bluuebunny/crossref_metadata_2025_split huggingface dataset:
First real-world study on the effectiveness and tolerability of rimegepant for acute migraine therapy in Chinese patients
Authors: Yang Zhao , Wang Xiaodan , Niu Mengyue , Wei Qiao , Zhong Huizhu , Li Xiaoyan , Yuan Weihong , Xu Wenli , Zhu Shuo , Yu Shengyuan , Liu Jun , Yan Jianzhou , Kang Wenyan , Huang Peijian 
Published: September 2024

Abstract
Background
Rimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients.

Methods
This was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs.

Results
By November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p < 0.05) and a marked increase in the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose compared with predose. AEs were reported by 6% of participants in the FP, and all AEs were mild.

Conclusions
In the real world, rimegepant is effective in the acute treatment of migraine patients in China. The low incidence rate of AEs highlighted the favourable tolerability profile of rimegepant.

Trial registration
Clinicaltrials.gov NCT05709106. Retrospectively registered on 2023-02-01.

Graphical Abstract
Occlusive retinal vasculitis associated with intravitreal Faricimab injections
Authors: Reichel Felix F. , Kiraly Peter , Vemala Roopa , Hornby Stella , De Silva Samantha R. , Fischer M. Dominik 
Published: September 2024

Abstract
Purpose
We describe a case of occlusive vasculitis associated with intravitreal Faricimab (Vabysmo) injections.

Methods
A retrospective case report.

Results
A 52-year old man treated with monthly Faricimab injections for diabetic macula oedema presented with sudden reduced vision, new retinal hemorrhages, significant retinal vascular occlusions and ischemia. After screening for differential diagnoses was unremarkable, the patient was treated with oral and intravitreal steroid therapy under which the occlusive vasculitis was stabilized.

Conclusion
Occlusive vasculitis, though rare, is a potential complication of Faricimab therapy. Comprehensive reporting and large-scale analyses are essential to better understand and manage this adverse event.
Mugen-UMAP: UMAP visualization and clustering of mutated genes in single-cell DNA sequencing data
Authors: Li Teng , Zou Yiran , Li Xianghan , Wong Thomas K. F. , Rodrigo Allen G. 
Published: September 2024

Abstract
Background
The application of Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and visualization has revolutionized the analysis of single-cell RNA expression and population genetics. However, its potential in single-cell DNA sequencing data analysis, particularly for visualizing gene mutation information, has not been fully explored.

Results
We introduce Mugen-UMAP, a novel Python-based program that extends UMAP’s utility to single-cell DNA sequencing data. This innovative tool provides a comprehensive pipeline for processing gene annotation files of single-cell somatic single-nucleotide variants and metadata to the visualization of UMAP projections for identifying clusters, along with various statistical analyses. Employing Mugen-UMAP, we analyzed whole-exome sequencing data from 365 single-cell samples across 12 non-small cell lung cancer (NSCLC) patients, revealing distinct clusters associated with histological subtypes of NSCLC. Moreover, to demonstrate the general utility of Mugen-UMAP, we applied the program to 9 additional single-cell WES datasets from various cancer types, uncovering interesting patterns of cell clusters that warrant further investigation. In summary, Mugen-UMAP provides a quick and effective visualization method to uncover cell cluster patterns based on the gene mutation information from single-cell DNA sequencing data.

Conclusions
The application of Mugen-UMAP demonstrates its capacity to provide valuable insights into the visualization and interpretation of single-cell DNA sequencing data. Mugen-UMAP can be found at https://github.com/tengchn/Mugen-UMAP
Reporting and communication of sample size calculations in adaptive clinical trials: a review of trial protocols and grant applications
Authors: Zhang Qiang , Dimairo Munyaradzi , Julious Steven A. , Lewis Jen , Yu Zihang 
Published: September 2024

Abstract
Background
An adaptive design allows modifying the design based on accumulated data while maintaining trial validity and integrity. The final sample size may be unknown when designing an adaptive trial. It is therefore important to consider what sample size is used in the planning of the study and how that is communicated to add transparency to the understanding of the trial design and facilitate robust planning. In this paper, we reviewed trial protocols and grant applications on the sample size reporting for randomised adaptive trials.

Method
We searched protocols of randomised trials with comparative objectives on ClinicalTrials.gov (01/01/2010 to 31/12/2022). Contemporary eligible grant applications accessed from UK publicly funded researchers were also included. Suitable records of adaptive designs were reviewed, and key information was extracted and descriptively analysed.

Results
We identified 439 records, and 265 trials were eligible. Of these, 164 (61.9%) and 101 (38.1%) were sponsored by industry and public sectors, respectively, with 169 (63.8%) of all trials using a group sequential design although trial adaptations used were diverse.
The maximum and minimum sample sizes were the most reported or directly inferred (n = 199, 75.1%). The sample size assuming no adaptation would be triggered was usually set as the estimated target sample size in the protocol. However, of the 152 completed trials, 15 (9.9%) and 33 (21.7%) had their sample size increased or reduced triggered by trial adaptations, respectively.
The sample size calculation process was generally well reported in most cases (n = 216, 81.5%); however, the justification for the sample size calculation parameters was missing in 116 (43.8%) trials. Less than half gave sufficient information on the study design operating characteristics (n = 119, 44.9%).

Conclusion
Although the reporting of sample sizes varied, the maximum and minimum sample sizes were usually reported. Most of the trials were planned for estimated enrolment assuming no adaptation would be triggered. This is despite the fact a third of reported trials changed their sample size. The sample size calculation was generally well reported, but the justification of sample size calculation parameters and the reporting of the statistical behaviour of the adaptive design could still be improved.
Hepatitis C virus attributable liver cancer in the country of Georgia, 2015–2019: a case–control study
Authors: Surguladze Sophia , Armstrong Paige A. , Beckett Geoff A. , Shadaker Shaun , Gamkrelidze Amiran , Tsereteli Maia , Getia Vladimer , Asamoah Benedict Oppong 
Published: September 2024

Abstract
Background
Hepatitis C virus (HCV) infection can lead to a type of primary liver cancer called hepatocellular carcinoma (HCC). Georgia, a high HCV prevalence country, started an HCV elimination program in 2015. In addition to tracking incidence and mortality, surveillance for the HCV-attributable fraction of HCC is an important indicator of the program’s impact. This study assesses HCV infection-attributable HCC in the Georgian population.

Methods
This case–control study utilized HCV programmatic and Georgian Cancer Registry data from 2015–2019. Bivariate logistic regression and age- and sex-stratified analyses assessed HCV and liver cancer association. HCV-attributable liver cancer proportions for the HCV-exposed and total population were calculated. A sub-analysis was performed for HCC cases specifically.

Results
The total study population was 3874 with 496 liver cancer cases and 3378 controls. The odds for HCV-infected individuals developing liver cancer was 20.1 (95% confidence interval [CI] 15.97–25.37), and the odds of developing HCC was 16.84 (95% CI 12.01–23.83) compared to the HCV-negative group. Odds ratios varied across strata, with HCV-infected older individuals and women having higher odds of developing both liver cancer and HCC. A large proportion of liver cancer and HCC can be attributed to HCV in HCV-infected individuals; however, in the general population, the burden of liver cancer and HCC cannot be explained by HCV alone.

Conclusion
HCV was significantly associated with a higher risk of developing liver cancer and HCC in the Georgian population. In addition, given Georgia’s high HCV burden, increased HCC monitoring in HCV-infected patients is needed.
Diagnosis of suspected pediatric distal forearm fractures with point-of-care-ultrasound (POCUS) by pediatric orthopedic surgeons after minimal training
Authors: Pohl Josephine Edith , Schwerk Philipp , Mauer René , Hahn Gabriele , Beck Ricardo , Fitze Guido , Schultz Jurek 
Published: September 2024

Abstract
Background
Several studies have advocated the use of ultrasound to diagnose distal forearm fractures in children. However, there is limited data on the diagnostic accuracy of ultrasound for distal forearm fractures when conducted by pediatric surgeons or trainees who manage orthopedic injuries in children. The objective of this study was to determine the diagnostic accuracy of point-of-care ultrasound (POCUS) for pediatric distal forearm fractures when conducted by pediatric surgeons and trainees after minimal training.

Methods
This diagnostic study was conducted in a tertiary hospital emergency department in Germany. Participants were children and adolescents under 15 years of age who presented to the emergency department with an acute, suspected, isolated distal forearm fracture requiring imaging. Pediatric surgeons and trainees, after minimal training for sonographic fracture diagnosis, performed 6-view distal forearm POCUS on each participant prior to X-ray imaging. All data was retrospectively collected from the hospital’s routine digital patient files. The primary outcome was the diagnostic accuracy of POCUS compared to X-ray as the reference standard.

Results
From February to June 2021, 146 children under 15 met all inclusion and exclusion criteria, and 106 data sets were available for analysis. Regarding the presence of a fracture, X-ray and Wrist-POCUS showed the same result in 99.1%, with 83/106 (78.3%) fractures detected in both modalities and one suspected buckle fracture on POCUS not confirmed in the radiographs. Wrist-POCUS had a sensitivity of 100% (95% CI [0.956, 1]) and a specificity of 95.8% (95% CI [0.789, 0.999]) compared to radiographs. In 6 cases, there were minor differences regarding a concomitant ulnar buckle. The amount of prior ultrasound training had no influence on the accuracy of Wrist-POCUS for diagnosing distal forearm fractures. All fractures were reliably diagnosed even when captured POCUS images did not meet all quality criteria.

Conclusion
Pediatric surgeons and trainees, after minimal training in POCUS, had excellent diagnostic accuracy for distal forearm fractures in children and adolescents using POCUS compared to X-ray.
Adipogenesis biomarkers as the independent predictive factors for breast cancer recurrence: a systematic review and meta-analysis
Authors: Hu Shihang , Tey Sze Keong , Kwong Ava 
Published: September 2024

Abstract
Background
Comprehensive analysis of clinical evidence for breast cancer adipogenesis with prognosis is lacking. This study aims to consolidate the latest evidence on the relationship between adipogenesis and breast cancer outcomes.

Data sources
: Medline, Web of Science, Embase, Scopus, Clinicaltrials.gov, Cochrane library.

Methods
A systematic review was conducted according to the PRISMA guidelines. Studies that reported the correlation between tumor adipogenesis and cancer recurrence or empirical pathological markers were included for meta-analysis. The standard reference for pathological markers determination was set as histopathological examination. The PROSPERO ID was CRD489135.

Results
Eleven studies were included in this systematic review and meta-analysis. Several adipogenesis biomarkers involved in the synthesis, elongation, and catabolism of fatty acids, such as FASN, Spot 14, pS6K1, lipin-1, PLIN2, Elovl6, and PPARγ, were identified as the potential biomarkers for predicting outcomes. Through meta-analysis, the predictive value of adipogenesis biomarkers for 5-year recurrence rate was calculated, with a pooled predictive risk ratio of 2.19 (95% CI: 1.11–4.34). In terms of empirical pathological markers, a negative correlation between adipogenesis biomarkers and ki-67 was observed (RR: 0.69, 95% CI: 0.61–0.79). However, no significant correlation was found between the adipogenesis and ER, PR, HER2, or p53 positivity.

Conclusions
Biomarker of adipogenesis in breast cancer is a significant predictor of long-term recurrence, and this prediction is independent of HR, HER2, and ki-67. The diverse roles of adipogenesis in different breast cancer subtypes highlight the need for further research to uncover specific biomarkers that can used for diagnosis and prediction.

Protocol registration
PROSPERO ID: CRD489135.
AI-based fully automatic analysis of retinal vascular morphology in pediatric high myopia
Authors: Zhao Yinzheng , Zhao Zhihao , Yang Junjie , Li Li , Nasseri M. Ali , Zapp Daniel 
Published: September 2024

Abstract
Purpose
To investigate the changes in retinal vascular structures associated with various stages of myopia by designing automated software based on an artificial intelligence model.

Methods
The study involved 1324 pediatric participants from the National Children’s Medical Center in China, and 2366 high-quality retinal images and corresponding refractive parameters were obtained and analyzed. Spherical equivalent refraction (SER) degree was calculated. We proposed a data analysis model based on a combination of the Convolutional Neural Networks (CNN) model and the attention module to classify images, segment vascular structures, and measure vascular parameters, such as main angle (MA), branching angle (BA), bifurcation edge angle (BEA) and bifurcation edge coefficient (BEC). One-way ANOVA compared parameter measurements between the normal fundus, low myopia, moderate myopia, and high myopia groups.

Results
The mean age was 9.85 ± 2.60 years, with an average SER of -1.49 ± 3.16D in the right eye and − 1.48 ± 3.13D in the left eye. There were 279 (12.38%) images in the normal group and 384 (16.23%) images in the high myopia group. Compared with normal fundus, the MA of fundus vessels in different myopic refractive groups was significantly reduced (P = 0.006, P = 0.004, P = 0.019, respectively), and the performance of the venous system was particularly obvious (P < 0.001). At the same time, the BEC decreased disproportionately (P < 0.001). Further analysis of fundus vascular parameters at different degrees of myopia showed that there were also significant differences in BA and branching coefficient (BC). The arterial BA value of the fundus vessel in the high myopia group was lower than that of other groups (P = 0.032, 95% confidence interval [CI], 0.22–4.86), while the venous BA values increased (P = 0.026). The BEC values of high myopia were higher than those of low and moderate myopia groups. When the loss function of our data classification model converged to 0.09, the model accuracy reached 94.19%.

Conclusion
The progression of myopia is associated with a series of quantitative retinal vascular parameters, particularly the vascular angles. As the degree of myopia increases, the diversity of vascular characteristics represented by these parameters also increases.
Evaluation of the immunization efficacy and adverse reactions of hepatitis B vaccination in children with thalassemia minor
Authors: Han Xue , Zhang Xi , Zhong Liling , Liu Ying , Gong Lifen , Zhang Jikai , Wang Hai , Chen Qingsong 
Published: September 2024

Abstract
Objective
To assess the immunization efficacy and incidence of adverse reactions after hepatitis B vaccination in children with thalassemia based on data from real-world studies.

Methods
A total of 625 children were recruited into this cross-sectional study. Subgroup analyses of different thalassemia types were performed using binary logistic regression, the factors affecting HBsAb levels were identified using multiple linear regression, and the dose-response relationship between the duration of immunization and seroconversion was explored using the restricted cubic spline (RCS) model to further assess the protective duration of the hepatitis B vaccine.

Results
HBsAb positivity in enrolled children was 87.3% in the thalassemia group and 81.4% in the control group. Multifactorial analysis revealed that the duration of immunization, age at completion of vaccination, and whether the first dose was delayed were significant factors influencing HBsAb levels in children (P < 0.05). The threshold for HBsAb positivity may be reached when the immunization duration reaches approximately 30 months. A subgroup analysis revealed that the HBsAb positivity rate was lower in children with β-thalassemia minor compared to those with α-thalassemia minor (P = 0.001, 95% CI: 0.097 ∼ 0.536). Adverse reactions after hepatitis B vaccination were dominated by general reactions, with a statistically significant difference in injection-site redness and swelling between the thalassemia and control groups (P < 0.05).

Conclusions
The immunization response to the hepatitis B vaccine in children with thalassemia minor was comparable to healthy children, with no abnormal adverse effects seen.
The viral load monitoring cascade in HIV treatment programmes in sub-Saharan Africa: a systematic review
Authors: Kippen Annalise , Nzimande Londiwe , Gareta Dickman , Iwuji Collins 
Published: September 2024

Abstract
Background
The United Nations’ 95-95-95 (95% of people with HIV being aware of their diagnosis, 95% of those aware of their diagnosis being on treatment and 95% achieving viral suppression) target aims to reduce morbidity and mortality of HIV. However, with 60% of new HIV infections occurring in sub-Saharan Africa (SSA), achieving this target in the region is challenging. Viral load (VL) monitoring is the gold-standard approach of assessing treatment efficacy, and its implementation into national health systems is a global health priority if elimination of HIV as a public health threat is to be achieved by 2030. This systematic review aims to investigate VL monitoring outcomes in SSA, and to identify gaps and possible interventions to help nations meet their 2030 targets.

Methods
A literature search of three electronic platforms (MEDLINE, EMBASE and Global Health) was undertaken from 1 January to 9 August 2024 to identify studies published in English and conducted in SSA. The primary outcome was the proportion of people living with HIV (PLHIV) on antiretroviral therapy (ART) with routine VL monitoring at the recommended time points (initially, 6 months, 12 months and annually). Secondary outcomes reported proportions of PLHIV who received routine VL monitoring who went on to complete the cascade of care after identified virological failure [enhanced adherence counselling (EAC), switch to second-line ART, and finally viral suppression].

Results
The initial search identified 342 papers, of which 35 studies were included for narrative synthesis. Included studies reported on findings from 14 African countries and demonstrated extensive variation in rates of VL monitoring (range: 24.3-99.7%, mean: 63.8%). Results were more unfavourable in the latter steps of the viral load monitoring cascade, with a range of 0-88%, and a switch to second-line ART mean of 42% (range: 4.4-93%). Studies with additional support, and those with community-based models of care, had higher rates of VL testing and viral suppression.

Conclusions
VL monitoring and management of virological failure are suboptimal in many SSA countries due to individual and health system-related challenges. Health system strengthening is vital to ensure the sustainability of HIV treatment programmes and the achievement of 95-95-95 targets by 2030.
Dizziness and vertigo sick leave before and after insurance restrictions – a descriptive Swedish nationwide register linkage study
Authors: Zborayova Katarina , Barrenäs Marie-Louise , Granåsen Gabriel , Kerber Kevin , Salzer Jonatan 
Published: September 2024

Abstract
Background
Vertigo and dizziness can be disabling symptoms that result in sick leave. Research regarding sickness absence due to dizziness has focused on specific vestibular diagnoses rather than the nonspecific vertigo/dizziness diagnoses. Strict sick leave regulations were introduced in Sweden in 2008. The aim of this study was to describe the vertigo/dizziness sick leave prevalence and duration considering both specific and nonspecific diagnoses according to International Classification of diseases 10th revision (ICD-10) on the 3-digit level, including the less specific “R” diagnoses.

Methods
Through Swedish nationwide registers we identified individuals aged 16–64 years who during the years 2005–2018 were sickness absent > 14 consecutive days – minimum register threshold – due to vertigo/dizziness diagnoses according to ICD10 codes: specific diagnoses (H81.0, H81.1, H81.2, H81.3, H81.4, G11x) and nonspecific (R42, R26, R27, H81.9). We described the demographic characteristics, prevalence and duration of such sick-leave spells. Data were stratified according to diagnostic groups: ataxias, vestibular and nonspecific.

Results
We identified 52,179 dizziness/vertigo sick leave episodes > 14 days in 45,353 unique individuals between 2005–2018, which constitutes 0.83% from all sick leave episodes in the given period.The nonspecific diagnoses represented 72% (n = 37741) of sick leave episodes and specific vestibular H-diagnoses 27% (n = 14083). The most common specific vestibular codes was Benign paroxysmal positional vertigo (BPPV) 9.4% (n = 4929). The median duration of sick leave was 31 days (IQR 21–61). Women on sick leave were younger than men (47 vs 51 years, p < 0.05) and had a higher proportion of nonspecific diagnoses compared with men (74% vs 70%, p < 0.05).

Conclusions
The vast majority of vertigo/dizziness sick leave episodes were coded as nonspecific diagnoses and occurred in women. BPPV, a curable vestibular condition, was the most common specific diagnosis. This suggests a potential for improved diagnostics. Women on sick leave due to dizziness/vertigo were younger and more often received nonspecific diagnostic codes. Future studies should determine the frequency of use of evidence based therapies and investigate further the gender differences.