bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analysis of microRNA and messenger RNA expression profiles reveals functional microRNA in infectious bovine rhinotracheitis virus-induced mitochondrial damage in Madin-Darby bovine kidney cells
Authors: Ma Yingcai , Guo Xueping , He Qin , Liu Lu , Li Zelong , Zhao Xiaomin , Gu Wenxi , Zhong Qi , Li Na , Yao Gang , Ma Xuelian 
Published: February 2024

Abstract
Background
Studies have confirmed that Infectious bovine rhinotracheitis virus (IBRV) infection induces mitochondrial damage. MicroRNAs (miRNAs) are a class of noncoding RNA molecules, which are involved in various biological processes and pathological changes associated with mitochondrial damage. It is currently unclear whether miRNAs participate in IBRV-induced mitochondrial damage in Madin-Darby bovine kidney (MDBK) cells.

Results
In the present study, we used high-throughput sequencing technology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for mitochondria-related miRNAs and messenger RNAs (mRNAs). In total, 279 differentially expressed miRNAs and 832 differentially expressed mRNAs were identified in 6 hours (IBRV1) versus 24 hours (IBRV2) after IBRV infection in MDBK cells. GO and KEGG enrichment analysis revealed that 42 differentially expressed mRNAs and 348 target genes of differentially expressed miRNAs were correlated with mitochondrial damage, and the miRNA-mitochondria-related target genes regulatory network was constructed to elucidate their potential regulatory relationships. Among the 10 differentially expressed miRNAs, 8 showed expression patterns consistent with the high-throughput sequencing results. Functional validation results showed that overexpression of miR-10a and miR-182 aggravated mitochondrial damage, while inhibition of miR-10a and miR-182 alleviated mitochondrial damage.

Conclusions
This study not only revealed the expression changes of miRNAs and mRNAs in IBRV-infected MDBK cells, but also revealed possible biological regulatory relationship between them. MiR-10a and miR-182 may have the potential to be developed as biomarkers for the diagnosis and treatment of IBRV. Together, Together, these data and analyses provide additional insights into the roles of miRNA and mRNA in IBRV-induced mitochondria damage
Awareness and knowledge of drug decriminalization among people who use drugs in British Columbia: a multi-method pre-implementation study
Authors: Greer Alissa , Xavier Jessica , Loewen Olivia K. , Kinniburgh Brooke , Crabtree Alexis 
Published: February 2024

Abstract
Background
In January 2023, British Columbia implemented a three-year exemption to Controlled Drugs and Substances Act, as granted by the federal government of Canada, to decriminalize the personal possession of small amounts of certain illegal drugs. This decriminalization policy, the first in Canada, was announced in response to the overdose emergency in British Columbia as a public health intervention that could help curb overdose deaths by reducing the impact of criminalization and increasing access to health and social services through stigma reduction.

Methods
The current multi-method study examines people who use drugs’ awareness and knowledge of British Columbia’s decriminalization model through cross-sectional quantitative surveys and qualitative interviews among people who use drugs from September–November 2022, immediately prior to the implementation of decriminalization.

Results
Quantitative findings show that two-thirds (63%) of people who use drugs were aware of the policy, but substantial knowledge gaps existed about the legal protections afforded (threshold amount, substances included, drug trafficking, confiscation). The qualitative findings suggest that people who use drugs misunderstood the details of the provincial decriminalization model and often conflated it with regulation. Results suggest that information sharing about decriminalization were minimal pre-implementation, highlighting areas for knowledge dissemination about people who use drugs' rights under this policy.

Conclusions
Given that decriminalization in British Columbia is a new and landmark reform, and that the success of decriminalization and its benefits may be undermined by poor awareness and knowledge of it, efforts to share information, increase understanding, and empower the community, may be required to promote its implementation and benefits for the community.
Evaluating the impact of the supporting the advancement of research skills (STARS) programme on research knowledge, engagement and capacity-building in a health and social care organisation in England
Authors: Tajuria Gulshan , Dobel-Ober David , Bradley Eleanor , Charnley Claire , Lambley-Burke Ruth , Mallen Christian , Honeyford Kate , Kingstone Tom 
Published: February 2024

Abstract
Objectives
To evaluate the impact a novel education programme - to improve research engagement, awareness, understanding and confidence - had on a diverse health and social care workforce. Barriers and facilitators to engagement were explored together with research capacity-building opportunities and ways to embed a research culture. The programme is entitled ‘Supporting The Advancement of Research Skills’ (STARS programme); the paper reports findings from a health and social care setting in England, UK.

Methods
A four-level outcome framework guided the approach to evaluation and was further informed by key principles of research capacity development and relevant theory. Quantitative data were collected from learners before and after engagement; these were analysed descriptively. Semi-structured online interviews were conducted with learners and analysed thematically. A purposive sample was achieved to include a diversity in age, gender, health and social care profession, and level of attendance (regular attendees, moderate attendees and non-attenders).

Results
The evaluation spanned 18 half-day workshops and 11 seminars delivered by expert educators. 165 (2% of total staff at Midlands Partnership University NHS Foundation Trust (MPFT)) staffs booked one or more education sessions; 128 (77%) including Allied Health Professionals (AHPs), psychologists, nursing and midwifery, and social workers attended one or more session. Key themes of engagement with teaching sessions, relevance and impact of training and promoting a research active environment were identified with relevant sub-themes. Positive impacts of training were described in terms of research confidence, intentions, career planning and application of research skills as a direct result of training. Lack of dedicated time for research engagement, work pressures and time commitments required for the programme were key barriers. Facilitators that facilitated engagement are also described.

Conclusions
Findings demonstrate the impact that a free, virtual and high-quality research education programme had at individual and organisational levels. The programme is the product of a successful collaboration between health and social care and academic organisations; this provides a useful framework for others to adapt and adopt. Key barriers to attendance and engagement spoke to system-wide challenges that an education programme could not address in the short-term. Potential solutions are discussed in relation to protecting staff time, achieving management buy-in, recognising research champions, and having a clear communication strategy.
Prediction of emergency department revisits among child and youth mental health outpatients using deep learning techniques
Authors: Saggu Simran , Daneshvar Hirad , Samavi Reza , Pires Paulo , Sassi Roberto B. , Doyle Thomas E. , Zhao Judy , Mauluddin Ahmad , Duncan Laura 
Published: February 2024

Abstract
Background
The proportion of Canadian youth seeking mental health support from an emergency department (ED) has risen in recent years. As EDs typically address urgent mental health crises, revisiting an ED may represent unmet mental health needs. Accurate ED revisit prediction could aid early intervention and ensure efficient healthcare resource allocation. We examine the potential increased accuracy and performance of graph neural network (GNN) machine learning models compared to recurrent neural network (RNN), and baseline conventional machine learning and regression models for predicting ED revisit in electronic health record (EHR) data.

Methods
This study used EHR data for children and youth aged 4–17 seeking services at McMaster Children’s Hospital’s Child and Youth Mental Health Program outpatient service to develop and evaluate GNN and RNN models to predict whether a child/youth with an ED visit had an ED revisit within 30 days. GNN and RNN models were developed and compared against conventional baseline models. Model performance for GNN, RNN, XGBoost, decision tree and logistic regression models was evaluated using F1 scores.

Results
The GNN model outperformed the RNN model by an F1-score increase of 0.0511 and the best performing conventional machine learning model by an F1-score increase of 0.0470. Precision, recall, receiver operating characteristic (ROC) curves, and positive and negative predictive values showed that the GNN model performed the best, and the RNN model performed similarly to the XGBoost model. Performance increases were most noticeable for recall and negative predictive value than for precision and positive predictive value.

Conclusions
This study demonstrates the improved accuracy and potential utility of GNN models in predicting ED revisits among children and youth, although model performance may not be sufficient for clinical implementation. Given the improvements in recall and negative predictive value, GNN models should be further explored to develop algorithms that can inform clinical decision-making in ways that facilitate targeted interventions, optimize resource allocation, and improve outcomes for children and youth.
Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2
Authors: Agostoni Piergiuseppe , Mapelli Massimo , Salvioni Elisabetta , Mattavelli Irene , Banfi Cristina , Bonomi Alice , Biondi Maria Luisa , Rovai Sara , Tamborini Gloria , Muratori Manuela , Ghulam Ali Sarah , Ghilardi Stefania , De Martino Fabiana , Vignati Carlo , Palermo Pietro , Gugliandolo Paola , Elia Davide , Moscucci Federica , Cassandro Roberto , Andreini Daniele , Mancini Elisabetta , Harari Sergio 
Published: February 2024

Abstract
Background
Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients’ reported symptomatology is still unclear.

Methods
Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function.

Results
We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102–123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap.

Conclusions
In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.
1-Pyrroline-5-carboxylate inhibit T cell glycolysis in prostate cancer microenvironment by SHP1/PKM2/LDHB axis
Authors: Chang Lei , Li Guohao , Jiang Shan , Li Jie , Yang Jin , Shah Kavita , Zhou Le , Song Hanrui , Deng Leyuan , Luo Zhiguo , Guo Yonglian , Yan Yutao 
Published: February 2024

Abstract
Background
Our previous studies demonstrated that 1-Pyrroline-5-carboxylate (P5C) released by prostate cancer cells inhibits T cell proliferation and function by increasing SHP1 expression. We designed this study to further explore the influence of P5C on T cell metabolism, and produced an antibody for targeting P5C to restore the functions of T cells.

Method
We co-immunoprecipated SHP1 from T cells and analyzed the proteins that were bound to it using liquid chromatography mass spectrometry (LC/MS-MS). The influence of P5C on T cells metabolism was also detected by LC/MS-MS. Seahorse XF96 analyzer was further used to identify the effect of P5C on T cells glycolysis. We subsequently designed and produced an antibody for targeting P5C by monoclonal technique and verified its effectiveness to restore the function of T cells in vitro and in vivo.

Result
PKM2 and LDHB bind SHP1 in T cells, and P5C could increase the levels of p-PKM2 while having no effect on the levels of PKM2 and LDHB. We further found that P5C influences T cell energy metabolism and carbohydrate metabolism. P5C also inhibits the activity of PKM2 and decreases the content of intracellular lactic acid while increasing the activity of LDH. Using seahorse XF96 analyzer, we confirmed that P5C remarkably inhibits glycolysis in T cells. We produced an antibody for targeting P5C by monoclonal technique and verified that the antibody could oppose the influence of P5C to restore the process of glycolysis and function in T cells. Meanwhile, the antibody also inhibits the growth of prostate tumors in an animal model.

Conclusion
Our study revealed that P5C inhibits the process of glycolysis in T cells by targeting SHP1/PKM2/LDHB complexes. Moreover, it is important that the antibody for targeting P5C could restore the function of T cells and inhibit the growth of prostate tumors.
Manifestations and management of Sjögren’s disease
Authors: Maleki-Fischbach Mehrnaz , Kastsianok Liudmila , Koslow Matthew , Chan Edward D. 
Published: February 2024

AbstractSjögren’s disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic complications have prognostic implications and need to be identified and managed in a timely manner. Treatment should be tailored to the type and severity of organ involvement, ideally based on multidisciplinary evaluation.
Effects of certain pre-analytical factors on the performance of plasma phospho-tau217
Authors: Bali Divya , Hansson Oskar , Janelidze Shorena 
Published: February 2024

Abstract
Introduction
Pre-analytical factors can cause substantial variability in the measurements of cerebrospinal fluid (CSF) and plasma biomarkers of Alzheimer’s disease (AD). However, their effects on the performance of one of the most promising plasma AD biomarkers, phosphorylated tau (p-tau)217, are not known.

Methods
We included 50 amyloid-β positive (Aβ+) and 50 Aβ− participants from the Swedish BioFINDER-1 study. Plasma and CSF p-tau217 were measured using an immunoassay developed by Lilly Research Laboratories. We examined the effect of four plasma handling conditions, i.e., (1) thawing at room temperature (RT) with no centrifugation, (2) thawing at RT followed by centrifugation, (3) thawing on ice with no centrifugation, and (4) thawing on ice followed by centrifugation. In addition, we also tested the effects of up to 3 freeze–thaw cycles on the associations of plasma p-tau217 with AD-related pathologies measured with CSF p-tau217 and CSF Aβ42/Aβ40.

Results
In the whole cohort (combining Aβ+ and Aβ− participants), we found significant correlations between plasma p-tau217 and both CSF p-tau217 (Rrange, 0.614–0.717, p < 0.001) and CSF Aβ42/Aβ40 (Spearman Rrange, − 0.515 to − 0.652, p < 0.001) for each of the four tested conditions. Correlations between plasma and CSF p-tau217 were also significant for all conditions in the Aβ+ group (Rrange, 0.506–0.579, p < 0.001). However, in this Aβ+ subgroup, correlations with CSF Aβ42/Aβ40 were only significant for centrifuged samples (thawed at RT, R =  − 0.394, p = 0.010; thawed on ice, R =  − 0.406; p = 0.007). In Aβ− participants, correlations between plasma and CSF p-tau217 were again significant only for centrifuged samples (thawed at RT, R = 0.394, p = 0.007; thawed on ice, R = 0.334; p = 0.022), with no correlations seen between plasma p-tau217 and CSF Aβ42/Aβ40 for any of the conditions. While the accuracy of plasma p-tau217 to identify individuals with abnormal CSF Aβ42/Aβ40 or CSF p-tau217 status was high, the AUCs for samples thawed at RT and analyzed without centrifugation were numerically lower than the AUCs of other conditions (CSF Aβ42/Aβ40 = 0.845 vs 0.872–0.884; CSF p-tau217 = 0.866 vs 0.908–0.924, pdiff > 0.11). P-tau217 concentration was consistently higher in non-centrifuged samples than in centrifuged samples (p ≤ 0.021). There were no differences between samples freeze-thawed once, twice, or three times.

Conclusion
Centrifugation improved the performance of plasma p-tau217, but thawing temperatures and up to three freeze–thaw cycles did not have a significant impact. These results may inform the future development of standardized sample-handling protocols for AD biomarkers.
Prevalence and trend of central nervous system–active medication polypharmacy among US commercially insured adults with vs without early-onset dementia: a multi-year cross-sectional study
Authors: Wei Yu-Jung Jenny , Shrestha Nistha , Chiang ChienWei , DeKosky Steven T. 
Published: February 2024

Abstract
Background
Limited data exist on the prevalence and trend of central nervous system (CNS)-active medication polypharmacy among adults with early-onset dementia (EOD) and whether these estimates differ for adults without EOD but with chronic pain, depression, or epilepsy, conditions managed by CNS-active medications.

Methods
A multi-year, cross-sectional study using 2012–2021 MarketScan Commercial Claims data was conducted among adults aged 30 to 64 years with EOD and those without EOD but having a diagnosis of chronic pain, depression, or epilepsy as comparison groups. For each disease cohort, the primary outcome was CNS-active medication polypharmacy defined as concurrent use of ≥ 3 CNS-active medications on the US Beers Criteria list that overlapped for > 30 consecutive days during 12 months following a randomly selected medical encounter with the disease diagnosis. A separate multivariate modified Poisson regression model was used to estimate time trends in CNS polypharmacy in each disease cohort. Differences in trend estimates between EOD and non-EOD disease cohorts were examined by an interaction between EOD status and yearly time.

Results
From 2013 to 2020, the annual crude prevalence of CNS polypharmacy was higher among adults with EOD (21.2%–25.0%) than adults with chronic pain (5.1%–5.9%), depression (14.8%–21.7%), or epilepsy (20.0%–22.3%). The adjusted annual prevalence of CNS polypharmacy among patients with EOD did not significantly change between 2013 and 2020 (adjusted prevalence rate ratio [aPRR], 0.94; 95% CI, 0.88–1.01), whereas a significant decreasing trend was observed among non-EOD cohorts with chronic pain (aPRR, 0.66; 95% CI, 0.63–0.69), depression (aPRR, 0.81; 95% CI, 0.77–0.85), and epilepsy (aPRR, 0.86; 95% CI, 0.83–0.89). The interaction analysis indicated that patients with epilepsy and depression (vs with EOD) had a decreasing probability of CNS-active medication polypharmacy over time (aPRR, 0.98 [95% CI, 0.98–0.99]; P < .001 for interaction for both conditions).

Conclusions
The prevalence of CNS polypharmacy among US commercially insured adults with EOD (vs without) was higher and remained unchanged from 2013 to 2021. Medication reviews of adults with EOD and CNS polypharmacy are needed to ensure that benefits outweigh risks associated with combined use of these treatments.
Evaluating the costs of adverse drug events in hospitalized patients: a systematic review
Authors: Durand Maxime , Castelli Christel , Roux-Marson Clarisse , Kinowski Jean-Marie , Leguelinel-Blache Géraldine 
Published: February 2024

Abstract
Background
Adverse drug events (ADEs) are not only a safety and quality of care issue for patients, but also an economic issue with significant costs. Because they often occur during hospital stays, it is necessary to accurately quantify the costs of ADEs. This review aimed to investigate the methods to calculate these costs, and to characterize their nature.

Methods
A systematic literature review was conducted to identify methods used to assess the cost of ADEs on Medline, Web of Science and Google Scholar. Original articles published from 2017 to 2022 in English and French were included. Economic evaluations were included if they concerned inpatients.

Results
From 127 studies screened, 20 studies were analyzed. There was a high heterogeneity in nature of costs, methods used, values obtained, and time horizon chosen. A small number of studies considered non-medical (10%), indirect (20%) and opportunity costs (5%). Ten different methods for assessing the cost of ADEs have been reported and nine studies did not explain how they obtained their values.

Conclusions
There is no consensus in the literature on how to assess the costs of ADEs, due to the heterogeneity of contexts and the choice of different economic perspectives. Our study adds a well-deserved overview of the existing literature that can be a solid lead for future studies and method implementation.

Trial registration
PROSPERO registration CRD42023413071.
Transformative synergy: SSEHCET—bridging mobile edge computing and AI for enhanced eHealth security and efficiency
Authors: Humayun Mamoona , Alsirhani Amjad , Alserhani Faeiz , Shaheen Momina , Alwakid Ghadah 
Published: February 2024

AbstractBlockchain technologies (BCT) are utilized in healthcare to facilitate a smart and secure transmission of patient data. BCT solutions, however, are unable to store data produced by IoT devices in smart healthcare applications because these applications need a quick consensus process, meticulous key management, and enhanced eprivacy standards. In this work, a smart and secure eHealth framework SSEHCET (Smart and Secure EHealth Framework using Cutting-edge Technologies) is proposed that leverages the potentials of modern cutting-edge technologies (IoT, 5G, mobile edge computing, and BCT), which comprises six layers: 1) The sensing layer-WBAN consists of medical sensors that normally are on or within the bodies of patients and communicate data to smartphones. 2) The edge layer consists of elements that are near IoT devices to collect data. 3) The Communication layer leverages the potential of 5G technology to transmit patients' data between multiple layers efficiently. 4) The storage layer consists of cloud servers or other powerful computers. 5) Security layer, which uses BCT to transmit and store patients' data securely. 6) The healthcare community layer includes healthcare professionals and institutions. For the processing of medical data and to guarantee dependable, safe, and private communication, a Smart Agent (SA) program was duplicated on all layers. The SA leverages the potential of BCT to protect patients' privacy when outsourcing data. The contribution is substantiated through a meticulous evaluation, encompassing security, ease of use, user satisfaction, and SSEHCET structure. Results from an in-depth case study with a prominent healthcare provider underscore SSEHCET's exceptional performance, showcasing its pivotal role in advancing the security, usability, and user satisfaction paradigm in modern eHealth landscapes.