bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of joint interactions in upper limb joint movements: a disability simulation study using wearable inertial sensors for 3D motion capture
Authors: Bhagat Nishtha , Raghavan Preeti , Kapila Vikram 
Published: November 2024

AbstractBackgroundRestriction of movement at a joint due to disease or dysfunction can alter the range of motion (ROM) at other joints due to joint interactions. In this paper, we quantify the extent to which joint restrictions impact upper limb joint movements by conducting a disability simulation study that used wearable inertial sensors for three-dimensional (3D) motion capture.MethodsWe employed the Wearable Inertial Sensors for Exergames (WISE) system for assessing the ROM at the shoulder (flexion–extension, abduction–adduction, and internal–external rotation), elbow (flexion–extension), and forearm (pronation-supination). We recruited 20 healthy individuals to first perform instructed shoulder, elbow, and forearm movements without any external restrictions, and then perform the same movements with restriction braces placed to limit movement at the shoulder, elbow, and forearm, separately, to simulate disability. To quantify the extent to which a restriction at a non-instructed joint affected movement at an instructed joint, we computed average percentage reduction in ROM in the restrictedversusunrestricted conditions. Moreover, we performed analysis of variance and post hoc Tukey tests (qstatistic) to determine the statistical significance (p < 0.05 denoted using *) of the differences in ROM of an instructed joint in the unrestrictedversusrestricted conditions.ResultsRestricting movement at the shoulder led to a large reduction in the average ROM for elbow flexion–extension (21.93%,q = 9.34*) and restricting elbow movement significantly reduced the average ROM for shoulder flexion–extension (17.77%,q = 8.05*), shoulder abduction–adduction (19.80%,q = 7.60*), and forearm pronation-supination (14.04%,q = 4.96*). Finally, restricting the forearm significantly reduced the average ROM for shoulder internal–external rotation (16.71%,q = 3.81*) and elbow flexion–extension (10.01%,q = 4.27*).ConclusionsJoint interactions across non-instructed joints can reduce the ROM of instructed movements. Assessment of ROM in the real-world using 3D motion capture, for example using the WISE system, can aid in understanding movement limitations, informing interventions, and monitoring progress with rehabilitation.
Ren-Shen-Bu-Qi decoction alleviates exercise fatigue through activating PI3K/AKT/Nrf2 pathway in mice
Authors: Chen Yangyang , Gao Tinghui , Bai Jing , Zhang Wenjing , Zhou Yutong , Zhao Ruichang , Deng Youhui , Liu Xiaogang , Huang Zhangjun , Wang Songtao , Shen Caihong , Liu Sijing , Guo Jinlin 
Published: November 2024

Abstract
Background
Fatigue is a prevalent issue that can lead individuals to a sub-health condition, impacting their work efficiency and quality of life. There are limited effective treatment options available for fatigue. Ren-Shen-Bu-Qi decoction (RSBQD) is a proprietary herbal remedy that is designed to address fatigue. However, the specific pharmacological mechanisms and basis of RSBQD are not yet fully understood.

Purpose
This study aimed to investigate the pharmacological effects and mechanisms of RSBQD in a mouse model of exercise fatigue.

Materials and methods
UPLC-Q-Orbitrap HRMS was used to analyze the chemical composition of RSBQD. The pharmacological basis and molecular mechanism of RSBQD on exercise fatigue were predicted using network pharmacology analysis. Subsequently, an exercise fatigue mouse model was established and used to analysis the effects of RSBQD. The potential mechanisms were verified by hematoxylin–eosin (HE) staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking.

Results
The results showed that 88 main components of RSBQD were identified, which have mainly belonged to flavonoids and carboxylic acid compounds. The network pharmacology analysis indicated that RSBQD ameliorate fatigue through PI3K/AKT signaling pathway. Notably, RSBQD prolonged the swimming time and diminished body weight loss of exercise fatigue mice (P < 0.05). Meanwhile, RSBQD significantly alleviated the injury of liver and kidney induced by exhaustive exercise, and decreasing the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and BUN levels (P < 0.05). In addition, RSBQD was found could relieve exercise fatigue by decreasing the content of creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid (LA), but increasing the blood glucose (GLU) and liver glycogen (HG) levels (P < 0.05). RSBQD also significantly increased the hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) but decreased hepatic malondialdehyde (MDA) levels. Moreover, RSBQD was able to upregulate protein level of activated Nrf2 and PI3K/AKT signaling pathways.

Conclusions
RSBQD mitigates exercise fatigue by reversing metabolic changes and reducing oxidative damage through the PI3K/AKT/Nrf2 signaling pathway. This study offers pharmacological support for the utilization of RSBQD in exercise fatigue treatment.

Graphical Abstract
Quality of life and mental health status in caregivers of pediatric patients with nephropathic cystinosis
Authors: González Karina , Eixarch Teresa , Nuñez Laura , Ariceta Gema 
Published: November 2024

AbstractThere are few studies assessing psychological burden and quality of life (QoL) in caregivers of pediatric patients with nephropathic cystinosis, a severe chronic disease. This observational, single-center study aimed to explore the levels of anxiety, depression, care burden, and QoL status in caregivers of patients with nephropathic cystinosis. The Hospital Anxiety and Depression Scale (HADS), the Zarit Caregiver Burden Scale, and the Short Form-36 (SF-36) were administered to caregivers of pediatric patients with nephropathic cystinosis. Nine caregivers of pediatric patients with nephropathic cystinosis participated in the study (6 boys and 3 girls; mean age, 12.6 ± 4.2 years). All participating caregivers were the patient’s mothers. Of the 9 caregivers, 6 showed anxiety/depression and 4 severe care burden. Overall, SF-36 QoL domains with a worse perception by caregivers were ‘general health’ and ‘health change over time’. Mothers without depression/anxiety and low care burden had better QoL perception (p = 0.02). All caregivers with high care burden showed anxiety/depression. In our study cohort, caregivers of pediatric patients with nephropathic cystinosis showed high levels of anxiety/depression, high care burden, and impaired QoL, highlighting the importance of detecting psycho-social issues to implement strategies that relieve family stress and improve coping strategies.
Study on the disease burden of patients with mucopolysaccharidosis type II in China
Authors: Yuan Ni , Li Min , Wang Shan-Shan , Yu Hua-Xin , Wang Ya-Qun , Dong Fan-Yu , Chen Han-Xiang , Duan Sheng-Nan , Luo Ji 
Published: November 2024

Abstract
Background
In this study, we investigated the patient population of Mucopolysaccharidosis type II (MPS II) in China, understood the basic situation, prevalence and diagnosis and treatment status of the patients, as well as the economic burden of the patients, and analyzed the influencing factors.

Methods
A cross-sectional study focusing on patients with MPS II was conducted in China in 2023. Participants in the study were drawn from the Beijing Zhengyu Mucopolysaccharide Rare Disease Care Center, which is the only non-profit organization in mainland China registered with the civil affairs department that focuses on mucopolysaccharidosis. Data were collected through an online questionnaire, which included basic patient information, disease status, self-assessment of quality of life, diagnosis and treatment, as well as direct and indirect medical costs. The demographic and diagnosis and treatment profile of patients were analyzed by descriptive statistics. Furthermore, univariate and multiple linear regression were used to explore the economic burden and influencing factors of patients with MPS II.

Results
The survival data of 145 patients were collected, the majority (98.62%) were male, and 78 were less than or equal to 10 years old. All patients were covered by medical insurance, mainly urban residents (135 cases). In terms of expenses, the 124 patients in the year before the survey incurred a total cost of about 14.7895 million yuan, and the direct economic burden accounted for 87.19%. Univariate analysis showed that age, number of hospitalizations, length of hospital stay, number of outpatient/emergency departments, hematopoietic stem cell transplantation (HSCT), and enzyme replacement therapy (ERT) were significantly associated with the economic burden of disease. Multiple regression analysis showed that the number of hospitalizations, days of hospitalization, number of outpatient/emergency departments and HSCT treatment were the main influencing factors.

Conclusions
This study found that patients with MPS II were difficult to diagnose and easily misdiagnosed, their physical functions were impaired in many aspects. The existing treatment options are not sufficient in terms of economy and effectiveness, and there is also a lack of corresponding policy guarantees and support, which makes patients and their families have to face huge financial pressure.
A nanoencapsulated oral formulation of fenretinide promotes local and metastatic breast cancer dormancy in HER2/neu transgenic mice
Authors: De Angelis Maria Laura , Francescangeli Federica , Aricò Eleonora , Verachi Paola , Zucchetti Massimo , Matteo Cristina , Petricci Elena , Pilozzi Emanuela , Orienti Isabella , Boe Alessandra , Eramo Adriana , Rossi Rachele , Corati Tiberio , Macchia Daniele , Pacca Anna Maria , Zeuner Ann , Baiocchi Marta 
Published: November 2024

Abstract
Background
Prevention and treatment of metastatic breast cancer (BC) is an unmet clinical need. The retinoic acid derivative fenretinide (FeR) was previously evaluated in Phase I-III clinical trials but, despite its excellent tolerability and antitumor activity in preclinical models, showed limited therapeutic efficacy due to poor bioavailability. We recently generated a new micellar formulation of FeR, Bionanofenretinide (Bio-nFeR) showing enhanced bioavailability, low toxicity, and strong antitumor efficacy on human lung cancer, colorectal cancer, and melanoma xenografts. In the present study, we tested the effect of Bio-nFeR on a preclinical model of metastatic BC.

Methods
We used BC cell lines for in vitro analyses of cell viability, cell cycle and migratory capacity. For in vivo studies, we used HER2/neu transgenic mice (neuT) as a model of spontaneously metastatic BC. Mice were treated orally with Bio-nFeR and at sacrifice primary and metastatic breast tumors were analyzed by histology and immunohistochemistry. Molecular pathways activated in primary tumors were analyzed by immunoblotting. Stem cell content was assessed by flow cytometry, immunoblotting and functional assays such as colony formation ex vivo and second transplantation assay in immunocompromised mice.

Results
Bio-nFeR inhibited the proliferation and migration of neuT BC cells in vitro and showed significant efficacy against BC onset in neuT mice. Importantly, Bio-nFeR showed the highest effectiveness against metastatic progression, counteracting both metastasis initiation and expansion. The main mechanism of Bio-nFeR action consists of promoting tumor dormancy through a combined induction of antiproliferative signals and inhibition of the mTOR pathway.

Conclusion
The high effectiveness of Bio-nFeR in the neuT model of mammary carcinogenesis, coupled with its low toxicity, indicates this formulation as a potential candidate for the treatment of metastatic BC and for the adjuvant therapy of BC patients at high risk of developing metastasis.
Interplay of paternal caregiving and screen use habits on early childhood development and children’s tantrums
Authors: Sari Emre , Yalçın Sıddıka Songül 
Published: November 2024

Abstract
Background
This study aims to examine the association for paternal care and father-child screen use with early childhood development and children’s temper tantrums.

Method
Study file included questions about paternal characteristics, child care, father-child screen habits, and utilized the UNICEF Early Childhood Development Index (ECDI). Factors influencing ECDI-on-track status and children’s responses when screen use was restricted were investigated with Chi-square test and multiple logistic regression.

Results
The study included 464 fathers having children aged 3–4 years. The findings showed that 89.7% of the children were on track in three out of the four ECDI subgroups. When screen use was restricted, 55.6% of the children engaged in another activity, while 44.4% reacted by crying. Multiple logistic regression analysis revealed that the father’s education level, the child’s age and gender, the starting age for screen usage, the child’s reaction to screen restriction, and having three or more books were associated with ECDI. Furthermore, the child’s reaction to screen restriction was related to the child’s and father’s screen time, the presence of three or more books, the adequacy of care, and being on track in the literacy-numeracy ECDI subgroup.

Conclusion
Screen usage habits significantly impact early childhood development and children’s reactions to screen restrictions. These findings underscore the importance of educating fathers about the effects of their own and their child’s media habits, the quality of fatherly caregiving, and the presence of books in fostering positive child development.
CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants
Authors: Oksza-Orzechowski Kazimierz , Quinten Edwin , Shafighi Shadi , Kiełbasa Szymon M. , van Kessel Hugo W. , de Groen Ruben A. L. , Vermaat Joost S. P. , Sepúlveda Yáñez Julieta H. , Navarrete Marcelo A. , Veelken Hendrik , van Bergen Cornelis A. M. , Szczurek Ewa 
Published: November 2024

AbstractTumours exhibit high genotypic and transcriptional heterogeneity. Both affect cancer progression and treatment, but have been predominantly studied separately in follicular lymphoma. To comprehensively investigate the evolution and genotype-to-phenotype maps in follicular lymphoma, we introduce CaClust, a probabilistic graphical model integrating deep whole exome, single-cell RNA and B-cell receptor sequencing data to infer clone genotypes, cell-to-clone mapping, and single-cell genotyping. CaClust outperforms a state-of-the-art model on simulated and patient data. In-depth analyses of single cells from four samples showcase effects of driver mutations, follicular lymphoma evolution, possible therapeutic targets, and single-cell genotyping that agrees with an independent targeted resequencing experiment.
Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial
Authors: Kunkel Joakim Bo , Holle Sarah Louise Duus , Hassager Christian , Pecini Redi , Wiberg Sebastian , Palm Pernille , Holmvang Lene , Bang Lia Evi , Kjærgaard Jesper , Thomsen Jakob Hartvig , Engstrøm Thomas , Møller Jacob Eifer , Lønborg Jacob Thomsen , Frydland Martin , Søholm Helle 
Published: November 2024

Abstract
Background
Inflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties.

Methods
This is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24–48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB).

Discussion
Modulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints.

Trial registration
Registered with the Regional Ethics Committee (H-21045751), EudraCT (2021–002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277–8523.
Associations between biomarkers and skeletal muscle function in individuals with osteoarthritis: a systematic review and meta-analysis
Authors: Smith Stephanie L. , Paul Lorna , Steultjens Martijn P. M. , Jones Rebecca L. 
Published: November 2024

Abstract
Objectives
Skeletal muscle dysfunction is the primary cause of functional limitations in osteoarthritis, associated biomarkers have the potential as targets for early disease identification, diagnosis, and prevention of osteoarthritis disability. This review aimed to identify associations between biomarkers and lower limb skeletal muscle function in individuals with osteoarthritis.

Methods
A systematic literature review and meta-analysis conducted in PubMed, MEDLINE, CINAHL, EMBASE, Scopus, SPORTDiscus and Web of Science databases from inception to 8th August 2023. Two independent reviewers performed the title, abstract, full-text screening, data extraction and methodological quality assessment. A meta-analysis was undertaken based on the available data.

Results
Twenty-four studies with 4101 participants with osteoarthritis were included (females: 78%; age range; 49 to 71 years). One study reported muscle-specific biomarkers (n = 3), whilst six studies reported osteoarthritis-specific markers (n = 5). Overall, 93 biomarkers were reported, predominately characterised as inflammatory (n = 35), metabolic (n = 15), and hormones (n = 10). Muscle strength and vitamin D reported a significant association (Hedge’s g: 0.58 (Standard Error (SE): 0.27; P = 0.03), k = 3 studies). Walking speed and high-sensitivity C-reactive protein reported no significant associations (Hedge’s g: -0.02 (SE: 0.05; P = 0.73), k = 3 studies).

Conclusion
Associations between biomarkers and lower limb skeletal muscle function in individuals with osteoarthritis was limited, the few studies exploring lower limb muscle measures were mainly secondary outcomes. Furthermore, biomarkers were largely related to overall health, with a lack of muscle specific biomarkers. As such, the mechanistic pathways through which these associations occur are less evident, and difficult to draw clear conclusions on these relationships.

Trial registration
Registered on PROSPERO (CRD42022359405).
Healthcare professionals’ views about delivering a rehabilitation programme for individuals living with Atrial Fibrillation: a cross – sectional survey
Authors: Alhotye Munyra , Evans Rachael , Ng Andre , Singh Sally J. 
Published: November 2024

Abstract
Background
People living with Atrial Fibrillation (AF) often experience symptoms such as irregular heartbeat, shortness of breath, and fatigue, which can significantly limit their physical activity and overall quality of life. The existing approach to managing AF predominantly revolves around medication and medical procedures, and no prescription of tailored rehabilitation program (RP) is currently offered for this population.

Aims
This study aims to gauge the perspectives of healthcare professionals regarding the implementation of a personalised RP for individuals living with AF and to identify the barriers hindering the referral process.

Methods
A cross-sectional online survey was conducted among healthcare professionals in the UK responsible for caring for adults with AF. The survey consisted of twelve questions designed to uncover healthcare professionals' views on RP for individuals with AF.

Results
A total of 209 respondents participated in the survey, with 57% being female and 43% identifying as specialist arrhythmia nurses. A significant majority (61%) of the participants expressed agreement that an RP could help individuals with AF regain their ability to carry out daily activities, and 58% believed that RP could effectively alleviate symptoms such as breathlessness and palpitations (52%). Virtually all respondents (99%) recommended that a tailored program should encompass education about AF, weight management, and symptom control (94%). Notably, the primary factor influencing their decision to make a referral was the low physical activity levels (80%). Transportation emerged as the chief obstacle to referring patients to the program (62%). A substantial majority (79%) favoured a home-based rehabilitation program as the optimal mean of delivery.

Conclusions
The responses from healthcare professionals reflect a keen interest in implementing a program tailored to individuals with AF, with patients' low physical activity levels being the primary motivator for referrals. Home-based rehabilitation was the preferred mode of delivery, followed by digital interventions.