bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Glycogen Synthase Kinase–3 Inhibitor CHIR99021 Reduces Fatty Infiltration and Muscle Atrophy After Rotator Cuff Tears: An In Vitro Experiment and In Vivo Mouse Model
Authors: Zhang Pu , Zhou Meng , Zhu Yiming , Xie Jianhao , Huo Ziqi , Zhang Dan , Li Pinxue , Guo Jianxun , Li Guangping , Li Xu , Wang Renxian , Jiang Chunyan 
Published: February 2025

Background: Rotator cuff tears (RCTs) can cause inflammation, muscle atrophy, and irreversible fatty infiltration, resulting in poor clinical outcomes. Effective therapeutic approaches to inhibit fatty infiltration in rotator cuff muscles remain limited. Purpose: To identify pathways associated with fatty infiltration through RNA sequencing and to evaluate the therapeutic potential of the glycogen synthase kinase–3 (GSK-3) inhibitor CHIR99021 based on enrichment of the Akt/GSK-3 pathway identified by RNA sequencing. Study Design: Controlled laboratory study. Methods: Supraspinatus muscle biopsy specimens from 6 patients with chronic full-thickness RCTs were analyzed by RNA sequencing. Fibro-adipogenic progenitors (FAPs) or C2C12 myoblasts were cultured with different doses of CHIR99021 to assess their effects on adipogenic or myogenic differentiation, respectively. RNA sequencing identified cellular pathways in FAPs treated with or without CHIR99021. A mouse RCT model was established by detaching the supraspinatus tendon, followed by treatment with or without CHIR99021 administered intraperitoneally. Muscle atrophy and fatty infiltration were assessed histologically and through gene expression analysis at 1 and 4 weeks after surgery. Results: RNA sequencing analysis identified a marked upregulation of the Akt/GSK-3 signaling pathway specifically in patients’ samples and FAPs with minimal fat accumulation. CHIR99021 suppressed adipogenic differentiation in FAPs and promoted myogenic differentiation in C2C12 cells. In the mouse RCT model, CHIR99021-treated mice exhibited reduced Oil Red O staining, a larger cross-sectional area, and less muscle weight loss in the supraspinatus muscle compared with the vehicle-treated mice. Gene expression analysis indicated increased myogenesis and reduced fatty infiltration at 1 and 4 weeks after surgery as well as increased expression levels of IL-6 and IL-15 in the CHIR99021 group compared with the control group at 1 week after surgery. Conclusion: The Akt/GSK-3 pathway was enriched in supraspinatus muscle samples and FAPs with low fat accumulation, highlighting its potential as a therapeutic target. The GSK-3 inhibitor CHIR99021 was shown to alleviate fatty infiltration and muscle atrophy after RCTs in vitro and in vivo in a mouse model. Clinical Relevance: The GSK-3 inhibitor CHIR99021 shows potential for treating muscle degeneration after RCTs.
Carbon footprint of a chemotherapy production unit within a hospital pharmacy: Time for green pharmacy
Authors: Chabane Manon , Fagnoni-Legat Christine , Hosotte Camille , Jehl-Rave Maryline , Barbier Garance , Bonnot-Perrin Sophie , Sadeghipour Farshid , Carrez Laurent , Limat Samuel , Kroemer Marie 
Published: February 2025

Background In the last decade, environmental impact assessment has become a major concern for human activities, which is particularly true for health. The french healthcare sector emits approximately 49 million tons of CO2 equivalent (CO2eq) per year, approximately 8% of the total national Green House Gas (GHG) emissions. In this context, assessing the carbon footprint of a resource-consuming unit like the cytotoxic drug production unit (CPU) is essential. The study aimed to assess the carbon footprint of a CPU. Methods A retrospective study was conducted in a french CPU producing more than 51,000 preparations per year in 2022. Global warming impact of CO2eq emissions were determined for medicines (using the French monetary Emission Factor), single-use material (using the Base Empreinte® database), energy of electrical devices, staff transportation and waste. Results The carbon footprint of the CPU was equal to 18’230.7 tons of CO2eq. Antineoplastic drugs accounted for more than 18’179 tons of CO2eq emissions. Excluding the medication part, it was equal to 51.7 tons of CO2eq. More precisely the distribution of CO2eq emission sources were staff transportation (35.9%), waste (21.1%), single-use sterile medical devices (18.1%), energy consumption (9.3%), disposable personal protective equipment (8.5%), and solvent bags and bottles (7.1%). Conclusion This study prompts us to identify the main sources of GHG emissions within a CPU. Areas for improvement to reduce global warming impact might be deprescribing of antineoplastic drugs, staff transport reduction using telecommuting or carpooling and rethinking our production process to reduce waste production.
Targeted shortwave diathermy combined with perceptual training for patients with severe traumatic optic neuropathy
Authors: Tang Qingping , Zhang Hua , Deng Huayang , Zhou Quan , Zhang Wei , Tian Mingqin , Huang Zilong , Jiang Hui , Jiang Weihong , Xie Zhihai 
Published: February 2025

Background Patients with severe traumatic optic neuropathy (TON) often show limited improvement in visual function despite therapy. Objective This study aims to investigate whether targeted shortwave diathermy (SWD) combined with perceptual training enhances visual function in patients with severe TON following endoscopic optic nerve decompression (EOND) surgery. Methods Forty patients with severe TON after EOND surgery were randomly assigned to either the rehabilitation (Reh) group ( n = 24) or the non-rehabilitation (Nreh) group ( n = 16). Subjects in the Reh group received targeted SWD therapy and perceptual training. Visual function, visual evoked potentials, and diffusion tensor imaging were evaluated. Results After 16 weeks of rehabilitation, the best-corrected visual acuity ( p = 0.006) and color vision scores ( p = 0.026) in the Reh group improved significantly more than those in the Nreh group. Two children who had completely lost their visual acuity 62 and 73 days after experiencing TON regained visual acuity scores of 1.0 logMAR or lower after rehabilitation. After 10 weeks of rehabilitation, the mean P100 amplitude ( p = 0.012) and fractional anisotropy (anterior segment, p = 0.032; middle segment, p = 0.014) of the affected nerves in the Reh group were significantly higher than those in the Nreh group. Conclusions Targeted SWD combined with perceptual training demonstrated beneficial effects in patients with severe TON after EOND surgery. Notably, this study provides the first evidence of visual function recovery occurring 73 days after complete vision loss in child with TON when combined rehabilitation was implemented.
Establishing the role of shear wave elastography in differentiating corporal rigidity between vasculogenic versus non-vasculogenic erectile dysfunction patients
Authors: Singh Pushpendra , Sharma Aditya Prakash , Chowhan Prabhjyot Singh , Gorsi Ujjwal , Mavuduru Ravimohan S , Rehsi Simarjit Singh , Lal Anupam , Mete Uttam K 
Published: February 2025

Introduction: Shear wave elastography is a new modality for the evaluation of erectile dysfunction by assessing the stiffness of corpora cavernosal tissue. We evaluated the shear wave elastography values in erectile dysfunction participants and compared shear wave elastography values between vasculogenic and non-vasculogenic erectile dysfunction participants. Methods: Overall, 40 participants with clinically diagnosed erectile dysfunction filled out an abridged five-item version of the international index of erectile dysfunction-5 questionnaire and underwent shear wave elastography as well as pharmacologically induced penile erection test after intracavernosal papaverine injection. Shear wave elastography values were obtained serially at 5-minute interval at two locations: Central (cavernosal artery centered circular region) and Peripheral (near the tunica albuginea). Shear wave elastography values were compared with the erectile dysfunction subtypes. Results: Median international index of erectile dysfunction-5 score was 11 (interquartile range: 9–14). Median central shear wave elastography values were significantly lower in the erectile state as compared to flaccid state in both vasculogenic (8.27 kPa (interquartile range: 6.3–12.5) vs 23.27 kPa (interquartile range: 15.9–28.6) p = 0.000) and non-vasculogenic (5.50 kPa (interquartile range: 4.4–6.7) vs 23.85 kPa (interquartile range: 17.8–33.6) p = 0.000) erectile dysfunction participants. Vasculogenic erectile dysfunction participants had significantly higher central shear wave elastography value in erectile state than non-vasculogenic erectile dysfunction participants (8.27 kPa (interquartile range: 6.3–12.5) vs 5.50 kPa (interquartile range: 4.4–6.7) p = 0.001). Receiver operating characteristics curve analysis revealed that the cut-off value for central shear wave elastography was 5.65 kPa in erectile state with the sensitivity, and specificity for predicting vasculogenic erectile dysfunction being 90.9% and 61.1%, respectively (area under the curve −0.816; standard error of 0.071 ( p = 0.001)). Conclusion: Central cavernosal shear wave elastography is a good modality to objectively quantify the penile rigidity and can be used to distinguish the subtype of ED.
Factors affecting the caregiver burden of family members to palliative care patients: A descriptive and cross-sectional study
Authors: Kes Duygu , Özcan Aynur , Adahan Didem 
Published: February 2025

Objectives Many factors affect caregiver burden. Limited studies exist on the effect of social support and fatigue on family caregivers. This study aims to explore the impact of fatigue and social support on the burden experienced by family caregivers of palliative care patients. Methods The study was conducted with 80 family caregivers. Data were collected using the Piper Fatigue Scale, the Burden Interview, and the Multidimensional Scale of Perceived Social Support. Regression analysis was used to evaluate the data. Results The regression analysis revealed that higher scores on the MSPSS were significantly associated with lower Burden Interview scores (p < 0.05). Conversely, higher PFS scores were significantly correlated with increased Burden Interview scores (p < 0.05). Discussion Both fatigue and social support play a critical role in shaping the caregiving burden experienced by family caregivers. Interventions aimed at reducing caregiver fatigue and enhancing social support may help alleviate this burden.
Levetiracetam dosing in continuous renal replacement therapy: A systematic review and development of a novel pharmacokinetic model to optimise dosing in critically ill patients. Do recommended doses achieve therapeutic drug concentrations?
Authors: Sweatman James , Al-Mahdi Sarraa , Lonsdale Dagan O , Leaver Susannah , Rhodes Andrew 
Published: February 2025

Aim: Levetiracetam is a widely used anti-epileptic in the critical care setting that is almost exclusively (>90%) renally excreted. The altered pharmacokinetics of levetiracetam have been widely studied in intermittent haemodialysis but the evidence and guidance on dosage in continuous renal replacement therapy is varied and poorly defined. Understanding this is critical as a significant number of critically unwell patients develop renal failure requiring continuous renal replacement therapy. The aim of this systematic review is to investigate the pharmacokinetics of levetiracetam in such patients and to understand the implications on dosing strategies. Methods: A systematic review of the available literature from 2000 to November 2022 was conducted. Seven articles were identified for inclusion from 54 records. A novel hybrid model was developed to evaluate the quality of pharmacokinetic and haemofiltration data. This data was used to develop a one-compartment model that simulated dosing strategies in 10,000 patients based on an assumed steady state of 72 hr and target trough concentrations of 12–46 mcg/mL. Results: From the seven articles included, pharmacokinetic data was retrieved for 24 individual patients. Total clearance was 3.49–4.63 L/hr (mean 3.55, S.D. 0.52). Elimination half-life was 5.66–12.88 hr (mean 9.41, S.D. 2.86). Volume of distribution was 0.45–0.73 L/kg. The proportion of total clearance attributable to continuous renal replacement therapy was 52%–73% (mean 54.7%, S.D. 13.5). Our simulations demonstrate that more than half of patients who received twice daily doses of 750 mg or greater without a loading dose achieved therapeutic drug concentrations. The time to achievement of therapeutic drug concentrations was greatly reduced by the addition of a 60 mg/kg loading dose (up to a maximum of 4.5 g). The use of a reduced loading dose or twice daily doses of 500 mg or less without loading were more likely to result in prolonged sub-therapeutic drug concentrations. Conclusion: Levetiracetam clearance in haemofiltration is similar to healthy adults with normal renal function (GFR > 90 mL/min). The use of reduced doses due to renal failure in critically ill patients may result in sub-therapeutic drug concentrations in a high number of patients. A twice daily dosing of 750–1000 mg with an initial loading dose of 60 mg/kg should be considered in such patients alongside therapeutic drug monitoring.
Clinical and functional outcomes of hand surgery for recessive dystrophic epidermolysis bullosa
Authors: Calavul Abdulkadir , Cici Hakan , Zeybek Hakan , Kılıç Ali İhsan 
Published: February 2025

Recessive dystrophic epidermolysis bullosa causes blistering and scarring of the hands, resulting in contractures fused web spaces and altered function. The aim of this study was to present the short- and mid-term clinical and functional results of a large case series of patients who underwent surgery for recessive dystrophic epidermolysis bullosa-related pseudosyndactyly. The study included 75 hands in 39 children (21 boys, 18 girls) with a mean age of 8 years (range, 4–15) and minimum follow-up of 1 year. Children were assessed with the Birmingham Epidermolysis Bullosa Severity Score Sheet and the ABILHAND-Kids questionnaire before operation and at final follow-up. There were varying degrees of recurrent scarring in all the hands by 24 months after operation. The ABILHAND-Kids questionnaire showed a significant improvement in ability to perform 17 of 21 tasks. In conclusion, despite recurrence that may develop in the short and mid term, surgical release can provide significant improvements in hand function. Level of Evidence: IV
Feasibility of a Glucose Manipulation Procedure for the Standardized Performance Evaluation of Continuous Glucose Monitoring Systems
Authors: Link Manuela , Eichenlaub Manuel , Waldenmaier Delia , Wehrstedt Stephanie , Pleus Stefan , Jendrike Nina , Öter Sükrü , Haug Cornelia , Hossmann Stefanie , Rothenbühler Martina , Brandt Derek , Freckmann Guido 
Published: February 2025

Background: In continuous glucose monitoring (CGM) system performance studies, it is common to implement specific procedures for manipulating the participants’ blood glucose (BG) levels during the collection of comparator BG measurements. Recently, such a procedure was proposed by a group of experts, and this study assessed its ability to produce combinations of BG levels and rates of change (RoCs) with certain characteristics. Methods: During three separate in-clinic sessions conducted over 15 days, capillary BG measurements were carried out every 15 minutes for 7 hours. Simultaneously, the participants’ BG levels were manipulated by controlling food intake and insulin administration to induce transient hyperglycemia and hypoglycemia. Subsequently, the combinations of BG levels and RoCs were categorized into dynamic glucose regions distinguishing between rapidly increasing BG levels (Alert high), hyperglycemia (BG high), rapidly falling BG levels (Alert low), and hypoglycemia (BG low). Results: A total of 24 adult participants with type 1 diabetes were included. Capillary BG-RoC combinations showed 7.5% in the Alert high region, 13.3% in the BG high region, 9.8% in the Alert low region, and 11.0% in the BG low region. No adverse events related to the glucose manipulation procedure were documented. Conclusions: As recommended by the experts, the percentage of data points in regions was ≥7.5%, demonstrating the procedure’s feasibility. However, given that the recommendation for the alert high region was only barely achieved, we suggest optimizations to the procedure and definition of dynamic glucose regions to facilitate the procedures’ adoption in standardized CGM performance evaluations.
Regulation and governance for the implementation and management of point-of-care testing in Australia: a scoping review
Authors: Prestedge Jacqueline , Kaufman Claire , Williamson Deborah A. 
Published: February 2025

Abstract

Background
Point-of-care testing (PoCT) is an increasingly important diagnostic tool in the healthcare system for accessible pathology testing in hospital, primary care, and community care settings. Clear regulation and governance models are important to ensure quality of PoCT results for patient care.

Methods
This review aimed to identify existing regulation and guidelines for management of PoCT and how this has been implemented within Australian healthcare services. We conducted a search of academic publications in PubMed and grey literature (national, state, and independent organisations) and other publicly available information from internet searches for governance of PoCT in Australia. Relevant data from these sources were extracted and narratively synthesised.

Results
Forty-seven sources (17 studies from PubMed, 30 grey literature) were included in the final review. Of the grey literature sources, fifteen current PoCT governance documents comprising of six standards, five guidelines and four frameworks at the international, national and jurisdictional level were included with an increasing number of grey literature sources since the onset of the COVID-19 pandemic in 2020. The seventeen included research articles were categorised according to implementation barriers and facilitators with the themes of workforce, clinical governance, PoCT workflow, and cost. An understanding of the clinical and cultural context for PoCT was the most frequently reported facilitator of PoCT, while the most frequently reported barrier was related to inadequate data management.

Conclusion
This review demonstrated limited and inconsistent sources on regulatory and governance models for implementing and managing PoCT in Australia. Identified PoCT programs showcased diverse implementation and governance models to support quality PoCT, with few reporting formal accreditation. Streamlined, practical regulation and governance for PoCT may increase adoption across healthcare settings while ensuring quality results and meeting the needs of patients and healthcare practitioners.
Association between maternal overprotection and premenstrual disorder: a machine learning based exploratory study
Authors: Tsuyuki Kaori , Egawa Miho , Ohsuga Takuma , Ueda Akihiko , Shimada Kazuki , Ueno Tsukasa , Hiyoshi Kazuko , Ueda Keita , Mandai Masaki 
Published: February 2025

Abstract

Background
Premenstrual disorder (PMD), which includes premenstrual syndrome and premenstrual dysphoric disorder, has a complex pathogenesis and may be closely related to emotional cognition and memory. However, the mechanisms underlying these associations remain unclear. Therefore, this study used machine learning to explore the roles of various factors that are not typically considered risk-factors for PMD.

Methods
A predictive model for PMD was constructed using a dataset of questionnaire responses and heartrate variability data collected from 60 participants during their follicular and luteal phases. Based on the Japanese version of the Premenstrual Symptom Screening Tool, the binary objective variable (PMD status) was defined as “PMD” for moderate-to-severe premenstrual syndrome and premenstrual dysphoric disorder and other conditions as “non-PMD.” The contribution of each feature to the predictive model was assessed using the Shapley Additive exPlanations (SHAP) model-interpretation framework.

Results
Of the 58 participants (providing 117 data points), 17 (34 data points) were in the PMD group and 41 (83 data points) were in the non-PMD group. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval: 0.82–0.98). Among the top 20 features with the highest SHAP values, six were associated with maternal bonding. Four of the six mother-related characteristics were associated with overprotection.

Conclusions
Based on these findings, parental bonding experiences, including maternal overprotection, may be associated with the presence of PMD.
Trauma outcomes differences in females: a prospective analysis of 76 000 trauma patients in the Asia-Pacific region and the contributing factors
Authors: Bin Kunji Mohamad Mohamad Iqhbal , Jamaluddin Sabariah Faizah , Ahmad Norhaiza , Bahar Arifah , Khalid Zarina Mohd , Binti Mohd Zaki Nuraina Aqilah , Norzan Nurul Azlean , Shin Sang Do , Shaun Goh E. , Chiang Wen-Chu , Kajino Kentaro , Song Kyoung Jun , Son Do Ngoc 
Published: February 2025

Abstract

Background
Trauma is a leading cause of mortality, particularly in low and middle-income countries. While extensively studied in North America and Europe, data from the Asia-Pacific are limited. An important area of research is the difference in trauma outcomes, which are theoretically noted to be better among females. However, the clinical findings are inconclusive among Asians. This study examines sex-based differences in trauma outcomes in Asia Pacific, focusing on in-hospital mortality and functional recovery at discharge.

Methods
This observational study, from the Pan-Asia Trauma Outcomes Study (PATOS), included 76,645 trauma patients from 12 Asian Pacific countries. We analysed in-hospital mortality and functionality at discharge using the Glasgow Outcome Scale (GOS) and the modified Rankin Scale (mRS). Logistic regression models were built to test the association of sex on the outcomes.

Results
Males exhibited higher in-hospital mortality (1.6%) compared to females (1.06%) ( p < 0.001). Adjusted logistic regression models showed that the female sex is not independently associated with in-hospital mortality. Females have a better functional outcome at discharge for patients younger than 50 years with ISS < 16. However, no significant differences existed between those > 50 years and ISS > 15.

Conclusion
This study indicates no difference in the general trauma outcomes in the Asia Pacific between females and males. Although younger females with less severe injuries had better functional outcomes, this advantage disappeared in severe injuries and those over 50 years. These results align with some previous studies, and understanding the nuances may lead to more tailored trauma care, potentially improving patient outcomes.