bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying lower extremity blood flow using low-dose CT perfusion: validation in a swine model
Authors: Shojazadeh Alireza , Hadjiabdolhamid Negin , Black Dale J , Antunes Ines , Lee Chaeeun , Li Wenbo , Molloi Sabee 
Published: November 2024

Abstract

Background
Quantitative assessment of blood flow in peripheral extremities in conjunction with simultaneous CT angiography measurements can improve risk assessment and provide a critical decision-making tool for patients across a wide spectrum of vascular disease severity.

Purpose
This study assessed the reproducibility and accuracy of lower extremity blood flow measurements with a low-dose first-pass analysis CT perfusion technique.

Materials and Methods
This prospective study utilized 16 Yorkshire Swine to obtain lower extremity blood flow CT measurements at baseline and under induced femoral stenosis using a vascular occluder. Thirty-three pairs of CT measurements evaluated reproducibility, and 43 CT measurements assessed accuracy against ultrasound flow probe references. Contrast agent and saline chaser were both injected peripherally at a rate of 5 mL/s. Bolus tracking was used, and a pre-contrast and post-contrast helical scan were acquired at the base and approximately the peak of the femoral enhancement (CT angiogram), respectively. The acquired data were then used as analytical inputs into a first-pass analysis model to derive perfusion in mL/min/g. The reproducibility and accuracy of lower extremity perfusion measurements were assessed via Mixed model regression and Bland-Altman analysis.

Results
Calculated CT perfusion measurements derived from first-pass analysis technique (PCT), and the reference standard ultrasound perfusion measurements (Pref) were related by PCT = 1.06 Pref + 0.00 (r2 = 0.90, Root-Mean-Square Error [RMSE] = 0.01 mL/min/g). The first (P1) and second (P2) CT perfusion measurements were related by P2 = 0.98 P1 + 0.02 (r = 0.97, RMSE = 0.11 mL/min/g). The average effective dose of perfusion measurement using first-pass analysis technique was calculated to be only 2.13 mSv.

Conclusion
The low-dose quantitative CT perfusion technique can accurately measure lower extremity perfusion (mL/min/g) using only 2 helical scans. The CT angiogram and perfusion measurements can be used as a comprehensive technique for morphological and physiological assessment of limb ischemia.
Uncovering the relationships among herring-like fossils (Clupei: Teleostei): a phylogenetic analysis
Authors: Kevrekidis Charalampos , Moritz Timo , Cerwenka Alexander F , Bauer Elena , Reichenbacher Bettina 
Published: November 2024

AbstractResearch interest in the diversity and evolutionary history of herring-like fossils (subcohort Clupei) has increased in recent decades. However, little is known about the relationships between fossils assigned to Clupei, particularly those that are demonstrably related to extant herring-like members of the order Clupeiformes. To help bridge this gap, we present a new morphological phylogeny that includes representatives of all major clupeiform lineages. The data matrix consists of 192 characters, drawn from 79 extant and 37 fossil taxa and selected to be readily identifiable in fossils. Most clupeiform families are recovered as monophyletic, and their interrelationships are generally compatible with previous morphological hypotheses. The phylogenetic positions of six fossil clupeiform taxa are resolved, as the results of all analyses (unconstrained/constrained parsimony and Bayesian inference) are consistent. Twenty-one fossil taxa are incertae sedis, including two species of Ellimmichtyiformes, which are recovered as Clupeoidei in the parsimony analyses. The relationships of the rest of the fossils are interpreted with varying degrees of certainty. The evolution of key morphological characters is discussed in light of the new results, and four fossil taxa are proposed as calibration points for future dating studies.
FOXO3 induces TUG1‐mediated miR‐375/GATA3 signaling axis to promote the survival of melanocytes in vitiligo
Authors: Nie Xiaojuan , Chen Lamei , Wang Baihe , Wang Shengnan , Li Yuanyuan 
Published: November 2024

AbstractVitiligo is characterized by the depletion of melanocytes due to the activation of CD8+ T cells. Taurine‐upregulated gene 1 (TUG1), a long noncoding RNA, is involved in melanogenesis. This study aimed to explore the role and mechanism of TUG1 in vitiligo. RT‐qPCR and western blot analyses demonstrated decreased TUG1 levels and increased miR‐375 levels in patients with vitiligo. MTT and transwell assays indicated that TUG1 upregulation facilitated melanocyte survival and inhibited CD8+ T cell migration. Dual luciferase reporter and chromatin immunoprecipitation assays verified that Forkhead box O3 (FOXO3) directly interacted with the TUG1 promoter, leading to the positive regulation of TUG1 expression. In addition, FOXO3 promoted melanocyte survival by enhancing the transcription of TUG1. Luciferase reporter assay and RNA immunoprecipitation assay confirmed that TUG1 upregulated GATA binding protein 3 (GATA3) expression by targeting miR‐375. TUG1 facilitated melanocyte survival by regulating the miR‐375/GATA3 axis. In vitiligo, melanocyte survival is promoted by the induction of the TUG1‐mediated miR‐375/GATA3 axis by FOXO3, which offers new therapeutic targets for vitiligo treatment.
Formyl peptide receptors in the microglial activation: New perspectives and therapeutic potential for neuroinflammation
Authors: Gao Juan , Su Gang , Liu Jifei , Shen Minghui , Zhang Zhenchang , Wang Manxia 
Published: November 2024

AbstractSecondary neurological impairment mediated by neuroinflammation is recognized as a crucial pathological factor in central nervous system (CNS) diseases. Currently, there exists a lack of specific therapies targeting neuroinflammation. Given that microglia constitute the primary immune cells involved in the neuroinflammatory response, a thorough comprehension of their role in CNS diseases is imperative for the development of efficacious treatments. Recent investigations have unveiled the significance of formyl peptide receptors (FPRs) in various neuroinflammatory diseases associated with microglial overactivation. Consequently, FPRs emerge as promising targets for modulating the neuroinflammatory response. This review aims to comprehensively explore the therapeutic potential of targeting FPRs in the management of microglia‐mediated neuroinflammation. It delineates the molecular characteristics and functions of FPRs, elucidates their involvement in the inflammatory response linked to microglial overactivation, and synthesizes therapeutic strategies for regulating microglia‐mediated neuroinflammation via FPR modulation, thereby charting a novel course for the treatment of neuroinflammatory diseases.
Land plant-specific H3K27 methyltransferases ATXR5 and ATXR6 control plant development and stress responses
Authors: Li Xiaoyi , Pan Jie , Zhang Huairen , Li Hui , Liu Qian , Jiang Danhua 
Published: November 2024

AbstractThe colonization of land by plants relies on numerous evolutionary innovations crucial for terrestrial adaptation. These include advances in sexual reproduction and the ability to properly respond to various environmental stresses, which involve precise control of their regulatory genes. A notable genetic innovation in land plants is the emergence of histone lysine methyltransferases ATXR5/6, which specifically catalyse the repressive histone H3 lysine 27 monomethylation (H3K27me1). However, the significance of the evolution of these enzymes in land plants remains unclear. In this study, we investigate the importance of ATXR5/6 by generating strongatxr5;atxr6double mutants inArabidopsis. Our results show that ATXR5/6 are essential for plant reproductive development and play a critical role in supporting normal plant growth by repressing the transcription of stress responsive genes. In addition, ATXR5/6 are necessary for maintaining H3K27 trimethylation (H3K27me3), likely by providing H3K27me1 as a substrate for further methylation. We also demonstrate that the function of ATXR5/6 in regulating reproductive development and responsive genes is conserved in the monocot rice. We propose that land plants may have evolved ATXR5/6 to assist in the transcriptional regulation necessary for terrestrial adaptation.
Comparison of Tooth Wear Among Young Sports Persons Involved in Individual and Team Sports- A Cross-Sectional Study
Authors: RamyaDurga Rangasamy , SriChinthu KenniyanKumar , Prasad Harikrishnan , Rajmohan Muthusamy , Perumal Prema , Yoithapprabhunath Thuckanickenpalayam Ragunathan , Shanmuganathan S. 
Published: November 2024

ABSTRACTBACKGROUNDTooth wear has multifactorial etiology & defined as non-self-reparable loss of hard tissue in the absence of dental caries or trauma. One of the valid aetiologies for pathological tooth wear is stress. During sports activity, athletes tend to clench their teeth involuntarily which results in tooth wear, especially in young sportspersons. Hence, we designed a study to evaluate and compare tooth wear among young sportspersons involved in individual and team sports.METHODSThe study population comprised 300 subjects and were divided into two groups, group 1 (150 individuals involved in individual sports activity) & group 2 (150 individuals involved in team sport activity) The Tooth wear index was assessed based on Smith & Knight scoring criteria (1984).RESULTS88.6% of study participants showed tooth wear in individual sports & 84% in team sports. Tooth wear was highest in the mandibular & maxillary central incisor of both individual & team sports individuals.CONCLUSIONWe found that both individual and team sports players showed tooth wear, especially in the incisal surface of mandibular & maxillary incisors, which might reflect the underlying stress or anxiety. This study is the first of its kind to evaluate and compare tooth wear among young sportspersons involved in individual and team sports in India.
Role of the gut microbiome in frequent gut colonization with extended-spectrum β-lactamase-producing Enterobacterales among Peruvian children
Authors: Nadimpalli Maya L. , Sehgal Neha , Rojas-Salvatierra Luismarcelo , Gilman Robert H. , Earl Ashlee M. , Worby Colin J. , Schwab Madison , Pickering Amy J. , Pajuelo Monica J. 
Published: November 2024

AbstractWe investigated whether differences in gut microbiome development could underlie differential susceptibility to gut colonization with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) over time among children in peri-urban Lima. Weekly stool and daily surveys were collected from 345 children <3 years old during a 2016-19 study of enteric infections. A subset of children (n=12) were rarely gut-colonized with ESBL-E from 1-16 months of age. We performed short-read metagenomic sequencing of stool collected at 3, 6, 7, 9, 12, and 16 months from these children and a random subset of 42 frequently colonized children, and characterized differences in antibiotic use, sociodemographic characteristics, and the gut microbiome over time. No gut microbiome differences were identified, but rarely colonized children were more likely to live in households of lower socioeconomic status and consumed fewer antibiotics. Differences in exposures, rather than gut microbiome development, might underlie patterns of ESBL-E gut colonization among children in peri-urban Lima.
Deciphering the Transcriptomic Landscape of Type 2 Diabetes: Insights from Bulk RNA Sequencing and Single-Cell Analysis
Authors: Tkachenko A.A. , Tonyan Z.N. , Nasykhova Y.A. , Barbitoff Y.A. , Renev I.N. , Danilova M.M. , Mikhailova A.A. , Glavnova O.B. , Chepanov S.V. , Selkov S.A. , Golovkin N.V. , Vlasova M.E. , Glotov A.S. 
Published: November 2024

AbstractType 2 diabetes (T2D) is a chronic metabolic disorder marked by insulin resistance and relative insulin deficiency, affecting over 422 million people globally and projected to increase, making it a major public health concern. This condition is associated with severe complications such as retinopathy, nephropathy, cardiovascular diseases, and neuropathy, highlighting the need for a deeper understanding of its mechanisms to develop more effective prevention and treatment strategies. Transcriptomic analysis, particularly through RNA-seq, has provided valuable insights into the gene expression patterns in T2D, highlighting pathways involved in insulin signaling, metabolic regulation, and inflammation. This approach, including single-cell RNA sequencing, helps overcome the challenges of immune cell population heterogeneity, enabling the identification of distinct cell types and their specific roles in T2D progression. In this paper, we present a dataset of single-cell and bulk RNA sequencing results comparing expression patterns in blood cells between diabetes and healthy samples and describe some preliminary analysis of the dataset, highlighting differences in both gene expression and cell type composition and putting them in the context of existing research of T2D.
Short Report: Investigating Oropouche as a possible etiology for fevers of unknown origin in a clinical cohort from Colombia, 2013-2015
Authors: Walsh Christine S. , Cardenas Jenny C. , Gutierréz-Silva Lady Y. , González Maria U. , Mores Christopher N. , Londono-Renteria Berlin , Christofferson Rebecca C. 
Published: November 2024

AbstractCurrently, the largest outbreak of Oropouche virus (OROV) in Latin America and the Caribbean, has also spread across the globe to Italy, Spain, and Germany, bringing this virus into the public domain. With over 8,000 cases and counting in Brazil, there have been two deaths in young women with no known comorbidities, and infection with Oropouche was associated with a late term stillbirth. While OROV has been sporadically detected in Colombia since 2017, with a handful of cases in Cúcuta and Leticia, the distribution of OROV prior to that remains unknown. Therefore, we undertook to test a clinical cohort of febrile patients from Colombia to determine if OROV was circulating within the human population earlier than previously determined. We screened 631 serum samples collected in 2014-2015 from three municipalities: Cúcuta, Los Patio, and Ocaña. We found evidence of OROV infection in three patients from Ocaña, though live virus was not recoverable from patient sera. These data suggest that OROV circulation, while sporadically detected in Colombia, has circulated earlier than previously thought. With the emergence and expansion of new or neglected viruses, there is a need to expand screening of febrile patients both retro- and prospectively to describe and better understand the distribution of arbovirus circulation in human populations. Surveillance for OROV across South America is necessary going forward, especially as the outbreak in Brazil continues.
Exploring the Molecular Pathways of Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease Using Proteomic Analysis
Authors: Kim Jin-Myung , Ahn Hee-Sung , Kim Mi Joung , Kwon Hye Eun , Ko Youngmin , Jung Joo Hee , Kwon Hyunwook , Kim Young Hoon , Yu Jiyoung , Kim Kyunggon , Shin Sung 
Published: November 2024

ABSTRACTIntroductionIntracranial aneurysm (IA) frequently coincides with autosomal dominant polycystic kidney disease (ADPKD), exhibiting incidence rates nearly 10 times higher than the general population. However, the exact mechanism of how these two conditions is related remains unclear. This study aims to identify mechanisms behind IA occurrence in ADPKD patients using proteomics and to discover potential protein biomarkers for early diagnosis.MethodPre-kidney transplantation ADPKD patients underwent cranial CT and/or MR angiography, with findings dictating assignment to either a control group (ADPKD without IA, n=20) or IA group (ADPKD with IA, n=9). During transplantation, bilateral nephrectomy was performed and native renal arteries were sampled for proteomic analysis via a liquid chromatography-tandem mass spectrometry. Differentially expressed proteins were subjected to bioinformatic analysis and a protein-protein interaction network analysis.ResultsEight proteins showed significant variation between IA and control groups, with four proteins upregulated (DIS3, RAB6A, MMS19, EXOC8) and four downregulated (CLUH, SYNC, MEF2D, WDR36) in IA group (Log2fold change (FC) >2 and false discovery rate (FDR] q-value <0.05) compared to the control group. These proteins correlated with pathways implicated in IA development, such as ciliopathy, exocytosis, inflammation, extracellular matrix remodelling, and apoptosis. These proteins were quantitatively validated using Western blot analysis and found to be consistent with proteomic data. Moreover, a connection was observed between protein expression and clinical metrics (bilirubin, prothrombin time, platelet count), indicating their potential as early diagnostic markers.ConclusionThis study is the first to employ renal artery samples to study underlying mechanisms for IA in ADPKD patients by proteomics. We identified and validated novel candidate markers that are either upregulated or downregulated in the IA group compared to the control group. This research’s finding opens new avenues for understanding and diagnosing IA in ADPKD, potentially leading to earlier diagnosis and targeted treatments.
A Phase Ib/II multi-arm, dose finding and expansion study of a novel thymidylate synthase inhibitor with immune modulating properties, NUC-3373, in combination with pembrolizumab or docetaxel in patients with advanced solid tumors (NuTide:303)
Authors: Middleton Gary , Spicer James , Aktas Burak , Dinizulu Habana , Wilson Richard H , Harrison David J , Oelmann Elisabeth , Bloss Jeff , Thistlethwaite Fiona 
Published: November 2024

AbstractBackgroundNUC-3373 is a novel thymidylate synthase (TS) inhibitor designed to directly deliver the active anti-cancer metabolite fluorodeoxyuridine-monophosphate (FUDR-MP or FdUMP) intracellularly. In addition to being a potent TS inhibitor, NUC-3373 has also been shown to cause DNA damage and promote the release of damage-associated molecular patterns. These diverse mechanisms position NUC-3373 as a potentially effective combination partner for several other anti-cancer agents.MethodsNuTide:303 is a Phase Ib/II open label, multi-arm, parallel cohort dose-finding and expansion study designed to evaluate optimal combination partners for NUC-3373. Module 1 planned to enroll up to 12 evaluable patients with advanced/metastatic solid tumors to determine the recommended dose for NUC-3373 in combination with leucovorin (LV) and pembrolizumab. Module 2 planned to enroll approximately 6-12 evaluable patients with advanced/metastatic non-small cell lung cancer (of any histology) or pleural mesothelioma to determine the recommended dose for NUC-3373 in combination with LV and docetaxel. A 3+3 dose escalation design was used in both modules, with safety parameters continually assessed and tumor assessments conducted at screening and every 8 weeks from C1D1 until progression.ResultsThirteen patients were enrolled in Module 1, with 9 evaluable for response. No DLTs were observed in these heavily pre-treated PD-(L)1 experienced patients with a variety of different tumor types. Four patients remained on treatment for >3 months and 3 patients were ongoing at the time of data cut-off. An objective response rate of 22% and a disease control rate of 67% were reported. NUC-3373 + LV + pembrolizumab was well tolerated, the most common treatment-related adverse events (AEs) were nausea, vomiting, and diarrhea and the majority of events were Grade 1 (100%) or 2 (85%). Four patients were enrolled in Module 2, with 3 evaluable for response. Two patients treated at the first dose level achieved stable disease and completed >6 months of treatment The most common treatment-related AEs were fatigue (n=4) and diarrhea (n=3) and the majority of events were Grade 1 (100%) or 2 (100%).ConclusionsPreliminary results from Module 1 show signals of anti-cancer activity and tolerability, providing support for further exploration of this combination in the Phase II part of the study. Preliminary results from Module 2 suggest that the probability of being able to escalate to typical efficacious doses of docetaxel used in combination is low due to overlapping toxicity. Further modifications to include the use of a different taxane in this combination are currently being considered.
Adjuvant Recombinant SARS-CoV-2 Spike Protein Vaccine Immunogenicity After Prior mRNA Vaccine Doses
Authors: Adelglass Jeffrey M. , Bradley Paul , Cai Miranda R. , Chau Gordon , Kalkeri Raj , Cloney-Clark Shane , Zhu Mingzhu , Cai Zhaohui , Eickhoff Mark , Plested Joyce S. , Mallory Raburn M. , Dunkle Lisa M. 
Published: November 2024

ABSTRACTBackgroundTo support heterologous vaccine regimens, periodic SARS-CoV-2 revaccination required immunogenicity and safety data for adjuvanted protein-based vaccines following prior mRNA doses.MethodsThis phase 3, open-label study (2019nCoV-312/NCT05875701) enrolled participants who received one dose of ancestral SARS-CoV-2 protein-based vaccine (NVX-CoV2373) in an earlier study (2019nCoV-307/NCT05463068) after a primary series and possibly one additional dose of mRNA vaccine. In the current study, participants received an additional dose of protein-based vaccine (ancestral [n=104] or Omicron BA.5 [n=40]) at least 180 days after their previous study dose. The primary objective was demonstration of noninferiority of neutralizing antibody (nAb) titers induced by the dose in this study versus the first dose of NVX-CoV-2373 in the earlier study. Safety was also evaluated.ResultsA total of 144 participants were enrolled. The ratio of anti-Wuhan nAbs (GMT, IU/mL [95% CI]) at Day 28 after this study dose (ancestral 393.2 [318.0–468.2]) versus previous study dose (396.6 [328.7–478.6]) was 1.0 (0.8, 1.2), meeting noninferiority. The seroresponse rate difference between doses was 7.4% (95% CI = −1.2%–16.5%), also meeting noninferiority. Omicron BA.5 nAb titers suggest cross-protection against emerging variants. The nAb ratio at Day 28 between Omicron dose in this study (835.0 [597.1–1167.6]) versus previous study ancestral dose (436.0 [305.6–622.2]) was 1.9 (1.5–2.5), exceeding superiority criterion. Local and systemic reactions were similar between doses and strains in both studies.ConclusionsA heterologous regimen of two adjuvanted recombinant spike protein-based vaccine doses after mRNA vaccination produced robust immune responses, exhibiting cross-reactivity to newer variants.