bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling Multiple CD8+ T-cell Functional Dimensions Enhances Breast Cancer Immune Assessment
Authors: Liang Zhuozhi , Li Shunrong , Pan Zhilong , Duan Yuanqiang , Ouyang Qian , Zhu Liling , Song Erwei , Chen Kai 
Published: December 2024

Abstract
CD8+ T-cell abundance is insufficient to assess antitumor immunity and shows poor performance in predicting breast cancer prognosis and immunotherapy response, presumably owing to the complexity of CD8+ T-cell functionalities. Although single-cell RNA sequencing can dissect the multifaceted functions of CD8+ T cells for better immune assessment, its clinical application is limited. In this study, we developed bulk RNA sequencing–based FuncDimen models from integrative analysis of single-cell RNA sequencing and matched bulk RNA sequencing data to evaluate CD8+ T-cell functionalities across five dimensions: tumor reactivity, cytotoxicity, IFNγ secretion, proliferation, and apoptosis. The FuncDimen models quantifying different functional dimensions of CD8+ T cells were validated in our breast cancer cohort and external databases using immunofluorescence and imaging mass cytometry. We calculated the FuncAggre score by weighted aggregation of all five FuncDimen models to encapsulate the overall antitumor immunity. In our breast cancer cohort and external databases, the FuncAggre score demonstrated superior predictive performance for breast cancer prognosis (time-dependent AUC: 0.56–0.70) and immunotherapy response (AUC: 0.71–0.83) over other immune biomarkers, regardless of the breast cancer molecular subtype. Together, the FuncDimen models offer a refined assessment of antitumor immunity mediated by CD8+ T cells in the clinic, enhancing prognostic prediction and aiding personalized immunotherapy in breast cancer.
Deuce: Dual-diversity Enhancement and Uncertainty-awareness for Cold-start Active Learning
Authors: Guo Jiaxin , Philip Chen C. L. , Li Shuzhen , Zhang Tong 
Published: December 2024

Abstract
Cold-start active learning (CSAL) selects valuable instances from an unlabeled dataset for manual annotation. It provides high-quality data at a low annotation cost for label-scarce text classification. However, existing CSAL methods overlook weak classes and hard representative examples, resulting in biased learning. To address these issues, this paper proposes a novel dual-diversity enhancing and uncertainty-aware (Deuce) framework for CSAL. Specifically, Deuce leverages a pretrained language model (PLM) to efficiently extract textual representations, class predictions, and predictive uncertainty. Then, it constructs a Dual-Neighbor Graph (DNG) to combine information on both textual diversity and class diversity, ensuring a balanced data distribution. It further propagates uncertainty information via density-based clustering to select hard representative instances. Deuce performs well in selecting class-balanced and hard representative data by dual-diversity and informativeness. Experiments on six NLP datasets demonstrate the superiority and efficiency of Deuce.
Comparisons of Montane Snow Water Equivalent Projections: Calculating Total Snow Mass in Regions with Projection Agreement and Divergence in the Western United States
Authors: Pflug Justin M. , Kumar Sujay V. , Livneh Ben , Gutmann Ethan D. , Gangrade Sudershan , Kao Shih-Chieh 
Published: December 2024

Abstract
Montane snowpack is a vital source of water in the western United States. Here, we use a large-ensemble approach to evaluate the agreement across 124 snow water equivalent (SWE) projections with statistically downscaled forcing between end-of-century (2076–95) and early twenty-first century (2106–35) periods. Comparisons were performed on dates corresponding with the end of winter (15 April) and midspring snowmelt (15 May) in five western U.S. domains. Using 1) the percent change to end-of-century SWE across different ensembles of snow projections and 2) the shift between early twenty-first century and end-of-century SWE distributions for each snow projection, we identified relationships between projections that were consistent across each domain. In low to midelevations, end-of-century SWE decreases were 48% and larger on 15 April. These regions had projected changes to SWE that were both high confidence and in relative agreement across projections. Despite this, the majority of 15 April SWE volume existed in higher elevations where the magnitude and direction (positive or negative) of SWE changes were most uncertain. The results of this study show that large-ensemble approaches can be used to measure coherence between snow projections and identify 1) the highest confidence changes to future snow water resources and 2) the locations and periods where and when improvements to snow projections would most benefit estimates of future snow water resources.

Significance Statement
A majority of spring and summer runoff in the western United States originates from mountain snowpack. Yet, future projections of snow in these regions are uncertain. We identify where snow projections agree and the proportion of snow that falls within regions where end-of-century projections of snow disagree as a result of disparate snow modeling approaches. Results show that a majority of the area of the Rocky Mountain and Cascade Mountain ranges have projected changes to snow that agree in relative magnitude, but most of the annual snow water supply exists in higher elevations where projections of snow diverge. These results highlight where further research may most improve our understanding of future snow water supplies and the associated downstream water resources.
KLF6 silencing attenuates MCAO-induced brain injury and cognitive dysfunction via targeting ferroptosis and activating the Nrf2/HO-1 pathway
Authors: Qian Hongyu , Zhou Sufang , Qian Rong , Li Qingye , Zhang Jian , Ding Yanbing , Wang Chuanxiang 
Published: December 2024

Introduction The incidence of cerebral ischemia-reperfusion injury (I/R) is complex which seriously threatens the life safety of patients. Neither its prevention nor its treatment has been successful so far. Proteins that bind to DNA and belong to the C2/H2 zinc finger family are known as Krüppel-like factors (KLFs). Among them, KLF6 plays a vital role in proliferation, metabolism, inflammation, and damage responses, although its function in I/R remains largely unexplored. Methods In this study, we induced cerebral ischemia in rats using the middle cerebral artery occlusion (MCAO) model. Neural function, cerebral infarction volume, cognitive function, cortical pathological lesions, ferroptosis, and oxidative stress were measured. Results Our findings indicated that the MCAO model exhibited signs of ferroptosis and a concurrent increase in KLF6 levels. Inhibition of KLF6 resulted in a significant decrease in the escape latency during swimming tests ( p < .05), an increase in the frequency of platform crossings, and prolonged duration in the target quadrant compared to the control group. Additionally, silencing KLF6 mitigated MCAO-induced brain injury and reduced oxidative stress and ferroptosis, as evidenced by altered levels of Nrf2/HO-1 signaling proteins. Discussion In conclusion, our results suggest that silencing KLF6 may protect against MCAO-induced pyroptosis, oxidative stress, and neurological dysfunction by inactivating the Nrf2/HO-1 signaling pathway. This study offers new perspectives on the molecular mechanisms related to MCAO and emphasizes the significance of targeting KLF6 for future therapeutic approaches.
Low Levels of High-Density Lipoprotein are Associated With Poor Prognosis in Patients With Early Triple-Negative Breast Cancer
Authors: Liu YongCheng , Wu Di , Wang HuiJuan , Zheng HeMing 
Published: December 2024

Background Although dyslipidemia has been shown to be associated with breast cancer prognosis, the prognostic value of high-density lipoprotein (HDL) in triple-negative breast cancer (TNBC) remains uncertain. The purpose of this study was to evaluate the relationship between preoperative HDL levels and prognosis in TNBC patients. Methods Preoperative HDL levels and clinical data from 287 patients who underwent TNBC surgery were retrospectively collected. Overall survival (OS) and disease-free survival (DFS) were analyzed via the Kaplan-Meier method and the Cox proportional hazards regression model. Results Via the combination of receiver operating characteristics and Kaplan-Meier analysis, we found that low HDL levels were a prognostic factor for TNBC. Patients with lower HDL levels had a significantly lower T1 ratio than patients with higher HDL levels and exhibited a significantly higher neoadjuvant chemotherapy ratio than patients with higher HDL levels. In univariate analysis, the DFS and OS of patients with low HDL levels were worse than those of patients with high HDL levels in terms of DFS (HR: 0.452; 95% CI: 0.237-0.862; P = 0.016) and OS (HR: 0.438; 95% CI: 0.199-0.968; P = 0.041). However, in the multivariate analysis, there was no difference observed between patients with low HDL levels and those with high HDL levels in terms of DFS or OS. According to the subgroup analysis, lymph node-negative (N-) patients with low levels of HDL had worse DFS and OS than did patients with high HDL levels. However, in lymph node-positive (N+) patients, there was no difference observed in prognosis between the high- and low-HDL groups. Discussion Low HDL levels are correlated with the progression of TNBC. Moreover, low HDL levels (particularly in patients who are N-) have been identified as a significant prognostic factor impacting the prognosis of TNBC patients; however, these levels do not represent an independent prognostic factor.
DNA Methylation Pattern and mRNA Expression Level of E-Cadherin and P16 Genes in Thrombotic Disorders
Authors: Abak Niloofar , Azad Mehdi , Ali Fatemeh Mohammad , Saberian Mostafa , Turkaman Saeed , Alizadeh Shaban 
Published: December 2024

Objective DNA methylation, as an epigenetic alteration, plays an essential role in the development of atherosclerosis and venous thrombosis. E-cadherin, a tumor suppressor gene and adhesion molecule, has a crucial function in platelet aggregation and hemostasis. P16, a cell cycle regulator, is involved in venous thrombosis. The aim of this study is to evaluate the DNA methylation patterns and expression levels of the E-cadherin and P16 genes in venous thromboembolism (VTE). Method Peripheral blood samples were collected from 32 patients, including those with deep vein thrombosis (DVT, n = 15), pulmonary embolism (PE, n = 8), DVT with PE (n = 4), intestinal thrombosis (IT, n = 3), and cerebral venous sinus thrombosis (CVST, n = 2), as well as from 10 healthy individuals. The DNA methylation patterns and gene expression levels of E-cadherin and P16 were analyzed using methylation-specific PCR (MSP) and Real-Time PCR, respectively. Results The promoter of the CDH1 gene was partially methylated in 84.4% of thrombotic patients and unmethylated in 15.6% ( P = 0.183). A significantly higher expression level of CDH1 was observed in the patients compared to the controls ( P = 0.001). The P16 gene promoter were unmethylated in all control and patient specimens. Compared to normal subjects, the expression level of the P16 was significantly increased in patients ( P = 0.000). Conclusion Our results indicated that DNA methylation is not the main gene expression regulatory mechanism for E-cadherin and P16 genes in thrombosis. Higher transcription levels of CDH1 and P16 in thrombotic patients may show their crucial roles in the pathogenesis of VTE.
Prevalence of feline hyperthyroidism in a laboratory-based sample of 27,888 cats in Spain
Authors: Pérez Domínguez Andrea , Santiago Tostado Raquel , Feo Bernabe Luis , Priego Corredor Anabel , Puig Prat Jordi 
Published: December 2024

Objectives The objective of the study was to investigate the prevalence of hyperthyroidism in Spain, including its geographical distribution and prevalence across different age groups. Methods A cross-sectional study was conducted. Samples submitted to a reference laboratory to evaluate serum total thyroxine concentration (TT4) during a 3-year period were evaluated (n = 27,888). A cat was considered hyperthyroid if the TT4 concentration was greater than 60.4 nmol/l (4.7 μg/dl). Hyperthyroid cats were classified based on their TT4 concentration at diagnosis as mildly (TT4 60.4–124.8 nmol/l [4.7–9.7 μg/dl]), moderately (TT4 124.8–249.68 nmol/l [9.7–19.4 μg/dl]) or severely (TT4 >249.6 nmol/l [>19.4 μg/dl]) hyperthyroid. The samples were also grouped by life stage, into young adults (1–6 years old), mature adults (7–10 years old) and seniors (>10 years old). The study included samples from 17 regions of Spain and geographical mapping was based on seven domains. Results One thousand seven hundred and twenty-two out of 27,888 cats (6.2%, 95% confidence interval [CI] = 5.9–6.5) were classified as hyperthyroid. Within the hyperthyroid group, ages ranged from 2 to 25 years old, with a median of 14 years. Within the hyperthyroid population, 14/368 (3.8%), 27/368 (7.3%) and 327/368 (88.8%) were young adults, mature adults and seniors, respectively. The prevalence of hyperthyroidism in this laboratory-based sample in Spain was 2.7 (95% CI = 0.4–5.7) to 6.9% (95% CI = 6.4–7.4), depending on the geographical region. During the study period, 8.2% of cases that were initially non-hyperthyroid were later diagnosed with hyperthyroidism. Conclusions and relevance Prevalence of hyperthyroidism in Spain is 6.2% (95% CI = 5.9–6.5) overall and 7.9% (95% CI = 7.2–8.8) in cats older than 10 years. The distribution of the disease is heterogeneous between different geographical regions. Further large-scale prospective studies are required to determine the risk factors in each region and understand the reasons for this variation.
Procedure-Related Mortality in Aspiration Thrombectomy for Pulmonary Embolism: A MAUDE Database Analysis of the Inari FlowTriever and Penumbra Indigo Systems
Authors: Warren Blair E. , Tan Kong Teng , Jaberi Arash , Donahoe Laura , de Perrot Marc , McInnis Micheal C. , Granton John T. , Mafeld Sebastian 
Published: December 2024

Background: Pulmonary embolism (PE) is an important cause of death and disability. Advances in catheter-directed therapies have led to the use of devices, such as the Inari FlowTriever and Penumbra Indigo system for aspiration thrombectomy (AT) for both massive and sub-massive PE. However, limited data exist on causes of procedural mortality. Methods: Analysis of the Food and Drug Administration’s (FDA) Manufacture and User Facility Device Experience (MAUDE) database was performed. Data for the Inari FlowTriever and Penumbra Indigo aspiration thrombectomy systems were evaluated for mortality events and classified by cause of death from January 1, 2015, to December 31, 2023. Results: The review identified 26 mortality events related to the Inari FlowTriever and 28 related to the Penumbra Indigo device. Pulmonary vascular perforation (n=26) and right heart injury/tamponade (n=9) were the most common source of mortality. Clot migration (n=4) and acute right heart failure (n=5) were less frequently observed. Conclusions: This study reveals more mortality events than have been captured in the literature to date. Vascular perforation and cardiac injury are the most common and also potentially preventable sources of mortality. Strategies to mitigate complications related to aspiration thrombectomy are described. Clinical Impact Analysis of mortality in aspiration thrombectomy (AT) for acute pulmonary embolism is necessary to better understand the safety profile of this procedure. This analysis of the MAUDE database reports the largest single cohort of 54 deaths. Potentially preventable procedure-related mortality in AT has been documented to be the result of vascular perforation and cardiac perforation with tamponade. Preparation for emergent pericardiocentesis should be considered in mechanical thrombectomy. Clot migration may result from thrombus maceration or migration of clot in transit, thus, careful pre-procedure examination for clot in transit with echocardiography is suggested.
Fair access challenges in maternal-fetal surgery trials
Authors: Cavolo Alice , Pizzolato Daniel , Gastmans Chris , Crombag Neeltje 
Published: December 2024

Maternal fetal surgery (MFS) trials have the potential to substantially increase the survival and quality of life of fetuses with life-threatening conditions, but they also entail relevant and yet overlooked fair access challenges. In this topic piece, we will present the fair access concerns in MFS trials/practice and their ethical ramifications as well as some possible ways to address them. The most obvious challenge is cost. Although the cost of the surgery itself is generally covered, costs are high for participants, including commute or housing near the hospital. This might hinder participations of parents from lower economic status. Strict eligibility criteria aimed at protecting participants further limit accessibility. These issues further affect the scientific validity of the trial. For example, the above-mentioned issues contribute to difficulties in recruitment which already lead to MFS trials delays and cancellations. They also contributed to homogeneous samples that are difficult to generalize. Hence, it is important that researcher first acknowledge the existence of fair access issues beyond those related to the cost of the surgery itself and that these issues affect participants’ right to fair access to the trial benefits as well as the scientific validity of the trial. Second, it is important that researchers actively try to foresee and reduce these issues.
Mediation role of body mass index in the relationship between food-specific serum immunoglobulin G reactivity and colorectal adenomas in a Chinese population: a cross-sectional study
Authors: Sun Guanchao , Ma Xiaona , Xu Shiping , Su Binbin , Chen Qianqian , Dong Xiaoyu , Wang Lihui , Wan Jun , Shi Hui 
Published: December 2024

Background: Colorectal adenomas (CAs) represent a significant global health issue, particularly in China, where lifestyle modifications have contributed to their increased prevalence. These adenomas are precursors to colorectal cancer. While high-fiber diets have been shown to decrease risk, the implications of food-specific serum immunoglobulin G reactivity (FSsIgGR) on CAs remain uncertain and warrant further investigation. Objectives: To investigate the association between FSsIgGR and the occurrence of CAs in the Chinese population, assess the mediating influence of body mass index (BMI), and offer insights into potential prevention strategies. Design: A retrospective cross-sectional study. Methods: This study is based on 8796 individuals who underwent colonoscopy at the Second Medical Center of Chinese PLA General Hospital from 2017 to 2021. We examined the relationship between FSsIgGR and CAs using logistic regression, controlling for various confounders. Interaction effects were explored through subgroup analysis. We addressed missing data using multiple imputation and confirmed the robustness of our findings through sensitivity analysis. The role of BMI as a mediator was quantified using structural equation modeling. Results: The cohort comprised 2703 patients diagnosed with CAs and 6093 polyp-free controls, with an average age of 50.1 years, of whom 70.1% were male. The analysis revealed a significant inverse association between FSsIgGR and the incidence of CAs (adjusted odds ratio = 0.97; 95% confidence interval: 0.95–0.99; p < 0.001). Dose–response analysis indicated a linear reduction in CAs risk correlating with an increased number of IgG-positive food items. Structural equation modeling showed that BMI mediated 6.02% of the effect on CAs risk ( p = 0.038). Conclusion: Our findings suggest that FSsIgGR correlates with a reduced risk of developing CAs, with BMI partially mediating this effect. These results add a novel dimension to CAs risk assessment and prevention, highlighting potential dietary interventions.
Intrinsic brain activity differences in drug-resistant epilepsy and well-controlled epilepsy patients: an EEG microstate analysis
Authors: Zhu Chaofeng , Zhang Jinying , Fang Shenzhi , Zhang Yuying , Li Juan , Wu Luyan , Huang Huapin , Lin Wanhui 
Published: December 2024

Background: Drug-resistant epilepsy (DRE) patients exhibit aberrant large-scale brain networks. Objective: The purpose of investigation is to explore the differences in resting-state electroencephalogram (EEG) microstates between patients with DRE and well-controlled (W-C) epilepsy. Design: Retrospective study. Methods: Clinical data of epilepsy patients treated at the Epilepsy Center of Fujian Medical University Union Hospital from January 2020 to May 2023 were collected for a minimum follow-up period of 2 years. Participants meeting inclusion and exclusion criteria were categorized into two groups based on follow-up records: W-C group and DRE group. To ensure that the recorded EEG data were not influenced by medication, all EEG recordings were collected before patients commenced any antiepileptic drug treatment. Resting-state EEG datasets of all participants underwent microstate analysis. This study comprehensively compared the average duration, frequency per second, coverage, and transition probabilities (TPs) of each microstate between the two groups. Results: A total of 289 individuals who met the criteria were included, categorized into the W-C group ( n = 112) and the DRE group ( n = 177). EEG microstate analysis revealed substantial variances between the two groups. The analysis highlights differences in three of four microstate classifications. Microstate transition analysis demonstrated altered probabilities in DRE patients. Increased probabilities were observed in TPAB, TPBA, TPBC, TPCB, TPBD, and TPDB. Decreased probabilities included TPCA, TPDA, TPAC, TPAD, TPCD, and TPDC. Conclusion: This study highlights distinctive EEG microstate parameters and TPs in DRE patients compared to those with W-C epilepsy. The results may potentially advance the clinical application of EEG microstates.