bluuebunny/crossref_metadata_2025_split huggingface dataset:
The minimum mass for star formation by dynamical fragmentation: dependence on epoch, dust abundance, and environment
Authors: Whitworth A P , Priestley F D , Wünsch R , Palouš J 
Published: March 2024

ABSTRACT
We estimate the minimum mass of a star formed by dynamical collapse and fragmentation, as a function of epoch, dust abundance, and environment. Epoch is parametrized by redshift, zred, through the variation in the temperature of the cosmic microwave background. The dust abundance is parametrized by the mass-fraction in dust, ZD, with the additional simplifying assumption that the intrinsic properties of dust do not change with ZD, only the amount of dust. Environment is parametrized by the energy-density of the ambient suprathermal radiation fields through a dilution factor ω⋆ (applied to a blackbody radiation field at $T_{\star }=10^4\, {\rm K}$). The critical condition is that a spherical proto-fragment should be able to cool, and therefore contract, fast enough to detach from neighbouring proto-fragments. The minimum mass increases with increasing redshift, increasing dust abundance, and increasing suprathermal background. Values in the range from $M_{{\rm MIN}}\sim 0.002\, {\rm M}_{\odot }$ to $M_{{\rm MIN}}\sim 0.2\, {\rm M}_{\odot }$ are obtained at the extremes of the parameter ranges we have considered (0 ≤ zred ≤ 8,  0.00016 &lt; ZD &lt; 0.04,  and  10−15 ≤ ω⋆ ≤ 10−8). Our results agree quite well with the predictions of detailed numerical simulations invoking similar redshifts and dust abundances, but our estimates are somewhat lower; we attribute this difference to resolution issues and the small-number statistics from the simulations. The increased minimum masses predicted at high redshift and/or high suprathermal background result in significantly bottom-light initial mass functions, and therefore low mass-to-light ratios, provided that the dust abundance is not too low. The changes due to high suprathermal background may be particularly important for star formation in galactic nuclei and at high redshift.
Triage of the Gaia DR3 astrometric orbits. II. A census of white dwarfs
Authors: Shahaf S , Hallakoun N , Mazeh T , Ben-Ami S , Rekhi P , El-Badry K , Toonen S 
Published: March 2024

ABSTRACT
The third data release of Gaia was the first to include orbital solutions assuming non-single stars. Here, we apply the astrometric triage technique of Shahaf et al. to identify binary star systems with companions that are not single main-sequence stars. Gaia’s synthetic photometry of these binaries is used to distinguish between systems likely to have white-dwarf companions and those that may be hierarchical triples. The study uncovered a population of nearly $3\, 200$ binaries, characterized by orbital separations on the order of an astronomical unit, in which the faint astrometric companion is probably a white dwarf. This sample increases the number of orbitally solved binary systems of this type by about two orders of magnitude. Remarkably, over 110 of these systems exhibit significant ultraviolet excess flux, confirming this classification and, in some cases, indicating their relatively young cooling ages. We show that the sample is not currently represented in synthetic binary populations, and is not easily reproduced by available binary population synthesis codes. Therefore, it challenges current binary evolution models, offering a unique opportunity to gain insights into the processes governing white-dwarf formation, binary evolution, and mass transfer.
Antiangiogenic exclusion rules in glioma trials: Historical perspectives and guidance for future trial design
Authors: Sener Ugur , Islam Mahnoor , Webb Mason , Kizilbash Sani H 
Published: March 2024

Abstract

Background
Despite the lack of proven therapies for recurrent high-grade glioma (HGG), only 8%–11% of patients with glioblastoma participate in clinical trials, partly due to stringent eligibility criteria. Prior bevacizumab treatment is a frequent exclusion criterion, due to difficulty with response assessment and concerns for rebound edema following antiangiogenic discontinuation. There are no standardized trial eligibility rules related to prior antiangiogenic use.

Methods
We reviewed ClinicalTrials.gov listings for glioma studies starting between May 2009 and July 2022 for eligibility rules related to antiangiogenics. We also reviewed the literature pertaining to bevacizumab withdrawal.

Results
Two hundred and ninety-seven studies for patients with recurrent glioma were reviewed. Most were phase 1 (n = 145, 49%), non-randomized (n = 257, 87%), evaluated a drug-only intervention (n = 223, 75%), and had a safety and tolerability primary objective (n = 181, 61%). Fifty-one (17%) excluded participants who received any antiangiogenic, one (0.3%) excluded participants who received any non-temozolomide systemic therapy. Fifty-nine (20%) outlined washout rules for bevacizumab (range 2–24 weeks, 4-week washout n = 35, 12% most common). Seventy-eight required a systemic therapy washout (range 1–6 weeks, 4-week washout n = 34, 11% most common). Nine permitted prior bevacizumab use with limitations, 18 (6%) permitted any prior bevacizumab, 5 (2%) were for bevacizumab-refractory disease, and 76 (26%) had no rules regarding antiangiogenic use. A literature review is then presented to define standardized eligibility criteria with a 6-week washout period proposed for future trial design.

Conclusions
Interventional clinical trials for patients with HGG have substantial heterogeneity regarding eligibility criteria pertaining to bevacizumab use, demonstrating a need for standardizing clinical trial design.
Concerns about the use of antimicrobials in swine herds and alternative trends
Authors: Rigueira Luciana L , Perecmanis Simone 
Published: March 2024

Abstract
Pig productivity in Brazil has advanced a lot in recent decades. Specialized breeds are more vulnerable to pathogens, which has boosted the use of antimicrobials by farmers. The selective pressure generated favors the emergence of resistant bacteria, which compromises the effectiveness of this treatment and limits therapeutic options. In addition to increasing costs and mortality rates in the production system, public awareness of this issue has increased. The authorities have imposed restrictive measures to control the use of antimicrobials and have banned their use as growth promoters. This literature review highlights biosecurity and animal welfare to prevent pig diseases. Hence, we describe alternatives to the use of antimicrobials in pig production for the selection of effective non-antibiotic feed additives that help maintain good health and help the pig resist disease when infection occurs.
The m6 RNA methylation regulator KIAA1429 is associated with autophagy‐mediated drug resistance in lung cancer
Authors: Ma Bo , Xiu Lei , Ding Lili 
Published: March 2024

AbstractN6‐methyladenosine (m6A) modification plays a crucial role in cancer progression. However, the role of m6A modification‐mediated autophagy underlying non‐small cell lung cancer (NSCLC) gefitinib resistance remains unknown. Here, we discovered that m6A methyltransferase KIAA1429 was highly expressed in NSCLC gefitinib‐resistant cells (PC9‐GR) as well as tissues, and KIAA1429 high expression was associated with poor survival. In addition, silent KIAA1429 repressed gefitinib resistance in NSCLC and reduced tumor growth in vivo. Mechanistically, KIAA1429 stabilized WTAP, a significant player in autophagy, by binding to the 3′ untranslated regions (3′‐UTR) of WTAP. In a word, our findings indicated that KIAA1429 could elevate NSCLC gefitinib resistance, which may provide a promising targeted therapy for NSCLC patients.
WNT2B activates macrophages via NF‐κB signaling pathway in inflammatory bowel disease
Authors: Lan Lin , Huang Chuxiang , Liu Danqiong , Cheng Yanling , Tang Rui , Gu Jianbiao , Geng Lanlan , Cheng Yang , Gong Sitang 
Published: March 2024

AbstractInflammation is a significant pathological manifestation of inflammatory bowel disease (IBD), yet its mechanism has remained unclear. Although WNT2B is enriched in the intestinal inflammatory tissue of IBD patients, the specific mechanism of WNT2B in the formation of intestinal inflammation remains unclear. This study was aimed to investigate whether macrophages expressing WNT2B can aggravate intestinal tissue inflammation. Samples were collected from both normal individuals and patients with IBD at multiple colon sites. Macrophages were identified using tissue immunofluorescence. IκB kinase (IKK)—interacting protein (IKIP), which interacts with WNT2B, was found by protein cross‐linking and protein mass spectrometry. The expression of WNT2B, IKIP, the NF‐κB pathway, and downstream molecules were analyzed. An acute colitis model of C57BL/6J mice was established using an adeno‐associated virus (AAV)‐mediated WNT2B knockdown system and 3% dextran sulfate sodium (DSS). The degree of intestinal inflammation in mice was assessed upon WNT2B knockdown in macrophages. Macrophages expressing WNT2B were found to be enriched in the colitis tissues of IBD patients. WNT2B in macrophages activated the NF‐κB pathway and enhanced the expression of downstream inflammatory cytokines. By competitively binding IKIP, WNT2B reduced the binding of IKIP to IKKβ and promoted the activation of the NF‐κB pathway. Using an AAV‐mediated WNT2B knockdown system, WNT2B expression in intestinal macrophages was suppressed, leading to a reduction in intestinal inflammation. WNT2B activated the NF‐κB pathway and enhanced the expression of downstream inflammatory cytokines by competitively binding to IKIP, potentially contributing to colon inflammatory injury in IBD.
Increased T2 Relaxometry in Mild Traumatic Brain Injury: An Individualised Marker of Acute Neuroinflammation?
Authors: Bedggood Mayan J. , Essex Christi A. , Theadom Alice , Holdsworth Samantha J. , Faull Richard L.M. , Pedersen Mangor 
Published: March 2024

AbstractMild traumatic brain injury (mTBI), often called concussion, is a prevalent condition that can have significant implications for people’s health, functioning and well-being. Current clinical practice relies on self-reported symptoms to inform return to sport, work or school decisions, which can be highly problematic. An objective technique to detect the impact of mTBI on the brain is needed. MRI-based T2 relaxation is a quantitative imaging technique that is susceptible to detecting fluid properties in the brain and is a promising marker for detecting subtle neuroinflammation. This study aimed to investigate the potential of T2 relaxometry MRI in assessing mTBI at the individual level.The current study included 20 male participants with acute sports-related mTBI (within 14 days post-injury) and 44 healthy controls. We statistically compared each mTBI participant’s voxel-wise T2 relaxometry map with the average of controls using a voxel-wise z-test with false discovery rate correction. In addition, five participants were re-scanned after clinical recovery, and their acute scans were compared to their recovery scans.Results revealed significantly increased T2 relaxation times in 19/20 (95%) of mTBI individuals, compared to controls, in multiple regions, including the hippocampus, frontal cortex, parietal cortex, insula, cingulate cortex and cerebellum. This suggests the presence of increased cerebral fluid in individuals with mTBI. Longitudinal results indicated a partial reduction in T2 relaxation for all five participants, suggesting a resolution over time.This research highlights the potential of T2 relaxometry MRI as a non-invasive method for assessing neuroinflammation in mTBI. Identifying and monitoring neuroinflammation could aid in predicting recovery and developing individualised treatment plans for individuals with mTBI. Future research would benefit from repeating all MRI scans at recovery to evaluate whether T2-relaxometry normalises or persists.
Universal Exome Sequencing in Critically Ill Adults: A Diagnostic Yield of 25% and Race-Based Disparities in Access to Genetic Testing
Authors: Gold Jessica , Kripke Colleen M. ,   Regeneron Genetics Center,   Penn Medicine BioBank, Drivas Theodore G. 
Published: March 2024

AbstractNumerous studies have underscored the diagnostic and therapeutic potential of exome or genome sequencing in critically ill pediatric populations. However, an equivalent investigation in critically ill adults remains conspicuously absent. We retrospectively analyzed whole exome sequencing (WES) data available through the PennMedicine Biobank (PMBB) from all 365 young adult patients, aged 18-40 years, with intensive care unit (ICU) admissions at the University of Pennsylvania Health System who met inclusion criteria for our study. For each participant, two Medical Genetics and Internal Medicine-trained clinicians reviewed WES reports and patient charts for variant classification, result interpretation, and identification of genetic diagnoses related to their critical illness.Of the 365 individuals in our study, 90 (24.7%) were found to have clearly diagnostic results on WES; an additional 40 (11.0%) had a suspicious variant of uncertain significance (VUS) identified; and an additional 16 (4.4%) had a medically actionable incidental finding. The diagnostic rate of exome sequencing did not decrease with increasing patient age. Affected genes were primarily involved in cardiac function (18.8%), vascular health (16.7%), cancer (16.7%), and pulmonary disease (11.5%). Only half of all diagnostic findings were known and documented in the patient chart at the time of ICU admission. Significant disparities emerged in subgroup analysis by EHR-reported race, with genetic diagnoses known/documented for 63.5% of White patients at the time of ICU admission but only for 28.6% of Black or Hispanic patients. There was a trend towards patients with undocumented genetic diagnoses having a 66% increased mortality rate, making these race-based disparities in genetic diagnosis even more concerning. Altogether, universal exome sequencing in ICU-admitted adult patients was found to yield a new definitive diagnosis in 11.2% of patients. Of these diagnoses, 76.6% conferred specific care-altering medical management recommendations.Our study suggests that the diagnostic utility of exome sequencing in critically ill young adults is similar to that observed in neonatal and pediatric populations and is age-independent. The high diagnostic rate and striking race-based disparities we find in genetic diagnoses argue for broad and universal approaches to genetic testing for critically ill adults. The widespread implementation of comprehensive genetic sequencing in the adult population promises to enhance medical care for all individuals and holds the potential to rectify disparities in genetic testing referrals, ultimately promoting more equitable healthcare delivery.
White Matter Integrity Differences in 2-year-old Children Treated with ECMO: A Diffusion-Weighted Imaging Study
Authors: Ruttorf Michaela , Filip Julia , Schaible Thomas , Weis Meike , Zöllner Frank G. 
Published: March 2024

AbstractSchool-aged and adolescent survivors of neonatal extracorporeal membrane oxygenation (ECMO) treatment still suffer from neurodevelopmental delays such as verbal, visuo-spatial and working memory problems, motor dysfunction and sensorineural hearing loss, respectively, later in life. These neurodevelopmental delays are normally assessed by neuropsychological testing within follow-up programs. The purpose of this study is to demonstrate that diffusion-weighted imaging (DWI) in 2-year-old survivors of neonatal ECMO treatment might be a predictor of neurodevelopmental outcome. Therefore, 56 children underwent DWI at 3 T. Fractional anisotropy (FA), first fibre partial volume fraction estimate (F1) and radial diffusivity (RD) are compared using tract-based spatial statistics adapted to a paediatric brain atlas and whole-brain voxelwise statistics with age and gender as covariates of no interest. A significant difference in FA, F1 and RD between no-ECMO and ECMO group is seen in major white matter tracts and subcortical white matter in gyri leading to the conclusion that these differences are driven by alterations in axon coherence. Additionally, we examine individual diffusion measures by looking at masks from 50 brain regions taken from a paediatric brain atlas. We find left anterior corona radiata, left and right corpus callosum (genu, body and splenium), left and right crus of fornix, left anterior limb of internal capsule, left anterior commissure, left tapetum and right uncinate fasciculus to have significantly different means in no-ECMO compared to ECMO group which matches the reports of neuropsychological delays found in behavioural tests. To conclude, analysing diffusion measures at an early stage of life serves as a good tool to detect structural white matter changes in survivors of neonatal ECMO treatment like lacking axon coherence in fibre bundles which develop early in life. The advantage of DWI lies in looking only at the neurobiology, e.g. white matter integrity. Compared to neuropsychological testing, DWI in this age range is a very time-efficient method which does not depend on the child’s active participation. Additional targeted training could help to mitigate the neurodevelopmental deficits ECMO survivors face later in life.
Radiotherapy combined with EGFR-TKIs for stage III EGFR-Mutated lung cancer: A retrospective cohort study
Authors: Gang Liu , Yuan Wei , Langge Gan , Mei Gan , Qingping Zheng , Jing Huang 
Published: March 2024

AbstractThe present study aimed to evaluate the efficacy and safety of combining thoracic RT with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors(TKIs) in managing stage III lung cancer with EGFR mutation. Cases of patients with stage III EGFR-mutant lung cancer who received thoracic RT between December 2014 and December 2022 from multiple hospitals including The People’s Hospital of Laibin, The First People’s Hospital of Yulin and Guangxi Medical University Kaiyuan Langdong Hospital, were collected. The patients were divided into two groups based on the initial treatment approach: RT + TKIs(RT+TKI) group and RT + chemotherapy (RT+CT) group. The primary measure of interest was progression-free survival (PFS), and additional measures evaluated included objective response rate (ORR), overall survival (OS), patterns of treatment failure and adverse events. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to compare survival rates among different subgroups. A total of 54 patients were ultimately included, with 36 in the RT+TKI group and 18 in the RT+CT group. Regarding short-term efficacy, the ORR for the RT+TKI and RT+CT groups were 86.1 and 66.7%, respectively, with no statistically significant difference (P=0.189). Regarding long-term efficacy, the median PFS for the RT+TKI and RT+CT groups was 26.0 and 11.0 months, respectively, showing a significant difference (P<0.01). The 3 and 5-year OS rates between the RT+TKI and RT+CT groups did not exhibit statistical significance (P=0.825). Subgroup analysis revealed a statistically significant difference in PFS between the combination of RT with third-generation TKIs and first-generation TKIs (P=0.046). The Del19 subgroup exhibited a prolonged median PFS compared with the L858R subgroup, although the difference was not statistically significant (P=0.854). In terms of adverse reactions, the incidence rates of grade ≥3 hematological toxicity and gastrointestinal reactions in the RT+TKI group were significantly lower than those in the RT+CT group (P<0.05). However, the incidence rate of grade ≥3 radiation-related pneumonitis was similar between the RT+TKI and RT+CT groups, with no statistically significant difference. The results suggest that combination of RT and TKIs has superior efficacy and is a safer therapeutic approach for stage III EGFR-mutated lung cancer compared with concurrent radio-chemotherapy.The present study was registered on theClinicalTrials.govwebsite on 2nd June 2023, with the trial registration numberNCT05934461.
Cross-validation coordinate analysis (CVCA): performing coordinate based meta-analysis using cross-validation
Authors: Tench C.R. 
Published: March 2024

AbstractCoordinate based meta-analysis (CBMA) can be used to estimate where a future neuroimaging study testing a particular hypothesis might report summary results (activation foci, for example). However, current methods cannot be validated for all possible analyses, and use empirical features that might not always be ideal. Indeed, the various algorithms that perform CBMA tend to produce somewhat different results even on the same data. Furthermore, the use of null hypothesis significance testing (NHST) in the algorithms is not strictly in keeping with meta-analysis, where the aim is usually effect estimation rather than statistical significance.Given the limitations of current CBMA algorithms, a new algorithm has been developed that will perform its analysis using cross validation: cross-validation coordinate analysis (CVCA). Although a full validation cannot be performed, CVCA optimises its parameters in such a way as to make the analysis results most similar to the held-out data. The algorithm can be used as a stand-alone meta-analysis method, or to provide confidence in results from other algorithms where no validation is performed.Software to perform CVCA is freely available.
Integrating Social Determinants of Health with SOFA Scoring to Enhance Mortality Prediction in Septic Patients: A Multidimensional Prognostic Model
Authors: Sarraf Elie , Sadr Alireza Vafaei , Abedi Vida , Bonavia Anthony S 
Published: March 2024

AbstractBackgroundThe Sequential Organ Failure Assessment (SOFA) score is an established tool for monitoring organ failure and defining sepsis. However, its predictive power for sepsis mortality may not account for the full spectrum of influential factors. Recent literature highlights the potential impact of socioeconomic and demographic factors on sepsis outcomes.ObjectiveThis study assessed the prognostic value of SOFA scores relative to demographic and social health determinants in predicting sepsis mortality, and evaluated whether a combined model enhances predictive accuracy.MethodsWe utilized the Medical Information Mart for Intensive Care (MIMIC)-IV database for retrospective data and the Penn State Health (PSH) cohort for prospective external validation. SOFA scores, social/demographic data, and the Charlson Comorbidity Index were used to train a Random Forest model using the MIMIC-IV dataset, and then to externally validate it using the PSH dataset.FindingsOf 32,970 sepsis patients in the MIMIC-IV dataset, 6,824 (20.7%) died within 30 days. The model incorporating demographic, socioeconomic, and comorbidity data with SOFA scores showed improved predictive accuracy over SOFA parameters alone. Day 2 SOFA components were highly predictive, with additional factors like age, weight, and comorbidity enhancing prognostic precision. External validation demonstrated consistency in the model’s performance, with delta SOFA between days 1 and 3 emerging as a strong mortality predictor.ConclusionIntegrating patient-specific information with clinical measures significantly enhances the predictive accuracy for sepsis mortality. Our findings suggest the need for a multidimensional prognostic framework, considering both clinical and non-clinical patient information for a more accurate sepsis outcome prediction.