bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cluster-based prognostication in glioblastoma: Unveiling heterogeneity based on diffusion and perfusion similarities
Authors: Foltyn-Dumitru Martha , Kessler Tobias , Sahm Felix , Wick Wolfgang , Heiland Sabine , Bendszus Martin , Vollmuth Philipp , Schell Marianne 
Published: December 2023

Abstract

Background
While the association between diffusion and perfusion magnetic resonance imaging (MRI) and survival in glioblastoma is established, prognostic models for patients are lacking. This study employed clustering of functional imaging to identify distinct functional phenotypes in untreated glioblastomas, assessing their prognostic significance for overall survival.

Methods
A total of 289 patients with glioblastoma who underwent preoperative multimodal MR imaging were included. Mean values of apparent diffusion coefficient normalized relative cerebral blood volume and relative cerebral blood flow were calculated for different tumor compartments and the entire tumor. Distinct imaging patterns were identified using partition around medoids (PAM) clustering on the training dataset, and their ability to predict overall survival was assessed. Additionally, tree-based machine-learning models were trained to ascertain the significance of features pertaining to cluster membership.

Results
Using the training dataset (231/289) we identified 2 stable imaging phenotypes through PAM clustering with significantly different overall survival (OS). Validation in an independent test set revealed a high-risk group with a median OS of 10.2 months and a low-risk group with a median OS of 26.6 months (P = 0.012). Patients in the low-risk cluster had high diffusion and low perfusion values throughout, while the high-risk cluster displayed the reverse pattern. Including cluster membership in all multivariate Cox regression analyses improved performance (P ≤ 0.004 each).

Conclusions
Our research demonstrates that data-driven clustering can identify clinically relevant, distinct imaging phenotypes, highlighting the potential role of diffusion, and perfusion MRI in predicting survival rates of glioblastoma patients.
Exploring the multifaceted role of NRF2 in brain physiology and cancer: A comprehensive review
Authors: Moubarak Maya M , Pagano Zottola Antonio C , Larrieu Claire M , Cuvellier Sylvain , Daubon Thomas , Martin Océane C B 
Published: December 2023

Abstract
Chronic oxidative stress plays a critical role in the development of brain malignancies due to the high rate of brain oxygen utilization and concomitant production of reactive oxygen species. The nuclear factor-erythroid-2-related factor 2 (NRF2), a master regulator of antioxidant signaling, is a key factor in regulating brain physiology and the development of age-related neurodegenerative diseases. Also, NRF2 is known to exert a protective antioxidant effect against the onset of oxidative stress-induced diseases, including cancer, along with its pro-oncogenic activities through regulating various signaling pathways and downstream target genes. In glioblastoma (GB), grade 4 glioma, tumor resistance, and recurrence are caused by the glioblastoma stem cell population constituting a small bulk of the tumor core. The persistence and self-renewal capacity of these cell populations is enhanced by NRF2 expression in GB tissues. This review outlines NRF2’s dual involvement in cancer and highlights its regulatory role in human brain physiology and diseases, in addition to the development of primary brain tumors and therapeutic potential, with a focus on GB.
The RALF signaling pathway regulates cell wall integrity during pollen tube growth in maize
Authors: Zhou Liang-Zi , Wang Lele , Chen Xia , Ge Zengxiang , Mergner Julia , Li Xingli , Küster Bernhard , Längst Gernot , Qu Li-Jia , Dresselhaus Thomas 
Published: December 2023

Abstract
Autocrine signaling pathways regulated by RAPID ALKALINIZATION FACTORs (RALFs) control cell wall integrity during pollen tube germination and growth in Arabidopsis (Arabidopsis thaliana). To investigate the role of pollen-specific RALFs in another plant species, we combined gene expression data with phylogenetic and biochemical studies to identify candidate orthologs in maize (Zea mays). We show that Clade IB ZmRALF2/3 mutations, but not Clade III ZmRALF1/5 mutations, cause cell wall instability in the sub-apical region of the growing pollen tube. ZmRALF2/3 are mainly located in the cell wall and are partially able to complement the pollen germination defect of their Arabidopsis orthologs AtRALF4/19. Mutations in ZmRALF2/3 compromise pectin distribution patterns leading to altered cell wall organization and thickness culminating in pollen tube burst. Clade IB, but not Clade III ZmRALFs, strongly interact as ligands with the pollen-specific Catharanthus roseus RLK1-like (CrRLK1L) receptor kinases Z. mays FERONIA-like (ZmFERL) 4/7/9, LORELEI-like glycosylphosphatidylinositol-anchor (LLG) proteins Z. mays LLG 1 and 2 (ZmLLG1/2), and Z. mays pollen extension-like (PEX) cell wall proteins ZmPEX2/4. Notably, ZmFERL4 outcompetes ZmLLG2 and ZmPEX2 outcompetes ZmFERL4 for ZmRALF2 binding. Based on these data, we suggest that Clade IB RALFs act in a dual role as cell wall components and extracellular sensors to regulate cell wall integrity and thickness during pollen tube growth in maize and probably other plants.
IntraCranial pressure prediction AlgoRithm using machinE learning (I-CARE): Training and Validation Study
Authors: Fong Nicholas , Feng Jean , Hubbard Alan , Dang Lauren Eyler , Pirracchio Romain 
Published: December 2023

OBJECTIVES:
Elevated intracranial pressure (ICP) is a potentially devastating complication of neurologic injury. Developing an ICP prediction algorithm to help the clinician adjust treatments and potentially prevent elevated ICP episodes.

DESIGN:
Retrospective study.

SETTING:
Three hundred thirty-five ICUs at 208 hospitals in the United States.

SUBJECTS:
Adults patients from the electronic ICU (eICU) Collaborative Research Database was used to train an ensemble machine learning model to predict the ICP 30 minutes in the future. Predictive performance was evaluated using a left-out test dataset and externally evaluated on the Medical Information Mart for Intensive Care-III (MIMIC-III) Matched Waveform Database.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Predictors included age, assigned sex, laboratories, medications and infusions, input/output, Glasgow Coma Scale (GCS) components, and time-series vitals (heart rate, ICP, mean arterial pressure, respiratory rate, and temperature). Each patient ICU stay was divided into successive 95-minute timeblocks. For each timeblock, the model was trained on nontime-varying covariates as well as on 12 observations of time-varying covariates at 5-minute intervals and asked to predict the 5-minute median ICP 30 minutes after the last observed ICP value. Data from 931 patients with ICP monitoring in the eICU dataset were extracted (46,207 timeblocks). The root mean squared error was 4.51 mm Hg in the eICU test set and 3.56 mm Hg in the MIMIC-III dataset. The most important variables driving ICP prediction were previous ICP history, patients’ temperature, weight, serum creatinine, age, GCS, and hemodynamic parameters.

CONCLUSIONS:
IntraCranial pressure prediction AlgoRithm using machinE learning, an ensemble machine learning model, trained to predict the ICP of a patient 30 minutes in the future based on baseline characteristics and vitals data from the past hour showed promising predictive performance including in an external validation dataset.
ACR–ARS Practice Parameter for Radiation Oncology
Authors: Lo Simon , Chao Samuel , Harris Eleanor , Knisely Jonathan , Luh Join Y. , Mohindra Pranshu , Quang Tony S. , Ye Jason , Small William , Schechter Naomi R. 
Published: December 2023

Aim/Objectives/Background:
This practice parameter was revised collaboratively by the American College of Radiology (ACR), and the American Radium Society. This practice parameter provides updated reference literature regarding radiation oncology practice and its key personnel.

Methods:
This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters—Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the American Radium Society.

Results:
This practice parameter provides a comprehensive update to the reference literature regarding radiation oncology practice in general. The overall roles of the radiation oncologist, the Qualified Medical Physicist, and other specialized personnel involved in the delivery of external-beam radiation therapy are discussed. The use of radiation therapy requires detailed attention to equipment, patient and personnel safety, equipment maintenance and quality assurance, and continuing staff education. Because the practice of radiation oncology occurs in a variety of clinical environments, the judgment of a qualified radiation oncologist should be used to apply these practice parameters to individual practices. Radiation oncologists should follow the guiding principle of limiting radiation exposure to patients and personnel while accomplishing therapeutic goals.

Conclusions:
This practice parameter can be used as an effective tool to guide radiation oncology practice by successfully incorporating the close interaction and coordination among radiation oncologists, medical physicists, dosimetrists, nurses, and radiation therapists.
COVID-19 pandemic re-shaped the global dispersal of seasonal influenza viruses
Authors: Chen Zhiyuan , Tsui Joseph L.-H. , Gutierrez Bernardo , Moreno Simon Busch , Plessis Louis du , Deng Xiaowei , Cai Jun , Bajaj Sumali , Suchard Marc A. , Pybus Oliver G. , Lemey Philippe , Kraemer Moritz U. G. , Yu Hongjie 
Published: December 2023

AbstractUnderstanding how the global dispersal patterns of seasonal influenza viruses were perturbed during and after the COVID-19 pandemic is needed to inform influenza intervention and vaccination strategies in the post-pandemic period. Although global human mobility has been identified as a key driver of influenza dispersal1, alongside climatic and evolutionary factors2,3, the impact of international travel restrictions on global influenza transmission and recovery remains unknown. Here we combine molecular, epidemiological, climatic, and international travel data within a phylodynamic framework to show that, despite human mobility remaining the principal driver of global influenza virus dissemination, the pandemic’s onset led to a shift in the international population structure and migration network of seasonal influenza lineages. We find that South Asia and Africa played important roles as exporters and phylogenetic trunk locations of influenza in 2020 and 2021, and we highlight the association between population movement, antigenic drift and persistence during the intensive non-pharmaceutical interventions (NPIs) phase. The influenza B/Yamagata lineage disappeared in a context of reduced relative genetic diversity, moderate lineage turnover, and lower positive selection pressure. Our results demonstrate that mobility perturbations reshaped the global dispersal dynamics of influenza viruses, with potential implications for vaccine design and genomic surveillance programmes. As the risk of future pandemics persists, our study provides an opportunity to assess the impact of NPIs during the pandemic on respiratory infectious diseases beyond the interplay between SARS-CoV-2 and influenza viruses.
The gender gap in the relationship between Metabolic Syndrome and Restrictive Ventilatory Defect
Authors: Chu Ya-Chun , Yang Chi-Chiang , Chen Shaw-Ji , Cheng Pei-Ling , Wu Mei-Chuan , Wu Hsin-Hung , Lai Jerry Cheng-Yen 
Published: December 2023

AbstractBackgroundGiven the fundamental physiological differences between the sexes, this study aimed to investigate the effect of metabolic syndrome on ventilatory defects stratified by sex.MethodsWe conducted a nationwide, pooled, cross-sectional study. Data of 45,788 participants (men, n=15,859; women, n=29,929) aged 30 years or more were obtained from the Taiwan Biobank. Age-sex adjusted and multivariate logistic regression models were used to estimate the risk of developing impaired pulmonary function (restrictive or obstructive ventilatory defect) in individuals with or without metabolic syndromes. Separate models were also used to estimate for the risk of metabolic syndrome scores and the risk of individual metabolic abnormalities on the risk of restrictive ventilatory defect.ResultsThe overall prevalence of metabolic syndrome was estimated to be 15.9% in Taiwan, much higher in men than in women (18.6% versus 14.4%). Significant association was observed on the effect of metabolic syndromes on the risk of restrictive ventilatory defect. The risk of developing restrictive ventilator defect was 35% higher in participants with metabolic syndromes (odds ratio, 1.35; 95% confidence interval, 1.26-1.45) than those without metabolic syndromes. Elevated blood pressure and triglycerides abnormality were important predictors of restrictive ventilator defect.Sex-stratified subgroup analyses of the individual metabolic abnormalities indicated that men with abdominal obesity and women with dysglycemia were more likely to develop restrictive ventilatory defect.ConclusionOur study evidences suggested that metabolic syndromes were important predictors of impaired pulmonary function and increased risk of developing restrictive ventilatory defects, and its risk increased with increasing numbers of metabolic abnormalities.
Causal association between serum bilirubin and ischemic stroke: Multivariable Mendelian Randomization
Authors: Shin Jong Won , Jung Keum Ji , Kimm Heejin , Jee Sun Ha 
Published: December 2023

AbstractBACKGROUNDPast studies have mainly focused on total bilirubin levels, and have not clearly distinguished between direct and indirect bilirubin, a subgroup of bilirubin. In this study, the differences between these subgroups were clearly examined, and the causal association with ischemic stroke was examined in more detail.METHODSUtilizing Two sample Multivariable Mendelian randomization (MVMR) analyses, summary data for bilirubin were extracted from the KCPS-II (Korean Cancer Prevention Study-II; n=159,844) and the KoGES (Korean Genome and Epidemiology Study; n=72,299), while ischemic stroke data were derived from the BBJ (Bio Bank Japan; n=201,800).RESULTSThe crude two-sample MR analysis revealed a significant negative association between total bilirubin and ischemic stroke in KoGES data (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.75-0.98). Subsequent bivariable MR analyses, controlling for lipid profile, also showed significant results. In KCPS-II data, direct bilirubin showed significance in both crude (0.65, 0.43-0.97) and bivariable analyses, while indirect bilirubin demonstrated significant associations in MVMR analyses (0.76, 0.59-0.98), emphasizing its role in mitigating the risk of ischemic stroke.CONCLUSIONSOur study establishes a causal association between genetically determined levels of serum bilirubin (total, direct, and indirect) and a reduced risk of ischemic stroke in an Asian population. Notably, the protective effect was predominantly associated with indirect bilirubin. The findings highlight the significance of considering bilirubin subgroup in understanding the mechanisms underlying endogenous antioxidants and its impact on ischemic stroke.
Healthcare utilisation in people with long COVID: an OpenSAFELY cohort study
Authors: Lin Liang-Yu , Henderson Alasdair D , Carlile Oliver , Dillingham Iain , Butler-Cole Ben FC , Marks Michael , Briggs Andrew , Jit Mark , Tomlinson Laurie A , Bates Chris , Parry John , Bacon Sebastian CJ , Goldacre Ben , Mehrkar Amir , MacKenna Brian ,   The OpenSAFELY Collaborative, Eggo Rosalind M , Herrett Emily 
Published: December 2023

AbstractBackgroundLong COVID, characterised by various symptoms and complications, potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined.ObjectiveThis study aims to assess the healthcare utilisation of individuals with long COVID.MethodsWith the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records.ResultsWe identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.07, 95% CI: 7.54 – 8.64), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.47 – 1.50). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58 - 29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73 - 16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.47, 95% CI = 7.02 – 7.95), with costs being 43% higher than the comparator group (cost ratio = 1.43, 95% CI: 1.38 – 1.49). The long COVID group costs approximately £2,500 per person per year (predicted mean cost: £2,562.50, 95% CI: £2,335.60 - £2,819.22), and the comparator group costs £1,500 (predicted mean cost: £1,527.43, 95% CI: £1,404.33 - 1,664.45.) Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group.ConclusionLong COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID.
Exclusive Enteral Nutrition Initiates Individual Protective Microbiome Changes to Induce Remission in Pediatric Crohn’s Disease
Authors: Häcker Deborah , Siebert Kolja , Smith Byron J , Köhler Nikolai , Riva Alessandra , Mahapatra Aritra , Heimes Helena , Nie Jiatong , Metwaly Amira , Hölz Hannes , Manz Quirin , De Zen Federica , Heetmeyer Jeannine , Socas Katharina , Le Thi Giang , Meng Chen , Kleigrewe Karin , Pauling Josch K , Neuhaus Klaus , List Markus , Pollard Katherine S , Schwerd Tobias , Haller Dirk 
Published: December 2023

SummaryExclusive enteral nutrition (EEN) is the first-line therapy for pediatric Crohn’s disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naïve CD patients in response to EEN. Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, withLachnospiraceaeand medium chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes of diet-exposed fecal microbiota were further validated in a combined approach using gut chemostat cultures and microbiota transfer into germ-freeIl10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause IBD-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.
Assessing the Impact of Dental Malocclusion on the Body’s Postural Balance: Correlation between Angle Class, Pelvic Balance, and Center of Foot Pressure
Authors: Akensous Imad , Karkouri Samia , Iziki Chaimae , Rerhrhaye Wiam , Abdelkoui Anissa 
Published: December 2023

AbstractBackgroundThe purpose of this study was to determine the association between pelvic and center foot pressure (CoP) imbalances and angle class II or III malocclusions.MethodsOur study is a prospective, descriptive, and analytic study conducted on two groups: a test group of 53 patients who present malocclusion class II or III compared with 53 controls matched for age and gender. The evaluation of the center of foot pressure (CoP) and the confidence ellipse area (mm2) were performed by stabilometric platefrom using bipodal test in two occlusal conditions, in maximum intercuspation (MI) and with a cotton roll (CR), with and without visual cue. A pelvic level device was used to perform the pelvic balance examination. Statistical analysis used the chi-square test, the McNemar test, and the Pearson test.ResultsIn the case group, the bipodal test was poor (outside reference values) in MI open eyes, MI closed eyes, CR open eyes, and CR closed eyes in 47.2%, 62.3%, 58.5%, and 64.2%, respectively, vs 54.7%, 43.4%, 34.0%, and 67.9%, respectively, of controls (p <0.05). None subjects in the control group were diagnosed with pelvic imbalance, against five patients (9.4%) in the case group (p <0.05). Pelvic imbalance was noted in two patients in class II and only one patient in class III. For Class II, the bipodal test results were poor in MI open eyes, MI closed eyes, CR open eyes, and CR closed eyes conditions with percentages of 54.2%, 66.7%, 70.8%, and 58.3%, respectively (p <0.05). In Class III, results were generally good in MI open eyes (80%), but mostly poor in MIP and CR closed eyes (90%).ConclusionThere was a significant difference in pelvic imbalance between the case group and the control group. Angle Classes II and III had no significant correlation with pelvic tilt. The stabilometric examinations have shown that Angle class II influences the CoP displacement and the confidence ellipse area in MI open eyes conditions. This finding supports the hypothesis that dental malocclusion can have an effect on the postural system.