bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the Efficacy and Safety of Erenumab, a Monoclonal Antibody Targeting Calcitonin Gene-related Peptide (CGRP) Receptor, in Patients with Chronic and Episodic Migraine: A GRADE-assessed Systematic Review and Meta-analysis of Randomized Clinical Trials with Subgroup Analysis
Authors: Haseeb Mohamed E. , Mohammed Hazem E. , Yaser Hatem , Hanen George , Nasser Mohamed , Yaser Shehab , Bady Zeyad 
Published: October 2024

Abstract

Background
Migraine is a highly prevalent and disabling disease, affecting nearly 14% of the global population. Preventive medications involve drugs like beta-adrenergic blockers, antidepressants, and anticonvulsants. However, these drugs lacked effectiveness, and patients showed poor tolerance and low adherence to them. Erenumab, a calcitonin gene-related peptide receptor blocker, has recently shown promising results in migraine management. In this meta-analysis, the efficacy of Erenumab is investigated by employing a subgroup analysis approach.
Methods
A systematic search of six electronic databases was conducted until July 2024. Review Manager 5.4 software was utilized for the analysis, which was based on either weighted mean difference (MD) and standard deviation (SD) for continuous outcomes or risk ratio (RR) for dichotomous outcomes, with a confidence interval (CI) of 95%. A P-value < 0.05 indicated statistical significance. The study was registered on PROSPERO with registration number CRD42024573300. Additionally, we conducted subgroup analyses and assessed the quality of evidence using GRADE.
Results
A total of 20 randomized controlled trials (n = 5212) were included in our analysis. At three months, Erenumab showed statistically significant improvements in monthly migraine days (MMD), monthly acute migraine-specific medication days (MSMD), Headache Impact Test (HIT-6) score, and ≥ 50% reduction from baseline in MMD (MD: -1.78, 95% CI: [-2.37 to -1.20], P < 0.00001), (MD: -1.36, 95% CI: [-1.92 to -0.81], P < 0.00001), (MD: -2.83, 95% CI: [-3.83 to -1.82], P < 0.00001), and (RR: 1.52, 95% CI: [1.31 to 1.76], P < 0.00001), respectively. Subgroup analysis revealed that Erenumab was significantly more effective in patients with prior preventive treatment failures compared to patients with no prior failure. No significant difference in Erenumab`s response existed between episodic and chronic migraine or between 140 mg and 70 mg, except for MSMD in dose subgrouping. Only constipation and injection-site pain emerged as significant adverse effects in the Erenumab group.
Conclusions
This meta-analysis found that Erenumab significantly reduced migraine attack frequency, medication days, and physical impairment. It was more effective for patients with prior treatment failures. The 140 mg dose showed better MSMD reduction than 70 mg. Erenumab's safety profile was similar to that of placebo, with only constipation and injection-site pain noted.
Case report: CT Manifestations of Primary Esophageal Tuberculosis
Authors: Huang Zhong , Zhang Shaoyong , Liao Ruikun , Wang Zhi 
Published: October 2024

Abstract

Background
Primary esophageal tuberculosis is an uncommon manifestation of Mycobacterium tuberculosis infection in Asian adults, often presenting with nonspecific symptoms that can complicate diagnosis. This report details a case of primary esophageal tuberculosis in middle age female, emphasizing the diagnostic value of computed tomography (CT) imaging.
Case presentation
The patient, a 46-year-old female from Sichuan Province, China, experienced recurrent choking and mild retrosternal pain postprandially. She exhibited a weight loss of approximately 1 kg over a week, without additional symptoms such as dysphagia or fever. Esophagoscopy disclosed a small ulcer, and CT imaging revealed esophageal wall thickening with mucosal ulceration. A left thoracic lower and middle esophagectomy was conducted, with postoperative pathology confirming granulomatous inflammation, indicative of tuberculosis.
Conclusions
This case highlights the pivotal role of CT imaging in diagnosing primary esophageal tuberculosis. The imaging modality's ability to delineate subtle mucosal ulcerations and wall thickening provides a crucial diagnostic advantage, facilitating accurate and timely diagnosis of this rare condition.
Exploring the deficiencies in technical skills postgraduate surgical training prior to the COVID- 19 pandemic: A systematic review and thematic analysis
Authors: Siddharth Aditi , Tucker Nadia Muspratt , Sakurai Hikari , Aitken Debbie , Higham Helen 
Published: October 2024

Abstract

Background: Postgraduate surgical training has evolved significantly, transitioning from traditional apprenticeship models to more structured competency-based programs. Despite these changes, concerns persist regarding the adequacy of technical skills (TS) training, exacerbated by modern challenges such as working time restrictions and the impact of the COVID-19 pandemic. This systematic review aimed to explore and understand TS training for doctors in postgraduate surgical training programs, focusing on issues prior to the COVID-19 pandemic.
Methods. The search strategy was registered with PROSPERO a priori. Following PRISMA guidance, literature searches were conducted on electronic databases: Medline, Embase and grey literature using specific search criteria of studies published from 2016 to 2018. Studies that discussed TS postgraduate training in surgical specialities were eligible for inclusion. Data were extracted and analysed using inductive coding and thematic analysis.
Results: Seventeen studies were included in the final analysis, predominantly from high-income countries. Thematic analysis revealed two main deficiencies in TS training: inadequate use of a multimodal approach and insufficient structure in training programs. Simulation training, while beneficial, was underutilised. Additionally, there were significant global discrepancies in training length and required competencies, with trainees often feeling less independent than expected upon programme completion.
Conclusion: The review identifies critical areas for improving surgical training, emphasizing the need for a multimodal training approach and a more structured framework for delivery. These findings are particularly relevant for post-pandemic recovery efforts in surgical education, providing a foundation for targeted improvements in training programs.
H-NMR metabolomics identifies three distinct metabolic profiles differentially associated with cardiometabolic risk in patients with obesity in the Di@bet.es cohort
Authors: Ozcariz Enrique , Guardiola Montse , Amigó Núria , Valdés Sergio , Oualla-Bachiri Wassima , Rehues Pere , Rojo-Martínez Gemma , Ribalta Josep 
Published: October 2024

Abstract

Background:
Obesity is a complex, diverse and multifactorial disease that has become a major public health concern in the last decades. The current classification systems relies on anthropometric measurements, such as BMI, that are unable to capture the physiopathological diversity of this disease. The aim of this study was to redefine the classification of obesity based on the different H-NMR metabolomics profiles found in individuals with obesity to better assess the risk of future development of cardiometabolic disease.
Materials and methods:
Serum samples of a subset of the Di@bet.es cohort consisting of 1387 individuals with obesity were analyzed by H-NMR. A K-means algorithm was deployed to define different H-NMR metabolomics-based clusters. Then, the association of these clusters with future development of cardiometabolic disease was evaluated using different univariate and multivariate statistical approaches. Moreover, machine learning-based models were built to predict the development of future cardiometabolic disease using BMI and waist-to-hip circumference ratio measures in combination with H-NMR metabolomics.
Results:
Three clusters with no differences in BMI nor in waist-to-hip circumference ratio but with very different metabolomics profiles were obtained. The first cluster showed a metabolically healthy profile, whereas atherogenic dyslipidemia and hypercholesterolemia were predominant in the second and third clusters, respectively. Individuals within the cluster of atherogenic dyslipidemia were found to be at a higher risk of developing type 2 DM in a 8 years follow-up. On the other hand, individuals within the cluster of hypercholesterolemia showed a higher risk of suffering a cardiovascular event in the follow-up. The individuals with a metabolically healthy profile displayed a lower association with future cardiometabolic disease, even though some association with future development of type 2 DM was still observed. In addition, H-NMR metabolomics improved the prediction of future cardiometabolic disease in comparison with models relying on just anthropometric measures.
Conclusion:
This study demonstrated the benefits of using precision techniques like H-NMR to better assess the risk of obesity-derived cardiometabolic disease.
Multiple Mesenchymal Stem Cell Derived Extracellular Vesicle Administration Accelerates Healing and Ameliorates Tissue Scarring Compared with Single Application in Full Thickness Cutaneous Wounds
Authors: Golroudbari Hasti Tashak , Rajablou Nadia , Soltani Zahra Ebrahim , Heirani-Tabasi Asieh , Nazari Hojjatollah , Arabmohammadi Parisa , Banikarimi Armaghan , Behboudi Behnam , Kazemeini Alireza , Tarafdari Azadeh , Tafti Seyed Mohsen Ahmadi 
Published: October 2024

Abstract

Background
Impaired wound healing is still challenging for patients and health care providers. Healing is a complex multiphasic process that is mediated by paracrine signaling. In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) derived extracellular vesicles (EVs) have shown promising effects on healing acceleration by modifying intercellular interactions. However, they will be promptly washed out after local injection and are almost depleted from the injured site in five days. Therefore, single-dose administration may fail to affect all phases of the healing process. In this study, we evaluated the advantages of multi-administration over its single injection following full-thickness cutaneous wound induction in rats.
Methods
EVs were isolated from human umbilical cord mesenchymal stem cells and characterized. These particles were administered locally in the EV-treated wounds. The level of inflammatory (TNF-α and TGF-β) and angiogenesis (CD31) factors were evaluated through the study to compare multiple dose EV administered, single dose EV administered, and control wounds with each other.
Results
In vivo results demonstrate that triple EV administration significantly attenuates inflammation and improves angiogenesis and collagen deposition in the injured area (p < 0.05).
Conclusion
This study suggests that multiple injections of EVs promotes wound closure and decreases scar formation mainly by maintaining adequate concentration in the wounded area.
A Randomized Phase II Trial of Nab-paclitaxel with or without Mifepristone for Advanced Triple-Negative Breast Cancer
Authors: Chen Nan , Matossian Margarite , Saha Poornima , Rampurwala Murtuza , Kamaraju Salaija , Hahn Olwen , Howard Frederick M , Fleming Gini F , Freeman Jincong Q , Karrison Theodore , Conzen Suzanne , Nanda Rita , Stringer-Reasor Erica M 
Published: October 2024

Abstract

Purpose
Glucocorticoid receptor (GR) activity may mediate chemoresistance in advanced triple-negative breast cancer (TNBC). Preclinical studies demonstrate that GR antagonism can augment the effect of taxanes in TNBC models. We hypothesized that pretreatment with mifepristone, a potent GR antagonist, would enhance nab-paclitaxel efficacy in advanced TNBC.
Methods
This trial was terminated early due to poor accrual. 29 of 64 planned patients were enrolled. Patients were randomized to receive nab-paclitaxel with or without mifepristone; oral mifepristone 300 mg was administered the day prior and day of each dose of nab-paclitaxel. The primary endpoint was progression free survival (PFS); secondary/exploratory endpoints included response rate and correlation of response with GR expression.
Results
The addition of mifepristone to nab-paclitaxel did not improve PFS (3.0m vs 3.0m, p = 0.687) or overall response rate (23% vs 31.5%) compared to nab-paclitaxel alone. There was a trend towards improved overall survival in the combination group, primarily driven by one long-term responder. Increased rates of grade 3 neutropenia (46% vs 7%) and febrile neutropenia were observed in the combination arm, while other toxicities were similar in both groups. Increased GR expression was not correlated with clinical response in the combination arm.
Conclusions
While there were responders to the combination, the study was underpowered to meet the primary endpoint. Higher rates of neutropenia were observed in the combination, but overall it was well-tolerated. Preclinical data in TNBC and clinical data in other malignancies support further investigation of GR modulators. Future studies should incorporate biomarkers to select patients who benefit from GR inhibition.
MRI Radiomics and Nutritional-Inflammatory Biomarkers: A Powerful Combination for Predicting Progression-Free Survival in Cervical Cancer Patients Undergoing Concurrent Chemoradiotherapy
Authors: Yan Qi , Wu Menghan , Zhang Jing , Yang Jiayang , Lv Guannan , Qu Baojun , Zhang Yanping , Yan Xia , Song Jianbo 
Published: October 2024

Abstract

Objective
This study aims to develop and validate a predictive model that integrates clinical features, MRI radiomics, and nutritional-inflammatory biomarkers to forecast progression-free survival (PFS) in cervical cancer (CC) patients undergoing concurrent chemoradiotherapy (CCRT). The goal is to identify high-risk patients and guide personalized treatment.
Methods
We performed a retrospective analysis of 188 patients from two centers, divided into training (132) and validation (56) sets. Clinical data, systemic inflammatory markers, and immune-nutritional indices were collected. Radiomic features from three MRI sequences were extracted and selected for predictive value. We developed and evaluated five models incorporating clinical features, nutritional-inflammatory indicators, and radiomics using C-index. The best-performing model was used to create a nomogram, which was validated through ROC curves, calibration plots, and decision curve analysis (DCA).
Results
Model 5, which integrates clinical features, Systemic Immune-Inflammation Index (SII), Prognostic Nutritional Index (PNI), and MRI radiomics, showed the highest performance. It achieved a C-index of 0.833 (95% CI: 0.792–0.874) in the training set and 0.789 (95% CI: 0.679–0.899) in the validation set. The nomogram derived from Model 5 effectively stratified patients into risk groups, with AUCs of 0.833, 0.941, and 0.973 for 1-year, 3-year, and 5-year PFS in the training set, and 0.812, 0.940, and 0.944 in the validation set.
Conclusions
The integrated model combining clinical features, nutritional-inflammatory biomarkers, and radiomics offers a robust tool for predicting PFS in CC patients undergoing CCRT. The nomogram provides precise predictions, supporting its application in personalized patient management.
The effect of acceptance and commitment counseling on the coping self-efficacy of mothers with unplanned pregnancy: A controlled clinical trial
Authors: Rabiee Masoumeh , Saed Omid , Nikjoo Roya , Ahmadnia Elahe 
Published: October 2024

Abstract

Background
Unplanned pregnancies present a significant challenge in reproductive health due to their unexpected nature, leading to adverse consequences for women, children, families, and society. Recognizing the importance of maternal self-efficacy in managing unplanned pregnancies, this study aimed to determine the impact of acceptance and commitment-based counseling on coping self-efficacy among mothers facing unplanned pregnancies.
Methods
This clinical trial involved 108 mothers with unplanned pregnancies in Ardabil city, located in northwest Iran. Participants were selected using convenience sampling, and block random allocation placed individuals into intervention and control groups. Data were collected through demographic and midwifery information forms, the London Measure of Unplanned Pregnancy (LMUP), Chesney’s Coping Self-Efficacy Scale (CES) and the Ghodratnama Social-Economic Questionnaire. The statistical analysis utilized SPSS version 16 and included T-Test, ANOVA, and repeated measures tests.
Results
The mean age of the intervention and control groups was 30.87 ± 6.32 and 29.11 ± 5.57, respectively. Most women in both groups (32.3%) were pregnant for the second time. The mean pregnancy age in the intervention and control groups was 13.22 ± 3.21 and 11.10 ± 4.16, respectively. Coping self-efficacy mean scores in the intervention group changed from 107.55 ± 35.84 before the intervention to 125.36 ± 34.78 two months after. In the control group, it changed from 98.6 ± 31.86 to 108.12 ± 22.38. There was no statistically significant difference in coping self-efficacy between the two study groups before the intervention. However, immediately after the intervention (p < 0.001) and two months later (p = 0.003), a significant difference was observed, demonstrating the effectiveness of acceptance and commitment-based counseling on coping self-efficacy among mothers with unplanned pregnancies.
Conclusion
Given the impact of acceptance and commitment-based counseling on coping self-efficacy among mothers with unplanned pregnancies, it is recommended to incorporate this counseling intervention into maternal care programs for unplanned pregnancies.
Trial registration
This study, identified as code A-11-38-10 at Zanjan University of Medical Sciences, was registered with the Iranian Clinical Trial Center under the code IRCT20151211025477N7 on August 28, 2023.
Value of Clinical Review for AI-Guided Deep Vein Thrombosis Diagnosis with Ultrasound Imaging by Non-expert Operators
Authors: Speranza Giancarlo , Mischkewitz Sven , Al-Noor Fouad , Kainz Bernhard 
Published: October 2024

Abstract

Deep vein thrombosis (DVT) carries high morbidity, mortality, and costs globally. Point of care ultrasound (POCUS) image acquisition by non-ultrasound-trained providers, supported by an AI-based guidance and remote image review system, is believed to improve the timeliness and cost-effectiveness of diagnosis. We examine a database of 381 patients with suspected DVT who underwent an AI-guided ultrasound scan by a non-ultrasound-trained nurse and an expert sonographer-performed compression ultrasound scan. Each AI-guided scan was reviewed remotely by blinded radiologists or blinded independent POCUS-certified American Emergency Medicine (EM) physicians. Remote reviewer and standard scan diagnoses were compared. The primary endpoint is AI-guidance system sensitivity with clinician review, secondary endpoints include specificity, positive predictive value, negative predictive value, image quality, inter-observer image quality and vein compressibility agreement. Data was analysed through the bootstrapping method, bootstrapping with a second reader for each scan, and a majority voting system. Eighty percent (n = 304) of scans were of sufficient diagnostic quality. Radiologist reviewer sensitivity ranged from 90%-95%, specificity from 74%-84%, NPV from 98%-99%, PPV from 30%-42%, and potential expert-led ultrasound scans avoided from 39%-50%. Inter-observer agreement for image quality was 0.15 and for compressibility 0.61. EM reviewer sensitivity ranged from 95%-98%, specificity from 97%-100%, NPV was 99%, PPV from 81%-100%, and potential expert-led ultrasound scans avoided from 29%-38%. Inter-observer agreement for image quality was 0.59 and for compressibility 0.67. Diagnosing lower extremity DVT through AI-guided image acquisition with clinician review is feasible. Performance is influenced by reviewer expertise. We find potential positive impacts on health economics, including safely avoiding expert-led ultrasound scans.
Abundance of root clusters in Kingia australis (Dasypogonaceae) highlights widespread non-symbiotic adaptations to nutrient-impoverished soils
Authors: Lamont Byron , Weinert Andrew , Duff Helen 
Published: October 2024

Abstract

Background and Aims: Recent erosion of a riverbank in southwestern Australia exposed previously unrecorded root clusters produced by the grasstree, Kingia australis (Dasypogonaceae). Our aim was to provide descriptions of these structures compared with currently known specialized roots.
Methods: Excavation of root clusters, quantification of their distribution/morphology, and histology.
Results: There were 260 clusters per m3 of soil to a depth of 1.6 m and concentrated at 50-70 cm. They averaged 8.4 x 5.5 cm in length x width with 5360 roots/rootlets per L of rhizosphere soil. Clusters comprised a parent lateral (with cortical aerenchyma), secondary parent roots 50 x 3 mm in length x width, and rootlets 10 x 1 mm. Clusters are perennial, new roots sometimes emerging from the previous winter-growing-season’ cluster. We refer to these novel structures as staghorn-coralloid roots. Total root length reached 70 m per L of soil. The epidermal surface averaged 1600 cm2 per L of soil. All roots are covered in root hairs, with parent lateral hairs 250 µm long to 700 µm for rootlets. They must push through a ±150-µm thick mucigel layer to reach the soil. Adding root hairs increased the surface area exposed to the rhizosphere by 4.4 times for a mere 3.3% increase in root volume. Endogenous fungal hyphae or (cyano)bacteria were not evident.
Conclusion: These root clusters link with proteoid, dauciform and capillaroid roots via their prolific production of extremely hairy rootlets with abundant mucigel, implying that they are functionally matched, but are otherwise morphologically and anatomically distinct.
Region‐specific brain decellularized scaffolds can recover cell viability in an oxygen-glucose deprivation model
Authors: Reginensi Diego , Ortiz Didio , Castillo Solangel , Burillo Andrea , Denis Bernardino , Khoury Nathalie , Xu Jing , Escobar Anthony A. Hurtado , Dave Kunjan R. , Perez-Pinzon Miguel A. , Gittens Rolando A. 
Published: October 2024

Abstract

Brain decellularized extracellular matrix (ECM) can be an attractive scaffold capable of mimicking the native ecosystem of the central nervous system tissue. In this study, we studied the in vitro response of neural lineage cells exposed to region-specific brain decellularized ECM scaffolds from three distinct neuroanatomical sections: cortex, cerebellum and remaining areas. First, the evaluation of each brain subregion was performed with the isotropic fractionator method to understand the cellular composition of the different cerebral areas. Second, each of the cerebral subregions was subjected to the decellularization process and their respective characterization using molecular, histological, and ultrastructural techniques. Third, the presence of neurotrophic factors in the decellularized brain scaffold was analyzed. Finally, we studied the region-specific brain decellularized ECM as a mimetic platform for the maturation of PC12 cells and for the recovery of cell viability in an oxygen-glucose deprivation model. Our results show that region-specific brain decellularized ECM can serve as a biomimetic scaffold capable of promoting the growth of neural lineage cells and, in addition, it possesses a combination of structural and biochemical signals (e.g., neurotrophic factors) that are capable of inducing cell phenotypic changes that can promote cell recovery and viability in a stroke/ischemia model in vitro.