bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of triple therapy and therapy sequence in treatment of BRAF-mutant metastatic melanoma. Response to overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study
Authors: Dummer Reinhard , Welti Michèle , Ramelyte Egle 
Published: August 2023

AbstractNovel therapies have achieved unprecedented benefit in survival of advanced melanoma patients. While immunotherapy (ICI) can be administered independent of mutational status, BRAF and MEK kinase inhibitors represent another effective treatment option for patients with BRAF mutant melanoma. Given the benefits these therapies demonstrate, the natural instinct was to combine. Three studies have investigated the benefit of combination of ICI using anti-PD-1 or anti-PD-L1 antibody and targeted therapy (TT) with BRAF and MEK inhibitors over TT and placebo. Among these studies, statistically significantly superior duration of response was observed, however overall and progression-free survival were only numerically superior, if at all. One triple combination was approved for BRAF mutant metastatic melanoma; however, the expected synergistic effect of triple therapy could not be universally confirmed and the observed benefits with triple seem to depend on statistical considerations rather than a biological reason. As patients with BRAF mutant melanoma have both ICI and TT as their first-line treatment options, the question whether the sequence matters was addressed. Two prospective trials compared first-line ICI, followed by TT at progression, or vice-versa, with additional “sandwich” approach (8 weeks of TT followed by ICI until progression, then TT again) in the Secombit study. The benefit of first-line ICI was demonstrated in both studies with Secombit study showing the “sandwich” approach to have similar effect. Current data advices for immunotherapy based regiments in patients with BRAF mutant melanoma or, possibly, sandwich approach. Whether triple therapy is superior to ICI monotherapy still needs to be addressed considering not only efficacy, but also safety.
Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration
Authors: Quick Joseph D. , Silva Cristian , Wong Jia Hui , Lim Kah Leong , Reynolds Richard , Barron Anna M. , Zeng Jialiu , Lo Chih Hung 
Published: August 2023

AbstractMicroglia are the resident innate immune cells in the brain with a major role in orchestrating immune responses. They also provide a frontline of host defense in the central nervous system (CNS) through their active phagocytic capability. Being a professional phagocyte, microglia participate in phagocytic and autophagic clearance of cellular waste and debris as well as toxic protein aggregates, which relies on optimal lysosomal acidification and function. Defective microglial lysosomal acidification leads to impaired phagocytic and autophagic functions which result in the perpetuation of neuroinflammation and progression of neurodegeneration. Reacidification of impaired lysosomes in microglia has been shown to reverse neurodegenerative pathology in Alzheimer’s disease. In this review, we summarize key factors and mechanisms contributing to lysosomal acidification impairment and the associated phagocytic and autophagic dysfunction in microglia, and how these defects contribute to neuroinflammation and neurodegeneration. We further discuss techniques to monitor lysosomal pH and therapeutic agents that can reacidify impaired lysosomes in microglia under disease conditions. Finally, we propose future directions to investigate the role of microglial lysosomal acidification in lysosome–mitochondria crosstalk and in neuron–glia interaction for more comprehensive understanding of its broader CNS physiological and pathological implications.
Prevalence of suicidal thoughts and attempts in the transgender population of the world: a systematic review and meta-analysis
Authors: Kohnepoushi Parisa , Nikouei Maziar , Cheraghi Mojtaba , Hasanabadi Parsa , Rahmani Hamza , Moradi Maryam , Moradi Ghobad , Moradpour Farhad , Moradi Yousef 
Published: August 2023

Abstract
Background
The aim of this meta-analysis was to determine global pooled prevalence of suicide thoughts and attempts in transgender population.

Methods
For doing comprehensive search strategy related to objectives in the presence meta-analysis, all international databases like PubMed (Medline), Scopus, Embase, Web of Sciences, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature (CINHAL) were searched from January 1990 to December 2022. The quality of the final selected studies was evaluated according to Newcastle–Ottawa Quality Assessment Scale for cross-sectional studies. The subgroup analysis was done based on type of transgender (female to male, male to female) and prevalence (point, period, and lifetime), country, and criteria of diagnosis. All analysis was done in STATA version 17.

Results
From the total number of 65 selected studies, 71 prevalence of suicidal thoughts, including point, period, and lifetime prevalence were extracted and combined. After combining these values, the prevalence of suicidal thoughts in the transgender population in the world was 39% in the past month (pooled point prevalence: 39%; 95% CI 35–43%), 45% in the past year (pooled period prevalence: 45%; % 95 CI 35–54%) and 50% during lifetime (pooled lifetime prevalence: 50%; % 95 CI 42–57%). Also, the prevalence of suicide attempt in the transgender population of the world was 16% in the past month (pooled point prevalence: 16%; 95% CI 13–19%), 11% in the past year (pooled period prevalence: 11%; % 95 CI 5–19%) and 29% during lifetime (pooled lifetime prevalence: 29%; % 95 CI 25–34%).

Conclusion
The present meta-analysis results showed the prevalence of suicidal thoughts and attempts in the transgender community was high, and more importantly, about 50% of transgenders who had suicidal thoughts, committed suicide.
Radiotherapy refusal in breast cancer with breast-conserving surgery
Authors: Liu Jiameng , Zhu Zhanlin , Hua Zhipeng , Lin Weijie , Weng Yiyin , Lin Juli , Mao Hehui , Lin Lifen , Chen Xuming , Guo Jujiang 
Published: August 2023

Abstract
Background
Although radiotherapy after breast-conserving surgery has been the standard treatment for breast cancer, some people still refuse to undergo radiotherapy. The aim of this study is to identify risk factors for refusal of radiotherapy after breast-conserving surgery.

Methods
To investigate the trend of refusing radiotherapy after breast-conserving surgery in patients with breast cancer using the Surveillance, Epidemiology, and End Results database. The patients were divided into radiotherapy group and radiotherapy refusal group. Survival results were compared using a multivariate Cox risk model adjusted for clinicopathological variables. Multivariate logistic regression was used to analyze the influencing factors of patients refusing radiotherapy after breast-conserving surgery and a nomogram model was established.

Results
The study included 87,100 women who underwent breast-conserving surgery for breast cancer between 2010 and 2015. There were 84,948 patients (97.5%) in the radiotherapy group and 2152 patients (2.5%) in the radiotherapy refusal group. The proportion of patients who refused radiotherapy after breast-conserving surgery increased from 2.1% in 2010 to 3.1% in 2015. The Kaplan–Meier survival curve showed that radiotherapy can improve overall survival (p < 0.001) and breast cancer specific survival (p < 0.001) in the patients with breast-conserving surgery. The results of multivariate logistic regression showed that age, income, marital status, race, grade, stage, subtype and chemotherapy were independent factors associated with the refusal of radiotherapy.

Conclusions
Postoperative radiotherapy can improve the benefits of breast-conserving surgery. Patients with old age, low income, divorce, white race, advanced stage, and no chemotherapy were more likely to refuse radiotherapy.
Laminar airflow ventilation systems in orthopaedic operating room do not prevent surgical site infections: a systematic review and meta-analysis
Authors: Ouyang Xueqian , Wang Qiaolin , Li Xiaohua , Zhang Ting , Rastogi Sanjay 
Published: August 2023

Abstract
Background
Laminar airflow (LAF) technologies minimize infectious microorganisms to enhance air quality and surgical site infections (SSIs). LAF lowers SSIs in some clinical studies but not others. This study analyzes laminar airflow ventilation's capacity to reduce orthopaedic surgery-related SSIs.

Methods
The PRISMA-compliant keywords were utilized to conduct a search for pertinent articles in various databases including PubMed, MEDLINE, CENTRAL, Web of Sciences, and the Cochrane databases. Observational studies, including retrospective, prospective, and cohort designs, satisfy the PICOS criteria for research methodology. The assessment of quality was conducted utilizing the Robvis software, while the meta-analysis was performed using the RevMan application. The study’s results were assessed based on effect sizes of odds ratio (OR) and risk ratio (RR).

Results
From 2000 to 2022, 10 randomized controlled clinical trials with 10,06,587 orthopaedic surgery patients met the inclusion criteria. The primary outcomes were: (1) Risk of SSI, (2) Bacterial count in sampled air and (3) Reduction in SSIs. The overall pooled OR of all included studies was 1.70 (95% CI 1.10–2.64), and the overall pooled RR was 1.27 (95% CI 1.02–1.59) with p < 0.05. LAF is ineffective at preventing SSIs in orthopaedic procedures due to its high-risk ratio and odds ratio.

Conclusions
The present meta-analysis has determined that the implementation of LAF systems does not result in a significant reduction in the incidence of surgical site infections (SSIs), bacterial count in the air, or SSIs occurrence in orthopaedic operating rooms. Consequently, the installation of said equipment in operating rooms has been found to be both expensive and inefficient.
Fibula allograft with cannulated screw fixation versus ordinary cannulated screw fixation for femoral neck fractures: a 10-year retrospective comparative study
Authors: Wei Yangwenxiang , Lin Tianye , Liu Yuhao , Chen Zhenqiu , Zhou Chi 
Published: August 2023

Abstract
Background
For femoral neck fractures in young and middle-aged patients, both fibula allograft with cannulated screw fixation and ordinary cannulated screw fixation are clinically effective treatments. However, for unstable femoral neck fractures, ordinary cannulated screw fixation is characterized by a high risk of postoperative complications and a high rate of mechanical failure after internal fixation. For this study, we systematically compared the long-term efficacy and postoperative complications of these two procedures.

Methods
A total of 156 subjects diagnosed as femoral neck fractures participated in our study. Subjects in the combination group underwent fibula allograft with cannulated screw fixation (n = 76), and those in the control group were treated with ordinary cannulated screw fixation (n = 80). Baseline characteristics, perioperative outcomes, Harris hip score (HHS) and EuroQoL five-dimension questionnaire (EQ-5D); and the incidence of postoperative and bone healing complications in the two groups were recorded and compared.

Results
The average follow-up time was more than 10 years. Intra-operative blood loss significantly increased in the combination group compared with the control group (P < 0.05). There were significantly improved performances in healing time, the time course of recovery of full-weight-bearing stepping, HHS and EQ-5D scores in the combination group compared with the control group (P < 0.05). Besides, the incidence rates of femoral head necrosis, nonunion, femoral neck shortening and total hip replacement were significantly lower in the combination group than those in the control group (P < 0.05).

Conclusion
Fibula allograft with cannulated screw fixation shows a better long-term therapeutic effect than ordinary cannulated screw fixation for femoral neck fractures in young and middle-aged patients. Patients receiving the combination strategy have faster and high-quality functional recovery after femoral neck fractures and a lower incidence rate of postoperative complications.
Predictors of osteoporotic fracture in postmenopausal women: a meta-analysis
Authors: Long Guanghua , Liu Chong , Liang Tuo , Zhang Zide , Qin Zhaojie , Zhan Xinli 
Published: August 2023

AbstractOsteoporosis affects more than 200 million women worldwide, with postmenopausal women being particularly susceptible to this condition and its severe sequelae disproportionately, such as osteoporotic fractures. To date, the current focus has been more on symptomatic treatment, rather than preventive measures. To address this, we performed a meta-analysis aiming to identify potential predictors of osteoporotic fractures in postmenopausal women, with the ultimate goal of identifying high-risk patients and exploring potential therapeutic approaches. We searched Embase, MEDLINE and Cochrane with search terms (postmenopausal AND fracture) AND (“risk factor” OR “predictive factor”) in May 2022 for cohort and case–control studies on the predictors of osteoporotic fracture in postmenopausal women. Ten studies with 1,287,021 postmenopausal women were found eligible for analyses, in which the sample size ranged from 311 to 1,272,115. The surveyed date spanned from 1993 to 2021. Our results suggested that age, BMI, senior high school and above, parity ≥ 3, history of hypertension, history of diabetes mellitus, history of alcohol intake, age at menarche ≥ 15, age at menopause < 40, age at menopause > 50, estrogen use and vitamin D supplements were significantly associated with osteoporotic fracture in postmenopausal women. Our findings facilitate the early prediction of osteoporotic fracture in postmenopausal women and may contribute to potential therapeutic approaches. By focusing on preventive strategies and identifying high-risk individuals, we can work toward reducing the burden of osteoporosis-related fractures in this vulnerable population.
TSPAN18 facilitates bone metastasis of prostate cancer by protecting STIM1 from TRIM32-mediated ubiquitination
Authors: Zhou Qianghua , Chen Xu , Yao Kai , Zhang Yangjie , He Haixia , Huang Hao , Chen Hao , Peng Shengmeng , Huang Ming , Cheng Liang , Zhang Qiang , Xie Ruihui , Li Kaiwen , Lin Tianxin , Huang Hai 
Published: August 2023

Abstract
Background
Bone metastasis is a principal cause of mortality in patients with prostate cancer (PCa). Increasing evidence indicates that high expression of stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE) significantly activates the calcium (Ca2+) signaling pathway and is involved in multiple steps of bone metastasis in PCa. However, the regulatory mechanism and target therapy of STIM1 is poorly defined.

Methods
Liquid chromatography-mass spectrometry analysis was performed to identify tetraspanin 18 (TSPAN18) as a binding protein of STIM1. Co-IP assay was carried out to explore the mechanism by which TSPAN18 inhibits STIM1 degradation. The biological function of TSPAN18 in bone metastasis of PCa was further investigated in vitro and in vivo models.

Result
We identified that STIM1 directly interacted with TSPAN18, and TSPAN18 competitively inhibited E3 ligase tripartite motif containing 32 (TRIM32)-mediated STIM1 ubiquitination and degradation, leading to increasing STIM1 protein stability. Furthermore, TSPAN18 significantly stimulated Ca2+ influx in an STIM1-dependent manner, and then markedly accelerated PCa cells migration and invasion in vitro and bone metastasis in vivo. Clinically, overexpression of TSPAN18 was positively associated with STIM1 protein expression, bone metastasis and poor prognosis in PCa.

Conclusion
Taken together, this work discovers a novel STIM1 regulative mechanism that TSPAN18 protects STIM1 from TRIM32-mediated ubiquitination, and enhances bone metastasis of PCa by activating the STIM1-Ca2+ signaling axis, suggesting that TSPAN18 may be an attractive therapeutic target for blocking bone metastasis in PCa.
Sex-related differences in adult patients with status epilepticus: a seven-year two-center observation
Authors: Baumann Sira M. , De Stefano Pia , Kliem Paulina S. C. , Grzonka Pascale , Gebhard Caroline E. , Sarbu Oana E. , De Marchis Gian Marco , Hunziker Sabina , Rüegg Stephan , Kleinschmidt Andreas , Pugin Jérôme , Quintard Hervé , Marsch Stephan , Seeck Margitta , Sutter Raoul 
Published: August 2023

Abstract
Background
Conflicting findings exist regarding the influence of sex on the development, treatment, course, and outcome of status epilepticus (SE). Our study aimed to investigate sex-related disparities in adult SE patients, focusing on treatment, disease course, and outcome at two Swiss academic medical centers.

Methods
In this retrospective study, patients treated for SE at two Swiss academic care centers from Basel and Geneva from 2015 to 2021 were included. Primary outcomes were return to premorbid neurologic function, death during hospital stay and at 30 days. Secondary outcomes included characteristics of treatment and disease course. Associations with primary and secondary outcomes were assessed using multivariable logistic regression. Analysis using propensity score matching was performed to account for the imbalances regarding age between men and women.

Results
Among 762 SE patients, 45.9% were women. No sex-related differences were found between men and women, except for older age and lower frequency of intracranial hemorrhages in women. Compared to men, women had a higher median age (70 vs. 66, p = 0.003), had focal nonconvulsive SE without coma more (34.9% vs. 25.5%; p = 0.005) and SE with motor symptoms less often (52.3% vs. 63.6%, p = 0.002). With longer SE duration (1 day vs. 0.5 days, p = 0.011) and a similar proportion of refractory SE compared to men (36.9% vs. 36.4%, p = 0.898), women were anesthetized and mechanically ventilated less often (30.6% vs. 42%, p = 0.001). Age was associated with all primary outcomes in the unmatched multivariable analyses, but not female sex. In contrast, propensity score-matched multivariable analyses revealed decreased odds for return to premorbid neurologic function for women independent of potential confounders. At hospital discharge, women were sent home less (29.7% vs. 43.7%, p < 0.001) and to nursing homes more often (17.1% vs. 10.0%, p = 0.004).

Conclusions
This study identified sex-related disparities in the clinical features, treatment modalities, and outcome of adult patients with SE with women being at a disadvantage, implying that sex-based factors must be considered when formulating strategies for managing SE and forecasting outcomes.
Early endovascular intervention for unfavorable remodeling of the thoracic aorta after open surgery for acute DeBakey type I aortic dissection: study protocol for a multicenter, randomized, controlled trial
Authors: Liu Yu , Li Ling , Xiao Zhenghua , Peng Liqing , Yang Peng , Lu Chen , Zhang Yu , Wang Haiyue , Hu Jia 
Published: August 2023

Abstract
Background
Total arch replacement with frozen elephant trunk has been developed with promising results for DeBakey type I aortic dissection. However, several problems, such as continuous perfusion of distal false lumen and unfavorable remodeling of distal aorta postoperatively, can seriously affect the long-term outcome. This trial aims to assess the effects of early minimally invasive endovascular repair on distal aortic remodeling and long-term clinical outcomes in patients with dominant false lumen and residual tears in the descending thoracic aorta after total arch replacement and frozen elephant trunk procedure.

Methods
This is a protocol for a two-arm, parallel, multicenter, randomized controlled trial. A total of 154 eligible patients will be recruited from four hospitals in China and randomized on a 1:1 basis either to the experiment group (endovascular repair in addition to routine antihypertensive therapy) or the control group (routine antihypertensive therapy without early surgical treatment). The primary outcome will be the five-year all-cause mortality. The secondary outcomes will include re-intervention, ischemic symptoms, organ dysfunction, and stent-related adverse events.

Discussion
If early minimally invasive endovascular repair could safely and effectively promote distal aortic remodeling and bring favorable long-term outcomes for patients with dominant false lumen and residual tears in the descending thoracic aorta after total arch replacement and frozen elephant trunk technique, it would improve the treatment strategy for DeBakey type I aortic dissection.

Trial registration
Chinese Clinical Trial Registry, CHiCTR2000030050. Registered on 11 March 2020.
Development of green micellar HPLC–DAD method for simultaneous determination of some sulbactam combinations used in COVID-19 regimen
Authors: Ragab Gamal H. , Saleh Hanaa M. , Abdulla Nermeen M. , Bahgat Eman A. 
Published: August 2023

AbstractIn a new attempt to separate some sulbactam combinations by green chemical method we came up with this research in which an ecofriendly, green, sustainable and selective method was established for separation of four antibiotics, namely, cefoperazone (CFP), cefixime (CFX), ampicillin (AMP) and sulbactam (SLB). No organic solvents were used in the composition of the mobile phase as it was replaced by mixing two surfactants together, sodium dodecyl sulfate (SDS) and polyoxyethylene-23-lauryl ether (Brij-35). Effect of varying the concentrations of the two surfactants on chromatographic separation was studied. Optimum separation was maintained using a mobile phase consisting of 0.01 mol/L SDS, 0.03 mol/L Brij-35, 0.4% Tri-ethylamine (TEA) and pH of 2.8 adjusted by using 1 M ortho-phosphoric acid on reversed phase Isère C18 BDS column with temperature of 40 °C at flow rate 1 mL/min, wavelength 215 nm, and the total run time was 6 min. Validation of the proposed method has been made according International Conference of Harmonization (ICH) guidelines at linearity range of 10–200 µg mL−1 for all drugs under study, high accuracy results (recovery range 98.39–100.35%). and the variation coefficient (RSD) of the points on the calibration curve was ranged from (0.1–1.7%) indicating precise method. The LOQ was (6.09 μg mL−1) for CFP, (6.07 μg mL−1) for CFX, (3.85 μg mL−1) for AMP and (7.20 μg mL−1) for SLB. Successful applications were made on marketed dosage forms with recovery range of (100.16–102.25%) and RSD of (0.03–1.88%). The method was verified on the Green Analytical Procedure Index (GAPI) and Analytical Greenness metric approach (AGREE) and it was found to be an excellent green alternative method.