bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identify the underlying true model from other models for clinical practice using model performance measures
Authors: Li Yan 
Published: January 2025

Abstract
Objective
To assess whether the outcome generation true model could be identified from other candidate models for clinical practice with current conventional model performance measures considering various simulation scenarios and a CVD risk prediction as exemplar.

Study design and setting
Thousands of scenarios of true models were used to simulate clinical data, various candidate models and true models were trained on training datasets and then compared on testing datasets with 25 conventional use model performance measures. This consists of univariate simulation (179.2k simulated datasets and over 1.792 million models), multivariate simulation (728k simulated datasets and over 8.736 million models) and a CVD risk prediction case analysis.

Results
True models had overall C statistic and 95% range of 0.67 (0.51, 0.96) across all scenarios in univariate simulation, 0.81 (0.54, 0.98) in multivariate simulation, 0.85 (0.82, 0.88) in univariate case analysis and 0.85 (0.82, 0.88) in multivariate case analysis. Measures showed very clear differences between the true model and flip-coin model, little or none differences between the true model and candidate models with extra noises, relatively small differences between the true model and proxy models missing causal predictors.

Conclusion
The study found the true model is not always identified as the “outperformed” model by current conventional measures for binary outcome, even though such true model is presented in the clinical data. New statistical approaches or measures should be established to identify the casual true model from proxy models, especially for those in proxy models with extra noises and/or missing causal predictors.
Assessing neonatal nurses: transitioning preterm infants to oral feeding - a multicenter cross-sectional study
Authors: Hendy Abdelaziz , Osman Yasmine M. , Alharbi Hanan F. , Alshammari Maha Suwailem Shuaib , Al-Jabri Mohammed Musaed Ahmed , Alzahrani Naif S. , Hendy Ahmed , Almarwani Abdulaziz Mofdy 
Published: January 2025

Abstract
Background
In Egypt, approximately 10% of preterm deliveries occur between 32 and fewer than 37 weeks, leading to high neonatal intensive care unit (NICU) admissions. Preterm infants often face oral feeding difficulties due to immature development, which can lead to extended hospital stays and increased health risks.

Aim
To assess neonatal nurses’ performance in terms of the transition to oral feeding in preterm infants, focusing on knowledge, practices, and attitudes.

Methods
A descriptive, quantitative, multicenter, cross-sectional study was conducted across 16 hospitals in five governorates in Egypt from November 2023 to March 2024 involving 553 neonatal nurses. The data were collected through a self-administered questionnaire assessing knowledge and attitudes and through an observed checklist for nurses’ practices. The study used statistical methods, including binary logistic regression, to analyze the data.

Results
The findings revealed significant knowledge gaps among nurses, particularly in terms of oro-motor function, suck-swallow-breathe patterns, and nonnutritive sucking. A total of 64.6% of the nurses had unsatisfactory knowledge, 58.6% had unsatisfactory practices, and 45% had a negative attitude toward the oral feeding transition. Key predictors of satisfactory practices included higher education levels, full-time employment, and positive attitudes.

Conclusion
This study highlights critical gaps in neonatal nurses’ knowledge and practices regarding the transition to oral feeding in preterm infants. Addressing these gaps through targeted educational interventions and ongoing support is essential for improving care quality and outcomes for infants. The findings revealed that a substantial proportion of nurses lacked adequate knowledge of critical areas, such as oro-motor function, the suck-swallow-breathe pattern, and nonnutritive sucking. These knowledge deficits could hinder the ability of nurses to provide optimal care during this crucial transition.
The role of hospital pharmacists in supporting the appropriate and safe use of CGT/ATMPs: a scoping review of current insights
Authors: Shi Junnan , Chen Xianwen , Hu Hao , Ung Carolina Oi Lam 
Published: January 2025

Abstract
Background
The role of hospital pharmacists in managing cell and gene therapy (CGT) and advanced therapy medicinal products (ATMPs) is gradually being recognized but the evidence about impact of their role has not been systematically reported.

Objective
This study was aimed to summarize the professional services provided by hospital pharmacists on managing CGT/ATMPs and the evidence about the effects on patient care, as well as to identify the perceptions about pharmacists assuming a role that supports the appropriate and safe use of CGT/ATMPs.

Methods
Literature from 4 electronic databases (PubMed, ScienceDirect, Web of Science, Scopus) were searched following PRISMA checklist to yield publications on the interventions provided by hospital pharmacists in the management of CGT/ATMPs dated since 1 January 2013 till 30 April 2023.

Results
Thirty-four publications were included in this review. Eight studies involving hospital pharmacists participating in interventions for 1,012 hematopoietic stem cell transplant (HSCT) patients from 8 hospitals in 5 countries were identified. Common pharmacist-led interventions centered on medicine administration, prescribing, and monitoring of medicines use, resulting in significant improvement in patient adherence, satisfaction and knowledge. Of 26 studies, the perspectives assuming their roles in CGT/ATMPs management were categorized when patients receiving ATMPs (n = 2), HSCT and cellular-based therapy (n = 12), gene therapy (n = 6), and the chimeric antigen receptor (CAR) T-cell therapy (n = 6), mainly covering procurement, influences on prescribing, preparation and delivery, administration, monitoring of medicines use, human resources, training and development. The anticipated impact was primarily intended to promote pharmacy practice, multidisciplinary collaboration and improve patient clinical outcomes.

Conclusion
Leveraging the role of hospital pharmacists in multidisciplinary healthcare teams to develop a coordinated approach that supports pharmacy practice will better meet the management of CGT/ATMPs. For hospital pharmacists to step up their role in the multidisciplinary healthcare team, advancing their skillset in terms of clinical practice standards and medication management is essential.
Late-life physical activity, midlife-to-late-life activity patterns, APOE ε4 genotype, and cognitive impairment among Chinese older adults: a population-based observational study
Authors: Zhao Xunying , Wu Xueyao , Ma Tianpei , Xiao Jinyu , Chen Xin , Tang Mingshuang , Zhang Li , Zhang Tao , Fan Mengyu , Liao Jiaqiang , Zhang Ben , Jiang Xia , Li Jiayuan 
Published: January 2025

Abstract
Background
Although physical activity (PA) has been linked to cognitive health, the nuanced relationships between different dimensions of PA and cognitive impairment remain inconclusive. This study investigated associations between late-life PA levels, midlife-to-late-life activity patterns, and cognitive impairment in Chinese older adults, considering potential moderation by apolipoprotein E (APOE) ε4 genotype.

Methods
We analyzed baseline data from 6,899 participants (median age 68 years, 55.78% female) in the West China Health and Aging Cohort study, with 6,575 participants having APOE genotyping data. Late-life PA and midlife-to-late-life activity patterns were assessed using the Global Physical Activity Questionnaire and a standardized question, respectively. Cognitive function was evaluated using the Chinese version of Mini-Mental State Examination. Logistic regression models were used to examine associations.

Results
Compared to low PA level, moderate (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.55 ~ 0.99) and high PA levels (OR = 0.60, 95%CI = 0.48 ~ 0.75) were associated with lower risk of cognitive impairment. Engaging in work-, transport-, recreation-related, and moderate-intensity PA were each significantly associated with lower cognitive impairment risk. Maintaining activity levels from midlife to late life was associated with lower cognitive impairment risk compared to decreasing levels (OR = 0.75, 95%CI = 0.60 ~ 0.94). These associations were more pronounced in APOE ε4 non-carriers, with an interaction observed between APOE ε4 genotype and recreation-related PA (P-value = 0.04).

Conclusions
Our findings underscore the multifaceted benefits of PA in mitigating cognitive impairment risk among older Chinese adults. Public health strategies should focus on promoting overall late-life PA levels, especially moderate-intensity PA, and maintaining activity levels comparable to midlife, with potential for personalized interventions based on genetic risk profiles.
The antiosteoporotic effect of oxymatrine compared to testosterone in orchiectomized rats
Authors: Shaban Anwaar M. , Ali Eman A. , Tayel Sara G. , Rizk Sara Kamal , El Agamy Dalia F. 
Published: January 2025

Abstract
Background
Castration of adult male rats led to the development of osteoporosis. Oxidative stress and inflammatory factors have been identified as potential causative factors. Notably, oxymatrine (OMT) possesses potent anti-inflammatory and antioxidant activities. This study aims to elucidate the antiosteoporotic effects of OMT compared to testosterone in an orchiectomized (ORX) rat model of osteoporosis.

Methods
A total of 60 Wistar male rats were divided into the following groups: control (CTRL), surgery + no orchiectomy (SHAM), ORX, ORX + testosterone, and ORX + OMT. Urinary deoxypyridinoline (DPD), calcium (Ca), and phosphorus (P), as well as serum testosterone, parathormone (PTH), alkaline phosphatase (ALP), osteocalcin, N-telopeptide of type I collagen (NTX I), tartrate resistance acid phosphatase (TRAP), and total Ca and P levels were evaluated. Bone was assessed for malondialdehyde (MDA), reduced glutathione (GSH), interleukin 6 (IL-6), Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) expression, and receptor activator of nuclear factor κB ligand/ osteoprotegerin (RANKL/OPG) ratio. Bone dual-energy X-ray absorptiometry (DEXA) scan and histological and immunohistochemical studies were performed.

Results
Testosterone or OMT treatment ameliorated the reduced bone mineral density (BMD) and bone mineral content (BMC) in the DEXA scan and the changes in PTH and Ca levels. Compared to the ORX group, bone formation, and turnover markers were also significantly reversed in the treatment groups. Treatment with testosterone or OMT significantly reduced bone MDA, IL-6, Keap1, RANKL, and RANKL/OPG ratio, and significantly elevated bone GSH, Nrf2, and HO-1. Moreover, testosterone or OMT treatment has restored cortical bone thickness and osteocyte number and reduced bone levels of TNF-α in ORX rats. Consequently, treatment with either testosterone or OMT exhibited nearly equal therapeutic efficacy; however, neither of them could normalize the measured parameters.

Conclusion
OMT treatment showed equal efficacy compared to testosterone in ameliorating osteoporosis in ORX rats, possibly by improving some inflammatory and oxidative stress parameters.
ONC213: a novel strategy to resensitize resistant AML cells to venetoclax through induction of mitochondrial stress
Authors: Carter Jenna L. , Su Yongwei , Al-Antary Eman T. , Zhao Jianlei , Qiao Xinan , Wang Guan , Edwards Holly , Polin Lisa , Kushner Juiwanna , Dzinic Sijana H. , White Kathryn , Buck Steven A. , Hüttemann Maik , Allen Joshua E. , Prabhu Varun V. , Yang Jay , Taub Jeffrey W. , Ge Yubin 
Published: January 2025

Abstract
Background
Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and a salvage therapy for relapsed/refractory patients who have been treated with intensive chemotherapy. While this is an important treatment option, many patients fail to achieve complete remission and of those that do, majority relapse. Leukemia stem cells (LSCs) are believed to be responsible for AML relapse and can be targeted through oxidative phosphorylation reduction. We previously reported that ONC213 disrupts oxidative phosphorylation and decreases Mcl-1 protein, which play a key role in venetoclax resistance. Here we investigated the antileukemic activity and underlying molecular mechanism of the combination of ONC213 + venetoclax against AML cells.

Methods
Flow cytometry was used to determine drug-induced apoptosis. Protein level changes were determined by western blot. An AML cell line-derived xenograft mouse model was used to determine the effects of ONC213 + venetoclax on survival. A patient-derived xenograft (PDX) mouse model was used to determine drug effects on CD45+/CD34+/CD38-/CD123 + cells. Colony formation assays were used to assess drug effects on AML progenitor cells. Mcl-1 and Bax/Bak knockdown and Mcl-1 overexpression were used to confirm their role in the mechanism of action. The effect of ONC213 + venetoclax on mitochondrial respiration was determined using a Seahorse bioanalyzer.

Results
ONC213 + venetoclax synergistically kills AML cells, including those resistant to venetoclax alone as well as venetoclax + azacitidine. The combination significantly reduced colony formation capacity of primary AML progenitors compared to the control and either treatment alone. Further, the combination prolonged survival in an AML cell line-derived xenograft model and significantly decreased LSCs in an AML PDX model.

Conclusions
ONC213 can resensitize VEN + AZA-resistant AML cells to venetoclax therapy and target LSCs ex vivo and in vivo.
Interplay of swine acute diarrhoea syndrome coronavirus and the host intrinsic and innate immunity
Authors: Zhao Fei , Cong Xiao , Huang Xiaobo , Zheng Yi , Zhao Qin , Wen Yiping , Wu Rui , Du Senyan , Cao Sanjie , Cong Feng , Wang Yiping 
Published: January 2025

AbstractSwine acute diarrhoea syndrome coronavirus (SADS-CoV), a novel HKU2-related coronavirus of bat origin, is a newly emerged swine enteropathogenic coronavirus that causes severe diarrhoea in piglets. SADS-CoV has a broad cell tropism with the capability to infect a wide variety of cells from human and diverse animals, which implicates its ability to hold high risks of cross-species transmission. The intracellular antiviral immunity, comprised of the intrinsic and innate immunity, represents the first line of host defence against viral infection prior to the onset of adaptive immunity. To date, there are no vaccines and drugs approved to prevent or treat SADS-CoV infection. Understanding of the mutual relationship between SADS-CoV infection and host immunity is crucial for the development of novel vaccines and drugs against SADS-CoV. Here, we review recent advancements in our understanding of the interplay between SADS-CoV infection and the host intrinsic and innate immunity. The extensive and in-depth investigation on their interactive relationship will contribute to the identification of new targets for developing intervention strategies to control SADS-CoV infection.
Molecular characterization of swine acute diarrhea syndrome coronavirus detected in Vietnamese pigs
Authors: Le Nam Phuong , Le Bac Tran , Le Van Phan , Park Jung-Eun 
Published: January 2025

AbstractSwine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine coronavirus that was recently identified in southern China in 2017. At present, there is a lack of nationwide epidemiological investigations of the newly emerged SADS-CoV. Because Vietnam is geographically adjacent to southern China, many diseases have spread from China to Vietnam. To assess SADS-CoV transmission to Vietnam, we conducted a retrospective study to detect SADS-CoV in samples collected from pig farms in northern Vietnam. Among the 69 fecal samples tested, 5 were positive for SADS-CoV. The spike gene sequence showed high genetic homology with strains circulating in China. Our study is the first to show that SADS-CoV has spread from China to Vietnam and highlights the need for global epidemiological investigations of SADS-CoV.
Maladaptive changes in the homeostasis of AEA-TRPV1/CB1R induces pain-related hyperactivity of nociceptors after spinal cord injury
Authors: Hu JiaQi , Fan WenYong , Xu Yue , Li XiaoFei , Zhang HaoYang , Li Shun , Xue Lei 
Published: January 2025

Abstract
Background
Neuropathic pain resulting from spinal cord injury (SCI) is associated with persistent hyperactivity of primary nociceptors. Anandamide (AEA) has been reported to modulate neuronal excitability and synaptic transmission through activation of cannabinoid type-1 receptors (CB1Rs) and transient receptor potential vanilloid 1 (TRPV1). However, the role of AEA and these receptors in the hyperactivity of nociceptors after SCI remains unclear.

Results
In this study, we investigated the effects of AEA and its receptors on the hyperexcitability of mouse dorsal root ganglion (DRG) neurons after SCI. Using a whole-cell patch-clamp technique, we found that the timing of SCI-induced hyperexcitability in nociceptors paralleled an increase in the endocannabinoid AEA content. The expression of TRPV1 and CB1R was also upregulated at different time points after SCI. High-dose extracellular administration of AEA increased the excitability of naive DRG neurons, leading to the transition from a rapidly accommodating (RA) hypoexcitable state to a highly excitable non-accommodating (NA) state. These AEA-induced transitions were facilitated by increased TRPV1 transcription. Pharmacological and Ca2+ imaging experiments revealed that AEA induced hyperexcitability in nociceptors after SCI via the AEA-TRPV1-Ca2+ pathway, whereas activation of CB1Rs reduced SCI-induced hyperexcitability and maintained cytosolic Ca2+ concentration ([Ca2+]cyto) at low levels in the early stages of SCI. As the AEA and TRPV1 levels increased after SCI, adaptive neuroprotection transitioned to a maladaptive hyperactive state, leading to sustained pain.

Conclusions
Taken together, this study provides new insights into how endocannabinoids regulate nociceptor activity after SCI, offering potential targets for the treatment of neuropathic pain.
Effectiveness of digital health applications on the quality of life in patients with overweight or obesity: a systematic review
Authors: Mäder Melanie , Schönfelder Tonio , Heinrich Ria , Militzer-Horstmann Carsta , Timpel Patrick 
Published: January 2025

Abstract
Background
Globally, more than half of the adult population is overweight, including those who are obese, which increases the risk of premature death and reduces quality of life (QoL). Technologies such as digital health applications (DiHA) can potentially improve clinical outcomes (e.g., health status, illness duration, QoL) or patient-related factors (e.g., therapy monitoring, adherence, health literacy). To date, there is no systematic review addressing the effectiveness of DiHA on the QoL in patients with overweight or obesity.

Objective
The objective was to investigate the impact of DiHA on QoL in overweight or obese patients.

Methods
A systematic literature search was conducted in MEDLINE via PubMed, Cochrane Library, and Embase via Ovid in 2023, supplemented by additional manual searches. The eligibility criteria included patients with overweight and/or obesity who used a digital intervention independently and without interaction with a healthcare professional. The outcome of interest was QoL. As potentially eligible trials had to demonstrate effectiveness, only randomized controlled trials (RCT) were included as the minimum evidence standard. The study screening (title-abstract, full-text) was conducted independently by two researchers using pre-specified eligibility criteria. CONSORT-EHEALTH checklist was used for data extraction of qualitative and quantitative data (study characteristics and study results) and the Cochrane Risk of Bias Tool (version 2) for quality assessment independently by two researchers.

Results
Seven RCT conducted in Europe and the United States were included in this systematic review with a total sample size of N = 946. Observation periods were heterogeneous and ranged from 3 to 24 months. The evaluated interventions consisted of websites or apps, all of which included nutrition and physical activity features, and functioned independently with minimal or no involvement of a healthcare professional. All studies showed a high risk of bias, no statistically significant improvement and no effects regarding QoL using different validated questionnaires.

Conclusions
This systematic review provides a comprehensive analysis of DiHA effectiveness on QoL in patients with overweight or obesity. Overall, there is heterogeneity regarding the operationalization of QoL and the examined interventions have no statistically significant impact on QoL. Comparable systematic reviews show that digital interventions have the potential to improve the QoL of these patients, but further RCT and high-quality studies are needed to assess the impact of DiHA on QoL.

Trial registration
PROSPERO CRD42023408994.
Characteristics of e-scooter and bicycle injuries at a university hospital in a large German city – a one-year analysis
Authors: Hartz Frederik , Zehnder Philipp , Resch Tobias , Römmermann Gregor , Hartmann Victoria , Schwarz Markus , Kirchhoff Chlodwig , Biberthaler Peter , Zyskowski Michael 
Published: January 2025

Abstract
Background
The increasing adoption of individual urban mobility in European cities is contributing to a rise in the number of bicycle and e-scooter users. Consequently, a corresponding increase in accidents, along with an additional burden on emergency departments, is anticipated, particularly in metropolitan areas. The objective of this prospective cross-sectional study was to gather detailed information regarding the patient demographics, accident mechanisms, and injury patterns of e-scooter riders in comparison to cyclists. Identifying any differences between these groups will provide a foundation for developing targeted prevention strategies and safety measures aimed at reducing the incidence of accidents and injuries.

Methods
All patients who presented to the emergency department of our level I university trauma center after an accident involving a traditional bicycle without electric assistance or an e-scooter in 2022 were recorded. Demographic data as well as information regarding the trauma mechanism, injury pattern, alcohol influence, treatment requirements and helmet use were analyzed and compared between the two groups.

Results
In 2022, a total of 626 patients were identified after a bicycle accident and 98 patients after an e-scooter accident. E-scooter riders were with a mean age of 31.0 years (standard deviation (SD) 10.7) significantly younger compared to bicycle riders at 43.2 years (SD 16.5; p < 0.001). More than half of the patients in both groups were male (e-scooter 69.4% versus bicycle 60.7%). E-scooter riders were more likely to be intoxicated (31.6% vs. 5.4%; p < 0.001), not wearing a helmet (93.9% vs. 78.4%; p < 0.001) and to have had accidents at nighttime (39.8% vs. 11.5%; p < 0.001). There was no significant difference between the distribution of minor (e-scooter 75.2% vs. bicycle 70.3%) and major (24.8% vs. 29.7%) injuries. In terms of body regions, e-scooter riders suffered from major injuries to the skull, facial cranium, cervical spine (43.8% e-scooter vs. 22.4% bicycle; p = 0.008) and less frequently to the trunk, thoracic and lumbar spine and pelvis (0.0% vs. 13.6%).

Conclusion
Compared to cyclists, injured e-scooter riders are younger, mostly do not wear a helmet and more often ride under the influence of alcohol. E-scooter accidents occur more frequently at night and the riders are more likely to suffer serious head injuries.