bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative iron management in hemodialysis and peritoneal dialysis patients: a systematic review
Authors: van Lieshout Thomas S. , Klerks Anastasia K. , Mahic Osman , Vernooij Robin W. M. , Eisenga Michele F. , van Jaarsveld Brigit C. , Abrahams Alferso C. 
Published: November 2024

BackgroundPatients with kidney failure undergoing dialysis often suffer from anemia. Iron deficiency, along with a shortage in erythropoietin, is a common cause. Peritoneal dialysis (PD) patients may have a different iron metabolism compared to hemodialysis (HD) patients. This study aims to compare both dialysis modalities regarding their differences in iron management.MethodsPubMed (MEDLINE) and Embase were screened for randomized controlled trials and observational studies including both patients on HD or PD with information on iron management. Outcomes for iron management for this systematic review included: prevalence of supplementation, route of administration, dose, frequency and hemoglobin and iron status parameters.Results15 eligible studies (930,436 patients), of which 8 cohort and 7 cross-sectional, were analyzed. The prevalence of intravenous (IV) iron supplementation ranged from 11.7% to 84.4% in HD patients, compared to 1.6% to 49.0% in PD patients. Ten studies reported that HD patients only received IV iron, while five studies reported this for PD patients. For oral iron supplementation, three studies involved HD patients, whereas seven studies involved PD patients. The cumulative monthly IV iron dose ranged from 108 to 750 mg in the HD group, compared to 65 to 250 mg in the PD group. Hemoglobin levels ranged from 10.0 to 12.0 g/dL in HD patients, versus 9.6 to 11.9 g/dL in PD patients.ConclusionIron management differs between HD and PD patients, with HD patients receiving higher doses and more frequent IV iron. There was significant heterogeneity in the outcomes between the studies, primarily due to the lack of a uniform global policy on iron management. Despite these differences, hemoglobin levels and iron status parameters were comparable between the two groups. Future research should explore the underlying mechanisms and broader impacts of iron treatment, including patient-reported outcomes, to optimize anemia management and improve quality of life for dialysis patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022336970.
Combining gene expression microarrays and Mendelian randomization: exploring key immune-related genes in multiple sclerosis
Authors: Ding Shuangfeng , Zhang Yunyun , Tang Yunzhe , Zhang Ying , Liu Mingyuan 
Published: November 2024

ObjectiveMultiple Sclerosis (MS) is an autoimmune disorder characterized by demyelination occurring within the white matter of the central nervous system. While its pathogenesis is intricately linked with the body’s immune response, the precise underlying mechanisms remain elusive. This study aims to explore potential immune-related genes associated with MS and assess the causal relationship between these genes and the risk of developing MS.MethodsWe retrieved expression datasets of peripheral blood mononuclear cells from MS patients from the Gene Expression Omnibus (GEO) database. Immune-related differentially expressed genes (IM-DEGs) were identified using the ImmPort database. GO and KEGG analyses were subsequently performed to elucidate the functions and pathways associated with the IM-DEGs. To visualize protein–protein interactions (PPIs), we used STRING, Cytoscape, and Cytohubba to construct networks of PPIs and hub genes. The diagnostic efficacy of hub genes was assessed using the nomogram model and ROC curve. The correlation of these hub genes was further validated in the mouse EAE model using quantitative PCR (qPCR). Finally, Mendelian randomization (MR) was performed to ascertain the causal impact of hub genes on MS.ResultsTwenty-eight IM-DEGs were selected from the intersection of DEGs and immune genes. These genes are involved mainly in antigen receptor-mediated signaling pathways, B cell differentiation, B cell proliferation, and B cell receptor signaling pathways. Using Cytoscape software for analysis, the top 10 genes with the highest scores were identified as PTPRC, CD19, CXCL8, CD79A, IL7, CR2, CD22, BLNK, LCN2, and LTF. Five hub genes (PTPRC, CD19, CXCL8, CD79A, and IL7) are considered to have strong diagnostic potential. In the qPCR validation, the relative expression of these five genes showed significant differences between the control and EAE groups, indicating that these genes may play a potential role in the pathogenesis of MS. The MR results indicate that elevated levels of CD79A (OR = 1.106, 95% CI 1.002–1.222, p = 0.046) are causally positively associated with the risk of developing MS.ConclusionThis study integrated GEO data mining with MR to pinpoint pivotal immune genes linked to the onset of MS, thereby offering novel strategies for the treatment of MS.
Efficacy analysis of electroacupuncture plus TDP in the treatment of peripheral facial paralysis: a systematic review and meta-analysis
Authors: Gao Hua-Wei , Xia Qing-Chang , Li Zhi-Hong , Chen Wei , Lu Yan 
Published: November 2024

ObjectiveThis study intends to carry out a systematic review and meta-analysis of electroacupuncture combined with TDP in the treatment of peripheral facial paralysis.MethodsCNKI, VIP, Wanfang, PubMed, Embase and Cochrane databases were searched for literatures on randomized or quasi-randomized controlled trials of electroacupuncture combined with TDP in the treatment of peripheral facial paralysis, and the references of the included studies were searched. Meta-analysis was performed using Stata15.0 software after risk of bias, quality assessment, and data extraction of the included articles by two reviewers independently.ResultsFifteen articles were finally included, with approximately 1,568 participants (920 in the treatment group and 648 in the control group). Meta-analysis showed that the effective rate of electroacupuncture combined with TDP in the treatment of peripheral facial paralysis was not significantly different from other treatment methods ([RR = 1.05, 95%CI (0.97, 1.12), p = 0.226]), and the recovery rate was better than other treatment methods ([RR = 1.14, 95%CI (1.05, 1.24), p = 0.002]). Subgroup analysis showed that when stratified by the inclusion of minors in the study population, it was observed that in studies including minors, the combination of electroacupuncture and TDP therapy demonstrated superior efficacy in treating peripheral facial paralysis compared to other therapeutic modalities [OR = 1.14, 95% CI (1.03, 1.25), p = 0.011]. Conversely, in studies where the population comprised solely adults, no significant difference was found between the combination therapy and other treatments [OR = 1.15, 95% CI (0.99, 1.33), p = 0.059]; whether electroacupuncture alone or other treatment methods, the recovery rate of electroacupuncture combined with TDP in the treatment of peripheral facial paralysis was better than other methods.ConclusionElectroacupuncture combined with TDP is superior to other treatment methods in the treatment of peripheral facial paralysis.
Clinical predictors of causative radiographic findings in adults with acute onset diplopia
Authors: Son Yubin , Suh Hie Bum , Choi Hee-young , Cabrera Michelle T. , Jeon Hyeshin 
Published: November 2024

ObjectiveThis study aimed to investigate the clinical factors that predict abnormal radiographic findings in adults with acute onset binocular diplopia.MethodsMedical records of consecutive patients aged &gt;20 years who presented with acute binocular diplopia were retrospectively reviewed. Patients were divided into positive and negative groups according to radiographic findings. Demographic and clinical characteristics were compared. The risk factors for positive radiographic findings were investigated, and the area under the receiver operating characteristic curve (AUC) was calculated.ResultsAmong 242 patients (145 males and 97 females), 44 (18.2%) were in the positive group and 198 (81.8%) in the negative group. Patients in the positive group were older (p = 0.005) and had more vasculopathic risk factors (p = 0.038). Severe duction limitation (&gt;50% reduction in motility) was present in 90.9% of patients in the positive group and 56.1% in the negative group (p &lt; 0.001). Abnormal slit lamp findings and pupillary exam abnormalities were also more frequent in the positive group than in the negative group (p = 0.027 and p = 0.036, respectively). Older age, higher intraocular pressure, abnormal slit-lamp findings, exophthalmos, and duction limitation were identified as risk factors for positive radiographic findings. A predictive model generated an AUC of 0.772.ConclusionOlder age and vasculopathic risk factors were associated with underlying radiographic pathologies, supporting the recommendation that neuroimaging should not be delayed in those patients. Careful ophthalmic evaluations may guide diagnosis and decision-making for immediate neuroimaging in cases of diplopia.
Interest paradigm for early identification of autism spectrum disorder: an analysis from electroencephalography combined with eye tracking
Authors: Sun Binbin , Calvert Elombe Issa , Ye Alyssa , Mao Heng , Liu Kevin , Wang Raymond Kong , Wang Xin-Yuan , Wu Zhi-Liu , Wei Zhen , Kong Xue-jun 
Published: November 2024

IntroductionEarly identification of Autism Spectrum Disorder (ASD) is critical for effective intervention. Restricted interests (RIs), a subset of repetitive behaviors, are a prominent but underutilized domain for early ASD diagnosis. This study aimed to identify objective biomarkers for ASD by integrating electroencephalography (EEG) and eye-tracking (ET) to analyze toddlers’ visual attention and cortical responses to RI versus neutral interest (NI) objects.MethodsThe study involved 59 toddlers aged 2-4 years, including 32 with ASD and 27 non-ASD controls. Participants underwent a 24-object passive viewing paradigm, featuring RI (e.g., transportation items) and NI objects (e.g., balloons). ET metrics (fixation time and pupil size) and EEG time-frequency (TF) power in theta (4-8 Hz) and alpha (8-13 Hz) bands were analyzed. Statistical methods included logistic regression models to assess the predictive potential of combined EEG and ET biomarkers.ResultsToddlers with ASD exhibited significantly increased fixation times and pupil sizes for RI objects compared to NI objects, alongside distinct EEG patterns with elevated theta and reduced alpha power in occipital regions during RI stimuli. The multimodal logistic regression model, incorporating EEG and ET metrics, achieved an area under the curve (AUC) of 0.75, demonstrating robust predictive capability for ASD.DiscussionThis novel integration of ET and EEG metrics highlights the potential of RIs as diagnostic markers for ASD. The observed neural and attentional distinctions underscore the utility of multimodal biomarkers for early diagnosis and personalized intervention strategies. Future work should validate findings across broader age ranges and diverse populations.
Derivation of a comprehensive semi-empirical proton RBE model from published experimental cell survival data collected in the PIDE database
Authors: Jin Jian-Yue , Yuan Jiankui , Qin Xiaohang , Li Yinghui , Yan Huagang , Oleinick Nancy L. , Yao Min , Pan Quintin , Kong Feng-Ming (Spring) , Machtay Mitchell 
Published: November 2024

We aimed to develop a comprehensive proton relative biological effectiveness (RBE) model based on accumulated cell survival data in the literature. Our approach includes four major components: (1) Eligible cell survival data with various linear energy transfers (LETs) in the Particle Irradiation Data Ensemble (PIDE) database (72 datasets in four cell lines); (2) a cell survival model based on Poisson equation, with α and β defined as the ability to generate and repair damage, respectively, to replace the classic linear–quadratic model for fitting the cell survival data; (3) hypothetical linear relations of α and β on LET, or α(LET)αx=αα+bα ∗ LET and β(LET)βx=αβ−bβ ∗ LET; and (4) a multi-curve fitting (MCF) approach to fit all cell survival data into the survival model and derive the aα, bα, aβ, and bβ values for each cell line. Dependences of these parameters on cell type were thus determined and finally a comprehensive RBE model was derived. MCF showed that (aα, bα, aβ, bβ) = (1.09, 0.0010, 0.96, 0.033), (1.10, 0.0015, 1.03, 0.023), (1.12, 0.0025, 0.99, 0.0085), and (1.17, 0.0025, 0.99, 0.013) for the four cell lines, respectively. Thus, aα = 1.12 ± 0.04, bα = 0.0019 ± 0.0008, aβ = 0.99 ± 0.03, and bβ = 0.013 ∗ αx, and approximately α∼1.12∗αx and β=(0.99−0.013∗αx∗LET)∗βx. Consequently, a relatively reliable and comprehensive RBE model with dependence on LET, αx, βx, and dose per fraction was finally derived for potential clinical application.
Knowledge landscape of Treg research in breast cancer: a bibliometric and visual analysis
Authors: Wu Zankai , Zhang Yanting , Gong Yiping , Hu Jin 
Published: November 2024

BackgroundRegulatory T (Treg) cells play a strategic role in maintaining immune homeostasis and their functions are closely linked to the development of different diseases, including cancer. This study aims to investigate the evolution patterns and popular research topics of Treg cells through bibliometric analysis.MethodThe Web of Science Core Collection database was used to extract publications related to Treg cells, which were then subjected to bibliometric analysis and visualization through VOSviewer, CiteSpace, and R software.ResultsBetween 2003 and 2023, a total of 666 articles were published. China and the United States had the highest citation counts, with Fudan University, Shanghai Jiao Tong University, and Tarbiat Modares University being the leading research institutions. Beckhove Philipp from the German Cancer Research Center and the National Center for Tumor Diseases in Heidelberg, and Christophe from the Cancer Research Center of Lyon, were the most prolific authors. Sakaguchi Shimon from the Immunology Frontier Research Center at Osaka University was the most cited author. “Frontiers in Immunology” published the most articles, while “Journal of Immunology” received the highest co-citations. Key terms in Treg research include immunotherapy, tumor microenvironment, prognosis, immunosuppression, and PD-L1. Among these, immunotherapy, prognosis, PD-L1, and immunosuppression have emerged as focal points of research in recent years.ConclusionWith active collaboration worldwide, research on Treg cells is rapidly advancing. Focusing on Treg cells as a potential target for cancer treatment shows great promise for future research, especially in terms of practical applications. This could offer valuable direction and fresh perspectives for further exploration of Treg cells in the medical field.
Investigating the impact of non-standard positioning on the accuracy of skull tracking algorithms using dual-panel imaging systems
Authors: Huang He , Zhang Lian , Bian Yunfei , Dong Yang , Lin Hongyu , Xu Hui , Li Ying 
Published: November 2024

ObjectiveThis study investigates the impact of non-standard positioning on the accuracy of 6D-skull tracking using dual-panel imaging systems. It explores whether positioning patients’ heads at various angles during intracranial lesion treatment affects the accuracy of the CyberKnife 6D-skull tracking system.Materials and methodsA heterogeneous density skull phantom was used to simulate various patient skull positioning angles. To accurately compare 6D-skull tracking and fiducial tracking, their center coordinates were pre-set to be identical in the treatment plan. The phantom was positioned using fiducial tracking, and the offset value recorded. The system was then switched to 6D-skull tracking to observe the corresponding offset. The difference between the two tracking methods was calculated, and a paired-sample T-test was conducted to assess statistical significance across different angles. Additionally, the gamma passing rate (criteria: 3%/3mm) was employed to quantitatively delineate dosimetric disparities attributable to positional variations.ResultsPaired sample T-tests on the deviations between rotational and translational parameters of fiducial tracking and skull tracking under identical conditions revealed no statistically significant differences between the methods across all selected angles. The minimal deviations and lack of statistical significance demonstrate that both tracking methods are equivalent in skull positioning. Furthermore, the gamma passing rate analysis showed that in all tested conditions, the rates exceeded 95%, which aligns with clinical requirements. This high passing rate indicates a high degree of dosimetric accuracy and consistency between the two tracking methods, providing robust assurance of treatment precision in skull positioning.ConclusionSince fiducial tracking is not affected by patient or phantom positioning, this study compares the registration results of 6D-skull tracking with fiducial tracking under the same conditions. The results show minimal deviations and no statistically significant differences, indicating that 6D-skull tracking is not dependent on the skull’s positioning angle. Furthermore, the gamma passing rate analysis was conducted to quantitatively assess the dosimetric differences arising from variations in patient positioning. Our results demonstrated that under all tested conditions, the gamma passing rates exceeded the clinically accepted threshold of 95%, confirming the clinical adequacy of both tracking methods in maintaining treatment precision. In clinical practice, patients do not need to maintain a strict supine position; the algorithm can accurately perform registration even if patients need to rotate their heads or lie prone. Clinical recommendations should prioritize patient comfort and safety without imposing overly strict requirements.
Dosimetric scorecards express precise clinical intent: alternate hippocampal-sparing whole-brain RapidPlan models favoring target coverage and homogeneity at 30 and 20 Gy
Authors: Rayn Kareem , Magliari Anthony , Clark Ryan , Rosa Lesley , Doucet Robert , Comeau Line , Nichol Alan , Ruo Russell , Roberge David 
Published: November 2024

IntroductionThis study develops two new multi-institutional hippocampal-sparing whole-brain RapidPlan™ models (HLS-EC-WB and HMS-EC-WB) inspired by CCTG-CE.7 featuring enhanced target coverage with varying hippocampal sparing (limited and moderate).MethodsNew dosimetric scorecards were created to quantify the models’ clinical intent. The models were trained using a multi-institution dataset, and a recursive method was employed to generate consistent, high-quality plans. The models were validated using a five-case set and compared at 20- and 30-Gy prescriptions.ResultsEach model scored highest on its associated dosimetric scorecard. The new models achieved higher brain PTV prescription coverage (98%–99%) compared to the previous HSWBv2 model (95.12%), with some trade-off in hippocampal sparing.ConclusionsThree high-quality automated RapidPlan™ models for hippocampal-sparing whole brain are now available, each with a distinct dosimetric scorecard. The new models prioritize increased PTV coverage at some expense to hippocampal sparing. All models, example plans, scorecards, and scoring tools are freely available online.
Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1
Authors: Wallen Zachary D. , Nesline Mary K. , Tierno Marni , Roos Alison , Schnettler Erica , Husain Hatim , Sathyan Pratheesh , Caveney Brian , Eisenberg Marcia , Severson Eric A. , Ramkissoon Shakti H. 
Published: November 2024

IntroductionMatching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics.MethodsIn this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC.ResultsTesting revealed distinct genomic profiles of lung adenocarcinoma and squamous cell carcinomas and detected variants with a current targeted therapy or clinical trial in &gt;72% of patient tumors. Known associations between genomic alterations and immunotherapy markers were observed including significantly lower TMB levels in tumors with therapy-associated alterations and significantly higher PD-L1 levels in tumors with ALK, MET, BRAF, or ROS1 driver mutations. Co-occurrence analysis followed by network analysis with gene module detection revealed known and novel co-occurrences between genomic alterations. Further, certain modules of genes with co-occurring genomic alterations had dose-dependent relationships with histology and increasing or decreasing levels of PD-L1 and TMB, suggesting a complex relationship between PD-L1, TMB, and genomic alterations in these gene modules.DiscussionThis study is the largest clinical study to date utilizing the TSO 500. It provides an opportunity to further characterize the landscape of NSCLC using this newer technology and show its clinical utility in detecting known and novel facets of NSCLC to inform treatment decision-making.