade quality and continuity for patients receiving care in jail and exiting to referral clinics; examine determinants of SAIA-MOUD adoption, implementation, and sustainment; and determine SAIA-MOUD’s cost and cost-effectiveness. Clinic teams with study team support will deliver the SAIA-MOUD intervention at the jail-based MOUD program and three referral clinics over a two-year intensive phase, followed by a one-year sustainment phase where SAIA implementation will be led by King County Jail MOUD staff without study support to enable pragmatic evaluation of sustained implementation.

Discussion
SAIA packages user-friendly systems engineering tools to guide decision-making by front-line care providers to identify low-cost, contextually appropriate health care improvement strategies. By integrating SAIA into MOUD care provision in jail and linked services, this pragmatic trial is designed to test a model for national scale-up.

Trial registration
ClinicalTrials.gov NCT06593353 (registered 09/06/2024; https://register.clinicaltrials.gov/prs/beta/studies/S000EVJR00000029/recordSummary).
Microglial CD2AP deficiency exerts protection in an Alzheimer’s disease model of amyloidosis
Authors: Zhang Lingliang , Huang Lingling , Zhou Yuhang , Meng Jian , Zhang Liang , Zhou Yunqiang , Zheng Naizhen , Guo Tiantian , Zhao Shanshan , Wang Zijie , Huo Yuanhui , Zhao Yingjun , Chen Xiao-fen , Zheng Honghua , Holtzman David M. , Zhang Yun-wu 
Published: December 2024

Abstract
Background
The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer’s disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive.

Methods
CD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes.

Results
We find that CD2AP is abundantly expressed in microglia and its levels are elevated in the brain of AD patients and the 5xFAD model mice at pathological stages. We demonstrate that CD2AP haploinsufficiency in microglia significantly attenuates cognitive and synaptic deficits, weakens the response of microglia to Aβ and the formation of disease-associated microglia (DAM), and alleviates synapse loss in 5xFAD mice. We show that CD2AP-deficient microglia exhibit compromised uptake ability. In addition, we find that CD2AP expression is positively correlated with the expression of the complement C1q that is important for synapse phagocytosis and the formation of DAM in response to Aβ deposition. Moreover, we reveal that CD2AP interacts with colony stimulating factor 1 receptor (CSF1R) and regulates CSF1R cell surface levels, which may further affect C1q expression.

Conclusions
Our results demonstrate that CD2AP regulates microgliosis and identify a protective function of microglial CD2AP deficiency against Aβ deposition, suggesting the importance of detailed investigation of AD-associated genes in different brain cells for thoroughly understanding their exact contribution to AD.
Detection and classification of long terminal repeat sequences in plant LTR-retrotransposons and their analysis using explainable machine learning
Authors: Horvath Jakub , Jedlicka Pavel , Kratka Marie , Kubat Zdenek , Kejnovsky Eduard , Lexa Matej 
Published: December 2024

Abstract
Background
Long terminal repeats (LTRs) represent important parts of LTR retrotransposons and retroviruses found in high copy numbers in a majority of eukaryotic genomes. LTRs contain regulatory sequences essential for the life cycle of the retrotransposon. Previous experimental and sequence studies have provided only limited information about LTR structure and composition, mostly from model systems. To enhance our understanding of these key sequence modules, we focused on the contrasts between LTRs of various retrotransposon families and other genomic regions. Furthermore, this approach can be utilized for the classification and prediction of LTRs.

Results
We used machine learning methods suitable for DNA sequence classification and applied them to a large dataset of plant LTR retrotransposon sequences. We trained three machine learning models using (i) traditional model ensembles (Gradient Boosting), (ii) hybrid convolutional/long and short memory network models, and (iii) a DNA pre-trained transformer-based model using k-mer sequence representation. All three approaches were successful in classifying and isolating LTRs in this data, as well as providing valuable insights into LTR sequence composition. The best classification (expressed as F1 score) achieved for LTR detection was 0.85 using the hybrid network model. The most accurate classification task was superfamily classification (F1=0.89) while the least accurate was family classification (F1=0.74). The trained models were subjected to explainability analysis. Positional analysis identified a mixture of interesting features, many of which had a preferred absolute position within the LTR and/or were biologically relevant, such as a centrally positioned TATA-box regulatory sequence, and TG..CA nucleotide patterns around both LTR edges.

Conclusions
Our results show that the models used here recognized biologically relevant motifs, such as core promoter elements in the LTR detection task, and a development and stress-related subclass of transcription factor binding sites in the family classification task. Explainability analysis also highlighted the importance of 5’- and 3’- edges in LTR identity and revealed need to analyze more than just dinucleotides at these ends. Our work shows the applicability of machine learning models to regulatory sequence analysis and classification, and demonstrates the important role of the identified motifs in LTR detection.
Emergency call utilization over a 10-years period: an observational study in Region Zealand, Denmark, 2013–2022
Authors: Møller Thea Palsgaard , Jensen Josefine Tangen , Ersbøll Annette Kjær , Blomberg Stig Nikolaj Fasmer , Christensen Helle Collatz 
Published: December 2024

Abstract
Background
Improving prehospital emergency care requires a comprehensive understanding of the efficiency of emergency medical services and demand fluctuations. The medical emergency call is the primary contact between citizens and the emergency medical dispatch center, serving as the gateway to accessing emergency assistance. This study aimed to characterize the emergency call population and analyze the development of emergency call utilization in Region Zealand in Denmark during a 10-years period.

Methods
This was an observational register-based study of administrative data from the emergency medical dispatch center in Region Zealand. Data was collected from 1 January 2013 to 31 December 2022. All unique emergency calls from residents to the emergency number “1-1-2” were included. Descriptive analyses were used to characterize the study population. Poisson regression models were used to calculate ratio estimates for the association between years and hospital catchment areas, using the incidence rate of emergency calls as outcome measure.

Results
A total of 641,457 emergency calls were included. A significant increase in the total number of emergency calls was found, with an increase from 58,454 annual calls to 80,819 calls over the study period. The incidence rate per 1000 residents per year increased from 71.1 to 95.2, a 35% increase. The southern part of the region had significantly more emergency calls per 1000 residents per year during the study period compared to the eastern part of the region (IRR 1.70). Demographically, males comprised 52.3% of cases, and patients aged 65 and older represented 48.2% of calls. Emergency calls were “Emergency level A” in 45.5% and “Emergency level B” in 39.1%. In 22.3% of cases, the emergency call was categorized as “Unclear problem.” The most frequent categories were “chest pain” (12.7%), “impaired consciousness” (9.6%), “breathing difficulties” (8.8%), “accidents” (7.9%), and “minor injuries” (7.6%).

Conclusions
The study revealed a significant increase in emergency calls, both in absolute numbers and per 1000 residents per year, indicating growing demand for emergency care, along with a surge in activity at the region's dispatch center. Regional disparities underscores the potential necessity for tailored developmental approaches over time.
Methoxyflurane in early analgesic therapy by ski patrol members on Swiss ski slopes – an observational cohort study
Authors: Benz Lena , Knapp Jürgen , Roten Fredy-Michel , Huber Markus , Steffen Richard 
Published: December 2024

Abstract
Background
Pain therapy is an important first-response measure in the pre-clinical care of trauma patients. Injured individuals on ski slopes are usually given first aid by members of the ski patrol. The early implementation of adequate pain therapy by these paramedical rescuers can increase patient satisfaction and have a positive effect on the entire treatment process. In this context, we analysed the administration of methoxyflurane by ski patrol members on Swiss ski slopes.

Methods
In this retrospective observational study, we evaluated 172 datasets, of which 149 concerned patients who were administered methoxyflurane. These datasets were taken from a quality-control survey related to the administration of methoxyflurane by members of the ski patrol in seven ski resorts in the Swiss Alps. The data was collected in the winter months of 2022/23. The ski patrol members had been previously trained by medical professionals and employed methoxyflurane following a defined algorithm, according to which patients with an initial numeric pain score of ≥ 4 qualified for the use of methoxyflurane. After each treatment, data on effectiveness and feasibility were collected by means of a standardised questionnaire. The primary outcome was defined as achieving effective pain therapy, which was designated as a reduction on the numerical rating scale of two or more points and a pain score of seven or less after administration. We then performed a linear regression analysis with the relative pain reduction as the outcome and sex, age, ski resort and injury class as covariates.

Results
Methoxyflurane led to effective pain reduction in around two-thirds of patients on the ski slopes and was easy to use for trained ski patrol members. Median pain reduction was 2 points (interquartile range: 1 to 3) on the NRS scale. The regression model showed lower reduction in pain in lower extremity injuries. Sex, age and initial pain score were not associated with the extent of pain reduction. No serious side effects were observed.

Conclusion
The administration of methoxyflurane by trained ski patrol members is a safe and effective option for early pain management in ski slope injuries. Methoxyflurane could thus represent a useful bridging measure, enabling the ski patrol to relieve moderate to severe pain until professional rescue services arrive. However, it does not seem ideal for lower leg injuries.