bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circ‐Sirt6 promotes the stability and expression of m6A modified Sirt6mRNA by recruiting IGF2BP2
Authors: Zhang Chuanfeng , Wang Jianing , Kong Peng , Sun Guangbin , Sun Hongfang , Yu Yuan 
Published: February 2025

AbstractCoronary artery disease (CAD) is the leading cause of death worldwide. Even though numerous circRNAs have been linked to the formation and progression of CAD, more circular RNA regulators still need to be uncovered in order to enhance the knowledge of the CAD regulatory networks. Microarray analysis was employed to identify aberrantly expressed circRNAs in vascular pathology, and the level of circ‐Sirt6 in abnormally proliferated vascular smooth muscle cells (VSMCs) was detected by qRT‐PCR. The effects of circ‐Sirt6, IGF2BP2, and Sirt6 on the proliferation and migration of VSMCs were examined by EdU incorporation assay and migration assays. The interaction between circ‐Sirt6, IGF2BP2, and Sirt6 was verified by RNA pull‐down assay, RIP, FISH, and immunofluorescent staining. Dot blot assay and m6A‐methylated RNA immunoprecipitation‐qPCR were performed to confirm that circ‐Sirt6 promoted m6A modification and stabilization of Sirt6 mRNA. According to our research, circ‐Sirt6 expression was markedly downregulated in VSMCs treated with PDGF‐BB and carotid artery balloon injury. The in vitro and in vivo proliferation and migration of VSMCs were inhibited by overexpression of circ‐Sirt6. Mechanistically, circ‐Sirt6 specifically binds to IGF2BP2 and promotes the stability and expression of Sirt6 mRNA by enhancing its m6A modification. Our findings highlight the importance of circ‐Sirt6‐mediated m6A in VSMC phenotype switching. Circ‐Sirt6 may be a novel biological target for CAD.
Dolutegravir induces endoplasmic reticulum stress at the blood–brain barrier
Authors: Huang Chang , Qu Qing Rui , Hoque Md. Tozammel , Bendayan Reina 
Published: February 2025

AbstractDolutegravir (DTG)‐based antiretroviral therapy is the contemporary first‐line therapy to treat HIV infection. Despite its efficacy, mounting evidence has suggested a higher risk of neuropsychiatric adverse effect (NPAE) associated with DTG use, with a limited understanding of the underlying mechanisms. Our laboratory has previously reported a toxic effect of DTG but not bictegravir (BTG) in disrupting the blood–brain barrier (BBB) integrity. The current study aimed to investigate the underlying mechanism of DTG toxicity. Primary cultures of mouse brain microvascular endothelial cells were treated with DTG and BTG at therapeutically relevant concentrations. RNA sequencing, qPCR, western blot analysis, and cell stress assays (Ca2+ flux, H2DCFDA, TMRE, MTT) were applied to assess the results. The gene ontology (GO) analysis revealed an enriched transcriptome signature of endoplasmic reticulum (ER) stress following DTG treatment. We demonstrated that therapeutic concentrations of DTG but not BTG activated the ER stress sensor proteins (PERK, IRE1, p‐IRE1) and downstream ER stress markers (eIF2α, p‐eIF2α, Hspa5, Atf4, Ddit3, Ppp1r15a, Xbp1, spliced‐Xbp1). In addition, DTG treatment resulted in a transient Ca2+ flux, an aberrant mitochondrial membrane potential, and a significant increase in reactive oxygen species in treated cells. Furthermore, we found that prior treatment with ER sensor or ER stress inhibitors significantly mitigated the DTG‐induced downregulation of tight junction proteins (Zo‐1, Ocln, Cldn5) and elevation of pro‐inflammatory cytokines and chemokines (Il6, Il23a, Il12b, Cxcl1, Cxcl2). The current study provides valuable insights into DTG‐mediated cellular toxicity mechanisms, which may serve as a potential explanation for DTG‐associated NPAEs in the clinic.
Focal Oral Elastosis: Case Series, Proposed Nomenclature, and Literature Review
Authors: Alabdulaaly Lama , Chung Dahee , Woo Sook-Bin 
Published: February 2025

Abstract:
Late-onset focal dermal elastosis is an uncommon elastic disorder seen in older individuals and biopsies demonstrate an increase in elastic fibers. Elastosis of the oral cavity is reported uncommonly. The aim of this study is to describe oral biopsies with similar histopathologic features to late-onset focal dermal elastosis and to introduce the term “focal oral elastosis.” We included oral biopsies that showed increased elastic fibers confirmed by Verhoeff-van Gieson histochemical stain. We identified 6 oral biopsies with prominent elastosis. There were 4 men, and the median age was 64.5 years. Elastosis was present in 5 nodular lesions and 1 papule. Lesions occurred on the gingiva (33.3%), palatal mucosa (33.3%), buccal mucosa (16.7%), and upper lip (16.7%). Deposition of amorphic bluish/amphophilic material in the subepithelial areas was seen in all cases confirmed with the Verhoeff-van Gieson stain. Our case series demonstrates the presence of elastic fibers in reactive lesions such as oral fibromas.
Late Recurrent Spitz Melanoma With a TMEM106B::BRAF Fusion
Authors: Koga Shunsuke , Karakousis Giorgos C. , Yang Guang , Elder David E. 
Published: February 2025

Abstract:
Melanoma is a clinically and genetically heterogeneous malignancy that can recur long after initial treatment. We report the case of a 70-year-old man who presented with metastatic cutaneous melanoma 36 years after the initial diagnosis. Initially diagnosed with nodular melanoma on the left heel at age 34 years, the patient experienced metastatic spread to the left groin lymph nodes by age 36 years, followed by various systemic therapies, including interferon and cytokine therapy, and subsequent observation, over 15 years. Two years before his current presentation, the patient noted a growing mass in his right thigh and an enlarged left inguinal lymph node. Fine-needle aspiration biopsy of the lymph node confirmed the recurrence of melanoma. He subsequently underwent inguinofemoral lymph node dissection and resection of the right thigh mass. Histopathological evaluation revealed melanoma characterized by tumorigenic proliferation of pleomorphic epithelioid and spindle cells with abundant eosinophilic cytoplasm, large nuclei with prominent nucleoli, sparse lymphocyte infiltration, and minimal necrosis, consistent with an initial diagnosis of Spitzoid melanoma. Genetic profiling using targeted next-generation sequencing identified a novel TMEM106B::BRAF fusion, along with CHEK2 and MUTYH mutations. The BRAF fusion supports the diagnosis of Spitz melanoma, a genetically defined subset of Spitzoid melanoma. This case represents the first report of a TMEM106B::BRAF fusion in melanoma, emphasizing the critical role of molecular profiling in diagnosing and managing this malignancy, and suggesting a potential avenue for future therapeutic exploration.
Unlocking the Potential of the HEART Pathway: Predicting MACE and Facilitating Nurse–Physician Collaboration in Chest Pain Unit
Authors: Behpour Zahra , Amirsardari Zahra , Aghakhani Haniye , Zanganehfar Mohammadesmaeil , Khaleghparast Shiva , Shabani Fidan , Bakhshandeh Hooman , Sadeghipour Parham 
Published: February 2025

Background and Objective:
The HEART pathway serves as a tool for predicting major adverse cardiac events (MACE) among patients presenting with acute chest pain, aiding in the early discharge of low-risk patients and reducing unnecessary cardiac investigations. This study aimed to evaluate physician–nurse reliability of the HEART pathway and investigate the efficacy of HEART pathway to predict 3-month MACE in patients with acute chest pain.

Methods:
We conducted a prospective study on 97 patients experiencing acute chest pain. A team of 3 professionals, a nurse, a cardiology resident, and a cardiology attending physician, performed risk stratification. We assessed interrater reliability among the raters as well as explored 3-month MACE outcomes.

Results:
Excellent pairwise agreements were found between the raters. Overall agreement among raters was excellent, with an intraclass correlation coefficient of 0.84 (95% confidence interval: 0.73–0.97). The HEART pathway score exhibited strong predictive power (area under curve: 0.85) for 3-month MACE. At a cutoff score of 4, sensitivity, specificity, and negative predictive values were 87.5%, 58.9%, and 95.8%, respectively.

Conclusions:
The HEART pathway score effectively predicts 3-month MACE in patients with acute nontraumatic chest pain. Moreover, the high agreement among the attending physician, the resident physician, and the nurse suggests that nurses could use this tool, potentially reducing the workload on physicians.
A Case of Uveal Melanoma Masquerading as Choroidal Lymphoma
Authors: Sahal H Saleh , Rima Stepanian , Joseph D Juliano , Robert Folberg , Lau-Sickon Laurie , Lisa J Faia , Adam J Weiner 
Published: February 2025

Purpose:
To present a case of uveal melanoma masquerading as choroidal lymphoma.

Methods:
A retrospective case report in which medical and imaging records, including fundus photography, optical coherence tomography, fundus autofluorescence, fluorescein angiography, and ultrasonography were reviewed.

Results:
A 77-year-old woman presented with decreased vision was found to have a diffuse, shallow, yellow choroidal mass associated with RPE pigmentary changes and exudative detachment in her right eye. Multi-modal imaging demonstrated thickened choroid with a “lumpy-bumpy” appearance on OCT, “leopard-spotting” on fundus autofluorescence, and a shallow “table-top” configuration on B scan. Systemic workup was unremarkable. The patient elected to undergo treatment with low-dose external beam radiation for presumed choroidal lymphoma. There was no response to radiation prompting retinochoroidal biopsy, which revealed spindle-cell uveal melanoma and resulted in enucleation.

Conclusion:
We present a case of uveal melanoma masquerading as choroidal lymphoma. This case highlights that uveal melanoma can rarely masquerade as other entities, including uveal lymphoma.
Phoenix Sepsis Criteria in Critically Ill Children: Retrospective Validation Using a United States Nine-Center Dataset, 2012–2018
Authors: Sanchez-Pinto L. Nelson , Daniels Latasha A. , Atreya Mihir , Faustino E. Vincent S. , Farris Reid W. D. , Geva Alon , Khemani Robinder G. , Rogerson Colin , Shah Sareen S. , Weiss Scott L. , Bennett Tellen D. 
Published: February 2025

Objectives:
To perform: 1) external validation of the Phoenix Sepsis Score and Phoenix sepsis criteria in a multicenter cohort of critically ill children with infection and a comparison with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria; 2) a study of Phoenix sepsis criteria performance in patient subgroups based on age and comorbidities; 3) an assessment of microbiological profile of children with Phoenix sepsis; and 4) a study of the performance of the Phoenix-8 score.

Design:
Secondary, retrospective analysis of a multicenter cohort study from 2012 to 2018.

Setting:
Nine PICUs in the United States.

Patients:
PICU admissions with suspected infection.

Interventions:
None.

Measurements and Main Results:
Among 25,680 encounters of children with suspected or confirmed infection on PICU admission (4.6% in-hospital mortality), 11,168 (43%) met Phoenix criteria for sepsis or septic shock (9% in-hospital mortality). The Phoenix criteria generally outperformed the IPSCC criteria at discriminating mortality in all critically ill children with infections and across all subgroup analyses, including age group, malignancy, or technology dependence. Of 11,168 patients who met Phoenix criteria, 28% were negative for IPSCC criteria for sepsis and these had higher in-hospital mortality than those who met IPSCC sepsis criteria but not Phoenix criteria (4.7% vs.1.7%; p < 0.001), which was similar to the mortality of patients without sepsis (1.3%). Sepsis was associated with respiratory or bloodstream infection, most commonly Pseudomonas aeruginosa or Staphylococcus aureus. The Phoenix-8 score had good discrimination of mortality in children with infections, comparable to or better than validated and widely used severity of illness and organ dysfunction scores.

Conclusions:
In 2012–2018, among U.S. patients with suspected or confirmed infection admitted to nine PICUs, those with the highest risk of mortality can be identified using the Phoenix sepsis criteria, including in children of different age groups and those with major comorbidities.
Kidney organ injury scaling: 2025 update
Authors: Keihani Sorena , Tominaga Gail T. , Matta Rano , Gross Joel A. , Cribari Chris , Kaups Krista L. , Crandall Marie , Kozar Rosemary A. , Werner Nicole L. , Zarzaur Ben L. , Coburn Michael , Myers Jeremy B. 
Published: February 2025

ABSTRACT
The American Association for the Surgery of Trauma initially published the organ injury scaling for the kidney in 1989, which was subsequently updated in 2018. This current American Association for the Surgery of Trauma kidney organ injury scaling update incorporates the latest evidence in diagnosis and management of renal trauma and is based upon a multidisciplinary consensus. These changes reflect the near universal use of computed tomography for renal trauma evaluation and the widespread adoption of conservative management across all grades of renal trauma.
Anticoagulant vs. antiviral therapy, recovery and neurodamage in Long COVID: a real-world prospective cohort study
Authors: Jamoulle Marc , Mignolet Margaux , Meyts Isabelle , Ladang Aurélie , Nicaise Charles , Van Weyenbergh Johan 
Published: February 2025

ABSTRACTRecent estimates consider that Long COVID affects 400 million people worldwide, of which <10% recover after two years. Predictive biomarkers and effective therapies are urgently needed for the clinical management of Long COVID. Neurological manifestations (poor memory, brain fog) are frequent, while neurodamage and neuroinflammatory markers UCHL1, GFAP and NFL were found to be increased in some but not all Long COVID cohorts. However, a direct link between two major Long COVID disease mechanisms, viral persistence and coagulation defects, and CNS damage is unclear. Therefore, we investigated the effect of combined anticoagulant (Asaflow + Clopidogrel) vs. antiviral (Paxlovid) treatment upon clinical outcome and neurodamage markers in Long COVID patients. Using multivariate logistic regression, we found that second-line antiviral treatment is the single best predictor of clinical recovery in a real-world Long COVID cohort (n=106) with long-term (220 person-years) follow-up. Our results support a putative role for viral persistence in Long COVID pathogenesis but also indicate a large therapeutic window for Paxlovid and other antivirals. A rapid decline in neurodamage markers (GFAP/NFL) upon antiviral treatment suggests CNS damage in Long COVID might be therapeutically targeted and should be considered in ongoing and future clinical trials.
panHiTE: a comprehensive and accurate pipeline for TE detection in large-scale population genomes
Authors: Hu Kang , Xu Minghua , Wang Jianxin 
Published: February 2025

AbstractTransposable elements (TEs) are key drivers of genomic variation and species evolution. Advances in high-throughput sequencing have enabled whole-genome sequencing of individuals or subspecies, facilitating the identification of population-specific variations. Detecting population-specific TE insertions at scale is crucial for understanding species-specific phenotypic traits. However, tools for constructing comprehensive pan-TE databases remain limited. To address this gap, we develop panHiTE, a population-scale TE detection and annotation tool with several core innovations. panHiTE features a deep learning-based long terminal repeat retrotransposon (LTR-RT) detection algorithm, outperforming existing tools in both sensitivity and precision. It also introduces a novel de-redundancy algorithm, which eliminates highly divergent redundant TE instances, significantly reducing the size of the TE library. Additionally, panHiTE can detect low-copy TEs, which are overlooked in individual genome analyses and absent from existing databases due to their rarity. Furthermore, panHiTE allows for TE-gene association analysis, enabling comprehensive insights into TE-driven phenotypic variation. panHiTE, powered by a Nextflow pipeline, enables efficient and scalable TE detection in large plant genomes and has successfully been applied to hundreds of plant population genomes, demonstrating its effectiveness and scalability.
Time for a standardized neurological assessment in acute setting: the modified Neurological Impairment scale
Authors: Padovani Alessandro , Mattioli Irene , Comunale Tiziana , Zoppi Nicola , Zatti Cinzia , Guso Enis , Catania Marcello , Morotti Andrea , Agosti Chiara , Gipponi Stefano , Turner-Stokes Lynne , Pilotto Andrea 
Published: February 2025

ABSTRACTBackgroundGiven the increasing diversity among neurological patients, standardized protocols are essential for evaluating the severity and complexity of the variety of conditions. Aim of the present work was to standardize the assessment of the severity and complexity of neurological impairment in an acute setting by using a modified version of the Neurological Impairment Scale (mNIS).Methodsconsecutively hospitalized neurological inpatients underwent a multidimensional standardized assessment of multimorbidity, frailty, functional dependency, and neurological impairment using mNIS and other validated scales. Inter-rater reliability of the mNIS total and sub-scores was evaluated. Construct validity was assessed separately in patients with Cerebrovascular disease performing correlations between corresponding sub-scores of mNIS, original NIS, and National Institutes of Health Stroke Scale (NIHSS). mNIS Complexity Index (mNIS-CI) for neurological severity was used to classify patients into subtle, mild, moderate, and severe impairment.Resultsone thousand eighty-one neurological patients admitted to a neurological ward from the emergency setting were enrolled. The inter-rater reliability was remarkable for mNIS total and sub-scores (ICC 0.90, 95% CI 0.82–0.95). The mNIS showed strong construct validity for total and sub-scores compared to other clinical scales (r 0.47-0.97, p<0.001) and 52.7% of patients scored at least one in one of the four newly listed items. The stratification of patients according to mNIS-CI exhibited high construct validity distinguishing the extent of impairment and involved domains.ConclusionsThe mNIS is valuable for measuring neurologic severity and complexity in acute inpatients and holds significant potential for application in different settings.What is already known on this topicStandardization of neurological assessment and development of functional rating scales of global impairment are pivotal to characterize and follow up patients both in the clinical practice and in the research setting.What this study addsmNIS is a valuable tool to measure neurologic severity and complexity in acute inpatients: the four added items are useful for capturing a broader spectrum of signs and symptoms; the severity and complexity scores provide different information about neurological status and domain imapired at individual level.How this study might affect research, practice, or policymNIS can be instrumental in grading the severity of neurological conditions, tracking clinical progress, and gauging response to treatments in the acute setting.
f4-statistics-based ancestry profiling and convolutional neural network phenotyping shed new light on the structure of genetic and spike shape diversity inAegilops tauschiiCoss
Authors: Koyama Yoshihiro , Nasu Mizuki , Matsuoka Yoshihiro 
Published: February 2025

AbstractAegilops tauschiiCoss., a progenitor of bread wheat, is an important wild genetic resource for breeding. The species comprises three genetically defined lineages (TauL1, TauL2, and TauL3), each displaying distinctive phenotypes in various agronomic traits, including spike shape. In the present work, we studied the relationship between population structure and spike shape variation patterns using a collection of 249 accessions.f4-statistics-based ancestry profiling confirmed the previously identified lineages and revealed a genetic component derived from TauL3 in the genomes of some southern Caspian and Transcaucasus TauL1 and TauL2 accessions. Spike shape variation patterns were analyzed using a convolutional neural network-based approach, trained on green and dry spike image datasets. This analysis showed that spike shape diversity is structured according to lineages and demonstrated that the lineages can be distinguished based on spike shape. The implications of these findings for the origins of common wheat and the intraspecific taxonomy ofAe. tauschiiare discussed.Plain Language SummaryWild wheat,Aegilops tauschii, represents a vast reservoir of alleles that have not yet been utilized in breeding. These alleles may confer beneficial phenotypes, such as drought tolerance and disease resistance, when introduced into bread wheat. To fully leverage this reservoir, it is essential to quickly identify strains with potentially useful alleles. InAe. tauschii, which consists of strain groups (lineages) with unique genetic makeups, this can be done by determining a strain’s lineage based on spike shape. In this work, we trained machine learning models for this purpose and found that spike shape diversity reflects lineage structure. These models demonstrated potential for practical use in assigning strains to their respective lineages based on spike shape. Our work opens new avenues for the application of machine learning in wheat improvement, as well as in the genetic and evolutionary studies of wheat morphology.
Combining machine learning and publicly available aerial data (NAIP and NEON) to achieve high-resolution remote sensing of grass-shrub-tree mosaics in the Central Great Plains (U.S.A.)
Authors: Noble Brynn , Ratajczak Zak 
Published: February 2025

AbstractWoody plant encroachment (WPE)—a phenomenon similar to species invasion—is shifting many grasslands and savannas into shrub and evergreen-dominated ecosystems. Tracking WPE is difficult because shrubs and small trees are much smaller than the coarse resolution of common remote sensing platforms (> 10 m2) and the impassibility of encroaching woody thickets slows ground-based approaches. Many agencies have been investing in fine resolution (< 2 m2) remote sensing through programs such as the United States Department of Agriculture (USDA) National Agriculture Imagery Program (NAIP) and the National Ecological Observatory Network (NEON). Both use low-flying planes and provide data to end users in an easy-to-use format at large spatial extents. By removing entry barriers, these publicly available open-source programs could increase the accessibility and extent of remote sensing. We compared two common methods of machine learning classification of land cover (random forests and support vector machines) factorially crossed with these two freely available remote sensing platforms to determine if we could quickly and accurately develop remote sensing of major vegetation types in a tallgrass prairie landscape undergoing encroachment by shrubs and trees. Our work took place at Konza Prairie Biological Station—a landscape scale experiment that results in a wide range of land cover types. All models had very high overall classification accuracy (>90%), with the NEON-based models a few percent more accurate than NAIP. A model using both inputs had the highest accuracy. However, the accuracies of NAIP and NEON models differed for woody vegetation: compared to NEON, NAIP accuracy was, 82-93% compared to 94-98% for shrubs, 72-92% compared to 93-98% for deciduous trees, and 52-78% compared to 83-86% for evergreen trees (specificallyJuniperus virginiana). NEON-based models relied on canopy height (LiDAR) to make classifications, whereas the several bands of light make similar contributions to accuracy in the NAIP models. Finally, we found that both machine learning approaches had similar accuracy, but random forests ran substantially faster. We conclude that with large training datasets, publicly available aerial imagery and similar products (e.g., UAVs, micro-satellites) can produce fine-scale, high-accuracy remote sensing of WPE in this region with low up-front costs.