bluuebunny/crossref_metadata_2025 huggingface dataset:
The independent predictive value of admission serum ferritin concentration for prognosis in elderly patients with community-acquired pneumonia in the emergency department
Authors: Zhang Xiangqun , Shang Na , Zhang Da , Wu Junyuan , Guo Shubin
Published: January 2025

Background

Community-acquired pneumonia (CAP) poses a significant health threat to the elderly population, leading to high morbidity and mortality rates. Serum ferritin, a critical indicator of iron metabolism, plays a pivotal role in inflammation and immune regulation. Nevertheless, its specific prognostic relevance in elderly patients with CAP remains unclear. This study aimed to evaluate the predictive capacity of serum ferritin in determining the prognosis of elderly patients with CAP and to investigate its effectiveness when combined with the sequential organ failure assessment (SOFA) or CURB-65 (confusion, uremia, respiratory rate, blood pressure, aged ≥65 years) scores.

Methods

This retrospective cohort study included 451 elderly patients (aged ≥65 years) diagnosed with CAP according to established criteria. Serum ferritin concentrations were measured upon admission and various prognostic indicators such as 28-day mortality, mechanical ventilation requirement, and vasopressor administration were analyzed in conjunction with white blood count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lactate (Lac), SOFA scores, and CURB-65 scores. The independent predictive value of ferritin was assessed through receiver operating characteristic (ROC) curve analysis and multivariate logistic regression.

Results

Among the 451 patients, 99 (22%) died within 28 days. The area under the curve (AUC) of serum ferritin for predicting 28-day mortality was 0.75 (95%CI: 0.695-0.805). Ferritin outperformed WBC, CRP, and PCT in predictive performance, and its performance was comparable to Lac. When combined with SOFA or CURB-65 scores, the AUC of ferritin for predicting 28-day mortality increased to 0.84 and 0.847, respectively (P<0.001). Moreover, the AUC of ferritin for predicting vasopressor administration was 0.707, which increased to 0.864 and 0.822 when combined with SOFA or CURB-65 scores, respectively (P<0.001). Ferritin could predict mechanical ventilation requirement with an AUC of 0.618, but it was not an independent risk factor, and its predictive ability was not significantly different from other indicators.

Conclusion

Admission serum ferritin is an independent predictor for the prognosis of elderly patients with CAP, and it exhibits a strong ability to predict the 28-day mortality and vasopressor administration. The combination of ferritin with SOFA and CURB-65 scores significantly improves the prognostic predictive potency.
Correlation between weight-adjusted waist index and coronary heart disease: NHANES 1999–2020
Authors: Liu Yan , Sun Shougang , Zou Qi , Tao Ting , Li Dian , Han Guodong , Wei Zhiliang
Published: January 2025

Background

The weight adjusted waist index (WWI) represents a novel indicator for assessing central obesity. The objective of this study is to investigate the association between WWI and coronary heart disease (CHD).

Method

The data of 44,528 participants in total were gathered from NHANES database from 1999 to 2020. WWI is calculated as the waist circumference (WC, cm) divided by the square root of the body weight (kg), and CHD was determined based on participants’ self-reports. The association between WWI and CHD was examined using multiple logistic regression analysis, restrictive cubic spline (RCS), receiver operating characteristic (ROC) curve, mediation analysis, subgroup and interaction analyses.

Result

This was a cross-sectional investigation. A total of 44,528 participants were included [50.23% male; mean WWI 10.89 (0.01) cm/√kg]. The multivariate logistic regression analysis revealed that in three models, one-standard-deviation increment in WWI was associated with an increased probability of CHD occurrence by 2.39 (2.22,2.57),1.47 (1.32,1.65), and 1.15 (1.00,1.32) times, respectively. Additionally, RCS analysis indicated a linear relationship between WWI and CHD. and the ROC analysis results showed that the discriminatory power of WWI for CHD was superior to that of body mass index (BMI) and WC. Glycated hemoglobin (HbA1c) partially mediated the relationship between WWI and CHD. Subgroup and interaction analyses confirmed that age, systolic blood pressure, and diabetes status had a significant impact on the association between WWI and CHD (P for interaction <0.05).

Conclusion

The level of WWI has been demonstrated to be associated with an increased risk of CHD. Specifically, as WWI increases, the risk of CHD becomes higher. On this basis, it is hypothesized that WWI may potentially serve as an independent risk factor for CAD, thereby highlighting the substantial value of WWI in the identification and management of CHD.
Prevalence of abnormal thyroid hormone levels in acute new-onset atrial fibrillation
Authors: Hytting Jakob , Celik Serkan , Bodeström Eriksson Linus , Mallios Panagiotis , Digerfeldt Christofer , Waldemar Annette , Wijkman Magnus , Singull Martin , Hubbert Laila
Published: January 2025

Introduction

Known risk factors for new-onset atrial fibrillation/flutter (NOAF) include thyrotoxicosis and subclinical hypothyroidism. While prior research has predominantly explored the link between thyrotoxicosis and NOAF, the presence of subclinical hypothyroidism among patients presenting with acute NOAF in the emergency department (ED) remains an underexplored area of inquiry. This study aimed to assess the prevalence of undiagnosed thyrotoxicosis and subclinical hypothyroidism in patients with acute NOAF diagnosed in the ED.

Methods

This registry-based cohort study was conducted in the ED at Vrinnevi Hospital in Sweden during the years 2018, 2020, and 2022, with a 1-year follow-up period. Patients ≥18 years diagnosed with NOAF in the ED, with no ongoing thyroid hormone substitution or previous documented thyroid abnormality within the past 2 years, were included. The primary outcome was the diagnosis of thyrotoxicosis or subclinical hypothyroidism either in the ED or during a 1-year follow-up period.

Results

486 patients with NOAF were included in the study (43.6% females). 329 (67.7%) underwent thyroid function testing in the ED or by the end of the 1-year follow-up. In total, 16 (4.9%) patients presented with subclinical hypothyroidism while 4 (1.2%) patients presented with clinical or subclinical thyrotoxicosis.

Discussion

This study found that subclinical hypothyroidism was more prevalent (4.9%) than thyrotoxicosis (1.2%) among patients presenting with acute NOAF. These findings contrast with previous research that has predominantly linked thyrotoxicosis with acute NOAF, suggesting the need for further studies including both subclinical hypothyroidism and thyrotoxicosis in patients with NOAF.
U-shaped association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and mortality risk in obese adults: evidence from NHANES 1999–2018
Authors: Lin Zi , Yi Tao , Hu Feng , Chen Jinhua , Chen Lianglong
Published: January 2025

Background

Obesity, often accompanied by dyslipidemia and increased cardiovascular risk, poses a significant threat to overall mortality. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has been identified as a valuable parameter for assessing dyslipidemia. The goal of the study was to elucidate the relationship between NHHR and mortality in obese populations.

Methods

Data for the study cohort were sourced from the National Health and Nutrition Examination Survey (1999–2018). The association between NHHR and mortality from all causes and cardiovascular disease was examined through multivariable Cox regression and restricted cubic splines (RCS). Segmented multivariable Cox regression and subgroup analyses were conducted when segmented effects were identified. The reliability of the results was confirmed through multiple sensitivity analyses.

Results

A total of 7,504 participants were included in the analysis. During a median follow-up of 119 months, 866 subjects died for all causes, of which 318 were related to cardiovascular diseases. A U-shaped association was found utilizing RCS analysis, with cardiovascular mortality and all-cause mortality exhibiting the lowest risk points at 3.409 and 3.369, respectively. The fully adjusted model revealed a negative relationship between the risk of cardiovascular mortality (HR = 0.68, 95% CI: 0.49–0.94) and all-cause mortality (HR = 0.82, 95% CI: 0.67–1.00) for per 1 mmol/L increase in NHHR levels below the cut-off value. On the other hand, above the cut-off point, NHHR was positively correlated with cardiovascular mortality (HR = 1.18, 95% CI: 1.02–1.36) and all-cause mortality (HR = 1.13, 95% CI: 1.01–1.28). The sensitivity results of this study were in accordance with earlier findings, and no significant interactions in NHHR levels were discovered across different subgroups.

Conclusions

In the obese adults, NHHR displayed a U-shaped relationship with cardiovascular and all-cause death. Monitoring and managing NHHR levels in obese population may help mitigate the risk of mortality.
A novel machine learning based framework for developing composite digital biomarkers of disease progression
Authors: Zhai Song , Liaw Andy , Shen Judong , Xu Yuting , Svetnik Vladimir , FitzGerald James J. , Antoniades Chrystalina A. , Holder Dan , Dockendorf Marissa F. , Ren Jie , Baumgartner Richard
Published: January 2025

Background

Current methods of measuring disease progression of neurodegenerative disorders, including Parkinson's disease (PD), largely rely on composite clinical rating scales, which are prone to subjective biases and lack the sensitivity to detect progression signals in a timely manner. Digital health technology (DHT)-derived measures offer potential solutions to provide objective, precise, and sensitive measures that address these limitations. However, the complexity of DHT datasets and the potential to derive numerous digital features that were not previously possible to measure pose challenges, including in selection of the most important digital features and construction of composite digital biomarkers.

Methods

We present a comprehensive machine learning based framework to construct composite digital biomarkers for progression tracking. This framework consists of a marginal (univariate) digital feature screening, a univariate association test, digital feature selection, and subsequent construction of composite (multivariate) digital disease progression biomarkers using Penalized Generalized Estimating Equations (PGEE). As an illustrative example, we applied this framework to data collected from a PD longitudinal observational study. The data consisted of Opal™ sensor-based movement measurements and MDS-UPDRS Part III scores collected at 3-month intervals for 2 years in 30 PD and 10 healthy control participants.

Results

In our illustrative example, 77 out of 235 digital features from the study passed univariate feature screening, with 11 features selected by PGEE to include in construction of the composite digital measure. Compared to MDS-UPDRS Part III, the composite digital measure exhibited a smoother and more significant increasing trend over time in PD groups with less variability, indicating improved ability for tracking disease progression. This composite digital measure also demonstrated the ability to classify between de novo PD and healthy control groups.

Conclusion

Measures from DHTs show promise in tracking neurodegenerative disease progression with increased sensitivity and reduced variability as compared to traditional clinical scores. Herein, we present a novel framework and methodology to construct composite digital measure of disease progression from high-dimensional DHT datasets, which may have utility in accelerating the development and application of composite digital biomarkers in drug development.
Equity across the educational spectrum: innovations in educational access crosswise all levels
Authors: Naim Arshi
Published: January 2025

Introduction

Educational equity remains a critical issue in the U.S., where disparities in access and outcomes exist across socioeconomic, racial, gender, and geographical areas. These inequities influence student success at all levels, from general education to higher education. The study aims to explore these disparities, identify their root causes, and examine their effects on educational opportunities and student outcomes. Current study addresses the gaps in resources, tuition affordability, and support mechanisms, this research highlights the urgent need for innovative solutions to bridge inequities. The study’s focus the importance of creating an inclusive and accessible educational framework that can benefit all learners.

Research methods

This study utilizes a quantitative approach to investigate educational inequities across various levels of education in the U.S. Data sources include national education databases, university records, standardized test scores, and financial aid statistics, providing a comprehensive view of the disparities. Regression analysis is employed to identify key indicators and assess the relationships between these factors and educational outcomes. By analyzing data across diverse contexts and demographics, the methodology ensures a clear understanding of the patterns and dynamics of inequality. This approach provides a data-driven groundwork for identifying effective strategies to enhance equity in education.

Results

The findings reveal significant disparities in educational access and outcomes, with socioeconomic status, race, gender, and geography emerging as prominent factors. General education is marked by unequal resource distribution, while higher education faces challenges with high tuition costs and limited financial aid for marginalized groups. The analysis highlights how these inequities hinder student achievement and perpetuate systemic barriers. However, the study also identifies successful interventions, such as targeted scholarships, inclusive teaching practices, and comprehensive support systems. These initiatives demonstrate tangible progress in mitigating disparities and creating pathways for a more equitable educational experience across the spectrum.

Discussion

The study emphasizes the implications of the findings from quantitative results, linking observed disparities to systemic issues in policy and practice. It suggests the need for scalable solutions, such as equitable funding models, affordable tuition policies, and inclusive curricula, to address persistent inequities. This research highlights the success of targeted interventions, the study advocates for expanding programs like scholarships and support services to under-served communities. While progress has been made, significant work remains to ensure equity across all educational levels in U.S. The study concludes with recommendations for policymakers and educators to adopt evidence-based strategies that promote access and inclusion, fostering a fairer educational system for all.
From past to present: tracing the trends of diabetes drug trials in mainland China
Authors: Ma Zengqing , Zhao Xin , Lin Yu , Zhang Hong , Wu Lianping , Tao Yang , Shi Hongjun , Li Susu
Published: January 2025

Background

This study aimed to analyze the changing trend of diabetes drugs clinical trials in China during 2013-2023, and provided a reference for the research and development of diabetes drugs.

Methods

Diabetes drug clinical trial data were obtained from the registration and information disclosure platform of the National Medical Products Administration (NMPA) between January 1, 2013, and December 31, 2023. Trends of clinical trials on diabetes drugs were systematically analyzed in terms of characteristics, trial design, time trends, drug type, and indications.

Results

From 2013 to 2023, a total of 1,256 diabetes drugs clinical trials have been registered on the NMPA platform, of which 1056 were chemical drugs and 184 were biological products. The indications are mainly type 2 diabetes mellitus (n=1237, 98.49%). Among them, 838 clinical trials have been completed, 379 were proceeding, and 39 have been terminated or suspended. There were 42 international multi-center clinical trials, and the remaining 1034 clinical trials were domestic. Bioequivalence trials were 691, accounting for 55.02%, followed by 340 phase I clinical trials and 169 phase III clinical trials. The leading units were mostly distributed in eastern China. The proportion of clinical trial sponsorship from domestic pharmaceutical companies is higher than that from overseas companies.

Conclusions

China has made significant advancements in diabetes drug research and development over the past decade. However, problems such as serious drug homogeneity, and insufficient innovation have become increasingly prominent. The government, clinical trial institutions, and pharmaceutical companies must collaborate to promote the high-quality development of drug clinical trials.
Global research hotspots and trends in oxidative stress-related diabetic nephropathy: a bibliometric study
Authors: Wang Xiao-rong , Wu Zeng , He Tong-tong , Chen Xiao-han , Jin Xiao-fei , Zuo Chun-yue , Yang Shao-ze , Gao Yu , Zhou Xiao-hong , Gao Wei-juan
Published: January 2025

Background

Oxidative stress is widely acknowledged as a key pathogenic mechanism in diabetic nephropathy (DN). In recent years, the role of oxidative stress in DN has garnered increasing attention. However, no bibliometric analysis has yet been conducted on the relationship between oxidative stress and DN. This study aims to systematically analyze the relevant literature, identify trends in research, assess current hotspots, and predict future directions.

Methods

We retrieved literature related to oxidative stress and DN from the Web of Science Core Collection database. We analyzed data on publication volume, countries/regions, institutions, journals, keywords, and other relevant metrics using VOSviewer, the Bibliometrix R package, and CiteSpace.

Results

From 2014 to 2024, a total of 4076 publications related to oxidative stress and DN were published across 755 journals, showing a consistent upward trend each year. China and the United States are the leading contributors in this field and demonstrate close collaborative efforts. The top contributors by country, institution, journal, and author include: China (1919 publications), Jilin University and Central South University (69 publications each), BIOMEDICINE & PHARMACOTHERAPY (117 publications), and Prof. Sun Lin (33 publications). The most frequent keyword is “oxidative stress” (3683 occurrences). In the co-citation analysis, Alicic RZ’s 2017 study was the most cited (144 citations). These findings highlight the critical importance of investigating the pathogenesis of DN from the oxidative stress perspective.

Conclusion

This study demonstrates a steady increase in research on oxidative stress in DN since 2014, highlighting its central role in the pathogenesis of DN. Future research should focus on the molecular mechanisms of oxidative stress in DN and explore its therapeutic potential, to provide new strategies for the prevention and treatment of DN.
The impact of low-carbon city pilot policy on carbon emission intensity: evidence from China using a multi-period difference-in-differences model
Authors: Shu Jia-Xian , Peng Jia-Jia , Zhang Jing
Published: January 2025

In the context of global efforts to combat climate change, highlighted by the 2024 UN Climate Change Conference (COP29) and the growing global emphasis on low-carbon development, this study investigates the impact of China’s low-carbon city pilot policies on carbon emission intensity. Using data from 283 Chinese cities between 2005 and 2021, a multi-period difference-in-differences (DID) model is employed to analyze the effects of these policies. The study also explores the mediating mechanisms, moderating effects, and heterogeneity across cities. The main findings are as follows: (1) The low-carbon city pilot policies significantly reduce carbon emission intensity, with the impact becoming stronger and more stable over time. (2) The reduction in carbon intensity is partially mediated by enhanced carbon sink levels and industrial structure upgrades, although technological investment does not have a significant effect. (3) Environmental regulations negatively moderate the policy’s effectiveness, while fiscal freedom and population growth rates positively influence its impact. (4) The effects of the policy are heterogeneous across cities, driven by differences in economic levels, geographical locations, industrial bases, resource endowments, and population sizes. This paper provides valuable empirical insights and policy recommendations for China’s low-carbon transition and for achieving its carbon neutrality and peak emission targets.
Drivers of diversification in sharks and rays (Chondrichthyes: Elasmobranchii)
Authors: Gayford Joel H. , Jambura Patrick L.
Published: January 2025

Elasmobranchs (sharks and rays) are a charismatic lineage of unquestionable ecological importance in past and present marine ecosystems. Represented by over 1200 species, elasmobranchs have undergone substantial shifts in taxonomic diversity since their origin. Quantifying these diversification trends and their underlying causes improves our understanding of macroevolutionary processes and the factors influencing community composition through deep time. Studies addressing drivers of diversification in Elasmobranchii have yielded conflicting results; some report clear relationships between specific traits and diversification events, whilst others fail to find support for such relationships. There is also some evidence to suggest that biotic interactions or environmental factors (global climatic change and tectonic events) have shaped elasmobranch diversification dynamics. In this review, we summarise the diversification dynamics of elasmobranchs over their evolutionary history, before considering the evidence for the three principal hypothesised drivers of diversification in this clade: trait evolution, biotic interactions, and environmental change. Finally, we discuss major limitations in the field, and how discordant methodologies and data sources hamper our current understanding of diversification in Elasmobranchii. Whilst future studies will undoubtedly be required to further unravel this complex relationship, no single factor can be considered the sole satisfactory explanation for observed deep time diversification trends in Elasmobranchii to the exclusion of the other.
Comprehensive analysis of ferroptosis-related genes reveals potential therapeutic targets in osteoporosis patients: a computational analysis and in vitro experiments
Authors: Chen Sihui , Jiang Yi , Xie Guoqin , Wu Peng , Zhu Jinyu
Published: January 2025

Background

Ferroptosis-related genes have been reported to play important roles in many diseases, but their molecular mechanisms in osteoporosis have not been elucidated.

Methods

Based on two independent GEO datasets (GSE35956 and GSE35958), and GSE35959 as the validation dataset, we comprehensively elucidated the pathological mechanism of ferroptosis-related genes in osteoporosis by GO analyses, KEGG analyses and a PPI network. Then, We used Western Blot (WB) and Quantitative real-time polymerase chain reaction (qPCR) to verify the expression level of KMT2D, a ferroptosis-related hub gene, in clinical samples. Subsequently, we predicted the upstream miRNA of KMT2D gene and analyzed the mechanism of KMT2D in osteoporosis, the potential prognostic value and its immune invasion of KMT2D in pan-cancer.

Results

This study identified KMT2D and MYCN, TP63, RELA, SOX2, and CDKN1A as key ferroptosis-related genes in osteoporotic cell aging. The independent dataset validated that the expression level of KMT2D was significantly upregulated in osteoporosis samples. The experimental verification results of qPCR and WB indicate that KMT2D is highly expressed in patients with osteoporosis. Further analysis revealed that the hsa-miR-204-5p-KMT2D axis may play an important role in the aging of osteoporotic cells. The analysis of KMT2D reveals that KMT2D may mainly play a role in the aging of osteoporotic cells through epigenetics and the value in pan-cancer.

Conclusion

The study provides a theoretical basis for the treatment of osteoporosis.
Development and external validation of a model to predict recurrence in patients with non-muscle invasive bladder cancer
Authors: Tang Jiajia , Fan Longmei , Huang Tianyu , Yang Rongrong , Yang Xinqi , Liao Yuanjian , Zuo Mingshun , Zhang Neng , Zhang Jiangrong
Published: January 2025

Background

Most patients initially diagnosed with non-muscle invasive bladder cancer (NMIBC) still have frequent recurrence after urethral bladder tumor electrodesiccation supplemented with intravesical instillation therapy, and their risk of recurrence is difficult to predict. Risk prediction models used to predict postoperative recurrence in patients with NMIBC have limitations, such as a limited number of included cases and a lack of validation. Therefore, there is an urgent need to develop new models to compensate for the shortcomings and potentially provide evidence for predicting postoperative recurrence in NMIBC patients.

Methods

Clinicopathologic characteristics and follow-up data were retrospectively collected from 556 patients with NMIBC who underwent transurethral resection of bladder tumors by electrocautery (TURBT) from January 2014 to December 2023 at the Affiliated Hospital of Zunyi Medical University and 167 patients with NMIBC who underwent the same procedure from January 2018 to April 2024 at the Third Affiliated Hospital of Zunyi Medical University. Independent risk factors affecting the recurrence of NMIBC were screened using the least absolute shrinkage and selection operator (Lasso) and Cox regression analysis. Cox risk regression models and randomized survival forest (RSF) models were developed. The optimal model was selected by comparing the area under the curve (AUC) of the working characteristics of the subjects in both and presented as a column-line graph.

Results

The study included data from 566 patients obtained from the affiliated hospital of Zunyi Medical University and 167 patients obtained from the third affiliated hospital of Zunyi Medical University. Tumor number, urine leukocytes, urine occult blood, platelets, and red blood cell distribution width were confirmed as independent risk factors predicting RFS by Lasso-Cox regression analysis. The Cox proportional risk regression model and RSF model were constructed based on Lasso, which showed good predictive efficacy in both training and validation sets, especially the traditional Cox proportional risk regression model. In addition, the discrimination, consistency, and clinical utility of the column-line graph were assessed using C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Patients at high risk of recurrence can be identified early based on risk stratification.

Conclusion

Internal and external validation has demonstrated that the model is highly discriminative and stable and can be used to assess the risk of early recurrence in NMIBC patients and to guide clinical decision-making.
Infiltrating lipid-rich macrophage subpopulations identified as a regulator of increasing prostate size in human benign prostatic hyperplasia
Authors: Lanman Nadia Atallah , Meco Era , Fitchev Philip , Kolliegbo Andree K. , Broman Meaghan M. , Filipovich Yana , Kothandaraman Harish , Cresswell Gregory M. , Talaty Pooja , Antoniak Malgorzata , Brumer Svetlana , Glaser Alexander P. , Higgins Andrew M. , Helfand Brian T. , Franco Omar E. , Wang Chi-Hsiung , Crawford Susan E. , Ratliff Timothy L. , Hayward Simon W. , Vickman Renee E.
Published: January 2025

Introduction

Macrophages exhibit marked phenotypic heterogeneity within and across disease states, with lipid metabolic reprogramming contributing to macrophage activation and heterogeneity. Chronic inflammation has been observed in human benign prostatic hyperplasia (BPH) tissues, however macrophage activation states and their contributions to this hyperplastic disease have not been defined. We postulated that a shift in macrophage phenotypes with increasing prostate size could involve metabolic alterations resulting in prostatic epithelial or stromal hyperplasia.

Methods

Single-cell RNA-seq of CD45+ transition zone leukocytes from 10 large (>90 grams) and 10 small (<40 grams) human prostates was conducted. Macrophage subpopulations were defined using marker genes and evaluated by flow cytometry.

Results

BPH macrophages do not distinctly categorize into M1 and M2 phenotypes. Instead, macrophages with neither polarization signature preferentially accumulate in large versus small prostates. Specifically, macrophage subpopulations with altered lipid metabolism pathways, demarcated by TREM2 and MARCO expression, accumulate with increased prostate volume. TREM2high and MARCOhigh macrophage abundance positively correlates with patient body mass index and urinary symptom scores. TREM2high macrophages have a statistically significant increase in neutral lipid compared to TREM2low macrophages from BPH tissues. Lipid-rich macrophages were observed to localize within the stroma in BPH tissues. In vitro studies indicate that lipid-loaded macrophages increase prostate epithelial and stromal cell proliferation compared to control macrophages.

Discussion

These data define two new BPH immune subpopulations, TREM2high and MARCOhigh macrophages, and suggest that lipid-rich macrophages may exacerbate lower urinary tract symptoms in patients with large prostates. Further investigation is needed to evaluate the therapeutic benefit of targeting these cells in BPH.
Interferon activation in bone marrow long-lived plasma cells in systemic lupus erythematosus
Authors: Alzamareh Diana F. , Meednu Nida , Nandedkar-Kulkarni Neha , Krenitsky Daria , Barnard Jennifer , Yasaka Ken , Durrett Wesley , Thakar Juilee , Rangel-Moreno Javier , Anolik Jennifer H. , Barnas Jennifer L.
Published: January 2025

While durable antibody responses from long-lived plasma cell (LLPC) populations are important for protection against pathogens, LLPC may be harmful if they produce antibodies against self-proteins or self-nuclear antigens as occurs in autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the elimination of autoreactive LLPC may improve the treatment of antibody-driven autoimmune diseases. However, LLPC remain a challenging therapeutic target. Here, we compare the matched bone marrow (BM) and peripheral blood (PBL) plasma cell (PC) compartments of SLE and healthy donors (HD). We show a similar distribution of CD138- and CD138+ PC, including putative LLPC (CD19- CD138+ CD38+), between SLE and HD BM. For both SLE and HD, CD138+ PC are at a higher frequency in BM than PBL. Expression of Ki-67 associates with the PBL compartment where it is found on all PC subsets regardless of CD19 or CD138 expression. Transcriptomic analysis identifies an interferon (IFN) gene signature in transitional B cells in the SLE BM, but surprisingly also in the BM PC derived from SLE. BM PC and B cells phosphorylate STAT1 in response to type I IFN stimulation in vitro, but with decreased fold change compared to those from the PBL. While BM PC bind type I IFN receptor-blocking antibody anifrolumab, it is to a lesser degree than circulating B cells. Anti-nuclear autoantibodies (ANA) are found in the BM supernatant and PBL serum of SLE patients. Both SLE and HD BM-derived PC have increased survival compared to their PBL counterparts when treated with verdinexor. In summary, these findings show evidence of IFN activation in BM PC from SLE.
Single-cell transcriptome analysis of medaka lymphocytes reveals absence of fully mature T cells in the thymus and the T-lineage commitment in the kidney
Authors: Sakaguchi Hiyori , Matsuda Masaru , Iwanami Norimasa
Published: January 2025

The cellular and molecular mechanisms underlying lymphocyte development are diverse among teleost species. Although recent scRNA-seq analyses of zebrafish hematopoietic cells have advanced our understanding of teleost hematopoiesis, comparative studies using another genetic model, medaka, which is evolutionarily distant among teleosts, is useful for understanding commonality and species-specificity in teleosts. In order to gain insight into how different molecular and cellular mechanisms of lymphocyte development in medaka and zebrafish, we established a recombination activating gene 1 (rag1) mutant medaka, which exhibited defects in V(D)J rearrangement of lymphocyte antigen receptor genes, accordingly lacking mature B and T cells. scRNA-seq analysis of wild type and rag1 mutant lymphocytes in the thymus and kidney characterized the developing stages of T and B cells, and found that most developed cd4+cd8– and cd4–cd8+ single-positive (SP) T-cell populations are absent in the thymus, and identified lymphoid progenitor cells already committed to the T lineage in kidney, implying unique features of medaka lymphocyte development.
Glycosylation profiling of triple-negative breast cancer: clinical and immune correlations and identification of LMAN1L as a biomarker and therapeutic target
Authors: Yu Qianru , Zhong Hanyi , Zhu Xinhao , Liu Chang , Zhang Xin , Wang Jiao , Li Zongyao , Shi Songchang , Zhao Haoran , Zhou Cixiang , Zhao Qian
Published: January 2025

Introduction

Breast cancer (BC) is the most prevalent malignant tumor in women, with triple-negative breast cancer (TNBC) showing the poorest prognosis among all subtypes. Glycosylation is increasingly recognized as a critical biomarker in the tumor microenvironment, particularly in BC. However, the glycosylation-related genes associated with TNBC have not yet been defined. Additionally, their characteristics and relationship with prognosis have not been deeply investigated.

Methods

Transcriptomic analyses were used to identify a glycosylation-related signature (GRS) associated with TNBC prognosis. A machine learning-based prediction model was constructed and validated across multiple independent datasets. The model's predictive capability was extended to evaluate the prognosis of TNBC individuals, tumor immune microenvironment and immunotherapy response. LMAN1L (Lectin, Mannose Binding 1 Like) was identified as a novel prognostic marker in TNBC, and its biological effects were validated through experimental assays.

Results

The GRS showed significant prognostic relevance for TNBC patients. The risk model effectively predicted molecular features, including immune cell infiltration and potential responses to immunotherapy. Experimental validation confirmed LMAN1L as a novel glycosylation-related prognostic gene, with low expression significantly inhibiting TNBC cell proliferation and migration.

Discussion

Our GRS risk model demonstrates robust predictive capability for TNBC prognosis and immunotherapy response. This model offers a promising strategy for personalized treatment and improved clinical outcomes in TNBC.
Inhibition SIRT1 to regulate FOXP3 or RORγt can restore the balance of Treg/Th17 axis in ulcerative colitis and enhance the anti-inflammatory effect of moxibustion
Authors: Zhu Yuanbing , Wang Yuemei , Zuo Xiaotong , Liu Shuqing , Cao Lishuang , Wang Junmeng , Yang Qingqing , Huang Qianhui , Huang Qin , Tian Muqiu , Ping Yanling , Wu Qiaofeng
Published: January 2025

Introduction

Ulcerative colitis (UC) is a chronic inflammatory disease. Patients with UC typically exhibit disruption of the Treg/Th17 immune axis, but its exact mechanism is still unclear.

Methods

This study first analyzed RNA- seq data from public databases of humans and mice, and in vitro cytology experiments were conducted to induce or inhibit the expression of SIRT1. In vivo, UC mice were treated with moxibustion and SIRT1 inhibitor EX-527 to confirm the changes in the transcription factors identified through analysis of the datasets.

Results

The results show that Treg/Th17 axis disruption is an important feature of UC. Differential gene expression and immune infiltration analysis showed that upstream transcription factors, including Forkhead box P3 (FOXP3), were significantly disrupted. In vitro cytology experiments, the results indicate that SIRT1 is activated in LPS induced inflammation, subsequently perturbing the Treg/Th17 immune balance axis. Finally, in vivo studies, the results have shown that administering EX-527 to inhibit SIRT1 leads to an increasing in FOXP3 expression and a decreasing in RORγt expression in UC colon tissue. In addition, the results indicate that traditional Chinese moxibustion can down regulate the expression of SIRT1, directly affecting the balance of Th17/Treg axis, and the combined use of EX-527 further improves the therapeutic effect of moxibustion.

Conclusion

Our research shows that inhibition SIRT1 can regulate Treg and Th17 immune balance axis. This finding indicates a new important potential target for the treatment of UC.
The role of M1/M2 macrophage polarization in the pathogenesis of obesity-related kidney disease and related pathologies
Authors: Dousdampanis Periklis , Aggeletopoulou Ioanna , Mouzaki Athanasia
Published: January 2025

Obesity is a rapidly growing health problem worldwide, affecting both adults and children and increasing the risk of chronic diseases such as type 2 diabetes, hypertension and cardiovascular disease (CVD). In addition, obesity is closely linked to chronic kidney disease (CKD) by either exacerbating diabetic complications or directly causing kidney damage. Obesity-related CKD is characterized by proteinuria, lipid accumulation, fibrosis and glomerulosclerosis, which can gradually impair kidney function. Among the immune cells of the innate and adaptive immune response involved in the pathogenesis of obesity-related diseases, macrophages play a crucial role in the inflammation associated with CKD. In obese individuals, macrophages enter a pro-inflammatory state known as M1 polarization, which contributes to chronic inflammation. This polarization promotes tissue damage, inflammation and fibrosis, leading to progressive loss of kidney function. In addition, macrophage-induced oxidative stress is a key feature of CKD as it also promotes cell damage and inflammation. Macrophages also contribute to insulin resistance in type 2 diabetes by releasing inflammatory molecules that impair glucose metabolism, complicating the management of diabetes in obese patients. Hypertension and atherosclerosis, which are often associated with obesity, also contribute to the progression of CKD via immune and inflammatory pathways. Macrophages influence blood pressure regulation and contribute to vascular inflammation, particularly via the renin-angiotensin system. In atherosclerosis, macrophages accumulate in arterial plaques, leading to chronic inflammation and plaque instability, which may increase the risk of CVD in CKD patients. This review focuses on the involvement of macrophages in CKD and highlights their role as a critical link between CKD and other pathologies. Targeting macrophage polarization and the ensuing macrophage-induced inflammation could be an effective therapeutic strategy for CKD and related diseases and improve outcomes for patients with obesity-related kidney disease.
Developing and validating a machine learning model to predict multidrug-resistant Klebsiella pneumoniae-related septic shock
Authors: Pan Shengnan , Shi Ting , Ji Jinling , Wang Kai , Jiang Kun , Yu Yabin , Li Chang
Published: January 2025

Background

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) infections pose a significant global healthcare challenge, particularly due to the high mortality risk associated with septic shock. This study aimed to develop and validate a machine learning-based model to predict the risk of MDR-KP-associated septic shock, enabling early risk stratification and targeted interventions.

Methods

A retrospective analysis was conducted on 1,385 patients with MDR-KP infections admitted between January 2019 and June 2024. The cohort was randomly divided into a training set (n = 969) and a validation set (n = 416). Feature selection was performed using LASSO regression and the Boruta algorithm. Seven machine learning algorithms were evaluated, with logistic regression chosen for its optimal balance between performance and robustness against overfitting.

Results

The overall incidence of MDR-KP-associated septic shock was 16.32% (226/1,385). The predictive model identified seven key risk factors: procalcitonin (PCT), sepsis, acute kidney injury, intra-abdominal infection, use of vasoactive medications, ventilator weaning failure, and mechanical ventilation. The logistic regression model demonstrated excellent predictive performance, with an area under the receiver operating characteristic curve (AUC) of 0.906 in the training set and 0.865 in the validation set. Calibration was robust, with Hosmer-Lemeshow test results of P = 0.065 (training) and P = 0.069 (validation). Decision curve analysis indicated substantial clinical net benefit.

Conclusion

This study presents a validated, high-performing predictive model for MDR-KP-associated septic shock, offering a valuable tool for early clinical decision-making. Prospective, multi-center studies are recommended to further evaluate its clinical applicability and effectiveness in diverse settings.
Tuberculous meningitis diagnosis and treatment: classic approaches and high-throughput pathways
Authors: Lin Fangbo
Published: January 2025

Tuberculous meningitis (TBM), a severe form of non-purulent meningitis caused by Mycobacterium tuberculosis (Mtb), is the most critical extrapulmonary tuberculosis (TB) manifestation, with a 30–40% mortality rate despite available treatment. The absence of distinctive clinical symptoms and effective diagnostic tools complicates early detection. Recent advancements in nucleic acid detection, genomics, metabolomics, and proteomics have led to novel diagnostic approaches, improving sensitivity and specificity. This review focuses on nucleic acid-based methods, including Xpert Ultra, metagenomic next-generation sequencing (mNGS), and single-cell sequencing of whole brain Tissue, alongside the diagnostic potential of metabolomic and proteomic biomarkers. By evaluating the technical features, diagnostic accuracy, and clinical applicability, this review aims to inform the optimization of TBM diagnostic strategies and explores the integration and clinical translation of multi-omics technologies.
Cetacean stranding records along the Shanghai–Zhejiang coastline in China: implications for distribution and conservation
Authors: Yuan Jing , Gao Yili , Wang Nan , Jiang Tianhua , Cheng Zhaolong
Published: January 2025

Cetacean ecology has been poorly studied in the Shanghai-Zhejiang waters of East China Sea, seriously hindering appropriate local conservation practices. Here stranding records from 1953 to 2023 around the Shanghai-Zhejiang waters were collated from literature, media, and social websites to clarify species composition and spatio-temporal variations of cetacean strandings. A total of 138 stranding records involving 197 individuals across 23 species were identified, comprising four Mysticeti and Odontoceti species. Cetacean stranding records occurred extensively along the Shanghai-Zhejiang coastline throughout the year and have grown swiftly since the 2000s. Narrow-ridged finless porpoise Neophocaena asiaeorientalis and common minke whale Balaenoptera acutorostrata were the most frequently stranded species. Over 84% of the stranding events involved only a single individual. Melon-headed whale Peponocephala electra predominated in mass stranding incidents. Spatially, the stranding reports showed a significant cluttering distribution pattern. Clustering of cetacean records occurred in the Yangtze River estuary, downstream region of Qiantang River, southeastern of Ningbo, and Oujiang River estuary. Seasonal analysis showed increased cetacean stranding events in spring, yet without a significant difference. Post-mortem examinations of stranded individuals showed that coastal fisheries and port activities were probably the dominant causes of local cetacean strandings. Standardizing cetacean stranding records, strengthening fisheries regulations, and rescue training programs are recommended to establish a dedicated cetacean stranding monitoring network, which is vital for cetacean conservation in this region.
Diagnostic accuracy of Bellavere’s score in cardiac autonomic neuropathy among chronic kidney disease patients: a study of prevalence and dialysis impact
Authors: Toshniwal Saket Satyasham , Kumar Sunil , Acharya Sourya , Ghali Abhishek , Raut Sarang , Deolikar Vinit , Reddy Harshitha , Kotak Palash , Wanjari Anil , Bawankule Shilpa
Published: January 2025

Background

Cardiac autonomic neuropathy (CAN) is a significant complication in chronic kidney disease (CKD), leading to increased morbidity and mortality. Early detection is essential for managing CKD patients effectively, especially those on hemodialysis. This study evaluated the prevalence CAN in CKD and diagnostic accuracy of Bellavere’s Score in predicting CAN in CKD patients, including those undergoing hemodialysis.

Methods

This prospective observational study included 200 CKD patients. Cardiac autonomic neuropathy was assessed using Bellavere’s Score, calculated through a series of autonomic function tests including heart rate variability and blood pressure responses. Bellavere’s Score was measured pre-and post-dialysis in hemodialysis patients. The diagnostic performance of the score was evaluated using receiver operating characteristic (ROC) curves to determine sensitivity, specificity, and likelihood ratios.

Results

Among the patients, 60% were diagnosed with CAN, with 35% having early CAN and 24% severe CAN. Bellavere’s Score showed high diagnostic accuracy across CKD stages, with sensitivity ranging from 75 to 89.29% and specificity from 69.09 to 96%. In CKD stage III patients, the sensitivity was 78.57% and specificity 91.4%. In stage V, sensitivity increased to 89.29%, though specificity dropped to 69.09%. For hemodialysis patients, Bellavere’s Score exhibited a sensitivity of 79.78% and specificity of 79.28%. The prevalence of CAN decreased significantly from 79.8% pre-dialysis to 64% post-dialysis (p < 0.01).

Conclusion

Bellavere’s Score provides a reliable and non-invasive approach for diagnosing CAN in CKD patients, with strong diagnostic performance across different disease stages and in hemodialysis. Larger studies are warranted to further validate its utility.
An integrative review on the risk factors, prevention, and control strategies for carbapenem-resistant Acinetobacter baumannii colonization in critically ill patients
Authors: Zhang Shihan , Xiao Jie , Li Yanan , Li Wei , Li Yihui , Pang Mingmin , Yan Meichen , Han Hui , Cui Yi , Zhang Xuehai , Wang Hao
Published: January 2025

The presence of carbapenem-resistant Acinetobacter baumannii (CRAb) has become one of the leading causes of life-threatening, hospital-acquired infections globally, especially with a notable prevalence in intensive care units (ICUs). The cross-transmission of microorganisms between patients and the hospital setting is crucial in the development of CRAb colonization and subsequent infections. Recent studies indicate that colonization typically precedes infection, suggesting the effectiveness and necessity of preventing CRAb colonization as a primary method to lower infection risks. As CRAb infections tend to draw more attention due to their severe symptoms and poor outcomes, understanding the link between colonization and infection is equally vital. To establish a foundation for prevention and control strategies against CRAb colonization in ICUs, we present a comprehensive review of research pertaining to CRAb in ICUs. This encompasses an analysis of the resistance mechanisms and epidemiological characteristics of CRAb, a discussion on associated risk factors, adverse outcomes, and an evaluation of detection methods and preventive strategies.