bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multidimensional assessment of adverse events associated with paliperidone palmitate: a real-world pharmacovigilance study using the FAERS and JADER databases
Authors: Lou Siyu , Cui Zhiwei , Ou Yingyong , Chen Junyou , Zhou Linmei , Zhao Ruizhen , Zhu Chengyu , Wang Li , Wu Zhu , Zou Fan 
Published: January 2025

Abstract

Objective
Paliperidone palmitate is a second-generation antipsychotic that has undergone extensive investigation in clinical trials. However, real-world studies assessing its safety in large populations are lacking. As such, this study aimed to comprehensively evaluate real-world adverse drug events (ADEs) linked to paliperidone palmitate by employing data mining techniques on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database.

Methods
The study retrieved ADE reports from the FAERS database covering the period from 2009 through the third quarter of 2024, and from the JADER database covering the period from 2013 through the second quarter of 2024. Utilizing disproportionality analyses such as the reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item Poisson shrinkage (MGPS), significant associations between ADEs and paliperidone palmitate were evaluated.

Results
A total of 27,672 ADE reports related to paliperidone palmitate were identified in FAERS, with 285 significantly disproportionate preferred terms (PTs) identified by all four algorithms. Paliperidone palmitate-associated ADEs encompassed 27 System Organ Classes (SOCs). The top three PTs with the highest reported cases were off-label use, drug ineffective, and hospitalization. Common ADEs included increased blood prolactin, galactorrhea, and schizophrenia, which was consistent with drug label. Noteworthy, unexpected signals not listed in the drug label were also identified, such as psychosexual disorders, prolactin-producing pituitary tumors, suicide attempt, and sudden death. The median onset time for all ADEs was 40 days. Furthermore, gender-based difference in risk signals was detected. Females are more likely to experience elevated blood prolactin and weight increase, whereas males are more prone to sexual dysfunction. Among the 1,065 ADE reports from the JADER database, we identified 51 positive signals, 35 of which overlapped with those found in FAERS, including schizophrenia, hyperprolactinemia, and erectile dysfunction.

Conclusion
The study findings from two independent databases serve as crucial references for ensuring the safe of paliperidone palmitate. Additionally, the gender-specific monitoring references provided can enhance clinical surveillance efforts and facilitate more effective risk identification.
Constructing a fall risk prediction model for hospitalized patients using machine learning
Authors: Kang Cheng-Wei , Yan Zhao-Kui , Tian Jia-Liang , Pu Xiao-Bing , Wu Li-Xue 
Published: January 2025

Abstract

Study objectives
This study aimed to identify the risk factors associated with falls in hospitalized patients, develop a predictive risk model using machine learning algorithms, and evaluate the validity of the model’s predictions.

Study design
A cross-sectional design was employed using data from the DRYAD public database.

Research methods
The study utilized data from the Fukushima Medical University Hospital Cohort Study, obtained from the DRYAD public database. 20% of the dataset was allocated as an independent test set, while the remaining 80% was utilized for training and validation. To address data imbalance in binary variables, the Synthetic Minority Oversampling Technique combined with Edited Nearest Neighbors (SMOTE-ENN) was applied. Univariate analysis and least absolute shrinkage and selection operator (LASSO) regression were used to analyze and screen variables. Predictive models were constructed by integrating key clinical features, and eight machine learning algorithms were evaluated to identify the most effective model. Additionally, SHAP (Shapley Additive Explanations) was used to interpret the predictive models and rank the importance of risk factors.

Results
The final model included the following variables: Adl_standing, Adl_evacuation, Age_group, Planned_surgery, Wheelchair, History_of_falls, Hypnotic_drugs, Psychotropic_drugs, and Remote_caring_system. Among the evaluated models, the Random Forest algorithm demonstrated superior performance, achieving an AUC of 0.814 (95% CI: 0.802–0.827) in the training set, 0.781 (95% CI: 0.740–0.821) in the validation set, and 0.795 (95% CI: 0.770–0.820) in the test set.

Conclusion
Machine learning algorithms, particularly Random Forest, are effective in predicting fall risk among hospitalized patients. These findings can significantly enhance fall prevention strategies within healthcare settings.
Trends and disparities in the surgical management of spinal fractures in Sweden during 2008–2023
Authors: Barle Niklas , Axenhus Michael 
Published: January 2025

Abstract

Background
Spinal fractures are a group of complex injuries whose management varies according to a number of factors. The aim of this study was to analyze trends in the management of spinal fracture surgery in Sweden from 2008 to 2023 with a focus on disparities based on gender, surgery method, age and geographical location. A secondary aim was to predict future incidence of spinal fracture surgeries.

Methods
Comprehensive open source data was obtained from the Swedish National Board of Health and Welfare. The data was stratified based on gender, surgery method, age and geographical location per year and analyzed for trends. Future trends were projected using regression modeling. The student’s T-test was used to compare means.

Results
The incidence of spinal fracture surgery decreased overall from 2008 to 2023 while maintaining an increased incidence for males compared to females. The highest incidence for osteosynthesis was 2.7 per 100 000 inhabitants in 2008 and 1 in 2023. This trend is projected to be reversed in 2030. Several surgery methods have decreased in usage and are projected to reach close to 0 in 2030. The patient group that underwent spinal fracture surgery had a higher mean age in 2023 compared to 2008. The incidence of spinal fracture surgery varied significantly across Sweden where region Östergötland performed 6.3 surgeries per 100 000 inhabitants and region Örebro performed 1.4.

Conclusions
We found several trends where males may undergo spinal fractures surgery more commonly than females. Probable influencing factors may be increased life-spans and osteoporosis. This may also explain the observed shift towards older age groups in spinal fracture surgery. The decreased use of several surgery methods may reflect changes in operational techniques, demographics, and more standardized care. Geographical disparities may indicate different local health care protocols and uneven healthcare utilization and access.

Trial registration
Not applicable.
Associations of time to the operating room on outcomes in odontogenic infection
Authors: N. James Jeffrey , Bloomquist Ryan , Brown Kiara , Looney Stephen , Walker Dylan , Day Tyler 
Published: January 2025

Abstract
The purpose of this study was to determine if there were correlations between the length of time from hospital admission to surgical intervention and the frequency of complications in patients with odontogenic infections. While odontogenic infection is well studied in terms of interventions and outcomes, less is known about hospital utilization and resource burden of odontogenic infection with respect to timeliness to intervention. A retrospective cohort analysis was used to examine correlations between time from admission to surgical intervention and clinical outcomes. Patients included in this study were divided into three categories of length of time to the operating room: 0–12 h, 12.1–24 h, and greater than 24 h. Time of admission, time of surgical intervention, patient demographics, admission lab values, and space involvement were measured and compared to the primary outcome variables including complications of intubation attempts and type, ICU admission, length of hospitalization, number of changes in antibiotic therapy, and frequency of return to the operating room. We found that the length of time to the OR had a statistically significant association with length of hospital stay (p = 0.003) and number of changes in antibiotic therapy (p = 0.033). While overall length of hospital stay is inherently dependent on length of time to the OR, this relationship highlights the importance of timeliness to definitive intervention in order to reduce hospital burden. This study provides evidence on how to prioritize odontogenic infections in a hospital setting. We recommend treating odontogenic infection in less than 24 h from the time of admission in order to reduce costs and improve outcomes for patients.
Caregivers’ experience of having a child with Down syndrome: a meta-synthesis
Authors: Zhang Xiao Nan , Zhang Shuo , Liu Chun Yan , Ni Zhi Hong , Lv Hai Tao 
Published: January 2025

Abstract

Background
This study aimed to integrate the experiences of caregivers of children with Down syndrome during the care process and understand their feelings and needs.

Methods
We used Page et al.’s (2021) Preferred Reporting Items for Systematic Reviews and Meta-synthesis Statement. Ten databases (Web of Science, PubMed, EMBASE, Cochrane Library, CINAHL, PsycInfo, China Biology Medicine, China National Knowledge Infrastructure, Wanfang Data, and China Science and Technology Journal Database) were searched for relevant studies published from the inception of the database to October 2023. Eight qualitative studies were analysed. The following seven themes were included: ‘feeding pressure’, ‘hope for education’, ‘societal rejection and stigma’, ‘psychological pressure’, ‘caring burden’, ‘family burden’, and ‘family adaptation and self-growth’.

Results
We found that feeding pressures, educational concerns, language difficulties, and discrimination and stigmatisation led to psychological, economic, and family stress in caregivers of children with Down syndrome. We document the need for strong coping mechanisms and support systems for these families from medical and psychological institutions and a need for public education and awareness.

Conclusions
We summarised the daily care experiences of caregivers of children with Down syndrome. Our findings provide a scientific basis for further research focused on reducing physical and mental pressure on caregivers and improving the quality of family life.
Navigating diabetes care inequities: an observational study linking chronic care model’s structural elements to process and outcomes of type 2 diabetes care in Belgium
Authors: Bos Philippe , Danhieux Katrien , Wouters Edwin , Olmen Josefien van , Buffel Veerle 
Published: January 2025

Abstract

Background
Although the Chronic Care Model (CCM) provides the essential structural components of practice organisation to deliver high-quality type 2 diabetes (T2D) care, little is known about which of its elements are most important, and the extent to which it may reduce social inequities in the quality of T2D care. This study aims to assess the association between the implementation of CCM’s structural elements and the quality of T2D care processes and outcomes in Flanders (Belgium), paying specific attention to differences by patients’ socioeconomic vulnerability.

Methods
We developed a longitudinal database combining information on primary care practices’ CCM implementation, with individual-level health insurance and medical lab data. Our sample included 7,593 T2D patients aged 40 years and above from 58 primary care practices in Flanders, followed up from 2017 to 2019. Medical lab data were available for a subsample of 4,549 patients. By estimating a series of hierarchical mixed-effects models, we assessed the association between primary care practices’ CCM implementation and two process and two outcome indicators of T2D care. In addition, we explored cross-level interactions with patients’ socioeconomic vulnerability.

Results
Patients were more likely to have their HbA1c tested twice a year and LDL cholesterol tested yearly in practices with a higher overall CCM implementation. Regarding the different CCM elements, the clinical information system and linkages to the community were significantly associated with higher odds of being up-to-date with HbA1c testing, whereas stronger community linkages was the only dimension significantly associated with yearly LDL cholesterol testing. While socioeconomic vulnerable patients were less likely to have their HbA1c tested twice yearly, this difference disappeared in the highest-scoring practices. Regarding the outcome indicators, only a negligible proportion of variation in HbA1c and LDL cholesterol levels was due to systematic differences between practices, and hence, no clinically relevant associations with the CCM elements were found.

Conclusion
Our pioneering findings support the social capital pathway, as CCM implementation is associated with a reduction in the healthcare inequity gap in the T2D care process. This suggests that promoting CCM implementation may improve healthcare equity, particularly in regions with significant socioeconomic disparities or high concentrations of deprived individuals.
Mixed vulnerabilities: the biological risk of high parity is aggravated by emergency referral in Benin, Malawi, Tanzania and Uganda
Authors: Straneo Manuela , Beňová Lenka , van den Akker Thomas , Abeid Muzdalifat S. , Ayebare Elizabeth , Dossou Jean-Paul , Handing Greta , Kandeya Bianca , Pembe Andrea B. , Hanson Claudia 
Published: January 2025

Abstract
Identification of interacting vulnerabilities is essential to reduce maternal and perinatal mortality in sub-Saharan Africa (SSA). High parity (≥ 5 previous births) is an underemphasized biological vulnerability linked to poverty and affecting a sizeable proportion of SSA births. Despite increased risk, high parity women rarely use hospitals for childbirth. We assessed whether emergency referral during childbirth was associated with adverse events in high parity women in hospitals in Benin, Malawi, Tanzania and Uganda. We used e-registry data collected in 16 hospitals included in the Action Leveraging Evidence to Reduce perinatal morbidity and morTality (ALERT) trial. Main outcomes were severe maternal outcomes and in-facility peripartum death (fresh stillbirth or very early neonatal death). Main exposure was parity; emergency (in-labour) referral was included as effect modifier with potential confounders. We used multivariable logistic regression including parity/referral interaction and post-regression margins analysis. Among 80,663 births, 4,742 (5.9%) were to high parity women. One third reached hospital following emergency referral. Severe maternal outcomes and peripartum mortality were over 2.5-fold higher in high parity women with emergency referral compared to the lowest risk group. To avert these adverse events, emergency referral must be avoided by ensuring high parity women give birth in hospitals.

Trial registration Pan African Clinical Trial Registry (www.pactr.org): PACTR202006793783148. Registered on 17th June 2020.
Towards personalized immersive virtual reality neurorehabilitation: a human-centered design
Authors: Cucinella Salvatore Luca , de Winter Joost C. F. , Grauwmeijer Erik , Evers Marc , Marchal-Crespo Laura 
Published: January 2025

Abstract

Background
Head-mounted displays can be used to offer personalized immersive virtual reality (IVR) training for patients who have suffered an Acquired Brain Injury (ABI) by tailoring the complexity of visual and auditory stimuli to the patient’s cognitive capabilities. However, it is still an open question how these virtual environments should be designed.

Methods
We used a human-centered design approach to help define the characteristics of suitable virtual training environments for ABI patients. We conducted (i) observations, (ii) interviews with eleven neurorehabilitation experts, and (iii) an online questionnaire with 24 neurorehabilitation experts to examine how therapists modify current training environments to promote patients’ recovery in conventional sensorimotor neurorehabilitation settings. Finally, (iv) we involved eight neurorehabilitation experts in a participatory design workshop to co-create examples of IVR training environments.

Results
Five phases of the recovery process (Screening, Planning, Training, Reflecting, and Discharging) and six key themes describing the characteristics of suitable (physical) training environments (Specific, Meaningful, Versatile, Educational, Safe, and Supportive) were identified. The experts agreed that modulating the number of elements (e.g., objects, people) or distractions (e.g., background noise) in the physical training environment enables therapists to provide their patients with suitable conditions to execute functional tasks. Additionally, the experts highlighted the importance of developing IVR training environments that are meaningful and realistic.

Conclusions
Through consultations with neurorehabilitation experts, we gained insights into how therapists adjust physical training environments to promote the execution of functional sensorimotor tasks in patients with diverse cognitive capabilities. Their recommendations on how to modulate and make IVR environments meaningful may contribute to increased motivation and skill transfer. Future studies on IVR-based neurorehabilitation should involve patients themselves.
The GLP-1R agonist semaglutide reshapes pancreatic cancer associated fibroblasts reducing collagen proline hydroxylation and favoring T lymphocyte infiltration
Authors: Cencioni Chiara , Malatesta Silvia , Vigiano Benedetti Virginia , Licursi Valerio , Perfetto Livia , Conte Federica , Ranieri Danilo , Bartolazzi Armando , Kunkl Martina , Tuosto Loretta , Larghi Alberto , Piro Geny , Agostini Antonio , Tortora Giampaolo , Corbo Vincenzo , Carbone Carmine , Spallotta Francesco 
Published: January 2025

Abstract

Background
Metabolic syndrome represents a pancreatic ductal adenocarcinoma (PDAC) risk factor. Metabolic alterations favor PDAC onset, which occurs early upon dysmetabolism. Pancreatic neoplastic lesions evolve within a dense desmoplastic stroma, consisting in abundant extracellular matrix settled by cancer associated fibroblasts (CAFs). Hereby, dysmetabolism and PDAC association was analyzed focusing on CAF functions.

Methods
PDAC development upon dysmetabolic conditions was investigated in: 1) high fat diet fed wild type immunocompetent syngeneic mice by orthotopic transplantation of pancreatic intraepithelial neoplasia (PanIN) organoids; and 2) primary pancreatic CAFs isolated from chemotherapy naïve PDAC patients with/without an history of metabolic syndrome.

Results
The dysmetabolic-associated higher PDAC aggressiveness was paralleled by collagen fibril enrichment due to prolyl 4-hydroxylase subunit alpha 1 (P4HA1) increased function. Upon dysmetabolism, P4HA1 boosts collagen proline hydroxylation, intensifies collagen contraction strength, precluding PDAC infiltration. Noteworthy, semaglutide, an incretin agonist, prevents the higher dysmetabolism-dependent PDAC stromal deposition and allows T lymphocyte infiltration, reducing tumor development.

Conclusions
These results shed light on novel therapeutic options for PDAC patients with metabolic syndrome aimed at PDAC stroma reshape.
Psychological symptoms, quality of life and dyadic relations in family members of intensive care survivors: a multicentre, prospective longitudinal cohort study
Authors: Rai Sumeet , Needham Dale M. , Brown Rhonda , Neeman Teresa , Sundararajan Krishnaswamy , Rajamani Arvind , Panwar Rakshit , Nourse Mary , van Haren Frank M. P. , Mitchell Imogen ,   for the PRICE study investigators
Published: January 2025

Abstract

Background
There is scarce literature evaluating long term psychological or Quality of Life (QoL) outcomes in family members of ICU survivors, who have not experienced invasive ventilation. The objective was to compare long-term psychological symptoms and QoL outcomes in family members of intubated versus non-intubated ICU survivors and to evaluate dyadic relationships between paired family members and survivors.

Methods
Prospective, multicentre cohort study among four medical-surgical ICUs in Australia. Adult family members of ICU survivors and family-survivor dyads had follow-up assessments (3 and 12 months after ICU discharge), using Impact of Event Scale-Revised; Depression, Anxiety Stress Scales-21; EQ-5D-5L. Dyadic relationships examined associations of psychological symptoms or QoL impairments.

Results
Of 144 family members (75% female, 54% partners/spouses) recruited, 59% cared for previously intubated survivors. Overall, 83% (110/132) of eligible family members completed ≥ 1 follow-up. In family members of intubated vs non-intubated survivors, clinically significant psychological symptoms (PTSD/depression/anxiety) were reported by 48% vs 33% at 3-months (p = 0.15); and 39% vs 25% at 12-months (p = 0.23). Family self-rated their QoL with a mean score of 83 (SD 13) on a visual analogue scale (range 0–100), and > 30% reported problems in pain/discomfort or anxiety/depression domains at 12-months. Family members were more likely to have persistent psychological symptoms of PTSD [OR 4.9, 95% CI (1.47–16.1), p = 0.01] or depression [OR 14.6, 95% CI (2.9–72.6), p = 0.001]; or QoL domain problems with pain/discomfort [OR 6.5, 95% CI (1.14–36.8), p = 0.03] or anxiety/depression [OR 3.5, 95% CI (1.02–12.1), p = 0.04], when the paired survivor also reported the same symptoms.

Conclusions
Almost one-third of the family members of ICU survivors reported persistent psychological symptoms and QoL problems at 12-months. There was a noticeable dyad effect with family members more likely to have persistent symptoms of PTSD, depression, and problems in QoL domains when the paired ICU survivors experienced similar symptoms. The family members of non-intubated ICU survivors had an equal propensity to develop long-term psychological distress and should be included in long-term outcome studies. Future recovery intervention trials should be aimed at ICU family-survivor dyads.

Trial registration ACTRN12615000880549