bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the association between adherence to home-based exercise recommendations and recovery of nonspecific low back pain: a prospective cohort study
Authors: Arensman R. M. , Pisters M. F. , Kloek C. J.J. , Koppenaal T. , Veenhof C. , Ostelo R. J.W.G. 
Published: August 2024

Abstract
Background
Adherence to home-based exercise (HBE) recommendations is critical in physiotherapy for patients with low back pain (LBP). However, limited research has explored its connection with clinical outcomes. This study examined how adherence to HBE relates to changes in physical function, pain intensity, and recovery from LBP in patients undergoing physiotherapy treatment.

Methods
Data from a multicenter cluster randomized controlled trial in the Netherlands involving patients with LBP from 58 primary care physiotherapy practices were used. Adherence to HBE was assessed with the Exercise Adherence Scale (EXAS) at each treatment session. Previously identified adherence trajectories served as a longitudinal measure of adherence and included the classes “declining adherence” (12% of participants), “stable adherence” (45%), and “increasing adherence” (43%). The main outcomes included disability (Oswestry Disability Index), pain (Numeric Pain Rating Scale), and recovery (pain-free for > 4 weeks), which were measured at baseline and after three months. Linear and binomial logistic regression analyses adjusted for confounders were used to examine adherence–outcome relationships.

Results
In the parent trial, 208 participants were included. EXAS scores were available for 173 participants, collected over a median of 4.0 treatment sessions (IQR 3.0 to 6.0). Forty-five (28.5%) patients considered themselves to have recovered after three months. The median changes in the Oswestry Disability Index and Numeric Pain Rating Scale were − 8 (IQR − 1 to -20) and − 2 (IQR − 0.5 to -4), respectively. The mean EXAS scores varied among patient classes: “declining adherence” (46.0, SD 19.4), “stable adherence” (81.0, SD 12.4), and “increasing adherence” (39.9, SD 25.3), with an overall mean of 59.2 (SD 25.3). No associations between adherence and changes in physical functioning or pain were found in the regression analyses.

Conclusions
No association between adherence to HBE recommendations and changes in clinical outcomes in patients with LBP was found. These findings suggest that the relationship between adherence to HBE recommendations and treatment outcomes may be more complex than initially assumed. Further research using detailed longitudinal data combined with qualitative methods to investigate patient motivation and beliefs may lead to a deeper understanding of the relationship between adherence and clinical outcomes in patients with LBP.
Ferula latisecta gels for synthesis of zinc/silver binary nanoparticles: antibacterial effects against gram-negative and gram-positive bacteria and physicochemical characteristics
Authors: Es-haghi Ali , Amiri Mohammad Sadegh , Taghavizadeh Yazdi Mohammad Ehsan 
Published: August 2024

AbstractThis study explores the potential antibacterial applications of zinc oxide nanoparticles (ZnO NPs) enhanced with silver (Ag) using plant gel (ZnO-AgO NPs). The problem addressed is the increasing prevalence of pathogenic bacteria and the need for new, effective antimicrobial agents. ZnO NPs possess distinctive physicochemical properties that enable them to selectively target bacterial cells. Their small size and high surface area-to-volume ratio allow efficient cellular uptake and interaction with bacterial cells. In this study, the average size of the synthesized ZnO-Ag nanoparticles was 77.1 nm, with a significant standard deviation of 33.7 nm, indicating a wide size distribution. The nanoparticles demonstrated remarkable antibacterial efficacy against gram-negative and gram-positive bacteria, with inhibition zones of 14.33 mm for E. coli and 15.66 mm for B. subtilis at a concentration of 300 µg/ml. Minimum inhibitory concentrations (MIC) were determined to be 100 µg/ml for E. coli and 75 µg/ml for S. saprophyticus. Additionally, ZnO-Ag NPs exhibited excellent biocompatibility, making them appropriate for various pharmacological uses. This study utilizes Ferula latisecta gels, offering a sustainable and eco-friendly approach to nanoparticle synthesis. Incorporating of Ag into ZnO NPs significantly enhances their antimicrobial properties, with the combined results showing great inhibition effects on pathogenic microbes. The findings suggest that ZnO-Ag NPs could be a promising candidate for addressing the challenges posed by drug-resistant bacterial infections and enhancing antimicrobial treatments.
Single-arm, first-in-human feasibility study results for an ultra-low-cost insulin pump
Authors: Payne Matthew , Pooke Francis , Wilkinson Tom M. , Holder-Pearson Lui , Chamberlain Bronté , de Bock Martin , Chase J. Geoffrey 
Published: August 2024

Abstract
Background
Use of Continuous Subcutaneous Insulin Infusion (CSII) has been shown to improve glycemic outcomes in Type 1 Diabetes (T1D), but high costs limit accessibility. To address this issue, an inter-operable, open-source Ultra-Low-Cost Insulin Pump (ULCIP) was developed and previously shown to demonstrate comparable delivery accuracy to commercial models in standardised laboratory tests. This study aims to evaluate the updated ULCIP in-vivo, assessing its viability as an affordable alternative for those who cannot afford commercially available devices.

Methods
This first-in-human feasibility study recruited six participants with T1D. During a nine-hour inpatient stay, participants used the ULCIP under clinical supervision. Venous glucose, insulin, and β-Hydroxybutyrate were monitored to assess device performance.

Results
Participants displayed expected blood glucose and blood insulin levels in response to programmed basal and bolus insulin dosing. One participant developed mild ketosis, which was treated and did not recur when a new pump reservoir was placed. All other participants maintained β-Hydroxybutyrate < 0.6 mmol/L throughout.

Conclusion
The ULCIP safely delivered insulin therapy to users in a supervised inpatient environment. Future work should focus on correcting a pump hardware issue identified in this trial and extending device capabilities for use in closed loop control. Longer-term outpatient studies are warranted.

Trial Registration
The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623001288617) on the 11 December 2023.
A multicenter cross-sectional study in China revealing the intrinsic relationship between medical students’ grade and their perceptions of the learning environment
Authors: Huang Runzhi , Qian Weijin , Xie Sujie , Cheng Mei , Gong Meiqiong , Xian Shuyuan , Jin Minghao , Zhang Mengyi , Tang Jieling , Lu Bingnan , Yang Yiting , Liu Zhenglin , Qu Mingyu , Ma Haonan , Wu Xinru , Yin Huabin , Wang Xiaonan , Liu Xin , Wang Yue , Chen Wenfang , Lin Min , Zhang Chongyou , Du Erbin , Lin Qing , Huang Zongqiang , Zhang Jie , Zhang Guoyang , Liu Yifan , Chen Yu , Liu Jun , Ji Shizhao 
Published: August 2024

Abstract
Background
Medical school learning environment (MSLE) has a holistic impact on students’ psychosomatic health, academic achievements, and personal development. Students in different grades perceive MSLE in different ways. Thus, it is essential to investigate the specific role of student’s grade in the perception of MSLE.

Methods
Using the Johns Hopkins Learning Environment Scale (JHLES) as a quantification instrument for the perception level of MSLE, 10,901 medical students in 12 universities in China were categorized into low or high JHLES group according to their questionnaires. We investigated the relationship between student’s grade and JHLES category by univariate analysis employing Pearson Chi-square test and Welch’s ANOVA. Then multivariable logistic regression analysis confirmed the predictive efficacy of student’s grade. A nomogram concerning the prediction of low JHLES score probability in medical students was also constructed.

Results
A significant difference between two JHLES categories among students in different grades was observed (p < 0.001), with the proportion of the high JHLES group dominating in grade 1, 5, and the graduate subgroups (p < 0.001). The mean JHLES score declined especially in the third and fourth graders compared to freshmen (p < 0.001), while the mean score among the fifth graders had a remarkable rebound from the third graders (p < 0.001). Most imperatively, identified by multivariable logistic regression analysis, students in grade 3 (OR = 1.470, 95% CI = 1.265–1.709, p < 0.001) and 4 (OR = 1.578, 95% CI = 1.326–1.878, p < 0.001) perceived more negatively than freshmen. The constructed nomogram provided a promising prediction model for student’s low JHLES score probability, with accuracy, accordance, and discrimination (area under the curve (AUC) = 0.627).

Conclusion
The student’s grade was a significant influencing factor in medical students’ perception of MSLE. The perceptions among the third and fourth graders got worse, probably due to the worrying changes in various aspects of MSLE during that period. The relevant and appropriate interventions to improve medical students’ perceptions are urgently needed.
Factors influencing patient experience in hospital wards: a systematic review
Authors: Guan Tingyu , Chen Xiao , Li Junfei , Zhang Yuxia 
Published: August 2024

Abstract
Background
Patient experience plays an essential role in improving clinical effectiveness and patient safety. It’s important to identify factors influencing patient experience and to improve quality of healthcare.

Objective
To identify factors that influence patient experience in hospital wards.

Methods
We conducted a systematic review including six databases; they were PubMed, CINAHL, Embase, PsycInfo, ProQuest, and Cochrane. Studies were included if they met the inclusion criteria. The JBI checklist was used to perform quality appraisal. We used 5 domains of the ecological model to organize and synthesize our findings to comprehensively understand the multi-level factors influencing the issue.

Result
A total of 138 studies were included, and 164 factors were identified. These factors were integrated into 6 domains. All domains but one (survey-related factors) could be mapped onto the attributes of the ecological framework: intrapersonal, interpersonal, institutional, community, and public policy level factors. All factors had mixed effect on patient experience. The intrapersonal level refers to individual characteristics of patients. The interpersonal level refers to interactions between patients and healthcare providers, such as the caring time spent by a nurse. The institutional level refers to organizational characteristics, rules and regulations for operations, such as hospital size and accreditation. The community level refers to relationships among organizations, institutions, and informational networks within defined boundaries, such as a hospital located in a larger population area. Public policy level refers to local, state, national, and global laws and policies, including health insurance policies. The sixth domain, survey-related factors, was added to the framework and included factors such as survey response rate and survey response time.

Conclusion
The factors influencing patient experience are comprehensive, ranging from intrapersonal to public policy. Providers should adopt a holistic and integrated perspective to assess patient experience and develop context-specific interventions to improve the quality of care.

PROSPERO registration number CRD42023401066
Super-enhancer omics in stem cell
Authors: Ma Hongying , Qu Jian , Pang Zicheng , Luo Jian , Yan Min , Xu Weixin , Zhuang Haihui , Liu Linxin , Qu Qiang 
Published: August 2024

AbstractThe hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of “super-enhancer omics”, inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.
Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism
Authors: Zhan Jianhao , Huang Le , Niu Liyan , Lu Wenhui , Sun Chengpeng , Liu Shanshan , Ding Zijun , Li Enliang 
Published: August 2024

AbstractCD73, a cell surface-bound nucleotidase, serves as a crucial metabolic and immune checkpoint. Several studies have shown that CD73 is widely expressed on immune cells and plays a critical role in immune escape, cell adhesion and migration as a costimulatory molecule for T cells and a factor in adenosine production. However, recent studies have revealed that the protumour effects of CD73 are not limited to merely inhibiting the antitumour immune response. Nicotinamide adenine dinucleotide (NAD+) is a vital bioactive molecule in organisms that plays essential regulatory roles in diverse biological processes within tumours. Accumulating evidence has demonstrated that CD73 is involved in the transport and metabolism of NAD, thereby regulating tumour biological processes to promote growth and proliferation. This review provides a holistic view of CD73-regulated NAD + metabolism as a complex network and further highlights the emerging roles of CD73 as a novel target for cancer therapies.
Assay for interferon gamma release as a novel marker in pediatric patients with systemic lupus erythematosus
Authors: Zhang Song , Li Xue , Chen Huishan , Gao Xianfei , Cai Zhe , Zeng Huasong 
Published: August 2024

Abstract
Background
The interferon-gamma (IFN-γ) release assay (IGRA) is an important laboratory diagnosis for latent Mycobacterium tuberculosis (TB) infection. The TB-IGRA measures the release of IFN-γ from peripheral blood cells, who are exposed to TB antigen (Ag), mitogen (MT), or negative/nil control (NL) in vitro. While, an exceptional higher TB Ag-NL level will reflect an elevation of peripheral lymphocytes released IFN-γ in a same condition. Therefore, we found that the elevated levels of TB Ag-NL could become a new biomarker for the diagnosis and treatment of pediatric systemic lupus erythematosus (SLE) patients.

Methods
We have analyzed the clinical data of 776 children who are underwent TB-IGRA testing in the Department of Allergy and Rheumatology of Guangzhou Women and Children’s Medical Center from 2018 to 2020. To investigate the association between TB Ag-NL and SLE, we have analyzed the clinical data of 47 SLE patients and TB Ag-NL testing results, and then evaluated the association between TB Ag-NL and SLE disease activity.

Results
The TB Ag-NL levels were significantly higher in patients with active SLE than those in inactive SLE (p = 0.0002). The TB Ag-NL levels were positively correlated with the SLE disease activity index (SLEDAI) and laboratory diagnosis parameters. The mean value of TB Ag-NL in SLE patients (0.04191 ± 0.07955, IU/mL) were significantly higher than those in patients with juvenile dermatomyositis (JDM) (0.0158 ± 0.0337, IU/mL, p = 0.036), juvenile idiopathic arthritis (JIA) (0.0162 ± 0.0388, IU/mL, p = 0.001), and healthy controls (HC) (0.0001 ± 0.0027, IU/mL, p = 0.0003). Therefore, the elevated TB Ag-NL levels could serve as a potential diagnostic biomarker of SLE, especially for the active SLE.

Conclusion
The detection of IFN-γ release levels by the TB-IGRA may be useful to assess SLE disease activity in pediatric patients with active SLE.
Activating transcription factor 3 mediates apoptosis and cell cycle arrest in TP53-mutated anaplastic thyroid cancer cells
Authors: Kooti Abolfazl , Abuei Haniyeh , Jaafari Alireza , Taki Shayan , Saberzadeh Jamileh , Farhadi Ali 
Published: August 2024

Abstract
Background
It is believed that loss of p53 function plays a crucial role in the progression of well to poorly differentiated thyroid cancers including anaplastic thyroid carcinoma (ATC). Given the poor prognosis of ATC due to its strong therapeutic resistance, there is a need to establish new therapeutic targets to extend the survival of ATC patients. Activating transcription factor 3 (ATF3) can inhibit the oncogenic activity of mutant p53 and, as a result, contribute to tumor suppression in several TP53-mutated cancers. Herein, we demonstrate that the ectopic overexpression of ATF3 leads to the suppression of oncogenic mutant p53 activity in chemo-resistant 8305 C thyroid cancer cells harboring R273C p53 gene mutation.

Methods
The biological behavior of 8305 C cells was assessed pre- and post-transfection with pCMV6-ATF3 plasmid using MTT assay, fluorescent microscopy, cell cycle, and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 overexpression on the cellular level of p53 was examined by western blotting assay. The mRNA expression levels of TP53, TAp63, ΔNp63, and SHARP1 were evaluated in ectopic ATF3-expressing cells compared to controls.

Results
The overexpression of ATF3 in 8305 C thyroid cancer cells significantly decreased cell viability and induced apoptosis and cell cycle arrest in vitro. The immunoblotting of p53 protein revealed that ATF3 overexpression significantly increased the level of mutant p53 in 8305C cells compared to mock-transfected control cells. Additionally, elevated mRNA levels of TAp63 and SHARP1 and a decreased mRNA level of ΔNp63 were observed in PCMV6-AC-ATF3-transfected 8305 C cells with significant differences compared to the mock and untreated cells.

Conclusion
In light of our findings, it is evident that therapeutic strategies aimed at increasing ATF3 expression or enhancing the interaction between ATF3 and mutant p53 can be a promising approach for the treatment of p53-mutated metastatic thyroid cancer.
The creation, implementation, and harmonisation of medical standard operating procedures and checklists of Finnish Helicopter Emergency Medical Service units
Authors: Tukia Simo , Pirnes Jari , Nurmi Jouni , Nordquist Hilla 
Published: August 2024

Abstract
Introduction
The purpose of this study was to investigate the creation, implementation, and harmonisation of medical Standard Operating Procedures (SOP) in Finnish Helicopter Emergency Medical Services (HEMS). The research questions are: (1) What factors influence the creation and implementation of medical SOPs for Finnish HEMS units? and (2) What can be done to harmonise the medical SOPs of Finnish HEMS units?

Methods
The research was conducted as a qualitative interview study with HEMS physicians who worked full-time in Finnish HEMS units or had worked in HEMS for more than five years. Three HEMS physicians from each of the six HEMS units in Finland participated in the study (n = 18). The thematic interviews (average duration 32 min) were transcribed (70,176 words in Finnish) and analysed using inductive content analysis.

Results
The results of the first research question formed three main categories: (1) Background to developing medical SOPs and checklists (CLs), (2) Creation of medical SOPs in Finnish HEMS units, and (3) Implementation of medical SOPs and CLs. The main categories were divided into eight upper categories and twelve subcategories. The results of the second research question formed four main categories: (1) Prerequisites for harmonising procedures, (2) System-level changes needed, (3) Integrating common medical SOPs into HEMS, and (4) Cultural change. The main categories were divided into nine upper categories and nine subcategories.

Conclusions
Medical SOPs and CLs are an integral part of Finnish HEMS. Each unit creates its own SOPs and CLs; their development, implementation, and follow-up are relatively unstructured. Harmonising existing SOPs would be possible, but developing common SOPs would require structural changes in HEMS and a stronger sense of community belonging among HEMS physicians.
Current genomic deep learning models display decreased performance in cell type-specific accessible regions
Authors: Kathail Pooja , Shuai Richard W. , Chung Ryan , Ye Chun Jimmie , Loeb Gabriel B. , Ioannidis Nilah M. 
Published: August 2024

Abstract
Background
A number of deep learning models have been developed to predict epigenetic features such as chromatin accessibility from DNA sequence. Model evaluations commonly report performance genome-wide; however, cis regulatory elements (CREs), which play critical roles in gene regulation, make up only a small fraction of the genome. Furthermore, cell type-specific CREs contain a large proportion of complex disease heritability.

Results
We evaluate genomic deep learning models in chromatin accessibility regions with varying degrees of cell type specificity. We assess two modeling directions in the field: general purpose models trained across thousands of outputs (cell types and epigenetic marks) and models tailored to specific tissues and tasks. We find that the accuracy of genomic deep learning models, including two state-of-the-art general purpose models―Enformer and Sei―varies across the genome and is reduced in cell type-specific accessible regions. Using accessibility models trained on cell types from specific tissues, we find that increasing model capacity to learn cell type-specific regulatory syntax―through single-task learning or high capacity multi-task models―can improve performance in cell type-specific accessible regions. We also observe that improving reference sequence predictions does not consistently improve variant effect predictions, indicating that novel strategies are needed to improve performance on variants.

Conclusions
Our results provide a new perspective on the performance of genomic deep learning models, showing that performance varies across the genome and is particularly reduced in cell type-specific accessible regions. We also identify strategies to maximize performance in cell type-specific accessible regions.