bluuebunny/crossref_metadata_2025_split huggingface dataset:
M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis
Authors: Zhu Xiaolan , Li Wenxin , Lu Minjun , Shang Junyu , Zhou Jiamin , Lin Li , Liu Yueqin , Xing Jie , Zhang Mengxue , Zhao Shijie , Lu Jingjing , Shi Xuyan 
Published: June 2024

Abstract
Background
Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms.

Methods
A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed.

Results
Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition.

Conclusion
H-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.

Graphical Abstract
Oncological outcomes of fertility-sparing surgery versus radical surgery in stage - epithelial ovarian cancer: a systematic review and meta-analysis
Authors: Guan Ziting , Zhang Changlin , Lin Xinmei , Zhang Jingwei , Li Tian , Li Jundong 
Published: June 2024

Abstract
Background
The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS.

Methods
We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460).

Results
From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53–1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50–0.99]; P = 0.04).

Conclusions
This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer.
Therapeutic intervention in neuroinflammation for neovascular ocular diseases through targeting the cGAS-STING-necroptosis pathway
Authors: Ni Biyan , Yang Ziqi , Zhou Tian , Zhou Hong , Zhou Yang , Lin Shiya , Xu Huiyi , Lin Xiaojing , Yi Wei , He Chang , Liu Xialin 
Published: June 2024

AbstractThe microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.
Support for sexual and reproductive health and rights in Sub-Saharan Africa: a new index based on World Values Survey data
Authors: Svallfors Signe , Båge Karin , Ekström Anna Mia , Dessie Yadeta , Wado Yohannes Dibaba , Fagbemi Mariam , Larsson Elin C. , Litorp Helena , Puranen Bi , Sundewall Jesper , Uthman Olalekan A. , Kågesten Anna E. 
Published: June 2024

Abstract
Background
Addressing attitudes is central to achieving sexual and reproductive health and rights (SRHR) and Agenda 2030. We aimed to develop a comprehensive index to measure attitudinal support for SRHR, expanding opportunities for global trend analyses and tailored interventions.

Methods
We designed a new module capturing attitudes towards different dimensions of SRHR, collected via the nationally representative World Values Survey in Ethiopia, Kenya, and Zimbabwe during 2020–2021 (n = 3,711). We used exploratory factor analysis of 58 items to identify sub-scales and an overall index. Adjusted regression models were used to evaluate the index according to sociodemographic characteristics, stratified by country and sex.

Results
A 23-item, five-factor solution was identified and used to construct sub-indices reflecting support for: (1) sexual and reproductive rights, (2) neighborhood sexual safety, (3) gender-equitable relationships, (4) equitable masculinity norms, and (5) SRHR interventions. These five sub-indices performed well across countries and socioeconomic subgroups and were combined into a comprehensive “SRHR Support Index”, standardized on a 1–100 scale (mean = 39.19, SD = 15.27, Cronbach’s alpha = 0.80) with higher values indicating more support for SRHR. Mean values were highest in Kenya (45.48, SD = 16.78) followed by Ethiopia (40.2, SD = 13.63), and lowest in Zimbabwe (32.65, SD = 13.77), with no differences by sex. Higher education and being single were associated with more support, except in Ethiopia. Younger age and urban residence correlated with more support among males only.

Conclusion
The SRHR Support Index has the potential to broaden SRHR attitude research from a comprehensive perspective – addressing the need for a common measure to track progress over time.
Virological outcomes of third-line antiretroviral therapy in a global context: a systematic reviews and meta-analysis
Authors: kitaw Tegene Atamenta , Abate Biruk Beletew , Yilak Gizachew , Tilahun Befkad Derese , Faris Abebe Merchaw , Walle Getachew Tesfaw , Haile Ribka Nigatu 
Published: June 2024

Abstract
Background
Despite remarkable progress, HIV’s influence on global health remains firm, demanding continued attention. Understanding the effectiveness of third-line antiretroviral therapy in individuals who do not respond to second-line drugs is crucial for improving treatment strategies. The virological outcomes of third-line antiretroviral therapy vary from study to study, highlighting the need for robust global estimates.

Methods
A comprehensive search of databases including PubMed, MEDLINE, International Scientific Indexing, Web of Science, and Google Scholar, was conducted. STATA version 17 statistical software was used for analysis. A random-effects model was applied to compute the pooled estimates. Subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also performed. The prediction interval is computed to estimate the interval in which a future study will fall. The GRADE tool was also used to determine the quality of the evidence.

Results
In this systematic review and meta-analysis, 15 studies involving 1768 HIV patients receiving third-line antiretroviral therapy were included. The pooled viral suppression of third-line antiretroviral therapy was 76.6% (95% CI: 71.5- 81.7%). The viral suppression rates at 6 and 12 months were 75.5% and 78.6%, respectively. Furthermore, third-line therapy effectively suppressed viral RNA copy numbers to ≤ 50 copies/mL, ≤ 200 copies/mL, and ≤ 400 copies/mL with rates of 70.7%, 85.4%, and 85.7%, respectively.

Conclusion
More than three-fourths of patients on third-line antiretroviral therapy achieve viral suppression. Consequently, improving access to and timely initiation of third-line therapy may positively impact the quality of life for those with second-line treatment failure.
From asymptomatic adult patient to cardiopulmonary resuscitation – treatment of ALCAPA with total arterial myocardial revascularisation and mitral valve repair
Authors: Al-Obaidi Mustafa , Hecker Florian , Walther Thomas , Holubec Tomas 
Published: June 2024

Abstract
Background
Anomalous left coronary artery originating from the pulmonary artery (ALCAPA), is a unique congenital anomaly, comprising only 0.24–0.46% of all congenital cardiac anomalies. Late presentations, ranging from asymptomatic cases to sudden cardiac arrest, are exceptionally rare. This unique case highlights the complexity of managing ALCAPA in adulthood and underscores the necessity of a comprehensive surgical approach addressing both coronary and valvular issues.

Presentation
A 34-year-old female patient, who had been diagnosed with ALPACA in her early childhood, suffered sudden cardiac arrest at work, followed by out-of-hospital resuscitation. The patient had been followed-up regularly until adolescence, however, she had refused surgery. In the diagnostic work-up following successful resuscitation severe mitral valve regurgitation was additionally revealed. Subsequently, the patient underwent surgery, involving coronary artery bypass grafting (CABG), using bilateral internal mammary arteries, and mitral valve repair, with an excellent postsurgical result. At 16-month follow-up, the patient was asymptomatic and quality of life had significantly improved.

Conclusion
This rare case initially presented as silent myocardial ischemia, resulting in reduced left ventricular function and secondary mitral incompetence. Surgical treatment of ALCAPA in adults poses greater challenges and a higher risk than in children. CABG procedure offers an excellent prognostic therapeutic strategy, since this procedure is a routine in adult cardiac surgery.
Construction of prediction models for novel subtypes in patients with arteriosclerosis obliterans undergoing endovascular therapy: an unsupervised machine learning study
Authors: Li Xiaocheng , Zhang Lin , Li Que , Zhang Jiangfeng , Qin Xiao 
Published: June 2024

Abstract
Background
Arteriosclerosis obliterans (ASO) is a chronic arterial disease that can lead to critical limb ischemia. Endovascular therapy is increasingly used for limb salvage in ASO patients, but the outcomes vary. The development of prediction models using unsupervised machine learning may lead to the identification of novel subtypes to guide patient prognosis and treatment.

Methods
This retrospective study analyzed clinical data from 448 patients with ASOs who underwent endovascular therapy. Unsupervised machine learning algorithms were employed to identify subgroups. To validate the precision of the clustering outcomes, an analysis of the postoperative results of the clusters was conducted. A prediction model was constructed using binary logistic regression.

Results
Two distinct subgroups were identified by unsupervised machine learning and characterized by differing patterns of clinical features. Patients in Cluster 2 had significantly worse conditions and prognoses than those in Cluster 1. For the novel ASO subtypes, a nomogram was developed using six predictive factors, namely, platelet count, ankle brachial index, Rutherford category, operation method, hypertension, and diabetes status. The nomogram achieved excellent discrimination for predicting membership in the two identified clusters, with an area under the curve of 0.96 and 0.95 in training cohort and internal test cohort.

Conclusion
This study demonstrated that unsupervised machine learning can reveal novel phenotypic subgroups of patients with varying prognostic risk who underwent endovascular therapy. The prediction model developed could support clinical decision-making and risk counseling for this complex patient population. Further external validation is warranted to assess the generalizability of the findings.
Splice_sim: a nucleotide conversion-enabled RNA-seq simulation and evaluation framework
Authors: Popitsch Niko , Neumann Tobias , von Haeseler Arndt , Ameres Stefan L. 
Published: June 2024

AbstractNucleotide conversion RNA sequencing techniques interrogate chemical RNA modifications in cellular transcripts, resulting in mismatch-containing reads. Biases in mapping the resulting reads to reference genomes remain poorly understood. We present splice_sim, a splice-aware RNA-seq simulation and evaluation pipeline that introduces user-defined nucleotide conversions at set frequencies, creates mixture models of converted and unconverted reads, and calculates mapping accuracies per genomic annotation. By simulating nucleotide conversion RNA-seq datasets under realistic experimental conditions, including metabolic RNA labeling and RNA bisulfite sequencing, we measure mapping accuracies of state-of-the-art spliced-read mappers for mouse and human transcripts and derive strategies to prevent biases in the data interpretation.
De novo biosynthesis of β-arbutin in Corynebacterium glutamicum via pathway engineering and process optimization
Authors: Zhang Bin , Gou Kexin , Xu Kexin , Li Zhimin , Guo Xiaoyan , Wu Xiaoyu 
Published: June 2024

Abstract
Background
β-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. β-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of β-arbutin.

Results
This study established the β-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of β-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a β-arbutin production titer of 7.94 g/L in the optimized fermentation medium.

Conclusions
This study represents the first successful instance of de novo β-arbutin production in C. glutamicum, offering a chassis cell for β-arbutin biosynthesis.
Mucinous cystadenoma and carcinoid tumor arising from an ovarian mature cystic teratoma in a 60 year-old patient: a case report
Authors: Jafari-Nozad Amir Masoud , Jahani Najmeh , Moniri Yoones 
Published: June 2024

Abstract
Background
Mature cystic teratomas (MCT) of the ovary are benign ovarian germ cell neoplasms. Malignant transformation is possible but rare and ovarian carcinoid tumors in MCT are among the most extremely rare subtypes.

Case presentation
We report a case of a 60-year-old Iranian woman suffering from postmenopausal bleeding and hypogastric pain for the last 40 days. An adnexal mass was detected during the physical examination. Ultrasound imaging showed a (55 × 58) mm mass in the left ovary. Total abdominal hysterectomy, bilateral salpingooophorectomy and comprehensive staging surgery were performed for the patient. Intraoperative frozen section of the left ovarian mass was indicative of a malignant tumor. She was diagnosed with a carcinoid tumor with benign mucinous cystadenoma arising on MCT of the ovary, confirmed in the histopathology and immunohistochemistry examination. The tumor was classified as low grade and no chemotherapy cycles were considered. The patient was followed up long-term and no recurrence was observed during 14 months of examinations.

Conclusion
Ovarian carcinoids arising from MCT are rare neuroendocrine neoplasms, and proper diagnosis of these tumors requires careful histopathology evaluation and appropriate examination. Therefore, it is necessary to consider these tumors as a possible differential diagnosis and evaluate them in individuals (especially postmenopausal women) who have abdominal pain or abnormal bleeding and a palpable mass.
Temporal trends of skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus in Gabon
Authors: Gouleu Christiane Sidonie , Daouda Maradona Agbanrin , Oye Bingono Sam O’neilla , McCall Matthew Benjamin Bransby , Alabi Abraham Sunday , Adegnika Ayola Akim , Schaumburg Frieder , Grebe Tobias 
Published: June 2024

Abstract
Background
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of mortality due to bacterial antimicrobial resistance. While S. aureus is common in skin and soft tissue infections (SSTI) in Africa, data on MRSA rates are scarce and reports vary widely across the continent (5%-80%). In this study, we describe the proportion of MRSA causing SSTI in Lambaréné, Gabon, over an 11-year period.

Methods
We retrospectively analyzed data from 953 bacterial specimens collected from inpatients and outpatients with SSTI at the Albert Schweitzer Hospital, Lambaréné, Gabon, between 2009 and 2019. We determined temporal changes in the prevalence of MRSA and identified risk factors for SSTI with MRSA.

Results
68% of all specimens with bacterial growth yielded S. aureus (n = 499/731), of which 7% (36/497) with antimicrobial susceptibility testing were identified as MRSA. Age above 18 years, admission to the surgical ward, and deep-seated infections were significantly associated with MRSA as the causative agent. After an initial decline from 7% in 2009, there was a marked increase in the proportion of MRSA among all S. aureus from SSTI from 3 to 20% between 2012 and 2019. The resistance rate to erythromycin was significantly higher in MRSA than in methicillin-susceptible S. aureus (73% vs. 10%), and clindamycin resistance was detected exclusively in MRSA isolates (8%).

Conclusion
The increasing proportion of MRSA causing SSTI over the 11-year period contrasts with many European countries where MRSA is on decline. Continuous surveillance of MRSA lineages in the hospital and community along with antibiotic stewardship programs could address the increasing trend of MRSA.
Intracerebral haemorrhage in multiple sclerosis: assessing the impact of disease-modifying medications
Authors: Ou Yong Brian M. , Awuah Wireko Andrew , Shah Muhammad Hamza , Sanker Vivek , Huk Jonathan Kong Sing , Venkata Sujashree Yadala , Patel Diti H. , Tan Joecelyn Kirani , Khan Noor Ayman , Kulasekaran Ajitha , Sarkar Manali , Abdul-Rahman Toufik , Atallah Oday 
Published: June 2024

AbstractMultiple Sclerosis (MS) is a complex autoimmune disorder that significantly impacts the central nervous system, leading to a range of complications. While intracranial haemorrhage (ICH) is a rare but highly morbid complication, more common CNS complications include progressive multifocal leukoencephalopathy (PML) and other CNS infections. This severe form of stroke, known for its high morbidity and mortality rates, presents a critical challenge in the management of MS. The use of disease-modifying drugs (DMDs) in treating MS introduces a nuanced aspect to patient care, with certain medications like Dimethyl Fumarate and Fingolimod showing potential in reducing the risk of ICH, while others such as Alemtuzumab and Mitoxantrone are associated with an increased risk. Understanding the intricate relationship between these DMDs, the pathophysiological mechanisms of ICH, and the individualised aspects of each patient's condition is paramount. Factors such as genetic predispositions, existing comorbidities, and lifestyle choices play a crucial role in tailoring treatment approaches, emphasising the importance of a personalised, vigilant therapeutic strategy. The necessity for ongoing and detailed research cannot be overstated. It is crucial to explore the long-term effects of DMDs on ICH occurrence and prognosis in MS patients, aiming to refine clinical practices and promote patient-centric, informed therapeutic decisions. This approach ensures that the management of MS is not only comprehensive but also adaptable to the evolving understanding of the disease and its treatments.