bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing immune checkpoint blockade in metastatic uveal melanoma: exploring the association of overall survival and the occurrence of adverse events
Authors: Koch Elias A. T. , Petzold Anne , Dippel Edgar , Erdmann Michael , Gesierich Anja , Gutzmer Ralf , Hassel Jessica C. , Haferkamp Sebastian , Kähler Katharina C. , Kreuzberg Nicole , Leiter Ulrike , Loquai Carmen , Meier Friedegund , Meissner Markus , Mohr Peter , Pföhler Claudia , Rahimi Farnaz , Schell Beatrice , Terheyden Patrick , Thoms Kai-Martin , Ugurel Selma , Ulrich Jens , Utikal Jochen , Weichenthal Michael , Ziller Fabian , Berking Carola , Heppt Markus V. 
Published: June 2024

IntroductionDespite recent advancements in the treatment of metastatic uveal melanoma (UM), the availability of further treatment options remains limited and the prognosis continues to be poor in many cases. In addition to tebentafusp, immune checkpoint blockade (ICB, PD-1 (+/-) CTLA-4 antibodies) is commonly used for metastatic UM, in particular in HLA-A 02:01-negative patients. However, ICB comes at the cost of potentially severe immune-related adverse events (irAE). Thus, the selection of patient groups that are more likely to benefit from ICB is desirable.MethodsIn this analysis, 194 patients with metastatic UM undergoing ICB were included. Patients were recruited from German skin cancer sites and the ADOReg registry. To investigate the association of irAE occurrence with treatment response, progression-free survival (PFS), and overall survival (OS) two cohorts were compared: patients without irAE or grade 1/2 irAE (n=137) and patients with grade 3/4 irAE (n=57).ResultsIn the entire population, the median OS was 16.4 months, and the median PFS was 2.8 months. Patients with grade 3/4 irAE showed more favorable survival than patients without or grade 1/2 irAE (p=0.0071). IrAE occurred in 44.7% (87/194), and severe irAE in 29.4% (57/194) of patients. Interestingly, irColitis and irHepatitis were significantly associated with longer OS (p=0.0031 and p=0.011, respectively).ConclusionsThis data may indicate an association between irAE and favorable survival outcomes in patients with metastatic UM undergoing ICB treatment and suggests that a reduced tolerance to tumor antigens could be linked to reduced tolerance to self-antigens.
Re-emergence of T lymphocyte-mediated synaptopathy in progressive multiple sclerosis
Authors: Sanna Krizia , Bruno Antonio , Balletta Sara , Caioli Silvia , Nencini Monica , Fresegna Diego , Guadalupi Livia , Dolcetti Ettore , Azzolini Federica , Buttari Fabio , Fantozzi Roberta , Borrelli Angela , Stampanoni Bassi Mario , Gilio Luana , Lauritano Gianluca , Vanni Valentina , De Vito Francesca , Tartacca Alice , Mariani Fabrizio , Rovella Valentina , Musella Alessandra , Centonze Diego , Mandolesi Georgia 
Published: June 2024

BackgroundSecondary progressive multiple sclerosis (SPMS) is defined by the irreversible accumulation of disability following a relapsing-remitting MS (RRMS) course. Despite treatments advances, a reliable tool able to capture the transition from RRMS to SPMS is lacking. A T cell chimeric MS model demonstrated that T cells derived from relapsing patients exacerbate excitatory transmission of central neurons, a synaptotoxic event absent during remitting stages. We hypothesized the re-emergence of T cell synaptotoxicity during SPMS and investigated the synaptoprotective effects of siponimod, a sphingosine 1-phosphate receptor (S1PR) modulator, known to reduce grey matter damage in SPMS patients.MethodsData from healthy controls (HC), SPMS patients, and siponimod-treated SPMS patients were collected. Chimeric experiments were performed incubating human T cells on murine cortico-striatal slices, and recording spontaneous glutamatergic activity from striatal neurons. Homologous chimeric experiments were executed incubating EAE mice T cells with siponimod and specific S1PR agonists or antagonists to identify the receptor involved in siponimod-mediated synaptic recovery.ResultsSPMS patient-derived T cells significantly increased the striatal excitatory synaptic transmission (n=40 synapses) compared to HC T cells (n=55 synapses), mimicking the glutamatergic alterations observed in active RRMS-T cells. Siponimod treatment rescued SPMS T cells synaptotoxicity (n=51 synapses). Homologous chimeric experiments highlighted S1P5R involvement in the siponimod’s protective effects.ConclusionTransition from RRMS to SPMS involves the reappearance of T cell-mediated synaptotoxicity. Siponimod counteracts T cell-induced excitotoxicity, emphasizing the significance of inflammatory synaptopathy in progressive MS and its potential as a promising pharmacological target.
Application of image processing technology based on field programmable gate array in mechanical part inspection
Authors: Lv Yi 
Published: June 2024

Introduction: In the field of industrial manufacturing, accurate inspection of mechanical components such as gears and bearings is of Paramount importance. However, the traditional mechanical testing methods are often disturbed by human factors, which not only affects the stability of the test results, but also leads to low efficiency and large error. In order to solve these problems, this research focuses on developing a new edge detection model.Methods: A novel edge detection model based on field-programmable gate array image processing technology was used in this study. The model uses adaptive threshold multi-directional edge detection technology to identify the edge features of mechanical gears and bearings, aiming at improving the precision of detection.Results and Discussion: After performance verification, the running time of the model was controlled within 11 s, and the detection error was limited to less than 9%. Compared with the control group and the experimental group, their performance was superior. Further analysis data show that the detection accuracy of this model is as high as 0.9004, its internal resource utilization rate is 88%, and the detection rate is as high as 91%, which are better than the comparison model.Conclusion: The proposed test model not only significantly improves the efficiency and accuracy of the test, but also fully meets the requirements of the test. This new edge detection model has potential application value in industrial manufacturing field, and provides a new solution for industrial manufacturing quality inspection.
Visualization of oil-lubrication ball bearings at high rotational speeds
Authors: Tohyama Mamoru , Ohmiya Yasuhiro , Hirose Michiru , Matsuyama Hiroki , Toda Takuya , Hasegawa Kenichi , Onizuka Takaaki , Sato Hideaki , Yokoi Masahiro , Sato Norikazu 
Published: June 2024

Deep-groove ball bearings for the eAxles of electric vehicles must adapt to higher rotational speed conditions because the speed of eAxle motors have been increasing as the size and weight of the motors decrease. Therefore, understanding the oil-lubricated conditions inside ball bearings at high rotational speeds is essential for optimizing their design for eAxles. To clarify the oil-lubricated conditions inside ball bearings at these high speeds, a new test apparatus was developed. This apparatus is capable of simultaneously measuring the friction torque of deep-groove ball bearings, the oil-film thickness on the rolling balls, and observing the oil distributions inside the bearings at rotational speeds up to 20,000 min-1. The oil-film thickness was measured using three-wavelength optical interferometry, and the oil distribution was observed using fluorescence. It was found that the oil-film thickness became constant at rotational speed conditions exceeding approximately 7,700 min-1. Oil starvations were observed on the raceway around the rolling ball, and these regions increased with increasing rotational speeds. Additionally, in the deep-groove ball bearing with a crown-shaped cage, the oil was mainly supplied to the rolling balls from the inner ring side through the space between the cage claws that held the ball. Moreover, the amount of mixed air tended to increase as the rotational speed increased to approximately 7,700 min-1. Those oil starvations and increasing air in oils were considered to be factors that prevent the increase in oil-film thickness. The findings of the reported study will contribute to the development of multibody dynamic technology for high-speed ball bearings necessary in electric vehicles.
The added value of a face-to-face pan-European course—what makes it worth it?
Authors: de Leeuw Robert , Huirne Judith A. F. , Rositto Christiano , Mabrouk Mohammed , Barri Pierre , Bongers Marlies , Thurkow Andreas , El-Balat Ahmed , Vlahos Nikon , Brolmann Hans 
Published: June 2024

IntroductionOver the past decade, digital education has seen widespread adoption, particularly accentuated during the COVID-19 pandemic. The post-COVID era has further emphasized the advantages of digital education in terms of cost, availability, and sustainability. However, concerns regarding the efficacy of digital education, particularly in skills-based learning and the absence of social interaction, have been raised. This paper will look at the added value of international, face-to-face, skills-based courses.MethodThis study evaluates the potential added value of face-to-face international skills courses using the European “Gynecology Experts Training for Upcoming Professionals” (GET-UP) course. Focus group discussions were conducted with participants and faculty members to explore beliefs, attitudes, and perceptions regarding face-to-face learning. Qualitative analysis was performed using thematic analysis to identify domains of added value.ResultsThe GET-UP course, conducted over 4 days with a diverse European faculty and participants, highlighted several added-value domains. Themes including diversity, role models, preparation, live interaction, and community emerged from the analysis, emphasizing the significance of face-to-face interaction in enriching the learning experience beyond attaining learning goals.DiscussionThe study underscores the importance of face-to-face interaction in educational settings, offering insights into diverse teaching methods, role modeling opportunities, enhanced preparation, live interactions, and fostering a sense of community. While digital education continues to evolve with interactive features, this study suggests that the inherent pressure and dynamics of face-to-face learning provide unique benefits that may not be easily replicated in digital environments. Future research should investigate and validate these findings further to inform educational practices effectively.
Identification of an inflammatory response-related gene prognostic signature and immune microenvironment for cervical cancer
Authors: Wu Zhuna , Zhuang Xuanxuan , Liang Meili , Sheng Liying , Huang Li , Li Yanting , Ke Yumin 
Published: June 2024

Background: Cervical cancer (CC) is the fourth most common cancer among women worldwide. As part of the brisk cross-talk between the host and the tumor, prognosis can be affected through inflammatory responses or the tumor microenvironment. However, further exploration of the inflammatory response-related genes that have prognostic value, microenvironment infiltration, and chemotherapeutic therapies in CC is needed.Methods: The clinical data and mRNA expression profiles of CC patients were downloaded from a public database for this study. In the TCGA cohort, a multigene prognostic signature was constructed by least absolute shrinkage and selection operator (LASSO) and Cox analyses. CC patients from the GEO cohort were used for validation. K‒M analysis was used to compare overall survival (OS) between the high- and low-risk groups. Univariate and multivariate Cox analyses were applied to determine the independent predictors of OS. The immune cell infiltration and immune-related functional score were calculated by single-sample gene set enrichment analysis (GSEA). Immunohistochemistry was utilized to validate the protein expression of prognostic genes in CC tissues.Results: A genetic signature model associated with the inflammatory response was built by LASSO Cox regression analysis. Patients in the high-risk group had a significantly lower OS rate. The predictive ability of the prognostic genes was evaluated by means of receiver operating characteristic (ROC) curve analysis. The risk score was confirmed to be an independent predictor of OS by univariate and multivariate Cox analyses. The immune status differed between the high-risk and low-risk groups, and the cancer-related pathways were enriched in the high-risk group according to functional analysis. The risk score was significantly related to tumor stage and immune infiltration type. The expression levels of five prognostic genes (LCK, GCH1, TNFRSF9, ITGA5, and SLC7A1) were positively related to sensitivity to antitumor drugs. Additionally, the expression of prognostic genes was significantly different between CC tissues and myoma patient cervix (non-tumorous) tissues in the separate sample cohort.Conclusion: A model consisting of 5 inflammation-related genes can be used to predict prognosis and influence immune status in CC patients. Furthermore, the inhibition or enhancement of these genes may become a novel alternative therapy.
Impact of butorphanol versus sufentanil on postoperative cognition and inflammation in elderly: a pilot study
Authors: Wen Qiannan , Sun Defeng , Yang Lin , Li Yuexian 
Published: June 2024

BackgroundThis randomized controlled trial aimed to compare the effects of butorphanol and sufentanil on early post-operative cognitive dysfunction (POCD) and systemic inflammation in older surgical patients.MethodsPatients (aged 65 years or above) undergoing surgeries with general anesthesia were randomized to either the butorphanol group (40 μg/kg during anesthesia induction) or the sufentanil group (0.4 μg/kg). Cognitive function changes during the perioperative period were assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale up to 3 days after surgery. POCD was defined as a Z-score or composite Z-score greater than 1.96 for both MMSE and MoCA scores. Circulating inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 10 (IL-10), were measured using enzyme-linked immunosorbent assay.ResultsThe study included 114 patients (median age: 71 years, 57.7% male). Compared to sufentanil, butorphanol significantly reduced the incidence of POCD on the first (11.5% versus 32.7%, p = 0.017) and third day (3.8% versus 15.4%, p = 0.046) after surgery. Additionally, patients receiving butorphanol had significantly lower circulating levels of TNF-α and IL-1β at the time of discharge from the post-anesthesia care unit and on the first and third day after surgery (p &lt; 0.05 for all comparisons). Furthermore, circulating IL-10 levels were significantly higher in patients receiving butorphanol (p &lt; 0.05 for all comparisons).ConclusionAdministration of butorphanol during anesthesia induction, as opposed to sufentanil, was associated with a significant reduction in the early incidence of POCD in older surgical patients, possibly attributed to its impact on systemic inflammation.Clinical trial registration: The present study was registered in the China Clinical Trial Center (ChiCTR2300070805, 24/04/2023).
Development of a predictive model for 1-year postoperative recovery in patients with lumbar disk herniation based on deep learning and machine learning
Authors: Chen Yan , Lin Fabin , Wang Kaifeng , Chen Feng , Wang Ruxian , Lai Minyun , Chen Chunmei , Wang Rui 
Published: June 2024

BackgroundThe aim of this study is to develop a predictive model utilizing deep learning and machine learning techniques that will inform clinical decision-making by predicting the 1-year postoperative recovery of patients with lumbar disk herniation.MethodsThe clinical data of 470 inpatients who underwent tubular microdiscectomy (TMD) between January 2018 and January 2021 were retrospectively analyzed as variables. The dataset was randomly divided into a training set (n = 329) and a test set (n = 141) using a 10-fold cross-validation technique. Various deep learning and machine learning algorithms including Random Forests, Extreme Gradient Boosting, Support Vector Machines, Extra Trees, K-Nearest Neighbors, Logistic Regression, Light Gradient Boosting Machine, and MLP (Artificial Neural Networks) were employed to develop predictive models for the recovery of patients with lumbar disk herniation 1 year after surgery. The cure rate score of lumbar JOA score 1 year after TMD was used as an outcome indicator. The primary evaluation metric was the area under the receiver operating characteristic curve (AUC), with additional measures including decision curve analysis (DCA), accuracy, sensitivity, specificity, and others.ResultsThe heat map of the correlation matrix revealed low inter-feature correlation. The predictive model employing both machine learning and deep learning algorithms was constructed using 15 variables after feature engineering. Among the eight algorithms utilized, the MLP algorithm demonstrated the best performance.ConclusionOur study findings demonstrate that the MLP algorithm provides superior predictive performance for the recovery of patients with lumbar disk herniation 1 year after surgery.
Early poststroke clinically significant fatigue predicts functional independence: a prospective longitudinal study
Authors: Juárez-Belaúnde Alan , Soto-León Vanesa , Dileone Michele , Orcajo Elena , León-Álvarez Natacha , Muñoz Alberto , Tornero Jesus , Oliviero Antonio 
Published: June 2024

BackgroundPoststroke fatigue is a prevalent issue among stroke survivors, significantly impeding functional recovery and diminishing their quality of life.AimThis prospective cohort study aims to investigate the association between poststroke fatigue and the extent of functional recovery in survivors of ischemic and hemorrhagic strokes. Additionally, it seeks to delineate the temporal progression of poststroke fatigue in these two stroke subtypes.MethodsWe assessed a cohort of 79 patients recovering from acute ischemic or hemorrhagic strokes. Poststroke fatigue was quantified using the Fatigue Severity Scale (FSS) and the Numeric Rating Scale (NRSfatigue). Patients’ condition was evaluated using the National Institute of Health Stroke Scale (NIHSS), and functional independence levels were determined using the Barthel Index for Activities of Daily Living (BIADL) and the Modified Rankin Scale (MRS). Depressive mood and pain were measured using the Beck Depression Inventory (BDI) and the Numeric Rating Scale for pain (NRSpain), respectively.ResultsOur primary findings indicate that the early manifestation of clinically significant fatigue (CSF) is predictive of a poorer trajectory in functional independence levels during recovery. Furthermore, we observed differing patterns of fatigue progression between ischemic and hemorrhagic strokes. Fatigue tends to ameliorate over time in hemorrhagic stroke cases, paralleling functional recovery, while it remains stable over time in ischemic stroke cases.ConclusionOur results underscore the detrimental impact of early poststroke fatigue on long-term outcomes. Furthermore, they highlight the imperative of managing poststroke fatigue, particularly during the subacute phase of stroke recovery.
The current landscape of machine learning-based radiomics in arteriovenous malformations: a systematic review and radiomics quality score assessment
Authors: Grossen Audrey A. , Evans Alexander R. , Ernst Griffin L. , Behnen Connor C. , Zhao Xiaochun , Bauer Andrew M. 
Published: June 2024

BackgroundArteriovenous malformations (AVMs) are rare vascular anomalies involving a disorganization of arteries and veins with no intervening capillaries. In the past 10 years, radiomics and machine learning (ML) models became increasingly popular for analyzing diagnostic medical images. The goal of this review was to provide a comprehensive summary of current radiomic models being employed for the diagnostic, therapeutic, prognostic, and predictive outcomes in AVM management.MethodsA systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, in which the PubMed and Embase databases were searched using the following terms: (cerebral OR brain OR intracranial OR central nervous system OR spine OR spinal) AND (AVM OR arteriovenous malformation OR arteriovenous malformations) AND (radiomics OR radiogenomics OR machine learning OR artificial intelligence OR deep learning OR computer-aided detection OR computer-aided prediction OR computer-aided treatment decision). A radiomics quality score (RQS) was calculated for all included studies.ResultsThirteen studies were included, which were all retrospective in nature. Three studies (23%) dealt with AVM diagnosis and grading, 1 study (8%) gauged treatment response, 8 (62%) predicted outcomes, and the last one (8%) addressed prognosis. No radiomics model had undergone external validation. The mean RQS was 15.92 (range: 10–18).ConclusionWe demonstrated that radiomics is currently being studied in different facets of AVM management. While not ready for clinical use, radiomics is a rapidly emerging field expected to play a significant future role in medical imaging. More prospective studies are warranted to determine the role of radiomics in the diagnosis, prediction of comorbidities, and treatment selection in AVM management.
Dyskinetic crisis in GNAO1-related disorders: clinical perspectives and management strategies
Authors: Domínguez Carral Jana , Reinhard Carola , Ebrahimi-Fakhari Darius , Dorison Nathalie , Galosi Serena , Garone Giacomo , Malenica Masa , Ravelli Claudia , Serdaroglu Esra , van de Pol Laura A. , Koy Anne , Leuzzi Vincenzo , Roubertie Agathe , Lin Jean-Pierre , Doummar Diane , Cif Laura , Ortigoza-Escobar Juan Darío 
Published: June 2024

BackgroundGNAO1-related disorders (GNAO1-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the GNAO1 gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in GNAO1-RD.ObjectivesThis study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies.MethodsA Delphi consensus process was conducted involving international experts in GNAO1-RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise.ResultsConsensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis.ConclusionThis consensus provides a foundation for understanding and managing dyskinetic crises in GNAO1-RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future GNAO1-RD research.