bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of histone demethylase KDM5A in osteoporotic fracture healing through epigenetic regulation of the miR-495/SKP2/Runx2 axis
Authors: Li Zhuoran , Zhang Junyan , Xu Tingting , Hao Zhiying , Li Yadong 
Published: February 2025

Abstract

Background
Osteoporosis represents a salient metabolic bone disorder. Histone demethylase plays a vital role in bone development and homeostasis. This study explored the mechanism of histone demethylase KDM5A affecting osteoporotic fracture healing via the miR-495/SKP2/Runx2 axis.

Methods
The murine model of osteoporotic fracture was established. The bone mineral density, maximum elastic stress, and maximum load were tested. The relative trabecular bone volume, bone trabecular thickness, and trabecular number at the proximal end of tibia were detected. The histopathological changes of femur tissues and bone microstructure were observed. Expressions of KDM5A and osteogenic factors were detected. The cell proliferation, alkaline phosphatase activity, and calcified nodules were measured. The binding relationships between KDM5A and miR-495 promoter, and miR-495 and SKP2 were verified. The interaction between SKP2 and Runx2 was detected. The ubiquitination level of Runx2 and the stability of Runx2 protein were detected.

Results
KDM5A was highly expressed in the murine model of osteoporotic fracture. Interference of KDM5A expression facilitated fracture healing in osteoporotic mice. KDM5A downregulated miR-495 expression by promoting the H3K4me3 methylation of the miR-495 promoter. Inhibition of miR-495 reversed the effect of KDM5A silencing on osteoblast proliferation, differentiation, and mineralization. miR-495 facilitated osteoblast proliferation, differentiation, and mineralization by targeting SKP2. SKP2 suppressed Runx2 expression through ubiquitination degradation. Inhibition of Runx2 reversed the promoting effect of SKP2 silencing on osteogenic differentiation.

Conclusion
KDM5A attenuated the inhibition of miR-495 on SKP2 and promoted the ubiquitination degradation of Runx2 protein by SKP2, thereby repressing osteoblast differentiation and retarding osteoporotic fracture healing.
Human urine stem cells protect against cyclophosphamide-induced premature ovarian failure by inhibiting SLC1A4-mediated outflux of intracellular serine in ovarian granulosa cells
Authors: Gu Hao-Cheng , Wang Ling-Fang , Zhang Yu-Wei , Zhuo You-Qiong , Zhang Zhou-Hang , Wei Xing-Yu , Liu Quan-Wen , Deng Ke-Yu , Xin Hong-Bo 
Published: February 2025

Abstract

Background
Cyclophosphamide (CTX) is the first-line medication for the treatment of breast cancer, although it potentially leads to severe ovarian dysfunction and even premature ovarian failure (POF). However, the mechanism of CTX-induced POF remains unclear. Mesenchymal stem cell-based therapy has been wildly used for treating numerous diseases. Therefore, our study aims to elucidate the underlying mechanism of CTX-induced POF and to explore the therapeutic effect of human urine stem cells (hUSCs) in POF.

Methods
CTX-induced POF or ovarian granulosa cell (GCs) apoptosis were treated with hUSCs and their exosomes in vitro and in vivo. Morphological, histological, and functional alternations were examined using multiple approaches. The effector molecules of hUSC-derived exosomes (hUSC-Exo) were determined by differential expression analysis in the ovaries. The target genes of miRNA were accessed by transcriptome sequencing in GCs, and the underlying mechanisms were further elucidated.

Results
hUSCs remarkably inhibited CTX-induced apoptosis and promoted the proliferation of GCs, respectively. In addition, we observed that miR-27b-3p was highly expressed in hUSC-Exo and markedly suppressed CTX-induced GC apoptosis by specifically inhibiting the expression of SLC1A4, a serine transporter, in ovarian GCs, which, in turn, elevated the concentration of the intracellular serine by inhibiting the outflux of cellular serine. More importantly, the knockdown of SLC1A4 or simple supplementation of serine suppressed CTX-induced apoptosis of GCs. Finally, we demonstrated that CTX-induced apoptosis of ovarian GCs was essential for POF by reducing the intracellular serine concentration via elevating the expression of SLC1A4, whereas hUSCs protected against CTX-induced POF via miR-27b-3p/SLC1A4/serine axis-mediated activation of the PI3K/AKT/mTOR signaling pathway.

Conclusions
Our study suggests that hUSC-based cell therapy or simple supplementation of serine may provide an efficient therapeutic approach for the prevention and treatment of CTX-induced POF clinically.

Graphical abstract
Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV
Authors: Chawana Tariro D. , Walsh Stephen R. , Stranix-Chibanda Lynda , Chirenje Zvavahera M. , Yu Chenchen , Zhang Lily , Seaton Kelly E. , Heptinstall Jack , Zhang Lu , Paez Carmen A. , Gamble Theresa , Karuna Shelly T. , Andrew Philip , Hanscom Brett , Sobieszczyk Magdalena E. , Edupuganti Srilatha , Gay Cynthia L. , Mannheimer Sharon B. , Hurt Christopher B. , Stephenson Kathryn E. , Polakowski Laura L. , Spiegel Hans , Yacovone Margaret , Regenold Stephanie , Yen Catherine , Baumblatt Jane AG. , Gama Lucio , Barouch Dan H. , Piwowar-Manning Estelle , Koup Richard A. , Tomaras Georgia D. , Hyrien Ollivier , Roxby Alison C. , Huang Yunda ,   on behalf of the HVTN 127/HPTN 087, HVTN 130/HPTN 089 and HVTN 136/HPTN 092 Study Teams
Published: February 2025

Abstract
VRC07-523LS is a safe and well-tolerated monoclonal antibody (mAb) targeting the CD4 binding site on the HIV envelope (Env) trimer. Efficacy of VRC07-523LS, in combination with mAbs targeting other HIV epitopes, will be evaluated in upcoming trials to prevent HIV acquisition in adults. However, differences in the pharmacokinetics (PK) of VRC07-523LS when administered alone vs. in combination with other mAbs have not been formally assessed. We performed a cross-protocol analysis of three clinical trials and included data from a total of 146 adults without HIV who received intravenous (n = 95) or subcutaneous (n = 51) VRC07-523LS, either alone (‘single’; n = 100) or in combination with 1 or 2 other mAbs (‘combined’; n = 46). We used an open, two-compartment population PK model to describe serum concentrations of VRC07-523LS over time, accounting for inter-individual variabilities. We compared individual-level PK parameters between the combined vs. single groups using the targeted maximum likelihood estimation method to adjust for participant characteristics. No significant differences were observed in clearance rate, inter-compartmental clearance, distribution half-life, or total VRC07-523LS exposure over time. However, for the combined group, mean central volume of distribution, peripheral volume of distribution, and elimination half-life were slightly greater, corresponding to slightly lower predicted concentrations early post-administration with high levels being maintained in both groups. These results suggest potential PK interactions between VRC07-523LS and other mAbs, but with small clinical impact in the context of HIV prevention. Our findings support coadministration of VRC07-523LS with other mAbs, and the use of the developed PK models to design future trials for HIV prevention.
Mini nutritional assessment short-form as a risk factor for mortality in patients with respiratory disease undergoing urgent hospitalization
Authors: Ishiwari Mayuko , Kono Yuta , Togashi Yuki , Kobayashi Kenichi , Kikuchi Ryota , Kogami Mariko , Suekawa Ami , Miyazawa Yasushi , Abe Shinji 
Published: February 2025

Abstract

Background
Studies of nutritional status in geriatric patients with respiratory diseases are limited. The aim of this study was to investigate the mortality risk of older patients undergoing urgent hospitalization for various respiratory diseases.

Methods
This was a retrospective study of patients aged ≥ 65 years with respiratory diseases who were urgently hospitalized between April 2022 and November 2024. The Mini Nutritional Assessment Short-Form (MNA-SF) was evaluated at the time of urgent admission, and the malnutrition risk was defined by the MNA-SF score < 11. Comorbidities and frailty were assessed using the Charlson comorbidity index (CCI) and Clinical frailty scale (CFS), respectively. Biomarkers of inflammation and acute respiratory failure such as neutrophil-to-lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), Respiratory rate-oxygenation (ROX) index, and the pulse oximetric saturation (SpO2)/fraction of inspired oxygen (FiO2) [S/F] ratio were calculated and analyzed as risk factors of in-hospital mortality.

Results
A total of 168 consecutive patients were enrolled in the study with median age of 77 years (interquartile range [IQR]: 72–84). Thirty-nine patients (23.2%) died during hospitalization, and the median time to death was 17 days (IQR: 10–25). Univariate analysis demonstrated that older age (> 77 years), low S/F ratio (< 315), low ROX (< 8.3), high NLR (> 6), high CFS (> 5), and low MNA-SF (< 11) were associated with in-hospital mortality, multivariate analysis revealed that low MNA-SF was an independent predictor.

Conclusions
The MNA-SF is a risk factor for mortality in older patients undergoing urgent hospitalization due to various respiratory diseases.
Risk factors in self-reported dissatisfied patients implanted with various presbyopia-correcting intraocular lenses after cataract surgery
Authors: Jeon Woosung , Yoon Chang Ho , Oh Joo Youn , Choi Hyuk Jin , Kim Mee Kum 
Published: February 2025

Abstract

Background
This study aimed to investigate the self-reported dissatisfaction rates and associated risk factors among patients who underwent cataract surgery using different types of presbyopia-correcting intraocular lenses (IOLs).

Methods
This retrospective case–control study analyzed the medical records in 340 eyes from 211 cataract surgery patients with presbyopia-correcting IOLs. The analyzed IOL types included bifocal (ReSTOR®), trifocal (PanOptix®), and extended depth-of-focus (EDOF; Symfony®) IOLs. The rates of self-reported dissatisfaction related to vision or photic disturbances were compared between these IOLs. Various factors, including sex, age, preoperative visual acuity and refractive status, and biometric indices, were analyzed to identify potential risk factors for dissatisfaction.

Results
The overall dissatisfaction rate was 18.5% (63/340). Among the IOL types, Symfony®-implanted eyes had the highest rate of near-vision dissatisfaction, while PanOptix®-implanted eyes showed similar proportions of photic disturbances and near-vision discomfort. The major risk factor identified for overall dissatisfaction, regardless of IOL type, was preoperative myopia, which aligns with the risk factor for near discomfort. Meanwhile, the risk factors for photic phenomena were revealed to be thinner corneal thickness and greater corneal astigmatism. By IOL types, preoperative myopia caused near-vision discomfort in Symfony® eyes, whereas greater corneal astigmatism and thinner corneas were linked to photic disturbances in PanOptix® eyes.

Conclusions
It suggests that near-vision discomfort is related to myopic factors, whereas photic disturbances are associated with ocular aberrations. The types of dissatisfaction vary depending on the designs of presbyopia-correcting IOLs.

Trial Registration
This retrospective study adhered to the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of the Seoul National University Hospital on March 13, 2023 (IRB No: 2303–025-1409).
Effectiveness of referral to a population-level telephone coaching service for improving health risk behaviours in people with a mental health condition: a randomised controlled trial
Authors: Hanly Grace , Campbell Elizabeth , Bartlem Kate , Dray Julia , Fehily Caitlin , Colyvas Kim , Reynolds Tahlia , Davidson Sandy , Jeong Sarah Yeun-Sim , Wiggers John , Wolfenden Luke , Bowman Jenny 
Published: February 2025

Abstract

Background
Telephone support services are a viable means of providing population-level support to reduce health risk behaviours. While research exists on the effectiveness of Quitlines to reduce smoking, there is limited other research investigating whether telephone services can provide effective behaviour change support for people with a mental health condition for behaviours including physical activity, healthy eating, and weight management. The aims of this trial were to evaluate the effectiveness of referral of people with a mental health condition to a population-level telephone coaching service to improve health risk behaviours and increase attempts to do so.

Methods
A parallel-group randomised controlled trial was conducted. Participants with a mental health condition (N = 681) were assigned to a control (health information pack) or intervention group (information pack and referral by the research team to a coaching program). Data were collected via telephone surveys at baseline and six months post-recruitment. Primary outcomes were: (1) weekly minutes of moderate-to-vigorous physical activity, (2) daily fruit serves, (3) daily vegetable serves, and (4) attempted behaviour change/weight loss (yes/no; composite measure). Secondary outcomes included weight, Body Mass Index (BMI), and attempts to change each health behaviour individually.

Results
Intention-to-treat analyses found no significant differential change between groups from baseline to six months for primary or secondary outcomes. By follow-up, 242/549 (44%) of intervention participants had enrolled in coaching and completed at least one call, with 16/242 having completed the program, 79 ongoing, and 147 withdrawn. Per-protocol analyses found attempting to improve at least one health behaviour/lose weight was significantly greater in enrolees (OR = 3.7, 95% CI 1.03—13.23) than the control group.

Conclusions
Referral to the program did not improve risk behaviours or weight/BMI but did support behaviour change attempts. Contributing factors may include low program completion by follow-up and impact of COVID-19. Further research is required to better understand participation in and benefits of telephone coaching services for people with a mental health condition.

Trial registration
Registered retrospectively with the Australian New Zealand Clinical Trials Registry (ACTRN12620000351910).
Managing low-back pain in rural Uganda: a qualitative study exploring the perspectives and practices of frontline health workers regarding LBP management in primary care
Authors: Harscouët Paul , Chimpaye Gloria Ndekezi , Kazibwe Herman , Kabakyenga Jerome , O’Callaghan Denise , Blake Catherine , Caulfield Brian , O’Sullivan Cliona 
Published: February 2025

Abstract

Background and aims
Low-back pain (LBP) is the main cause of years lived with disabilities (YLDs) worldwide and the second cause of YLDs in Uganda. In 2019, it was responsible for 7.4% of global YLDs and 5% of YLDs in Uganda. LBP takes a significant toll on people’s quality of life and disproportionately affects lower socioeconomic classes, elders, and women. In rural Uganda, LBP is managed in health centres by clinical officers and nurses with limited resources. This study aims to understand the perspectives and practices of these health workers.

Method
A qualitative design using semi-structured focus-group discussions was employed. Purposive sampling allowed us to identify relevant participants based on their roles as healthcare professionals working in primary care context in rural South-West Uganda. Data was analysed using thematic analysis.

Findings
LBP is a common and persistent complaint among patients presenting to rural health centres in Uganda. Manual labour and female specific health conditions were deemed to be common causes. There was a strong reliance on medication prescription, coupled with X-ray diagnosis, with little emphasis on education or exercise. Finally, findings highlighted major barriers for patients within the referral system to hospital care or rehabilitation.

Discussion
Education and training of frontline clinicians in terms of appropriate prescribing and rehabilitation for LBP is crucial. Evidence-based rehabilitation interventions need to be developed and adapted so that they can be delivered within the time and resource constraints of the health workforce, ensuring that they are acceptable and effective to patients in the context of rural Uganda.
Assessment of two methods for detecting carious dentin: an in vitro study
Authors: White Joel , Yansane Alfa , Kukreti Puja , Nahar Pragati , Orobia Paolo , Jensen Rachel , Plack Leslie , Vaderhobli Ram , Magnum Jonathan , Jenson Larry 
Published: February 2025

Abstract

Background
The objective of this study was to compare, in vitro, two dentinal caries lesion detector methods, Caries Finder and BlueCheck, to determine if they were substantially equivalent in their ability to aid visualization of demineralized dentin and to also to compare their performance compared to the traditional visual/tactile method of dentinal caries lesion detection in vitro.

Methods
Sixty-five extracted human teeth containing lesions rated as ICDAS 4,5 or 6 were chosen and then randomly assigned to two groups. Specimens were then evaluated in standard operatory conditions by three evaluators using the traditional visual and tactile method, the Caries Finder method, and the BlueCheck method of detection. The study employed a parallel, randomized controlled study design. To test the equivalence claim, a “two-one sided test” (TOST) approach was utilized.

Results
As compared to the traditional method, the Caries Finder method had a 0.9742 accuracy, 95% confidence interval [0.9578, 0.9855], 94.80% sensitivity, 98.53% specificity, 96.47% positive predictive value, 97.82% negative predictive value, 0.938 Kappa value, p < 2.2e-16). The BlueCheck method had a 0.9821 accuracy, 95% confidence interval [0.9682, 0.9910], 96.02% sensitivity, 99.09% specificity, 97.69% positive predictive value, 98.42% negative predictive value, 0.956 Kappa value, p < 2.2e-16). Inter-rater reliability and intra-rater reliability ratings were good to excellent.

Conclusions
The results of this study support the conclusion that the Caries Finder and BlueCheck methods compare favorably with the traditional method of carious dentin detection. Caries Finder and BlueCheck detection methods were found to have comparable performance in their ability to differentiate carious dentin from healthy tooth structure in vitro; however further in vivo validation is required to confirm clinical equivalence. Both show good to excellent inter-rater and intra-rater reliability.
Interdisciplinary strategies for establishing a trusting relation as a pre-requisite for existential conversations in palliative care: a grounded theory study
Authors: Lagerin Annica , Melin-Johansson Christina , Holmberg Bodil , Godskesen Tove , Hjorth Elin , Junehag Lena , Hagelin Carina Lundh , Ozanne Anneli , Sundelöf Johan , Udo Camilla 
Published: February 2025

Abstract

Background
Communication is central to implementing palliative care (PC) and effective interdisciplinary team functioning. Communication about existential issues is often urgent in PC, yet interdisciplinary teams frequently lack the time and education to meet these communication needs. Thus, more knowledge of existential conversations in different PC contexts is required.

Aim
This study aimed to gain an in-depth understanding of healthcare professionals’ (HCPs) experiences of existential conversations with patients with PC needs and their next-of-kin by generating a theoretical model.

Method
Seven focus-group interviews that included 26 HCPs who worked with PC patients in different care settings were carried out in 2020 and 2022. The grounded theory method was used to analyse and compare data from the interview transcripts.

Results
The HCPs’ primary concern in daily work was establishing a trusting relationship, a prerequisite for enabling existential conversations with a person with PC needs and/or their next-of-kin. The main concern was characterised by the core category maintaining presence and four categories describing interdisciplinary strategies that the HCPs used to achieve a trusting relationship and enable existential conversations in the late phase of life. Several potential barriers also hindered existential conversations. The theoretical model ‘meaningful existential conversations in PC’ was constructed.

Conclusions
The interdisciplinary strategies used to establish existential conversations, the potential barriers to these conversations and the model we present can be used as a basis for reflection in professional collaborative learning in PC, as a tool for teachers in educational PC programmes and as a guide for HCPs in PC.
Limitations of SpO2 / FiO2-ratio for classification and monitoring of acute respiratory distress syndrome—an observational cohort study
Authors: Erlebach Rolf , Pale Una , Beck Tilman , Markovic Sasa , Seric Marko , David Sascha , Keller Emanuela 
Published: February 2025

Abstract

Background
The ratio of pulse-oximetric peripheral oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) has been proposed as additional hypoxemia criterion in a new global definition of acute respiratory distress syndrome (ARDS). This study aims to evaluate the clinical and theoretical limitations of the SpO2/FiO2-ratio when using it to classify patients with ARDS and to follow disease progression.

Methods
Observational cohort study of ARDS patients from three high-resolution Intensive Care Unit databases, including our own database ICU Cockpit, MIMIC-IV (Version 3.0) and SICdb (Version 1.0.6). Patients with ARDS were identified based on the Berlin criteria or ICD 9/10-codes. Time-matched datapoints of SpO2, FiO2 and partial pressure of oxygen in arterial blood (PaO2) were created. Severity classification followed the thresholds for SpO2/FiO2 and PaO2/FiO2 of the newly proposed global definition.

Results
Overall, 708 ARDS patients were included in the analysis. ARDS severity was misclassified by SpO2/FiO2 in 33% of datapoints, out of which 84% were classified as more severe. This can be partially explained by imprecision of SpO2 measurement and equation used to transform SpO2/FiO2 to PaO2/FiO2. A high dependence of SpO2/FiO2-ratio on FiO2 settings was found, leading to major treatment effect and limited capability for tracking change in ARDS severity, which was achieved in less than 20% of events.

Conclusions
The use of SpO2/FiO2 interchangeably with PaO2/FiO2 for severity classification and monitoring of ARDS is limited by its inadequate trending ability and high dependence on FiO2 settings, which may influence treatment decisions and patient selection in clinical trials.