bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 3 trial of fixed dose combinations of fianlimab (anti–LAG-3) + cemiplimab (anti–PD-1) versus relatlimab + nivolumab in patients with unresectable or metastatic melanoma.
Authors: Khushalani Nikhil I. , Mani Jayakumar , Booth Jocelyn , Zhang Zoe , Salvati Mark , Lowy Israel , Fury Matthew G. , Lewis Karl , Manvelian Garen , Tawbi Hussein A. 
Published: June 2024

TPS9611 Background: Fianlimab (anti–lymphocyte activation gene 3 [LAG-3]) and cemiplimab (anti–programmed cell death-1 [PD-1]) are high-affinity, fully human, immunoglobulin G4 monoclonal antibodies. Concurrent LAG-3 blockade may enhance the efficacy of anti–PD-1 therapies. Relatlimab (anti–LAG-3) + nivolumab (anti–PD-1) monoclonal antibodies demonstrated benefit in progression-free survival (PFS) in advanced melanoma (Mel) patients compared with nivolumab alone in the RELATIVITY-047 study. In a multicohort Phase 1 study (NCT03005782), fianlimab + cemiplimab demonstrated reproducibly high clinical activity (objective response rate [ORR]: 61%, N=98) in three independent cohorts of advanced PD-(L)1–naïve metastatic Mel patients with an acceptable safety profile. Methods: This is a randomized, open-label, multicenter Phase 3 study (NCT06246916) comparing the fixed dose combination (FDC) of fianlimab + cemiplimab to the FDC of relatlimab + nivolumab in patients with unresectable or metastatic Mel. The primary objective is to demonstrate superiority of fianlimab + cemiplimab compared with relatlimab + nivolumab as measured by ORR assessed by blinded independent central review (BICR). This study will be conducted at approximately 80 sites across North America. Key inclusion criteria are: (1) aged ≥18 years; (2) histologically confirmed unresectable stage III or IV (metastatic) Mel; (3) no prior systemic therapy for unresectable or metastatic Mel; patients with adjuvant and/or neoadjuvant systemic therapies are eligible with a treatment-free and disease-free interval of >6 months; (4) measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1; (5) Eastern Cooperative Oncology Group performance status of ≤1; (6) adequate bone marrow, hepatic, and kidney function. Approximately 560 patients will be randomized in a 1:1 ratio to two treatment arms: Arm A: FDC of fianlimab (Dose 1) + cemiplimab (Dose 2) every 3 weeks intravenously (IV); Arm B: FDC of relatlimab 160 mg + nivolumab 480 mg every 4 weeks IV. All patients will be stratified based on metastatic stage (stage III vs M1a–b vs M1c–d), baseline lactate dehydrogenase level (≤ vs > upper limit of normal), and prior adjuvant and/or neoadjuvant systemic therapy. Patients will receive treatment until disease progression, unacceptable toxicity, withdrawal of consent, a study withdrawal criterion is met, or the sponsor terminates the study. The primary endpoint is ORR and key secondary endpoints are PFS and overall survival. Additional secondary endpoints are duration of response, disease control rate, investigator-assessed ORR and PFS, safety, pharmacokinetics, and immunogenicity. Clinical trial information: NCT06246916 .
Associations of Gestational Exposure to Air Pollution With Maternal Vitamin D Levels: A Meta-Analysis
Authors: Binter Anne-Claire , Ghassabian Akhgar , Zou Runyu , El Marroun Hanan , Lertxundi Aitana , Switkowski Karen M , Estarlich Marisa , Rodríguez-Dehli Ana Cristina , Esplugues Ana , Vrijkotte Tanja , Sunyer Jordi , Santa-Marina Loreto , Fernández-Somoano Ana , Polanska Kinga , McEachan Rosemary R C , Oken Emily , Tiemeier Henning , Guxens Mònica 
Published: June 2024

Abstract

Context
Maternal vitamin D level is an important determinant of pregnancy and child health outcomes. Exposure to air pollution is suspected to increase the risk of vitamin D deficiency, but the evidence is scarce.

Objective
We investigated the association between air pollution during pregnancy and maternal vitamin D levels.

Methods
A total of 15 935 pregnant women from 5 birth cohorts in Europe and the United States were included. Averaged concentrations of nitrogen oxides, fine and coarse particles, and composition of fine particles from conception until vitamin D measurement were estimated at participants’ residential addresses using land-use regression or other spatiotemporal models. Cohorts measured vitamin D as 25(OH)D or 25(OH)D3 levels in serum or plasma at early or mid-pregnancy. We defined suboptimal vitamin D levels as levels below 20 ng/mL. We performed logistic regression models for each cohort to estimate the association between air pollution exposure and suboptimal vitamin D levels and pooled cohort-specific estimates in a random-effect meta-analysis. Models were adjusted for sociodemographic and lifestyle characteristics and month of conception.

Results
We found an association between particulate matter (PM)2.5 and higher odds of suboptimal vitamin D levels (ie, below 20 ng/mL) (odds ratio per 5 μg/m3 increase in PM2.5, 1.43; 95% CI: 1.02, 1.99). There was no association between other air pollutant exposure and vitamin D levels.

Conclusion
PM2.5 exposure might contribute to suboptimal levels of vitamin D in pregnancy. Reducing air pollution exposure should be a priority because vitamin D deficiency may adversely influence offspring development.
Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial
Authors: Cortez Samuel , Moog Dominic , Lewis Christopher , Williams Kelley , Herrick Cynthia J , Fields Melanie E , Gray Teddi , Guo Zhaohua , Nicol Ginger , Baranski Thomas 
Published: June 2024

Abstract

Background
A goal of gender-affirming hormone therapy (GAHT) for transgender women is to use estradiol to suppress endogenous production of testosterone. However, the effects of different estradiol regimens and route of administration on testosterone suppression is unknown. This is the first open-label randomized trial comparing different GAHT regimens for optimal estradiol route and dosing.

Objective
To evaluate 1 month and 6 months testosterone suppression &lt;50 ng/dL with pulsed (once- or twice-daily sublingual 17-beta estradiol) and continuous (transdermal 17-beta estradiol) GAHT.

Methods
This study was conducted at an outpatient adult transgender clinic. Thirty-nine transgender women undergoing initiation of GAHT were randomly assigned to receive either once-daily sublingual, twice-daily sublingual, or transdermal 17-beta estradiol. All participants received spironolactone as an antiandrogen. Doses were titrated at monthly intervals to achieve total testosterone suppression &lt;50 ng/dL.

Results
Transdermal 17-beta estradiol resulted in more rapid suppression of total testosterone, lower estrone levels, with no differences in estradiol levels when compared to once-daily and twice-daily sublingual estradiol. Moreover, there was no difference in the mean estradiol dose between the once-daily and twice-daily sublingual 17-beta estradiol group.

Conclusion
Continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to once or twice daily sublingual estradiol. Most transgender women achieved cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches. Given no difference between once- or twice-daily sublingual estradiol, pulsed 17-beta estradiol likely provides no benefit for testosterone suppression.
Sacropolitics
Authors: Nugent David , Suhail Adeem 
Published: June 2024

Abstract
Two decades into the twenty-first century, a panoply of formerly separate movements, interests, organizations, and individuals have converged around shared anxieties about the future of life on earth. This article focuses on the implicit logic on which this “cult(ure) of extinction” is based. We refer to this logic as sacropolitics—the politics of mass public sacrifice. We suggest that sacropolitics describes a practical reimagining of the political emergent across the world during periods of acute crises, such as our shared present. Sacropolitics draws on multiple dispersed, decentralized sources and has emerged during a period of great turbulence and acrimony in the public sphere, when the very notion of truth is up for grabs. Despite its ambiguity, sacropolitics offers a range of related, collectively generated intimations or visions of what the future might be.
Moving Beyond Morphometrics and Alignment: Prospective Longitudinal Study on Cognition, Quality of Life, and Diffusion Metrics in Congenital Craniovertebral Junction Anomalies
Authors: Alle Prashanth , Thakar Sumit , Aryan Saritha 
Published: June 2024

BACKGROUND AND OBJECTIVES:
Chiari type I malformation (CMI) has been implicated to cause cognitive impairment. Unusual for a craniovertebral junction (CVJ) anomaly, this phenomenon is postulated to be related to microstructural changes across the brain. However, this has not been confirmed in a longitudinal study, in bony CVJ anomalies, or in the context of quality of life (QOL). This study aimed to analyze cognition, QOL, and diffusion tensor imaging (DTI) metrics before and after surgery for congenital CVJ anomalies and evaluate their correlations with conventional clinico-radiological factors.

METHODS:
Fifty-seven patients with congenital CVJ anomalies—CMI, atlantoaxial dislocation (AAD), and basilar invagination (BI)—were evaluated in this prospective longitudinal study over 3 years with a neuropsychological battery, QOL and functional scores, and DTI metrics. A total of 43 patients (23 with CMI; 20 with AAD or BI) with 1-year postsurgical data were included in the final analysis.

RESULTS:
Cognitive dysfunction in one or more domains was noted in 15 (65%) of the patients with CMI and 16 (80%) of the patients with AAD/BI. Memory and visual motor perception were the most-affected domains in both the cohorts. At the 1-year follow-up, the proportion of patients demonstrating an overall cognitive dysfunction did not change significantly (P > .05). All patients demonstrated significant postoperative improvement in functional and QOL scores at follow-up. DTI metrics improved in many regions postoperatively, but did not correlate with functional or cognitive changes (P > .05).

CONCLUSION:
Cognition is affected in a majority of patients with CMI, AAD, or BI. These patients experience good functional and QOL outcomes after surgery but most of them continue to exhibit cognitive impairment. DTI metrics improve after surgery, but do not correlate with cognitive changes. These findings underline the multidimensional nature of the pathology of these anomalies that complicate achieving the concept of a “successful” surgery.
Efficacy and safety of concurrent immune checkpoint inhibitors combined with radiotherapy or chemoradiotherapy for advanced non-small cell lung cancer: A systematic review and single-arm meta-analysis
Authors: Cui Ran , Li Yun , Yu Xinlin , Wei Chun , Jiang Ou 
Published: June 2024

Background
The recent usage of immunotherapy combined with chemoradiotherapy has improved survival in advanced non-small cell lung cancer (NSCLC) patients. However, determining the most effective therapy combination remains a topic of debate. Research suggests immune checkpoint inhibitors (ICIs) post-chemoradiotherapy enhance survival, but the impact of concurrent ICIs during chemoradiotherapy on rapid disease progression is unclear. This meta-analysis aims to assess the effectiveness and safety of concurrent ICIs with radiotherapy or chemoradiotherapy in advanced non-small cell lung cancer.

Methods
We searched PubMed, Embase, the Cochrane Library, and Web of Science for relevant studies, extracting data on overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs).

Results
The analysis included ten studies with 490 participants. Stage III NSCLC ORR was 81.8%, while Stage IV ORR was 39.9%. One-year PFS and OS for Stage III were 68.2% and 82.6%, compared to 27.9% and 72.2% for Stage IV. Common adverse events included anemia (46.6%), nausea (47.6%), rash (36.4%), and radiation pneumonitis (36.3%).

Conclusions
Our meta-analysis shows concurrent ICIs with chemoradiotherapy are effective and safe in advanced NSCLC, particularly in stage III patients at risk of progression before starting ICIs after chemoradiotherapy. The findings support further phase III trials. The review protocol was registered on PROSPERO (CRD42023493685) and is detailed on the NIHR HTA programme website.
The psychosocial determinants of adherence to home-based rehabilitation strategies in parents of children with cerebral palsy: A systematic review
Authors: Niyonsenga Japhet , Uwingeneye Liliane , Musabyemariya Inès , Sagahutu Jean Baptiste , Cavallini Francesca , Caricati Luca , Eugene Rutembesa , Mutabaruka Jean , Jansen Stefan , Monacelli Nadia 
Published: June 2024

Introduction
Involving parents of children with cerebral palsy (C-CP) in home exercise programmes (HEP) is globally practiced strategy closely linked to improved physical performance and functional outcomes for the child. Nevertheless, non-adherence to HEP is increasing at an alarming rate, and little is known about the factors influencing adherence to HEP (AHEP) especially in parents of C-CP. This systematic review aimed to identify the factors enhancing AHEP among parents of C-CP to reinforce the efficacy of rehabilitation practices proposed by health professionals, researchers, and educators.

Materials and methods
We conducted searches in PubMed, Scopus, CINHAL, PsycINFO, and Embase for articles published up to March 2023, that investigated the factors influencing AHEP among parents of C-CP. A narrative synthesis was conducted using the search results and pertinent material from other sources.

Results
Overall, non-adherence rates to HEP were moderate to high, ranging from 34% to 79.2%. Strong evidence suggests that factors enhancing AHEP fall into three categories: child-related (such as younger age and better gross motor function [GMF]), the caregiver-related (including high self-efficacy and knowledge, strong social support, low levels of depression, anxiety and stress symptoms, and a low perception of barriers), and the physiotherapist-related. For the latter category, the parent’s perception of a supportive and collaborative relationship with the therapist is one of the conditions most favourably influences AHEP.

Conclusion
Our findings highlight that factors influencing AHEP are multifactorial. Some, such as GMF or the economic and social conditions of the family, are challenging to change. However, the relationship between therapist and parent is an aspect that can be strengthened. These results underscore the importance of substantial training and psychosocial support for therapists to enhance their awareness and competence in building supportive relationship with parents.
El maestro que prometió el mar. Una historia de vida y un film conmovedores
Authors: Costa Rico Anton 
Published: June 2024

Un comentario en relación con la vida de Antoni Benaiges maestro durante los cursos de 1934 a 1936 en la localidad de Bañuelos de Bureba, en la provincia española de Burgos. Llevó a cabo una práctica educativa emancipadora, de alto contenido cívico y despertando en los niños la pasión por aprender y por expresar su palabra. El golpe de estado franquista de julio de 1936 sembró un reguero de muerte entre demócratas ocasionado, también, su muerte y silenciando su vida, redescubirta en el presente a través de una minuciosa observación microhistórica, dando lugar a varias publicacions y a un hermoso film.
Optimization of garment sewing operation standard minute value prediction using an IPSO-BP neural network
Authors: Shen Haina , Ji Xiaofen 
Published: June 2024

Abstract
Standard minute value serves as a pivotal metric guiding the arrangement and balancing of production cycles in clothing production lines, and plays a crucial role in cost pricing and production order arrangement for clothing products. Given the complexity of the garment sewing process, ten influencing factors including fabric weight, fabric thickness, fabric density, stitching length, stitching shapes, cut pieces numbers, notch numbers, sewing technologies, sewing machine, and auxiliary accessories were identified. Upon this foundation, a standard sewing time prediction model, Improved particle swarm optimization - Back-propagation neural network (IPSO-BP), was proposed, focusing on non-quantitative factors. The IPSO-BP model was trained using actual sewing data from a women’s clothing production company. Compared to the unoptimized BP neural network, the IPSO-BP model demonstrated significant advantages in terms of convergence speed and prediction accuracy. Therefore, the IPSO-BP model proposed in this study holds promise for predicting standard sewing hours effectively.
Multivariate anomaly detection models enhance identification of errors in routine clinical chemistry testing
Authors: Farrell Christopher J.L. 
Published: June 2024

Abstract

Objectives
Conventional autoverification rules evaluate analytes independently, potentially missing unusual patterns of results indicative of errors such as serum contamination by collection tube additives. This study assessed whether multivariate anomaly detection algorithms could enhance the detection of such errors.

Methods
Multivariate Gaussian, k-nearest neighbours (KNN) distance, and one-class support vector machine (SVM) anomaly detection models, along with conventional limit checks, were developed using a training dataset of 127,451 electrolyte, urea, and creatinine (EUC) results, with a 5 % flagging rate targeted for all approaches. The models were compared with limit checks for their ability to detect atypical EUC results from samples spiked with additives from collection tubes: EDTA, fluoride, sodium citrate, or acid citrate dextrose (n=200 per contaminant). The study additionally assessed the ability of the models to identify 127,449 single-analyte errors, a potential weakness of multivariate models.

Results
The KNN distance and SVM models outperformed limit checks for detecting all contaminants (p-values <0.05). The multivariate Gaussian model did not surpass limit checks for detecting EDTA contamination but was superior for detecting the other additives. All models surpassed limit checks for identifying single-analyte errors, with the KNN distance model demonstrating the highest overall sensitivity.

Conclusions
Multivariate anomaly detection models, particularly the KNN distance model, were superior to the conventional approach for detecting serum contamination and single-analyte errors. Developing multivariate approaches to autoverification is warranted to optimise error detection and improve patient safety.
Hybrid effect of neem seed and groundnut shell bio-fillers on the mechanical, water absorption and thermal properties of jute fiber reinforced epoxy composites
Authors: Deepak Suresh Kumar R. , Gurusamy P. , Dinesh D. 
Published: June 2024

Abstract
Natural composites possess good qualities like light weight, harmlessness, cheapness and ease of processing. However, their performance is limited compared to conventional material. Hence, it is required to improve the performance of natural composites to extend their usage in various industrial applications. In this research, an attempt has been made to improve the performance of epoxy–jute natural composite using different natural fillers made of neem seed and groundnut shell particles. Initially, the epoxy–jute composite [N:G (0:0)] was prepared and the properties of the composite were investigated. Additionally, natural-fillers were incorporated into the N:G (0:0) composite, and a variety of composites were produced. These included N:G (1:0), N:G (3:1), N:G (1:1), N:G (1:3), and N:G (0:1), with the weight fractions of neem and groundnut shell particles adjusted accordingly. The properties of the aforementioned composites were compared with the properties of N:G (0:0) composite. Results revealed that the particle reinforced composite exhibited significant improvement in the properties of the composites. Moreover, in comparison to the other composites, the N:G (0:1) composite exhibited superior tensile strength (43.28 MPa), flexural strength (46.08 MPa), impact resistance (13.93 kJ m−2), and hardness (24.7 HV). This could be due to the fibrous structure of groundnut shell compared to neem seed which was fragile in nature. Furthermore, the same composite displayed less water absorption (2.8 % at 6 days time period). Moreover, the N:G (1:0) composite exhibited the least thermal conductivity (0.31 W m−1 K−1). Based on results, it was concluded that the bio-fillers such as neem seed and groundnut shell particles assisted improvement the properties of epoxy–jute composite.
A study on the application of multidimensional feature fusion attention mechanism based on sight detection and emotion recognition in online teaching
Authors: Huang Yurong , Yang Guang 
Published: June 2024

Abstract
Online teaching is not limited by time, but the problem of low learning efficiency is common. To address this problem, the study proposes an attention mechanism for multidimensional feature fusion, which first detects faces, uses a supervised gradient descent algorithm for face feature point detection, and improves the least-squares ellipse-fitting algorithm to detect the open/closed state of human eyes. The sight detection method is also improved, and the fuzzy inference method is used to identify students’ emotions, and the modules are fused to achieve multidimensional feature fusion attention detection for online teaching. The study found that the average accuracy rate was 84.5% with glasses and 92.0% without glasses. The research method with glasses had an average time consumption of 17 ms, while the method without glasses took 15 ms, indicating higher detection accuracy and faster real-time performance. The improved approach led to higher recognition accuracy and accuracy rate. The detection accuracy of a single feature and the research method was 74.1 and 91.9%, respectively. It shows that the research method helps in the detection of students’ attention in online teaching.
Innovative use of Shona ideophones within an adolescent community of practice
Authors: Cook Toni , McGilly Clara , Miranda Case 
Published: June 2024

Abstract
This paper focuses on a nonnormative linguistic practice involving ideophones (nyaudzosingwi) among a Shona-speaking adolescent community of practice in urban Zimbabwe. Ideophones occupy a special position in Shona’s ethnolinguistic repertoire; they are culturally and linguistically salient, and highlighted in Shona classroom instruction. The perspective of Zimbabwe’s educational establishment is at odds with the on-the-ground situation, in which ideophones are exclusively the purview of older rural speakers. This dynamic puts young Shona speakers in a difficult situation: to succeed educationally, one is required to use ideophones, yet they are not a natural part of youth language. To balance these competing demands, young Shona speakers have developed a new use around ideophones that highlights the incongruity of balancing between being a “good Shona student” (fluency in “deep” Shona that eschews English influence) and a modern Shona subject (proficiency in English, upwardly socially mobile) by using them for unserious, comedic effect, where the humor deliberately derives from the idiosyncrasy of a young Shona speaker using ideophones. We also find a reduction in the morphosyntactic environments in which ideophones appear, in that they are always required to be introduced by a verbal element, and always the active form -ti, never the passive form -nzi.