bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scupa: Single-cell unified polarization assessment of immune cells using the single-cell foundation model
Authors: Liu Wendao , Zhao Zhongming 
Published: February 2025

Abstract

Motivation
Immune cells undergo cytokine-driven polarization in response to diverse stimuli, altering their transcriptional profiles and functional states. This dynamic process is central to immune responses in health and diseases, yet a systematic approach to assess cytokine-driven polarization in single-cell RNA sequencing data has been lacking.

Results
To address this gap, we developed Single-cell unified polarization assessment (Scupa), the first computational method for comprehensive immune cell polarization assessment. Scupa leverages data from the Immune Dictionary, which characterizes cytokine-driven polarization states across 14 immune cell types. By integrating cell embeddings from the single-cell foundation model Universal Cell Embeddings, Scupa effectively identifies polarized cells across different species and experimental conditions. Applications of Scupa in independent datasets demonstrated its accuracy in classifying polarized cells and further revealed distinct polarization profiles in tumor-infiltrating myeloid cells across cancers. Scupa complements conventional single-cell data analysis by providing new insights into dynamic immune cell states, and holds potential for advancing therapeutic insights, particularly in cytokine-based therapies.

Availability and Implementation
The code is available at https://github.com/bsml320/Scupa.

Supplementary information
Supplementary data are available at Bioinformatics online.
Jellyfish: integrative visualization of spatio-temporal tumor evolution and clonal dynamics
Authors: Lavikka Kari , Maarala Altti Ilari , Oikkonen Jaana , Hautaniemi Sampsa 
Published: February 2025

Abstract

Summary
Spatial and temporal intra-tumor heterogeneity drives tumor evolution and therapy resistance. Existing visualization tools often fail to capture both dimensions simultaneously. To address this, we developed Jellyfish, a tool that integrates phylogenetic and sample trees into a single plot, providing a holistic view of tumor evolution and capturing both spatial and temporal evolution. Available as a JavaScript library and R package, Jellyfish generates interactive visualizations from tumor phylogeny and clonal composition data. We demonstrate its ability to visualize complex subclonal dynamics using data from ovarian high-grade serous carcinoma.

Availability and implementation
Jellyfish is freely available with MIT license at https://github.com/HautaniemiLab/jellyfish (JavaScript library) and https://github.com/HautaniemiLab/jellyfisher (R package)
Patient-reported outcomes 3 and 18 months after mastectomy and immediate prepectoral implant-based breast reconstruction in the UK Pre-BRA prospective multicentre cohort study
Authors: Harvey Kate L , Johnson Leigh , Sinai Parisa , Mills Nicola , White Paul , Holcombe Christopher , Potter Shelley ,   The Pre-BRA Feasibility Study Steering Group, Barry Peter , Cawthorn Simon , Gardiner Matthew , Irwin Gareth , Kirwan Cliona , McKenzie Mairead , McKenzie Shireen , O’Connell Rachel , Oni Georgette , Rattay Tim , Roy Pankaj , Skillman Joanna , Soumian Soni , Vidya Raghavan , Whisker Lisa , Williams Samantha 
Published: February 2025

Abstract

Introduction
Prepectoral techniques are becoming standard of care for implant-based breast reconstruction due to reduced impact on chest wall function and improved patient satisfaction. Evidence to support these benefits, however, is lacking. Here, patient-reported outcomes (PROs) of prepectoral breast reconstruction (PPBR) in the Pre-BRA cohort are reported.

Methods
Women undergoing PPBR after mastectomy for breast cancer or risk reduction between July 2019 and December 2020 were recruited. Participants completed the BREAST-Q preoperatively and at 3 and 18 months following surgery together with a single item evaluating overall satisfaction at 18 months. Women completing at least one BREAST-Q scale at any timepoint were eligible for inclusion. Questionnaires were scored according to the developers’ instructions and scores compared over time. Exploratory analysis, adjusting for baseline scores was performed to explore factors impacting PROs.

Results
In total 338 of 343 (98.5%) women undergoing PPBR at 40 UK centres were included in the analysis. Compared with baseline scores, women reported statistically significant and clinically meaningful decreases in both ‘Physical’ and ‘Sexual well-being’ at 3 and 18 months. Adjusting for baseline, at 18 months, those experiencing implant loss or having surgery for malignancy reported lower scores in all BREAST-Q domains. Overall, two-thirds of women (167/251) rated the outcome of their reconstruction as ‘excellent/very good’, but experiencing major complications, implant loss, and being dissatisfied with wrinkling/rippling in the reconstructed breast were associated with reduced satisfaction.

Conclusions
PPBR impacts postoperative physical well-being and PROs are variable. These findings should be discussed with patients to support informed decision-making based on realistic expectations of outcome.

Study registration
ISRCTN11898000.
Anti-seizure medication tapering correlates with daytime delta band power reduction in the cortex
Authors: Besné Guillermo M , Evans Nathan , Panagiotopoulou Mariella , Smith Billy , Chowdhury Fahmida A , Diehl Beate , Duncan John S , McEvoy Andrew W , Miserocchi Anna , de Tisi Jane , Walker Matthew C , Taylor Peter N , Thornton Chris , Wang Yujiang 
Published: February 2025

Abstract
Anti-seizure medications are the primary treatment for epilepsy; yet medication tapering effects have not been investigated in a dose, region and time-dependent manner, despite their potential impact on research and clinical practice. We examined over 3000 h of intracranial EEG recordings in 32 subjects during long-term monitoring, of which 22 underwent concurrent anti-seizure medication tapering. We estimated anti-seizure medication plasma levels based on known pharmaco-kinetics of all the major anti-seizure medication types. We found an overall decrease in the power of delta band (δ) activity around the period of maximum medication withdrawal in most (80%) subjects, independent of their epilepsy type or medication combination. The degree of withdrawal correlated positively with the magnitude of δ power decrease. This dose-dependent effect was evident across all recorded cortical regions during daytime; but not in subcortical regions, or during night time. We found no evidence of a differential effect in seizure onset, spiking, or pathological brain regions. The finding of decreased δ band power during anti-seizure medication tapering agrees with previous literature. Our observed dose-dependent effect indicates that monitoring anti-seizure medication levels in cortical regions may be feasible for applications such as medication reminder systems, or closed-loop anti-seizure medication delivery systems. Anti-seizure medications are also used in other neurological and psychiatric conditions, making our findings relevant to a general neuroscience and neurology audience.
Neural substrates of multidimensional psychological characteristics of remembering episodes with autobiographical significance
Authors: Hashimoto Ryu-ichiro , Aoki Ryuta , Ohta Haruhisa , Itahashi Takashi 
Published: February 2025

Abstract
Autobiographic remembering often involves types of constructive processes for psychological experiences and hypothetical scenarios of past events. Previous psychological research revealed a range of phenomenological and functional characteristics associated with recalls of episodes with high autobiographical significance. However, neural bases of such psychological characteristics and their association with memory construction processes remain unclear. In this functional magnetic resonance imaging study, we collected autobiographical episodes from 28 young adults and their extensive metrics of phenomenological and functional characteristics related to autobiographical significance. We then sought to identify neural correlates of the psychological characteristics by measuring brain activity while participants recalled specified episodes as accurately as possible or in counterfactual simulation. Multiple-regression analysis using latent factors of psychological characteristics revealed that a factor representing autobiographical significance was associated with activation in the posterior medial memory system, including the angular cortex, precuneus, and posterior cingulate cortex, during counterfactual simulation. Furthermore, representation similarity analysis using patterns of factor scores revealed significant clusters in the posterior medial system and parts of cerebellar parcels, mainly during counterfactual simulation. These findings indicate that multidimensional psychological characteristics of episodes with autobiographical significance are associated with hypothetical constructive processes in the cortical posterior medial system and cerebellum.
Test–retest reliability of resting-state EEG intrinsic neural timescales
Authors: Tang Xiaoling , Wang Shan , Xu Xinye , Luo Wenbo , Zhang Mingming 
Published: February 2025

Abstract
Intrinsic neural timescales, which reflect the duration of neural information storage within local brain regions and capacity for information integration, are typically measured using autocorrelation windows (ACWs). Extraction of intrinsic neural timescales from resting-state brain activity has been extensively applied in psychiatric disease research. Given the potential of intrinsic neural timescales as a neural marker for psychiatric disorders, investigating their reliability is crucial. This study, using an open-source database, aimed to evaluate the test–retest reliability of ACW-0 and ACW-50 under both eyes-open and eyes-closed conditions across three sessions. The intraclass correlation coefficients (ICCs) were employed to quantify the reliability of the intrinsic neural timescales. Our results showed that intrinsic neural timescales exhibited good reliability (ICC &gt; 0.6) at the whole-brain level across different index types and eye states. Spatially, except for the right temporal region in the eyes-open condition, all other regions showed moderate-to-high ICCs. Over 60% of the electrodes demonstrated moderate-to-high intrinsic neural timescale ICCs under both eyes-open and eyes-closed conditions, with ACW-0 being more stable than ACW-50. Moreover, in the new dataset, the above results were consistently reproduced. The present study comprehensively assessed the reliability of intrinsic neural timescale under various conditions, providing robust evidence for their stability in neuroscience and psychiatry.
Causal relationships between immune cell phenotypes and primary glomerular diseases: genetic evidence from bidirectional Mendelian randomization study
Authors: Tang Wenhao , Li Qiu , Yang Xueying , Yang Haiping 
Published: February 2025

Abstract

Background
Primary glomerular diseases (PGDs), including nephrotic syndrome (NS), membranous nephropathy (MN), and IgA nephropathy (IgAN), are complex renal conditions influenced by immune system dysregulation. Although associations between immune cell phenotypes and PGDs have been observed, the precise causal relationships have not been fully elucidated.

Methods
Utilizing genetic association data from genome-wide association studies (GWASs), we investigated 731 immunophenotypes in relation to PGDs. A bidirectional two-sample Mendelian Randomization (MR) approach, primarily employing inverse variance weighting (IVW), was conducted to establish causality. MR-Egger, weighted median, simple mode, and weighted mode were used as complementary methods to reinforce the robustness and validity of the results. Sensitivity analyses further validated the sensitivity and stability of our results.

Results
We identified 38 immunophenotypes suggestively related to IgAN, with 20 as risk factors and 18 as protective effects. Six immunophenotypes remained significant after Bonferroni correction: The percentage of CD25hi among T cells; the percentage of CD25hi CD45RA- CD4 not Treg among T cells; the percentage of CD25hi CD45RA- CD4 not Treg within CD4 + T cell population; CX3CR1 expression on monocyte; CD40 expression on monocyte; and CD64 expression on CD14 + CD16- monocyte. In the validation analysis of IgAN, CD3 expression on effector memory CD4 + T cells further confirmed the predisposing risk role of effector memory T cells in the development of IgAN. Additionally, the MR analysis demonstrated suggestive associations between 25 immunophenotypes and MN (8 risk factors and 17 protective factors), as well as between 22 immunophenotypes and NS (10 risk factors and 12 protective factors). Lastly, by intersecting the immunophenotypes showing suggestive associations with PGDs, we identified two common immunophenotypes shared by IgAN and MN, three by IgAN and NS, and one by MN and NS.

Conclusions
This genetic-level investigation uncovers causal associations between immunophenotypes and PGDs, providing valuable insights into the immunological underpinnings of PGDs. Our findings suggest potential targets for treatment strategies, thereby facilitating more personalized and effective therapeutic approaches in PGDs management.
Critical thermal limits of the seasonal migrant, Euxoa auxiliaris (Lepidoptera: Noctuidae)
Authors: Kennedy Taylor E , Sing Sharlene E , Peterson Robert K D 
Published: February 2025

Abstract
The larval stage of the army cutworm, Euxoa auxiliaris (Grote), is an agricultural pest in the Great Plains region of North America. Adult migration to alpine aggregation sites to escape extreme summer temperatures and depleted food resources provides a critical food resource for the grizzly bear, Ursus arctos horribilis (Linnaeus, Carnivora: Ursidae), in the Rocky Mountains. However, little is understood about the ecological consequences of the thermal tolerance of adult E. auxiliaris. Therefore, we investigated thermal tolerance of lab-reared and wild-caught individuals by assessing their critical thermal limits (CTLmax and CTLmin). Using a ramping tolerance assay, we began at 25 °C and adjusted the temperature at a rate of 0.3 °C/min until individuals lost control of their righting response. Adult moths had a CTLmax (lab-reared: 44.13 °C, wild-caught moths: 43.28 °C) typical for a temperate lepidopteran species. However, their CTLmin (lab-reared: −2.24 °C, wild-caught: −1.9 °C) reflects an extraordinary ability to remain active and feed when ambient temperatures are low. These findings provide insights into the thermal ecology of E. auxiliaris which are essential for predicting the range distribution of the species, and, consequently, the continued availability of this key food source for Rocky Mountain grizzly bears. As climate change continues to affect ambient temperatures, these results underscore the importance of studying thermal tolerance to anticipate ecological shifts and ensure the conservation of both E. auxiliaris and the grizzly bears that depend on them.
Eclipsed Mitral Regurgitation and the Role of Multimodality Imaging - A Case Report
Authors: Kounas S , Pilatis N , Solomou E , Koukos M , Aroni M 
Published: February 2025

Abstract

Background
Eclipsed mitral regurgitation (MR) is a rare, reversible condition that leads to transient severe MR and acute heart failure in patients with preserved left ventricular (LV) ejection fraction. Its diagnosis is challenging due to its intermittent presentation, necessitating advanced imaging techniques to reveal the underlying pathology.

Case Summary
We present a case of a 74-year-old female with recurrent severe MR associated with a non-obstructive lesion in the proximal left anterior descending (LAD) artery. Multimodality imaging played a pivotal role in diagnosing this condition, as conventional vasodilator stress tests failed to uncover the ischemic mechanism. Exercise stress echocardiography and myocardial perfusion scintigraphy successfully demonstrated a small ischemic region affecting the mitral valve apparatus, which triggered severe MR during physical exertion. This dynamic ischemia, undetected by routine tests, was essential in diagnosing the pathophysiology behind the patient’s recurrent MR. Following percutaneous coronary intervention (PCI) to the LAD, her symptoms resolved, confirming the ischemic origin of the MR.

Conclusion
This case underscores the critical role of multimodality imaging in revealing the pathophysiology of recurrent MR. Advanced imaging techniques, particularly under physiologic stress, are crucial for diagnosing dynamic ischemia and its impact on valvular function. By identifying the ischemic cause of MR, individualized treatment strategies, such as PCI, can be implemented, avoiding unnecessary valve surgery and improving patient outcomes.
Rapidly Progressive Mitral Valve Disease from Nonbacterial Thrombotic Endocarditis to Mitral Stenosis in Systemic Lupus Erythematosus: A Case Report
Authors: Ichikawa-Ogura Saaya , Mochizuki Yasuhide , Toyosaki Eiji , Fukuoka Hiroto , Shinke Toshiro 
Published: February 2025

Abstract

Background
Libman-Sacks endocarditis (LSE), a nonbacterial thrombotic endocarditis (NBTE) linked to systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), typically causes valve regurgitation and embolism but can rarely mimic rheumatic mitral stenosis (MS).

Case summary
This case involves a 59-year-old woman with a history of APS and SLE who presented with worsening dyspnoea and congestive heart failure. Initially, severe mitral regurgitation (MR) due to NBTE resolved with vitamin K antagonist therapy, yet she subsequently developed significant MS with commissural fusion, a rheumatic-like feature. Despite stable SLE activity, echocardiography revealed severe MS with high pulmonary pressures, warranting surgical valve replacement. Intraoperative findings confirmed rheumatic-like degeneration, but the patient experienced a fatal cerebral infarction post-surgery, likely due to APS.

Discussion
This case highlights the progression of NBTE-related MR to rheumatic-like MS in an SLE patient with APS, an unusual clinical course. It underscores the importance of echocardiographic monitoring in similar cases, as chronic inflammatory changes in APS might mimic rheumatic pathology, necessitating vigilant management and timely intervention.
A case report of Long COVID and Chronic active myocarditis
Authors: Elia S , De Vecchi S , D’Amario D , Patti G 
Published: February 2025

Abstract

Background
Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as “Long COVID”, are progressively emerging in the population. While it was clear from the pandemic outbreak that pre-existing cardiac conditions were exacerbated by the infection even after its resolution, little is known about the rare cases of de novo heart failure onset, whose mechanisms are still not fully understood.

Case Summary
A 74-year-old man was admitted to the emergency department with SARS-Cov-2 bilateral interstitial pneumonia at the CT scan. A few months after he developed acute myocarditis that slowly led to progressive myocardial fibrosis, systolic dysfunction, and a pro-arrhythmic state. Furthermore, these manifestations were associated with growing “mental dullness” and chronic psychophysical asthenia. The patient underwent two CMR over three years witnessing the worsening of cardiac involvement and started full pharmacological therapy for heart failure. We report here the initial presentation, medical care, and clinical course of this patient.

Discussion
In SARS-Cov-2 patients, Long COVID-related myocarditis is one of the more severe complications.
A thorough multimodal evaluation of these patients should be conducted, as presentation symptoms can appear subtle or misleading. Early identification of a chronic process of myocardial damage is crucial to implement early therapeutic strategies and prevent the potential worsening of heart failure.
Trial-level Surrogacy of non-High-Density and Low-Density Lipoprotein Cholesterol Reduction on the Clinical Efficacy of Statins
Authors: Liaigre Léa , Guigui Alicia , Manceau Marc , Cracowski Jean-Luc , Khouri Charles , Roustit Matthieu 
Published: February 2025

Abstract

Aims
Low-density lipoprotein cholesterol (LDL-c) and non-high-density lipoprotein cholesterol (non-HDL-c) are prognostic factors of cardiovascular risk. However, their validity as trial-level surrogates for cardiovascular outcomes is debated. This study aimed to determine whether LDL-c and non-HDL-c are reliable surrogates for cardiovascular events in statin trials, and to explore discrepancies in previous studies.

Methods and results
We conducted an umbrella review of meta-analyses of randomized controlled trials (RCTs) assessing statin efficacy versus placebo or usual care on all-cause mortality and cardiovascular events. We search studies published between 1987 and August 2023 from PubMed, Embase, and the Cochrane Library. Baseline lipid levels, absolute rate differences (ARD), and hazard ratios or risk ratios (RR) for major cardiovascular events and all-cause or cardiovascular mortality were analysed. Weighted linear regressions between log RR or ARD, and absolute difference in non-HDL-c or LDL-c were performed. The coefficients of determination (R2trial) were calculated, with their 95%CI computed through bootstrapping. The surrogate threshold effect (STE) was also estimated. Twenty RCTs and 194,686 participants were included, with a median follow-up of 4.85 years. Statin treatment showed significant efficacy in improving all clinical outcomes. However, the association between treatment effects on LDL-c or non-HDL-c reduction and clinical outcomes was weak. The R²trial were ranging from 0 to 0.1 for LDL-c, and from 0 to 0.04 for non-HDL-c. The STE for MACE was 0.76 (0.36-1.69) mmol/L for LDL-c, and 0.87 (0.49-2.19) mmol/L for non-HDL-c.

Conclusion
Neither LDL-c nor non-HDL-c demonstrated trial-level surrogacy for predicting treatment effects on mortality and cardiovascular events in statin trials. Although they are relevant biomarkers for the follow-up of patients treated with statins, their reduction does not reliably predict a similar reduction in cardiovascular risk. As such, they should not be used as pivotal evidence in drug trials.