bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics
Authors: Karlsson William Kristian , Ashina Håkan , Cullum Christopher Kjær , Christensen Rune Häckert , Al-Khazali Haidar Muhsen , Amin Faisal Mohammad , Ashina Messoud ,   on behalf of the REFORM Investigators, Iljazi Afrim , Thomsen Andreas Vinther , Chaudhry Basit Ali , Tesfay Betel , Thuraiaiyah Janu , Kokoti Lili , Rasmussen Nadja Bredo , Domínguez-Moreno Rogelio , Do Thien Phu , Zhuang Zixuan Alice 
Published: June 2023

Abstract
Background
Erenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion of patients do not respond to it. The Registry for Migraine study (REFORM) was initiated to discover biomarkers that can predict response to erenumab in patients with migraine. The specific objective was to investigate differences in erenumab efficacy based on clinical information, blood-based biomarkers, structural and functional magnetic resonance imaging (MRI), and response to intravenous infusion of calcitonin gene-related peptide (CGRP). In this first report of the REFORM study, we provide a comprehensive description of the study methodology, and present the baseline characteristics of the study population.

Methods
The REFORM study was a single-center, prospective, longitudinal cohort study in adults with migraine who were scheduled to receive preventive treatment with erenumab as part of a separate, open-label, single-arm phase IV trial. The study included four periods: a 2-week screening period (Weeks -6 to -5), 4-week baseline period (Week -4 to Day 1), 24-week treatment period (Day 1 to Week 24), and a 24-week follow-up period without treatment (Week 25 to Week 48). Demographic and clinical characteristics were recorded using a semi-structured interview, whilst outcome data were obtained using a headache diary, patient-reported outcomes, blood sampling, brain MRI, and responsiveness to intravenous infusion of CGRP.

Results
The study enrolled 751 participants, with a mean age ± SD of 43.8 ± 12.2 years, of which 88.8% (n = 667) were female. At enrollment, 64.7% (n = 486) were diagnosed with chronic migraine, and 30.2% (n = 227) had history of aura. The mean monthly migraine days (MMDs) was 14.5 ± 7.0. Concomitant preventive medications were used by 48.5% (n = 364) of the participants, and 39.9% (n = 300) had failed ≥ 4 preventive medications.

Conclusion
The REFORM study enrolled a population with a high migraine burden and frequent use of concomitant medications. The baseline characteristics were representative of patients with migraine in specialized headache clinics. Future publications will report the results of the investigations presented in this article.

Trial registration
The study and sub-studies were registered on ClinicalTrials.gov (NCT04592952; NCT04603976; and NCT04674020).
Comparative genomics of smut fungi suggest the ability of meiosis and mating in asexual species of the genus Pseudozyma (Ustilaginales)
Authors: Steins Lena , Guerreiro Marco Alexandre , Duhamel Marine , Liu Fei , Wang Qi-Ming , Boekhout Teun , Begerow Dominik 
Published: June 2023

Abstract
Background
The Ustilaginales comprise hundreds of plant-parasitic fungi with a characteristic life cycle that directly links sexual reproduction and parasitism: One of the two mating-type loci codes for a transcription factor that not only facilitates mating, but also initiates the infection process. However, several species within the Ustilaginales have no described parasitic stage and were historically assigned to the genus Pseudozyma. Molecular studies have shown that the group is polyphyletic, with members being scattered in various lineages of the Ustilaginales. Together with recent findings of conserved fungal effectors in these non-parasitic species, this raises the question if parasitism has been lost recently and in multiple independent events or if there are hitherto undescribed parasitic stages of these fungi.

Results
In this study, we sequenced genomes of five Pseudozyma species together with six parasitic species from the Ustilaginales to compare their genomic capability to perform two central functions in sexual reproduction: mating and meiosis. While the loss of sexual capability is assumed in certain lineages and asexual species are common in Asco- and Basidiomycota, we were able to successfully annotate potentially functional mating and meiosis genes that are conserved throughout the whole group.

Conclusion
Our data suggest that at least the key functions of a sexual lifestyle are maintained in the analyzed genomes, challenging the current understanding of the so-called asexual species with respect to their evolution and ecological role.
Identification of novel prognostic circRNA biomarkers in circRNA-miRNA-mRNA regulatory network in gastric cancer and immune infiltration analysis
Authors: Yan Jianing , Ye Guoliang , Jin Yanping , Miao Min , Li Qier , Zhou Hanxuan 
Published: June 2023

Abstract
Background
Gastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs.

Objective
Our study aimed to construct the circRNA-miRNA-mRNA regulatory network and analyze the function and prognostic significance of the network using bioinformatics tools.

Methods
We first downloaded the GC expression profile from the Gene Expression Omnibus database and identified differentially expressed genes and differentially expressed circRNAs. Then, we predicted the miRNA-mRNA interaction pairs and constructed the circRNA-miRNA-mRNA regulatory network. Next, we established a protein-protein interaction network and analyzed the function of these networks. Finally, we primarily validated our results by comparison with The Cancer Genome Atlas cohort and by performing qRT-PCR.

Results
We screened the top 15 hub genes and 3 core modules. Functional analysis showed that in the upregulated circRNA network, 15 hub genes were correlated with extracellular matrix organization and interaction. The function of downregulated circRNAs converged on physiological functions, such as protein processing, energy metabolism and gastric acid secretion. We ascertained 3 prognostic and immune infiltration-related genes, COL12A1, COL5A2, and THBS1, and built a nomogram for clinical application. We validated the expression level and diagnostic performance of key prognostic differentially expressed genes.

Conclusions
In conclusion, we constructed two circRNA-miRNA-mRNA regulatory networks and identified 3 prognostic and screening biomarkers, COL12A1, COL5A2, and THBS1. The ceRNA network and these genes could play important roles in GC development, diagnosis and prognosis.
Strigolactones and abscisic acid interactions affect plant development and response to abiotic stresses
Authors: Korek Magdalena , Marzec Marek 
Published: June 2023

AbstractStrigolactones (SL) are the youngest group of plant hormones responsible for shaping plant architecture, especially the branching of shoots. However, recent studies provided new insights into the functioning of SL, confirming their participation in regulating the plant response to various types of abiotic stresses, including water deficit, soil salinity and osmotic stress. On the other hand, abscisic acid (ABA), commonly referred as a stress hormone, is the molecule that crucially controls the plant response to adverse environmental conditions. Since the SL and ABA share a common precursor in their biosynthetic pathways, the interaction between both phytohormones has been largely studied in the literature. Under optimal growth conditions, the balance between ABA and SL content is maintained to ensure proper plant development. At the same time, the water deficit tends to inhibit SL accumulation in the roots, which serves as a sensing mechanism for drought, and empowers the ABA production, which is necessary for plant defense responses. The SL-ABA cross-talk at the signaling level, especially regarding the closing of the stomata under drought conditions, still remains poorly understood. Enhanced SL content in shoots is likely to stimulate the plant sensitivity to ABA, thus reducing the stomatal conductance and improving the plant survival rate. Besides, it was proposed that SL might promote the closing of stomata in an ABA-independent way. Here, we summarize the current knowledge regarding the SL and ABA interactions by providing new insights into the function, perception and regulation of both phytohormones during abiotic stress response of plants, as well as revealing the gaps in the current knowledge of SL-ABA cross-talk.
Association between serum β2-microglobulin levels and the risk of all-cause and cardiovascular disease mortality in chinese patients undergoing maintenance hemodialysis
Authors: Jin Yu-Xin , Zhang Shuang , Xiao Jia , Wang Zhi-Hong , Dong Cui , You Lian-Lian , Kuai Ting-Ting , Zhang Yu , Liu Shu-Xin 
Published: June 2023

Abstract
Background
The association between serum β2-microglobulin (β2M) levels and the risk of all-cause and cardiovascular disease (CVD) mortality and the incidence of cardiovascular events (CVEs) in patients undergoing maintenance hemodialysis (MHD) is inconclusive. Furthermore, no study has been performed in China on the significance of serum β2M levels in MHD patients. Therefore, this study investigated the aforementioned association in MHD patients.

Methods
In this prospective cohort study, 521 MHD patients were followed at Dalian Municipal Central Hospital affiliated with Dalian University of Technology from December 2019 to December 2021. The serum β2M levels were categorized into three tertiles, and the lowest tertile served as the reference group. Survival curves were calculated by the Kaplan–Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. Sensitivity analysis was performed by excluding patients with CVD at baseline.

Results
During the follow-up period of 21.4 ± 6.3 months, there were 106 all-cause deaths, of which 68 were caused by CVD. When excluding CVD patients at baseline, there were 66 incident CVEs. Kaplan–Meier analysis revealed that the risk of all-cause and CVD mortality in the highest tertile of serum β2M levels was significantly higher than that in the lowest tertile (P < 0.05), but not for the CVEs (P > 0.05). After adjusting for potential confounders, serum β2M levels were positively associated with the risk of all-cause (HR = 2.24, 95% CI = 1.21–4.17) and CVD (HR = 2.54, 95% CI = 1.19–5.43) mortality, and a linear trend was evident (P < 0.05). Besides, the results of sensitivity analysis were consistent with the main findings. However, we didn’t observed the significant association between serum β2M levels and CVEs (P > 0.05).

Conclusion
The serum β2M level may be a significant predictor of the risk of all-cause and CVD mortality in MHD patients. Further studies are needed to confirm this finding.
Practices and factors associated with active management of the third stage of labor in East Africa: systematic review and meta-analysis
Authors: Gelaw Kelemu Abebe , Assefa Yibeltal , Birhan Belete , Gebeyehu Natnael Atnafu 
Published: June 2023

AbstractBackgroundActive management of the third stage of labor involves prophylactic uterotonics, early cord clamping, and controlled cord traction to deliver the placenta. It is designed to facilitate the delivery of the placenta by increasing uterine contractions during the third stage of labor. It is also used to prevent postpartum hemorrhage by averting uterine atony.This systematic review and meta-analysis’s emphasis was on the practice and factors associated with active management of the third stage of labor in East Africa.MethodsPubMed, Web of Science, Science Direct (Scopus), Google Scholar, African Journals Online, and the Cochrane Library electronic databases were used. Data were extracted using Microsoft Excel, and STATA version 14 was used for analysis. A p-value of 0.05 is regarded to indicate potential publication bias: the funnel plot, Begg, and Egger’s regression test were used to examine publication bias. Using I2statistics, the heterogeneity of the studies was evaluated. Pooled analysis was carried out. By country, a subgroup analysis was conducted.ResultsThirteen studies were included in this systematic review and meta-analysis. The pooled prevalence of the practice of active management of the third stage of labor in East Africa was 34.42%. Received training (OR = 6.25, 95%CI = 3.69, 10.58), years of experience (OR = 3.66, 95%CI = 2.35, 5.71), and good knowledge (OR = 3.66, 95%CI = 2.35, 5.71) were statically associated with the practice of active management of third stage of labor.ConclusionThe pooled prevalence of practice for active management of the third stage of labor in East Africa was low. Factors that were statistically associated with the practice were received training, years of experience, and good knowledge. Obstetric care providers should continue to receive training in all components of active management of the third stage of labor through training and education programs.
Prominent corneal nerves in pure mucosal neuroma syndrome, a clinical phenotype distinct from multiple endocrine neoplasia type 2B
Authors: Yin L , Wang YNZ , Zhu J , Tan CY , Sun C , Yao Y 
Published: June 2023

Abstract
Background
Pure mucosal neuroma syndrome (MNS), an autosomal dominant neurocutaneous disorder, is a rare discrete subgroup in multiple endocrine neoplasia (MEN) type 2B, which present without associated endocrinopathies of MEN2B but with typical physical features such as prominent corneal nerves.
Case presentation
This report describes a 41-year-old patient with complaint of itchy eyes and irritation, presenting with blocked gland orifices in the upper and lower eyelids, light conjunctival hyperemia, a semitransparent neoplasm measuring 2 mm*2 mm on the nasal limbus suggestive of neuromas, and prominent corneal nerves. In vivo confocal microscopy (IVCM) revealed structural alterations—namely a prominent hyperreflective, thickened nerve plexus and a normal endothelium—in both eyes. Testing for SOS1 mutation was positive. This patient may represent a discrete subgroup termed pure mucosal neuroma syndrome (MNS), which presents with the characteristic appearance of MEN2B but without RET gene mutations.

Conclusion
Prominent corneal nerves have been described in some diseases, such as multiple endocrine neoplasia (MEN) type 1 and type 2A and 2B, congenital ichthyosis, Refsum’s disease, leprosy, etc. Ophthalmic assessment including prominent corneal nerves has proven valuable in asymptomatic individuals of MEN2B. Our case illustrates the importance of recognizing the ocular features of MNS, a rare presentation of MEN2B, in order to prevent prophylactic thyroidectomy in these patients for prophylactic thyroidectomy is not mandatory in MNS. However, regular monitoring and genetic counseling are still necessary.
Repeated intra-articular injections of umbilical cord-derived mesenchymal stem cells for knee osteoarthritis: a phase I, single-arm study
Authors: Ao Yunong , Duan Jiangjie , Xiong Na , Qian Nannan , Zhang Rui , Yang Liu , Yu Shicang , Wang Fuyou 
Published: June 2023

Abstract
Introduction
Stem cell therapy has emerged as an effective treatment for multiple diseases, and some studies also demonstrate that it may be a promising treatment for osteoarthritis (OA). However, few studies have clarified the safety of repeated intra-articular injection of human umbilical cord-derived mesenchymal stem cells (UC-MSCs). To promote its application in treating OA, we conducted an open-label trial to investigate the safety of repeated intra-articular injections of UC-MSCs.

Methods
Fourteen patients with OA (Kellgrene-Lawrence grade 2 or 3) who received repeated intra-articular injections of UC-MSCs were evaluated in three months of follow-up. The primary outcomes were the adverse events, and the second outcomes included visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores and SF-12 quality of life score.

Results
A total of 5 of 14 patients (35.7%) experienced transient adverse reactions, which resolved spontaneously. All patients showed some improvement in knee function limitation and pain after receiving stem cell therapy. VAS score 6.0 to 3.5, WOMAC score 26.0 to 8.5, MOCART score 42.0 to 58.0, SF-12 score 39.0 to 46.0.

Conclusion
Repeated intra-articular injection of UC-MSCs demonstrates safety in treating OA and does not induce serious adverse events. This treatment may transiently improve symptoms in patients with knee OA and may be a potential therapeutic option for OA.
Construction of the XGBoost model for early lung cancer prediction based on metabolic indices
Authors: Guan Xiuliang , Du Yue , Ma Rufei , Teng Nan , Ou Shu , Zhao Hui , Li Xiaofeng 
Published: June 2023

Abstract
Background
Lung cancer is a malignant tumour, and early diagnosis has been shown to improve the survival rate of lung cancer patients. In this study, we assessed the use of plasma metabolites as biomarkers for lung cancer diagnosis. In this work, we used a novel interdisciplinary mechanism, applied for the first time to lung cancer, to detect biomarkers for early lung cancer diagnosis by combining metabolomics and machine learning approaches.

Results
In total, 478 lung cancer patients and 370 subjects with benign lung nodules were enrolled from a hospital in Dalian, Liaoning Province. We selected 47 serum amino acid and carnitine indicators from targeted metabolomics studies using LC‒MS/MS and age and sex demographic indicators of the subjects. After screening by a stepwise regression algorithm, 16 metrics were included. The XGBoost model in the machine learning algorithm showed superior predictive power (AUC = 0.81, accuracy = 75.29%, sensitivity = 74%), with the metabolic biomarkers ornithine and palmitoylcarnitine being potential biomarkers to screen for lung cancer. The machine learning model XGBoost is proposed as an tool for early lung cancer prediction. This study provides strong support for the feasibility of blood-based screening for metabolites and provide a safer, faster and more accurate tool for early diagnosis of lung cancer.

Conclusions
This study proposes an interdisciplinary approach combining metabolomics with a machine learning model (XGBoost) to predict early the occurrence of lung cancer. The metabolic biomarkers ornithine and palmitoylcarnitine showed significant power for early lung cancer diagnosis.
Using machine learning to develop a clinical prediction model for SSRI-associated bleeding: a feasibility study
Authors: Goyal Jatin , Ng Ding Quan , Zhang Kevin , Chan Alexandre , Lee Joyce , Zheng Kai , Hurley-Kim Keri , Nguyen Lee , He Lu , Nguyen Megan , McBane Sarah , Li Wei , Cadiz Christine Luu 
Published: June 2023

Abstract
Introduction
Adverse drug events (ADEs) are associated with poor outcomes and increased costs but may be prevented with prediction tools. With the National Institute of Health All of Us (AoU) database, we employed machine learning (ML) to predict selective serotonin reuptake inhibitor (SSRI)-associated bleeding.

Methods
The AoU program, beginning in 05/2018, continues to recruit ≥ 18 years old individuals across the United States. Participants completed surveys and consented to contribute electronic health record (EHR) for research. Using the EHR, we determined participants who were exposed to SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine). Features (n = 88) were selected with clinicians’ input and comprised sociodemographic, lifestyle, comorbidities, and medication use information. We identified bleeding events with validated EHR algorithms and applied logistic regression, decision tree, random forest, and extreme gradient boost to predict bleeding during SSRI exposure. We assessed model performance with area under the receiver operating characteristic curve statistic (AUC) and defined clinically significant features as resulting in > 0.01 decline in AUC after removal from the model, in three of four ML models.

Results
There were 10,362 participants exposed to SSRIs, with 9.6% experiencing a bleeding event during SSRI exposure. For each SSRI, performance across all four ML models was relatively consistent. AUCs from the best models ranged 0.632–0.698. Clinically significant features included health literacy for escitalopram, and bleeding history and socioeconomic status for all SSRIs.

Conclusions
We demonstrated feasibility of predicting ADEs using ML. Incorporating genomic features and drug interactions with deep learning models may improve ADE prediction.
A survey of social well-being among employees, retirees, and nursing students: a descriptive-analytical study
Authors: Vakilabad Reza Nemati , Kheiri Roya , Islamzadeh Negin , Afshar Pouya Farokhnezhad , Ajri-Khameslou Mehdi 
Published: June 2023

Abstract
Background
Social well-being is one of the essential dimensions of individual health. Nursing is one of the occupations that can affect a person’s well-being. This study aimed to determine social well-being among employees, retirees, and nursing students.

Methods
This is a cross-sectional descriptive study. 321 samples participated in this study. Convenience sampling method was used to collect samples. Two questionnaires of demographic characteristics and the Keyes Social Well-being Questionnaire were used to collect data. Descriptive statistics, independent t-test, one-way analysis of variance (ANOVA), and Linear regression analysis by the Backward Elimination method were applied using SPSS 14.0.

Results
The mean total social well-being score of this study’s participants was 100 ± 16.43. The mean social well-being score among nursing employees was 109.58 ± 15.98, among nursing retirees was 95.67 ± 12.55, and among nursing students was 93.14 ± 14.81. Nursing students had lower social well-being scores than nursing employees and retirees (p < 0.001). Linear regression analysis showed a significant relationship between the number of children (p = 0.04) (β = -0.11), marital status (p = 0.04) (β = 2.95), and employment status (p < 0/001) (β = 0.451) and social well-being and predicted 25% of the total variance of social well-being.

Conclusion
According to the results of this study, the social well-being of retirees and nursing students was significantly lower than nursing employees. Therefore, the educational and healthcare systems of the countries must take the necessary measures to improve the Social well-being of this group of people.