bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound Measurement of Thyroid Volume in Healthy Children
Authors: Özdikici Mete 
Published: February 2025

Abstract
Various thyroid diseases can lead to changes in the volume of the gland. Therefore, it is important to know the normal thyroid volume. The primary aim of this investigation was to establish normative values for thyroid gland volume using ultrasonography in children aged 0–18 years in Turkey.
A retrospective analysis was conducted on thyroid ultrasound findings from 800 children (400 boys, 400 girls) between 2019 and 2020. Pediatric age groups were classified into 20 categories for children aged 0–18. Among these 20 groups, the initial 3 pertain to the 0–1 age range, encompassing infants aged 0–1 month, 1–6 months, and 6–12 months. Each age group consisted of 20 boys and 20 girls.
The volume of each thyroid lobe was computed in milliliters using Brunn's formula, which involves multiplying the maximal anteroposterior diameter, mediolateral diameter, and craniocaudal diameter of the lobe by the correction factor 0.479.
Data analysis employed the Statistical Package for the Social Sciences, SPSS version 24.0. All analyses were conducted at a 95% confidence interval, and significance was set at P < 0.05.
Mean thyroid volumes of 800 children were determined for each age group. Thyroid volume exhibited a strong correlation with age. The Pearson correlation coefficient was 0.987 (P = 0.001).
Given the scarcity of comprehensive studies in the literature focusing on thyroid volume in children aged 0–18 across various age groups, we believe that our findings for each age group can provide valuable insights for daily clinical practice.
New Surgical Frailty Scoring Tool: Modified 4-Factor Functional Frailty Index (mFF-4)
Authors: Agathis Alexandra Z , Wu Jeanne , Divino Celia M 
Published: February 2025

Background:
Frailty is the age-related decline in functional reserve, resulting in physical and disease vulnerability. The established 5-Factor Modified Frailty Index (mFI-5), based on the National Surgical Quality Improvement Program (NSQIP) database, is predictive but does not encompass core components of frailty – namely physical abilities, cognitive status, and nutrition. Thus, we sought to establish a scoring index more indicative of the frailty phenotype.

Study Design:
Our retrospective study included patients ≥ 75 years of age, from NSQIP 2021-2022. The Modified 4-Factor Functional Frailty Index (mFF-4) is calculated by summing each present variable: prior falls, dementia, low body mass index, and non-independent functional status. Patients were stratified into frailty levels: none (mFF-4=0), intermediate (mFF-4=1), and high (mFF-4=2+). Area under the curve (AUC) and Akaike information criterion (AIC) values assessed predictability relative to the reference mFI-5. Odds ratios for 30-day outcomes were calculated using logistic regression.

Results:
The sample included n=265,041. Median age was 79 (interquartile range 77-84). The mFF-4 AUCs were consistently higher than mFI-5; mFF-4=2+ AUCs were 0.8679 for mortality, 0.7298 for postoperative complications, and 0.7645 for geriatric outcomes. Delta(AICs) values exceeded 2, favoring mFF-4 models. Compared to non-frail, mFF-4=2+ had increased odds of mortality (odds ratio 2.47, confidence interval 2.31-2.63), postoperative complications (1.37, 1.32-1.43), and geriatric outcomes (4.54, 4.30-4.79).

Conclusions:
The new mFF-4 scoring tool embodies the true frailty phenotype to accurately predict 30-day outcomes across surgical subspecialties and the overall population. It can serve as a new NSQIP “frailty” definition, while also providing a framework for surgeons and patients alike to conceptualize the elevated risks it poses.
The benefits and risks of maternal RSV vaccination on mortality in South Africa: a modelling study
Authors: Monoi Ayaka , Endo Akira , Procter Simon R , Leuba Sequoia I. , Flasche Stefan , Jit Mark ,   Maternal RSV vaccine benefit-risk advisory group, Beutels Philippe , Cohen Cheryl , Feikin Daniel R. , Koltai Mihaly , Madhi Shabir A. , Moyes Jocelyn , Munywoki Patrick K. , Nyiro Joyce , Nyawanda Bryan O. , Sparrow Erin , Zar Heather J 
Published: February 2025

AbstractBackgroundMaternal respiratory syncytial virus (RSV) vaccine, RSV prefusion F protein vaccine (RSVpreF (Abrysvo®)), was found to be safe and efficacious in its phase III trial. However, post-hoc stratified analyses identified an excess of preterm births in the intervention arm in two upper middle-income countries, most prominently in South Africa. This study weighs the potential benefits and risks in mortality associated with maternal RSV vaccination in South Africa, assuming the increased risk of preterm births observed in the trial was caused by vaccination.Methods and FindingsWe compared the estimated RSV-associated infant deaths averted by vaccination (benefits) and neonatal mortality potentially associated with vaccine-associated risk in preterm birth (risks) in South Africa. The benefit model estimated the South African RSV disease burden in 2011-16 and waning vaccine protection during infancy. The risk model estimated excess neonatal mortality using gestational age (GA)-specific mortality data from a South African cohort study and the GA-specific birth distribution in South Africa in the trial, but did not incorporate the mortality risk found in the vaccine trial in which no excess deaths occurred.The benefit model estimated that vaccination would reduce RSV-associated infant deaths by 31 (95% Credible Interval (Crl): 27, 35) per 100,000 live births born to vaccinated mothers in South Africa. The risk model suggested that neonatal deaths would increase by 44 (95%CrI: −43, 210) with vaccination at 24-36 GA weeks, totaling 1.4 (95%CrI: −1.4, 7.0) excess neonatal deaths for every infant RSV death prevented. Using the data for infants born to mothers vaccinated at 27-36 GA weeks, the predicted risks sharply dropped and in 98% of the simulations the benefits outweighed the risks.ConclusionsIf RSVpreF increases preterm birth risk, and if this increases neonatal mortality, then the benefit-risk analysis did not show that the direct benefits of vaccination in reducing RSV-associated infant mortality would substantially outweigh the risks of preterm birth-associated neonatal mortality in South Africa with vaccination from 24 GA weeks. There was large uncertainty in the analyses due to small numbers of preterm births. With vaccination from the third trimester, the benefit-risk analysis favoured vaccination.
Joint linear modeling of transcriptomics and proteomics is predictive of cancer metastasis
Authors: Sharma Ronit , Meimetis Nikolaos , Begzati Arjana , Nagar Shashwat Depali , Kellman Benjamin , Baghdassarian Hratch M. 
Published: February 2025

AbstractCancer metastasis, a process in which cancer cells migrate to secondary sites, accounts for 90% of cancer deaths. While machine learning has been used to predict metastasis in a variety of ways, they tend to be specific to tumor types or classification tasks. Here, we provide a pan-cancer machine learning model that is easily interpretable and directly links the transcriptomic and proteomic profiles of hundreds of cancer cell lines from DepMap with metastasis in a tissue-agnostic manner. We show that, for the relatively small sample size here, linear models perform just as well as non-linear models, including neural networks. We also demonstrate that transcriptomics outperforms proteomics for predictive tasks. However, the combination of both transcriptomics and proteomics leads to an overall increase in performance, indicating that these modalities can complement each other. Finally, we demonstrate that those features identified as most important by the joint omics linear model fit are over-represented in biological pathways related to metastasis, suggesting that the model learns relevant information that may be useful in identifying universal biomarkers or therapeutic targets of cancer metastasis.
Hypoxia-Induced Cardiopulmonary Remodeling and Recovery: Critical Roles of the Proximal Pulmonary Artery, Macrophages, and Exercise
Authors: Ramachandra Abhay B. , Sharma Prapti , De Man Ruben , Nikola Fadi , Guerrera Nicole , Doddaballapur Pramath , Cavinato Cristina , Choi Rira , Raredon Micha Sam Brickman , Szafron Jason M. , Zhuang Zhen W. , Barnthaler Thomas , Justet Aurelien , Akingbesote Ngozi D. , Abu Hussein Nebal S. , Diggs Lonnette , Perry Rachel J. , Adams Taylor S. , Singh Inderjit , Kaminski Naftali , Yan Xiting , Tellides George , Humphrey Jay D. , Manning Edward P. 
Published: February 2025

AbstractHypoxemia impairs cardiopulmonary function. We investigated pulmonary artery remodeling in mice exposed to chronic hypoxia for up to five weeks and quantified associated changes in cardiac and lung function, without or with subsequent normoxic recovery in the absence or presence of exercise or pharmacological intervention. Hypoxia-induced stiffening of the proximal pulmonary artery stemmed primarily from remodeling of the adventitial collagen, which resulted in part from altered inter-cellular signaling associated with phenotypic changes in the mural smooth muscle cells and macrophages. Such stiffening appeared to precede and associate with both right ventricular and lung dysfunction, with changes emerging to similar degrees regardless of the age of onset of hypoxia during postnatal development. Key homeostatic target values of the wall mechanics were recovered by the pulmonary arteries with normoxic recovery while other values recovered only partially. Overall cardiopulmonary dysfunction due to hypoxia was similarly only partially reversible. Remodeling of the cardiopulmonary system due to hypoxia is a complex, multi-scale process that involves maladaptations of the proximal pulmonary artery.
Small, Open-Source Text-Embedding Models as Substitutes to OpenAI Models for Gene Analysis
Authors: Gan Dailin , Li Jun 
Published: February 2025

AbstractWhile foundation transformer-based models developed for gene expression data analysis can be costly to train and operate, a recent approach known as GenePT offers a low-cost and highly efficient alternative. GenePT utilizes OpenAI’s text-embedding function to encode background information, which is in textual form, about genes. However, the closed-source, online nature of OpenAI’s text-embedding service raises concerns regarding data privacy, among other issues. In this paper, we explore the possibility of replacing OpenAI’s models with open-source transformer-based text-embedding models. We identified ten models from Hugging Face that are small in size, easy to install, and light in computation. Across all four gene classification tasks we considered, some of these models have outperformed OpenAI’s, demonstrating their potential as viable, or even superior, alternatives. Additionally, we find that fine-tuning these models often does not lead to significant improvements in performance.
Regional and whole-brain neurofunctional alterations during pain empathic processing of physical but not affective pain in migraine patients
Authors: Liu Dan , Li Menghan , Jiang Heng , Mi Yiqi , Xu Xiaolei , Zhou Yali , Hou Yaxian , Shen Yuquan , Maes Michael , Xiao Xiao , Zhou Feng , Giani Luca , Kendrick Keith M. , Becker Benjamin , Ferraro Stefania 
Published: February 2025

AbstractBackgroundAccumulating evidence suggests that migraine patients present abnormal brain responses to salient sensory and emotional stimuli. However, it is still unclear whether this is a generalized or domain-specific phenomenon. Employing a well-validated fMRI paradigm, we investigated pain empathic reactivity across two domains: observation of physical pain (noxious stimulation) and affective pain (facial expressions). On the basis of a generalized hyperexcitability/hyperreactivity in migraine, we hypothesized abnormal responses to both dimensions of pain empathy.MethodsWe collected fMRI and psychometric data from 21 migraine patients and matched controls. Univariate and multivariate neuroimaging analyses were utilized to examine domain-specific dysregulations in (a) neural reactivity in meta-analytically defined shared regions of pain-empathy processing, and (b) whole-brain neurofunctional signatures of physical and affective pain empathy (VPS, Zhou et al., 2020). Logistic regression models and machine learning-based classification were employed to determine differences between groups (migraine or control).ResultsMigraine patients exhibit increased neural responses during empathy for physical pain in the bilateral inferior frontal gyrus (slightly more pronounced on the right side), with alterations on the right significantly associated with the pain experienced during the attack. On the whole-brain level, the predictive accuracy of the VPS for physical pain empathy was shown to be significantly higher for patients as compared to controls, reaching 100% accuracy. Across analyses, we did not find evidence of altered empathy processing for affective pain.ConclusionContrary to our hypothesis, our results indicate that migraine patients present a domain-specific increased brain responsivity, localized in the bilateral inferior frontal gyrus but also extending to subtle whole brain patterns, during empathy for physical pain stimuli, but not during empathy for affective pain. Based on the evidence that the neural pathways for empathy for physical pain and experimental pain robustly overlap, these results indicate a specific hyperresponsivity of the pain pathways, with the inferior frontal gyrus likely playing a regulatory role in modulating pain-related processes. Finally, the results underscore the translational application potential of neuroaffective multivariate signatures as neuromarkers for pathological dysregulations in affective and pain-related processes.
Relationship Between Circulating FGF21 and Bone Mineral Density: An Exploratory Study
Authors: Peterson Matthew , Czanstkowski Sydney , Richardson Kathleen A. , Funderburk LesLee 
Published: February 2025

AbstractIntroductionFibroblast growth factor 21 (FGF21) has metabolic regulating effects on the body and exhibits endocrine-like effects on the body. Prior research has indicated that FGF21 may modulate bone density; however, the extent to which FGF21 can alter bone density and the effect of biological sex remains understudied.MethodsA total of 25 individuals (Female = 13, Male =12) volunteered to have their whole body bone density measured using Dual X-Ray Absorptiometry (DEXA) and blood drawn on two separate occasions. Serum samples were analyzed for FGF21 concentration and concentration value was averaged between the two samples, all blood samples were drawn during the mid-follicular phase in female participants. The relationship between FGF21 and markers of bone density was examined using Pearson correlations.ResultsWhole-body BMD (wb-BMD) was negatively correlated with FGF21 across the whole sample (r= -0.53,p< 0.05). When stratifying the sample by biological sex, wb-BMD was negatively correlated with FGF21 in females (r= -0.72,p< 0.05) and in males (r= -0.18,p> 0.05); however, in males this relationship was not statistically significant.ConclusionFGF21 appears to be negatively correlated to bone density in humans with a significant relationship in females but not in males.
Transepithelial/endothelial electrical measurement using a low-cost and customizable Arduino-based sensor
Authors: Lattanzi Davide , Montesi Ludovica , Sartini Alice , Rauti Rossana 
Published: February 2025

AbstractTransepithelial/transendothelial electrical resistance (TEER) is a label-free assay that is commonly used to assess tissue barrier integrity. Although commercial TEER meters are available, they are expensive and difficult to customize, which hinders researchers hoping to incorporate them in other research platforms. In the past few years, microcontrollers have risen in popularity for electrical signaling and general programming, of which Arduino is the most popular platform due to its scalability, simplicity and low price. This work presents the development of a completely customized, user-friendly and low-cost TEER meter that is Arduino-based and capable of continuous measurements and automated data collection. We demonstrate the stability of the instrument to measure long-term real-time barrier formation and disruption of an epithelial and endothelial cell line. The design simplicity and low-cost of the components make this technology transferrable to other laboratories for TEER and biological barriers research.
The circulating cell-free DNA landscape in sepsis is dominated by impaired liver clearance
Authors: Cano-Gamez Kiki , Maclean Patrick , Inoue Masato , Hussainy Sakineh , Foss Elisabeth , Wainwright Chloe , Qin Hanyu , McKechnie Stuart , Song Chun-Xiao , Knight Julian C. 
Published: February 2025

AbstractCirculating cell-free DNA (cfDNA) is a promising molecular biomarker. However, its utility in severe infection remains poorly understood. Here, we isolated cfDNA from sepsis patients and controls, demonstrating a 41-fold increase in the amount of cfDNA in circulation during disease. We used sequencing to reconstruct cfDNA methylomes, fragmentation profiles, and nucleosome footprints across 56 samples. We observed no difference in cfDNA composition between patients and controls, challenging the idea that cfDNA increases due to higher immune cell death during sepsis. Instead, we suggest that liver dysfunction prevents efficient clearance of cfDNA during disease. This was supported by fragmentation and end-motif patterns, both of which showed evidence of cfDNA being exposed to circulating nucleases for a prolonged period, proportionally to the extent of liver dysfunction. Variation in cfDNA of megakaryocyte-erythroid progenitor origin was also a significant contributor in sepsis, increasing over time. Moreover, we showed that cfDNA retains nucleosome footprints with cell type-specific gene activity information. We developed a novel approach to study nucleosome phasing that successfully recovers tissue-specific signatures. By combining this with single-cell data, we demonstrated that sepsis patients with liver dysfunction have higher amounts of cfDNA derived from Kupffer cells and the liver parenchyma. In conclusion, we present the first high-throughput multi-modal study of cfDNA during sepsis, which will serve as a reference point for future studies on the role of this biomarker in critical illness.
Understanding the Bidirectional Relationship Between Chronic Respiratory Disease and Cardiovascular Disease Using Genetic Evidence
Authors: Naesilla  , Quint Jennifer , Zuber Verena 
Published: February 2025

ABSTRACTBackgroundChronic respiratory diseases (CRD) and cardiovascular diseases (CVD) are leading global health burdens. Despite being common, CRD and CVD comorbidity is often underestimated due to overlapping symptoms and risk factors. Consequently, their relationship remains unclear.Aims and ObjectivesTo determine the bidirectional genetic relationship between CRD and CVD and explore smoking and inflammation as potentially shared joint risk factors.MethodsWe conducted bidirectional Mendelian randomization (MR) to explore CRD-CVD relationships. Summary statistics from genome-wide association studies were retrieved for COPD, asthma, coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), and ischemic stroke (IS). We performed additional analysis including univariable MR for smoking, multivariable MR adjusting for smoking, and cis-MR to investigate the role of inflammatory markers.ResultsOur MR analysis found limited genetic evidence of relationships between CRD toward CVD, and vice versa. However, a nominally significant genetic association was observed between asthma and an increased risk of AF (ORIVW1.036, 95% CI: 1.003-1.070), remaining weakly significant after adjusting for smoking (ORIVW1.040, 95%CI 1.008 – 1.074). Genetically predicted lifetime smoking strongly increased all CRD and CVD risk. Additionally, genetically proxied IL6R concentration associated with increased asthma risk and decreased CAD, MI, AF, and IS risk, while IL1RN decreased COPD risk but increased CAD and MI risk.ConclusionWhile we found limited genetic evidence linking CRD and CVD, smoking and inflammatory markers commonly affect both. These findings highlight the complexity of CRD-CVD comorbidities, whose pathophysiology likely does not involve direct causation of each other.
Post Stroke Cognitive Impairment: more than a lesion-symptom model
Authors: Huygelier Hanne , Moore Margaret Jane , Odom Annick , Tuts Nora , Thielen Hella , Mancuso Mauro , Gillebert Céline R. , Demeyere Nele 
Published: February 2025

AbstractPost-stroke cognitive impairment (PSCI) is highly heterogeneous, reflecting both domain-specific deficits associated with focal lesions and broader impairments linked to premorbid health and demographic factors. In the current study we investigated whether PSCI can be distinguished into distinct across-domain cognitive profiles and how such PSCI profiles are associated with lesion neuroanatomy, demographic and premorbid health factors.This cross-sectional study employed data-driven analyses (i.e., Latent Class Analysis) on 2172 stroke survivors who completed a domain-specific cognitive screen (i.e., Oxford Cognitive Screen) within 6 months after stroke (M = 19; Mdn = 7, SD = 35.7 days). In addition, the association of the PSCI profiles with lesion and demographic characteristics was investigated.We identified two viable cognitive class solutions: a 5-class model capturing classical and novel PSCI profiles and a more detailed 13-class model reflecting a broader set of distinct cognitive profiles that commonly occur after stroke. The 5-class solution distinguished classical lateralized deficits (e.g., aphasia, neglect) alongside a minimal impairment and non-lateralized global impairment profile. In contrast, the 13-class solution provided finer-grained differentiation, particularly for non-lateralized cognitive profiles which were more strongly associated with premorbid health and education level. Importantly, lesion anatomy alone could not fully account for class distinctions. While lesion location was predictive, particularly, in hyper-acute stages, profiles for patients tested 2 weeks post-stroke revealed less influence of lesion location and more of lesion volume.These findings underscore the importance of considering both anatomical and premorbid factors in understanding PSCI. By providing a nuanced classification of PSCI profiles, this study establishes a foundation for future translational research aimed at improving clinical care and predicting cognitive trajectories.