bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA methylation patterns of circadian and ultradian genes are altered in the peripheral blood of patients with hidradenitis suppurativa
Authors: Radhakrishna Uppala , Ratnamala Uppala , Jhala Devendrasinh D. , Uppala Lavanya V. , Vedangi Aaren , Saiyed Nazia , Shah Sushma R. , Patel Maulikkumar , Rawal Rakesh M. , Mazza Tommaso , Jemec Gregor B. E. , Mazzoccoli Gianluigi , Damiani Giovanni
Published: November 2024

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects hair follicles in areas with apocrine sweat glands, such as the underarms, groin, and buttocks. The pathogenesis of HS is not fully understood, but considering the key role played by the biological clock in the control of immune/inflammatory processes the derangement of circadian and ultradian pathways could be hypothesized.

Methods

We analyzed genome-wide DNA methylation patterns in peripheral blood from 24 HS cases and 24 controls using the Infinium HumanMethylation450 BeadChip array (Illumina), followed by bioinformatics and statistical analyses.

Results

We found that several circadian and ultradian genes were differentially methylated in HS patients, predominantly exhibiting hypomethylation. These genes were enriched in pathways such as MAPK and WNT cascades, acute phase response, cytokine release, inflammation, innate immune response, xenobiotic detoxification, and oxidative stress response.

Conclusion

Altered DNA methylation patterns of genes related to circadian and ultradian pathways could contribute to immune system derangement and inflammatory processes chronicization in addition to other comorbidities hallmarking HS onset and progression, at the same time representing possible druggable targets.
Efferocytosis: the resolution of inflammation in cardiovascular and cerebrovascular disease
Authors: Zhang Bingtao , Zou Yan , Yuan Zixuan , Jiang Kun , Zhang Zhaoxiang , Chen Shujuan , Zhou Xiaoming , Wu Qi , Zhang Xin
Published: November 2024

Cardiovascular and cerebrovascular diseases have surpassed cancer as significant global health challenges, which mainly include atherosclerosis, myocardial infarction, hemorrhagic stroke and ischemia stroke. The inflammatory response immediately following these diseases profoundly impacts patient prognosis and recovery. Efficient resolution of inflammation is crucial not only for halting the inflammatory process but also for restoring tissue homeostasis. Efferocytosis, the phagocytic clearance of dying cells by phagocytes, especially microglia and macrophages, plays a critical role in this resolution process. Upon tissue injury, phagocytes are recruited to the site of damage where they engulf and clear dying cells through efferocytosis. Efferocytosis suppresses the secretion of pro-inflammatory cytokines, stimulates the production of anti-inflammatory cytokines, modulates the phenotype of microglia and macrophages, accelerates the resolution of inflammation, and promotes tissue repair. It involves three main stages: recognition, engulfment, and degradation of dying cells. Optimal removal of apoptotic cargo by phagocytes requires finely tuned machinery and associated modifications. Key molecules in efferocytosis, such as ‘Find-me signals’, ‘Eat-me signals’, and ‘Don’t eat-me signals’, have been shown to enhance efferocytosis following cardiovascular and cerebrovascular diseases. Moreover, various additional molecules, pathways, and mitochondrial metabolic processes have been identified to enhance prognosis and outcomes via efferocytosis in diverse experimental models. Impaired efferocytosis can lead to inflammation-associated pathologies and prolonged recovery periods. Therefore, this review consolidates current understanding of efferocytosis mechanisms and its application in cardiovascular and cerebrovascular diseases, proposing future research directions.
Current and emerging tools for simultaneous assessment of infection and rejection risk in transplantation
Authors: Tharmaraj Dhakshayini , Mulley William R. , Dendle Claire
Published: November 2024

Infection and rejection are major complications that impact transplant longevity and recipient survival. Balancing their risks is a significant challenge for clinicians. Current strategies aimed at interrogating the degree of immune deficiency or activation and their attendant risks of infection and rejection are imprecise. These include immune (cell counts, function and subsets, immunoglobulin levels) and non-immune (drug levels, viral loads) markers. The shared risk factors between infection and rejection and the bidirectional and intricate relationship between both entities further complicate transplant recipient care and decision-making. Understanding the dynamic changes in the underlying net state of immunity and the overall risk of both complications in parallel is key to optimizing outcomes. The allograft biopsy is the current gold standard for the diagnosis of rejection but is associated with inherent risks that warrant careful consideration. Several biomarkers, in particular, donor derived cell-free-DNA and urinary chemokines (CXCL9 and CXCL10), show significant promise in improving subclinical and clinical rejection risk prediction, which may reduce the need for allograft biopsies in some situations. Integrating conventional and emerging risk assessment tools can help stratify the individual’s short- and longer-term infection and rejection risks in parallel. Individuals identified as having a low risk of rejection may tolerate immunosuppression wean to reduce medication-related toxicity. Serial monitoring following immunosuppression reduction or escalation with minimally invasive tools can help mitigate infection and rejection risks and allow for timely diagnosis and treatment of these complications, ultimately improving allograft and patient outcomes.
Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer
Authors: Qin Gaofeng , Chen Zengkuan , Tian Weihong , Chen Hongbo , Zhang Yu , Wei Wangzhi
Published: November 2024

Introduction

ETAA1 is recruited to DNA damage sites via its RPA -binding and ATR -activating domain (AAD) motifs, where RPA binding is crucial for ETAA1’s regulation of ATR activity.

Methods & results

Our findings associate Programmed Death- Ligand1 (PD-L1) with the RPA1-ETAA1 axis, suggesting that upregulated RPA1 -dependent ETAA1 may facilitate PD-L1 nuclear accumulation. We observed strong correlations between ETAA1 and RPA1 with the components involved in HDAC2-mediated deacetylation, clathrin -dependent endocytosis, and PD-L1 nucleocytoplasmic shuttling, aligning with the established regulatory pathway of PD-L1 nuclear translocation. Moreover, nuclear PD-L1 transactivates a panel of pro-inflammatory and immune response transcription factors, potentially reshaping the tumor immune microenvironment. We identified a landscape of infiltrating lymphocytes influenced by ETAA1, finding that levels of ETAA1 were negatively correlated with CD8+ T and Natural Killer T (NKT) cells, but positively correlated with CD4+ T helper 2 (Th2) cells, cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), neutrophils and regulatory T cells (Tregs), suggesting a potential role in immune evasion. Further analysis shows that the RPA1-ETAA1 axis is significantly associated with multiple metastasis mediators and unfavorable liver cancer progression, with higher expression observed in advanced stages and poorly differentiated subgroups.

Discussion & conclusion

These findings expand the role of the RPA1-ETAA1 axis beyond DNA repair, highlighting its potential as a target for cancer therapy.
Sedimentary dynamics in southern Mariana Trench and its controlling factors in past 440 kyr
Authors: Shen Zhongshan , Wang Haifeng , Chen Yanping , Cai Yun , Yi Liang
Published: November 2024

Understanding sediment dynamics and their controlling factors is essential for Quaternary studies, yet they remain poorly documented in the Mariana Trench. In this work, we examine this basic character from a sediment core collected at a depth of 6470 m from the southern part of the Mariana Trench, documenting changes in sedimentary dynamics over the past ~440 kyr. Our primary findings are as follows: (1) The median grain size is 13.6 ± 12.0 μm, and minimal changes in clay (30.9 ± 9.4%) and silt (56.6 ± 4.0%) contents, indicating a low-dynamic depositional environment; (2) Three grain-size components were identified, characterized by modal changes of ~4/60 μm, ~20 μm, and >100 μm. By comparing these results with various environmental proxies, including glacial-interglacial alternations, eolian input, and bottom-water intensity, we suggest that marine productivity has a dominant influence on deep-sea sediment dynamics, though post-depositional processes also contribute. Additionally, topographical conditions and sea-water chemistry appear to be related to the presence of coarse particles, possibly through coarse transport and micro-nodule development. Overall, grain-size parameters provide a valuable investigative tool for understanding the various influences on sediment dynamics in this region.
Long non-coding RNA H19 as a prognostic biomarker for oral squamous cell carcinoma
Authors: Kumar Kiran , Hallikeri Kaveri , Oli Ajay Kumar , Radder Kiran , Jain Apoorva , Shilpasree A. S. , Dhanapal Raghu , Tabnjh Abedelmalek Kalefh , Selvaraj Siddharthan
Published: November 2024

Background

H19, a 2.3 kb lncRNA, has been linked to tumor metastasis and progression, but its significance in oral squamous cell carcinoma (OSCC) remains unclear. H19 was initially thought to have a tumor-suppressive function, but recent studies have shown that it possesses both tumor-promoting and suppressive functions. The variation in H19 expression may be due to the influence of tobacco or low basal expression levels. However, there are limited studies available on the association between H19 and its role in the prognosis of OSCC.

Objective

The present study analyzes the expression of H19 correlated with clinicopathological parameters, tobacco habit, loco-regional recurrence, and overall survival.

Methods

A longitudinal study was undertaken using 96 formalin-fixed paraffin-embedded (FFPE) OSCC tissues and 30 FFPE adjacent normal mucosa (NM) tissues from patients who had surgery between 2015 and 2018. The tissues were subjected to quantitative reverse-transcription PCR (qRT-PCR) to determine H19 expression. The differential expression levels of H19 in OSCC were compared to clinicopathological variables and risk habits using the t-test and ANOVA. H19 expression correlated overall survival was analyzed by drawing the Kaplan–Meier curve followed by the log-rank test. A multivariate Cox proportional hazards regression analysis was performed to determine the ability of H19 to independently predict loco-regional recurrence and overall survival for OSCC.

Result

H19 was significantly underexpressed in OSCC compared to NM in both the study cases and the TCGA OSCC database. The lower expression of H19 was significantly associated with the tobacco smoking habit and was not associated with any clinical or pathological features. Multivariate Cox’s proportional hazards regression analysis indicated that low H19 expression and positive lymph node metastasis were independent predictors of overall survival for OSCC. Higher age, higher TNM staging, and low H19 expression were independent predictors of loco-regional recurrence.

Conclusion

The findings in the present study indicate that H19 is a novel prognostic marker and may provide a therapeutic strategy for the targeted treatment of OSCC, and tobacco may play a role in the expression of H19.
Adherence to recommended diet among patients with diabetes mellitus type 2 on follow-up at Adama Hospital Medical College, Ethiopia
Authors: Abose Saron , Dassie Godana Arero , Megerso Abebe , Charkos Tesfaye Getachew
Published: November 2024

Introduction

Non-adherence to dietary guidelines is a significant challenge in managing diabetes mellitus and its complications. Its consequences were significantly associated with a deterioration in patients’ quality of life and an increased socioeconomic burden on healthcare delivery systems. This study aimed to assess the magnitude of adherence to recommended diet and associated factors among patients with diabetes mellitus type 2 on follow-up care at Adama Hospital Medical College Oromia, Ethiopia.

Methods

A hospital-based cross-sectional study design was conducted. Participants were selected through systematic random sampling. Data were collected using structured, interviewer-administered questionnaires. The perceived dietary adherence questionnaire was used to assess the level of dietary adherence. A simple binary logistic regression was used to identify candidate variables, while a multivariable logistic regression assessed factors associated with adherence to the recommended diet. A p-value <0.05 were considered as statistically significant. All analyses were performed using SPSS and R programming software.

Result

A total of 405 participants were included in the study, with a response rate of 96.2%. The magnitude of non-adherence to the recommended diet was 64.2% (95% confidence interval [CI]: 59.8, 68.6). In the multivariable logistic regression model, patients with low and middle income (AOR = 8.0; 95% CI: 3.4, 19.2) and (AOR = 2.75; 95% CI: 1.49, 5.55) respectively, high glycemic level (AOR = 2.15; 95% CI: 1.17, 3.94), food insecure (AOR = 12.7; 95% CI: 5.79, 28.2), poor diabetic knowledge (AOR = 2.88; 95% CI: 1.49, 5.55) and low perceived susceptibility (AOR = 2.97; 95% CI: 1.62, 5.45) were significantly associated factors for non-adherence to recommended diet among patients with diabetes mellitus type 2.

Conclusion

This study revealed that approximately two-thirds of patients with type 2 diabetes mellitus experienced non-adherence to the recommended diet. Key factors linked to dietary non-adherence among T2DM patients include low to middle income, elevated glycemic levels, household food insecurity, limited diabetes knowledge, and low perceived susceptibility. An integrated approach that combines socioeconomic support, nutritional guidance, and risk awareness may greatly enhance dietary adherence and optimize diabetes management.
The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function
Authors: Abildinova Gulshara Zh , Benberin Valeriy V. , Vochshenkova Tamara A. , Afshar Alireza , Mussin Nadiar M. , Kaliyev Asset A. , Zhussupova Zhanna , Tamadon Amin
Published: November 2024

The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic–pituitary–adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.
Novel insights into cuproptosis inducers and inhibitors
Authors: Zhang Ligang , Deng Ruiting , Liu Lian , Du Hongli , Tang Dongsheng
Published: November 2024

Cuproptosis is a new pattern of Cu-dependent cell death distinct from classic cell death pathways and characterized by aberrant lipoylated protein aggregation in TCA cycle, Fe-S cluster protein loss, HSP70 elevation, proteotoxic and oxidative stress aggravation. Previous studies on Cu homeostasis and Cu-induced cell death provide a great basis for the discovery of cuproptosis. It has gradually gathered enormous research interests and large progress has been achieved in revealing the metabolic pathways and key targets of cuproptosis, due to its role in mediating some genetic, neurodegenerative, cardiovascular and tumoral diseases. In terms of the key targets in cuproptosis metabolic pathways, they can be categorized into three types: oxidative stress, mitochondrial respiration, ubiquitin-proteasome system. And strategies for developing cuproptosis inducers and inhibitors involved in these targets have been continuously improved. Briefly, based on the essential cuproptosis targets and metabolic pathways, this paper classifies some relevant inducers and inhibitors including small molecule compounds, transcription factors and ncRNAs with the overview of principle, scientific and medical application, in order to provide reference for the cuproptosis study and target therapy in the future.
A multimodal travel route recommendation system leveraging visual Transformers and self-attention mechanisms
Authors: Juan Zhang , Zhang Jing , Gao Ming
Published: November 2024

Introduction

With the rapid development of the tourism industry, the demand for accurate and personalized travel route recommendations has significantly increased. However, traditional methods often fail to effectively integrate visual and sequential information, leading to recommendations that are both less accurate and less personalized.

Methods

This paper introduces SelfAM-Vtrans, a novel algorithm that leverages multimodal data—combining visual Transformers, LSTMs, and self-attention mechanisms—to enhance the accuracy and personalization of travel route recommendations. SelfAM-Vtrans integrates visual and sequential information by employing a visual Transformer to extract features from travel images, thereby capturing spatial relationships within them. Concurrently, a Long Short-Term Memory (LSTM) network encodes sequential data to capture the temporal dependencies within travel sequences. To effectively merge these two modalities, a self-attention mechanism fuses the visual features and sequential encodings, thoroughly accounting for their interdependencies. Based on this fused representation, a classification or regression model is trained using real travel datasets to recommend optimal travel routes.

Results and discussion

The algorithm was rigorously evaluated through experiments conducted on real-world travel datasets, and its performance was benchmarked against other route recommendation methods. The results demonstrate that SelfAM-Vtrans significantly outperforms traditional approaches in terms of both recommendation accuracy and personalization. By comprehensively incorporating both visual and sequential data, this method offers travelers more tailored and precise route suggestions, thereby enriching the overall travel experience.
The BE (2)-M17 neuroblastoma cell line: revealing its potential as a cellular model for Parkinson’s disease
Authors: Carvajal-Oliveros Angel , Román-Martínez Camila , Reynaud Enrique , Martínez-Martínez Eduardo
Published: November 2024

Parkinson’s disease is a pathology with a wide range of in vivo and in vitro models available. Among these, the SH-SY5Y neuroblastoma cell line is one of the most employed. This model expresses catecholaminergic markers and can differentiate and acquire various neuronal phenotypes. However, challenges persist, primarily concerning the variability of growth media, expression of dopaminergic markers, and a wide variety of differentiation protocols have been reported in the literature without direct comparison between them. This lack of standardized differentiation conditions impacts result reproducibility and it makes it very difficult to compare the results obtained from different research groups. An alternative cellular model is the neuroblastoma BE (2)-M17 which exhibits a high basal expression of numerous dopaminergic markers such as tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT). The BE (2)-M17 cells show neuronal properties, grows rapidly in conventional media, and can easily be differentiated to increase their dopaminergic phenotype. In this review, we will thoroughly explore the properties of the BE (2)-M17 cell line and discuss its potential as an excellent model for studying Parkinson’s disease.
Enhanced brain tumor diagnosis using combined deep learning models and weight selection technique
Authors: Gasmi Karim , Ben Aoun Najib , Alsalem Khalaf , Ltaifa Ibtihel Ben , Alrashdi Ibrahim , Ammar Lassaad Ben , Mrabet Manel , Shehab Abdulaziz
Published: November 2024

Brain tumor classification is a critical task in medical imaging, as accurate diagnosis directly influences treatment planning and patient outcomes. Traditional methods often fall short in achieving the required precision due to the complex and heterogeneous nature of brain tumors. In this study, we propose an innovative approach to brain tumor multi-classification by leveraging an ensemble learning method that combines advanced deep learning models with an optimal weighting strategy. Our methodology integrates Vision Transformers (ViT) and EfficientNet-V2 models, both renowned for their powerful feature extraction capabilities in medical imaging. This model enhances the feature extraction step by capturing both global and local features, thanks to the combination of different deep learning models with the ViT model. These models are then combined using a weighted ensemble approach, where each model's prediction is assigned a weight. To optimize these weights, we employ a genetic algorithm, which iteratively selects the best weight combinations to maximize classification accuracy. We trained and validated our ensemble model using a well-curated dataset comprising labeled brain MRI images. The model's performance was benchmarked against standalone ViT and EfficientNet-V2 models, as well as other traditional classifiers. The ensemble approach achieved a notable improvement in classification accuracy, precision, recall, and F1-score compared to individual models. Specifically, our model attained an accuracy rate of 95%, significantly outperforming existing methods. This study underscores the potential of combining advanced deep learning models with a genetic algorithm-optimized weighting strategy to tackle complex medical classification tasks. The enhanced diagnostic precision offered by our ensemble model can lead to better-informed clinical decisions, ultimately improving patient outcomes. Furthermore, our approach can be generalized to other medical imaging classification problems, paving the way for broader applications of AI in healthcare. This advancement in brain tumor classification contributes valuable insights to the field of medical AI, supporting the ongoing efforts to integrate advanced computational tools in clinical practice.
Bioimaging marine crustacean brain: quantitative comparison of micro-CT preparations in an Alpheid snapping shrimp
Authors: Chapuis Lucille , Andres Cara-Sophia , Gerneke Dane A. , Radford Craig A.
Published: November 2024

Non-invasive bioimaging techniques like X-ray micro-computed tomography (μCT), combined with contrast-enhancing techniques, allow the 3D visualization of the central nervous system in situ, without the destruction of the sample. However, quantitative comparisons of the most common fixation and contrast-enhancing protocols are rare, especially in marine invertebrates. Using the snapping shrimp (Alpheus richardsoni) as a model, we test three common fixation and staining agents combinations to prepare specimens prior to μCT scanning. The contrast ratios of the resulting images are then quantitatively compared. Our results show that a buffered iodine solution on a specimen fixed with 10% formalin offers the best nervous tissue discriminability. This optimal combination allows a semi-automated segmentation of the central nervous system organs from the μCT images. We thus provide general guidance for μCT applications, particularly suitable for marine crustaceans. Species-specific morphological adaptations can then be characterized and studied in the context of evolution and behavioral ecology.
Sugary beverages intake and risk of chronic kidney disease: the mediating role of metabolic syndrome
Authors: Dai Xiao-Yu , Chen Xiang-Yu , Jia Li-Na , Jing Xiao-Tong , Pan Xiao-Yan , Zhang Xing-Yu , Jing Zhong , Yuan Jin-Qiu , He Qiang-Sheng , Yang Li-Ling
Published: November 2024

Background

Although several studies linked the sugary beverages to chronic kidney disease (CKD), the role of different types of sugary beverages in the development of CKD remained inconsistent. This study aimed to examine the associations of sugar-sweetened beverages (SSBs), artificially-sweetened beverages (ASBs), and natural juices (NJs) with CKD risk, and assess the extent to which the associations were mediated through metabolic syndrome (MetS).

Methods

This is a prospective analysis of 191,956 participants from the UK Biobank. Participants with information on beverage consumption and no history of CKD at recruitment were included. Daily consumptions of SSBs, ASBs and NJs were measured via 24-h dietary recall. Cox models were fitted to calculate the hazard ratios (HRs) and confidence intervals (CIs) of sugary beverages intakes on CKD risk. The causal mediation analyses were conducted to investigate whether MetS explained the observed associations.

Results

We documented 4,983 CKD cases over a median of 10.63 years follow-up. Higher consumption of SSBs and ASBs (>1 units/d compared with none) was associated with an elevated risk of CKD (HR: 1.45; 95% CI: 1.30–1.61, P-trend < 0.001 for SSBs and 1.52, 95% CI: 1.36–1.70 for ASBs). In contrast, we observed a J-shaped association between NJs and CKD with the with lowest risk at 0–1 unit/day (0–1 unit/d vs. 0, HR 0.86; 95% CI 0.81–0.91). The proportions of the observed association of higher intakes of SSBs and ASB with CKD mediated by MetS were 12.5 and 18.0%, respectively.

Conclusions

Higher intakes of ASBs and SSBs were positively associated with the development of CKD, while moderate consumption of NJs was inversely associated with CKD risk. More intensified policy efforts are warranted to reduce intake of SSBs and ASBs for CKD prevention.
Elevated uric acid to serum albumin ratio: a predictor of short-term outcomes in Chinese heart failure patients
Authors: Liu Xianling , Chu Aihui , Ding Xiahao
Published: November 2024

Background

The prognostic value of the uric acid to albumin ratio (UAR) in heart failure (HF) remains underexplored. The objective of this research was to investigate the link between UAR and short-term outcomes in Chinese HF patients.

Methods

We analyzed data from 1893 HF patients, out of an initial cohort of 2008, who had available UAR measurements. The skewed distribution of UAR data was addressed by applying a Log-10 (lg) transformation and stratifying patients into three groups accordingly (low to high). The final outcome was identified as mortality or hospital readmission within 28 days. We employed restricted cubic spline analysis (RCS), Kaplan–Meier survival curves, and Cox proportional hazards models to evaluate the link between UAR and short-term outcomes.

Results

Among 1893 patients with HF [≥ 70 years, 1,382 (73.0%); female, 1,100 (58.1%)], the incidence of 28-day outcome was 8.6%. The RCS analysis suggested a positive relationship between lg(UAR) and 28-day outcomes, with no evidence of nonlinearity (p = 0.008). The cumulative incidence of 28-day readmission/death indicated that patients in the tertile 3 faced a significantly elevated risk of adverse outcomes (p < 0.001). Cox proportional hazards models showed that an elevated UAR was associated with a greater likelihood of 28-day mortality or hospital readmission (HR = 2.433, 95% CI: 1.638–3.615, p < 0.001). Even after accounting for possible confounding variables, the result still existed (HR = 1.594, 95% CI: 1.032–2.462, p = 0.036). Moreover, the associations were consistent in various subgroups, and sensitivity analysis (all p > 0.05).

Conclusion

Increased UAR correlates with a heightened risk of short-term death or hospital readmission in Chinese individuals suffering from HF. Maintaining a relatively lower UAR could potentially improve the clinical prognosis for these patients.
Case report: A rare low-grade fumarate hydratase-deficient renal cell carcinoma
Authors: Sun Di , Hu Baohong , Li Xinna , Yang Ping , Yu Guohua
Published: November 2024

Aim

To study and analyze the clinicopathological features of low-grade fumarate hydratase-deficient renal cell carcinoma in order to improve the understanding of the diagnosis and management of rare and specific morphological cases of this tumor.

Methods

A case of low-grade FH-deficient renal cell carcinoma in a male is reported, and its clinicopathological features were analyzed and literature review was performed.

Results

A 48-year-old middle-aged male with no relevant positive clinical signs was admitted to the hospital with an incidental finding of a mass in the lower pole of the left kidney during abdominal CT examination. Pathomorphology showed that the tumor cells were arranged in a variety of structures and the cells were low grade eosinophilic. Immunohistochemistry showed Pax-8 (+), Vim (partially +), FH (-), CK7 (-), CD117 (-), P504s (partially +), CD10 (partially +), CA-9 (-), TFE3 (partially +), SDHB (+), CK20 (-), and Ki-67 (+, about 2%). Final pathologic diagnosis: FH-deficient renal cell carcinoma (low grade).

Conclusion

Single pure low-grade FH-deficient renal cell carcinoma of the kidney is extremely rare, and the image structure of this tumor exhibits diverse manifestations, which needs to be differentiated from many renal tumors in clinicopathological diagnosis in order to prevent misdiagnosis.
A unique tripartite collision tumor of the esophagus: a case report and literature review
Authors: Luo Shuai , Tian Xiaoxue , Xu Ting , Wang Jinjing
Published: November 2024

Background

The coexistence of two or more distinct neoplasms within the same anatomical site characterizes collision tumors. While the presence of dual tumors is frequently observed in esophageal cases, the simultaneous occurrence of three distinct tumor types is extremely rare, posing significant challenges for pathological evaluation and diagnosis. Surgical resection remains the primary treatment, with generally favorable outcomes.

Case presentation

A 58-year-old male with a two-month history of progressively worsening dysphagia over the past 10 days underwent a gastrointestinal barium meal examination, which revealed an irregular filling defect measuring approximately 89×50 mm in the mid-thoracic esophagus. Subsequent gastroscopic biopsy confirmed undifferentiated pleomorphic sarcoma in the mid-esophageal tissue. As the dysphagia advanced, a partial esophagectomy with lymph node dissection was performed. Postoperative pathology revealed a composite tumor consisting of adenoid cystic carcinoma, undifferentiated pleomorphic sarcoma, and focal squamous cell carcinoma. Squamous cell carcinoma metastasis was identified in one lymph node. No adjuvant therapies, such as chemotherapy, radiotherapy, targeted therapy, or immunotherapy, were administered following surgery. The patient had been under monitoring for 101 months, with no signs of recurrence or metastasis.

Conclusion

This case represents the first documented instance of a tripartite collision tumor in the esophagus, composed of undifferentiated pleomorphic sarcoma, squamous cell carcinoma, and adenoid cystic carcinoma, with clear histological distinction. A thorough review of the literature was performed to summarize clinicopathological features. Surgical resection leads to a favorable prognosis. Tumors containing both carcinomatous and sarcomatous elements tend to have a more favorable prognosis compared to those composed entirely of carcinomatous tissue, providing valuable insights for future diagnostic and therapeutic strategies.
The diagnostic efficacy of seven autoantibodies in early detection of ground-glass nodular lung adenocarcinoma
Authors: Guo Hua , Zhao Wei , Li Chunsun , Wu Zhen , Yu Ling , Wang Miaoyu , Wei Yuanhui , Wang Zirui , Liu Shangshu , Yin Yue , Yang Zhen , Chen Liangan
Published: November 2024

Background

Persistent ground-glass nodules (GGNs) carry a potential risk of malignancy, however, early diagnosis remained challenging. This study aimed to investigate the cut-off values of seven autoantibodies in patients with ground-glass nodules smaller than 3cm, and to construct machine learning models to assess the diagnostic value of these autoantibodies.

Methods

In this multi-center retrospective study, we collected peripheral blood specimens from a total of 698 patients. A total of 466 patients with ground-glass nodular lung adenocarcinoma no more than 3cm were identified as a case group based on pathological reports and imaging data, and control group (n=232) of patients consisted of 90 patients with benign nodules and 142 patients with health check-ups. Seven antibodies were quantified in the serum of all participants using enzyme-linked immunosorbent assay (ELISA), and the working characteristic curves of the subjects were plotted to determine the cut-off values of the seven autoantibodies related ground-glass nodular lung adenocarcinoma early. Subsequently, the patients were randomly divided into a training and test set at a 7:3 ratio. Eight machine-learning models were constructed to compare the diagnostic performances of multiple models. The model performances were evaluated using sensitivity, specificity, and the area under the curve (AUC).

Results

The serum levels of the seven autoantibodies in case group were significantly higher than those in the control group (P < 0.05). The combination of the seven autoantibodies demonstrated a significantly enhanced diagnostic efficacy in identifying ground-glass nodular lung adenocarcinoma early when compared to the diagnostic efficacy of the autoantibodies when used respectively. The combined diagnostic approach of the seven autoantibodies exhibited a sensitivity of 84.05%, specificity of 91.85%, and AUC of 0.8870, surpassing the performance of each autoantibody used individually. Furthermore, we determined that Sparrow Search Algorithm-XGBoost (SSA-XGBOOST) had the best diagnostic performance among the models (AUC=0.9265), with MAGEA1, P53, and PGP9.5 having significant feature weight proportions.

Conclusions

Our research assessed the diagnostic performance of seven autoantibodies in patients with ground-glass nodules for benign-malignant distinction, and the nodules are all no more than 3cm especially. Our study set cut-off values for seven autoantibodies in identifying GGNs no more than 3cm and constructed a machine learning model for effective diagnosis. This provides a non-invasive and highly discriminative method for the evaluation of ground-glass nodules in high-risk patients.
Diagnosis progress of carcinoma of unknown primary
Authors: Qiao Yun , Wang Mei , Hui Kaiyuan , Jiang Xiaodong
Published: November 2024

Carcinoma of unknown primary (CUP) is a common and complex type of tumor in clinical practice, where the primary site cannot be determined through conventional diagnostic methods, posing significant challenges for clinical diagnosis and treatment. In recent years, advancements in gene expression profiling and genetic testing technologies have provided new perspectives for CUP research, driving progress in this field. By analyzing gene expression profiles, researchers can more effectively identify the tissue origin of tumors, thereby improving diagnostic accuracy. At the same time, the potential application of genetic testing is continuously being explored, offering new possibilities for personalized treatment. This article aims to discuss the latest advancements in the diagnosis of CUP, analyze the importance of gene expression profiling and genetic testing in tumor origin identification and their clinical applications, and summarize current research progress and future research directions, with the goal of providing a theoretical basis for the early diagnosis and treatment of CUP.
Association between various types of corticosteroids and mortality for severe community-acquired pneumonia in adults: a systematic review and network meta-analysis
Authors: Wang Peng , Wan Jun , You Qiaoyu , Zheng Yuxin , Xu Wenhao , He Jialing , Peng Liyuan , Jorge Luis Cuyubamba Dominguez , Feng Yuning , Xu Ping , Li Xinrong , Chong Weelic , Hai Yang , Jia Lu , Fang Fang , Zhang Yu
Published: November 2024

Objective

This study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections. The study seeks to address the gaps identified in the latest guidelines regarding the optimal use of different corticosteroid types and to provide recommendations for clinical practice.

Data Sources

This study conducted a comprehensive search of Medline, Embase, and the Cochrane Central Register of Controlled Trials, covering the period from inception until 22 June 2023. Randomized clinical trials for corticosteroid use among adults with SCAP were collected.

Study Selection

Two researchers independently assessed study eligibility based on titles and abstracts, with any disagreements resolved through discussion or consultation with a third researcher.

Data Extraction

Two researchers independently collected and clarified study details, with a third researcher adjudicating in case of disputes.

Data Synthesis

The data from 13 randomized clinical trials involving 2,495 patients, were analyzed using a random-effects model. Eleven trials were assessed as low risk, while two were assessed as high risk. Trials were rated as having low bias risk. Results, presented as risk ratios (RR) with a 95% confidence interval (CI), indicated that hydrocortisone outperformed prednisolone (RR 0.35; 95% CI 0.10–0.94), methylprednisolone (RR 0.41; 95% CI 0.15–0.89), and placebo (RR 0.35; 95% CI 0.16–0.59) in reducing 30-day mortality. A rankogram plot suggested that hydrocortisone had the highest probability of being the most effective treatment for this outcome within the analyzed group.

Conclusion

In this network meta-analysis, while hydrocortisone showed greater efficacy than prednisolone, methylprednisolone, and placebo in reducing 30-day mortality in patients with SCAP, further Randomized Controlled Trials (RCTs) are required to confirm these findings before drawing definitive conclusions.

Systematic Review Registration:

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438389, identifier CRD42023438389.
Molecular targets and mechanisms of Sijunzi decoction in the treatment of Parkinson’s disease: evidence from network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation
Authors: Jiang Yang , Wu Wanfeng , Xie Le , Zhou Yue , Yang Kailin , Wu Dahua , Xu Wenfeng , Fang Rui , Ge Jinwen
Published: November 2024

Aim

To explore the molecular mechanism of Sijunzi Decoction (SJZD) in the treatment of Parkinson’s disease (PD) through the application of network pharmacology, molecular docking, and molecular dynamics simulations, complemented by experimental verification.

Methods

The BATMAN-TCM, GeneCards, and DisGeNet databases were searched to screen the active components and therapeutic targets of SJZD. Cytoscape (3.7.1) was used to create a network diagram of the components and targets. The STRING platform was used to construct a protein-protein interaction (PPI) network. The Bioconductor database and RX64 (4.0.0) software were used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the core target genes. The binding sites and binding energies between SJZD active components and the target were analyzed by molecular docking and dynamic simulation. Finally, the therapeutic effect and mechanism of SJZD were verified by Cell Counting Kit-8 (CCK-8) and Western blotting (WB).

Results

This research identified 188 active compounds in SJZD, 1568 drug targets, 2069 PD targets, and 451 intersection targets related to PD. According to network analysis, Adenosine Triphosphate, Tridecanoic Acid, Hexadecanoic Acid, Pentadecanoic Acid, and Adenosine were identified as the core components of SJZD in the treatment of PD. The five targets with the highest Degree values in the PPI network were AKT1, INS, TNF, IL-6, and TP53. The GO and KEGG enrichment analyses, in turn, determined that the administration of SJZD for the treatment of PD may engage processes such as xenobiotic stimulation and biological stimulus response. Furthermore, AGE-RAGE and cAMP signaling pathways related to diabetic complications may be involved. Molecular docking and kinetic simulations showed that IL-6 and AKT1 bind best to Adenosine. Experimental results showed that SJZD significantly reduced 6-OHDA-induced apoptosis of SH⁃SY5Y cells by activating the PI3K/AKT signaling pathway and regulating the expression of apoptosis factors such as Bcl⁃2 and Bax.

Conclusion

SJZD is essential in the processes of apoptosis and neuronal protection, acting through various components that target multiple pathways. Notably, the PI3K/AKT pathway is a verified SJZD-PD target, providing a reference for clinical precision drug use for PD.
Charting the therapeutic landscape: a comprehensive evidence map on medical cannabis for health outcomes
Authors: Montagner Patrícia , de Salas Quiroga Adán , Ferreira Arthur Schveitzer , Duarte da Luz Barbara Marinho , Ruppelt Bettina Monika , Schlechta Portella Caio Fabio , Abdala Carmen Verônica Mendes , Tabach Ricardo , Ghelman Ricardo , Blesching Uwe , Perfeito João Paulo Silvério , Schveitzer Mariana Cabral
Published: November 2024

The therapeutic potential of medical cannabis has garnered significant attention in recent years, prompting an urgent need for a comprehensive understanding of its effectiveness across various health outcomes. This article presents an Evidence Map that systematically summarizes clinical evidence on the use of medical cannabis, including the health conditions it addresses, the interventions employed, and the resulting clinical outcomes. The objective is to map the effectiveness of medical cannabis in relation to a wide range of health outcomes. The systematic review process involved two independent, blinded literature researchers who screened the search output using Rayyan software. For studies deemed relevant, full texts were obtained to clarify inclusion or exclusion criteria, and any disagreements were resolved through group discussion. Out of 1,840 initial references, 279 potential studies were selected and read in full, resulting in the inclusion of 194 studies in this evidence map. The results highlight the use of various cannabis formulations, including those based on isolated cannabidiol (CBD). Seventy-one distinct health outcomes were identified in the systematic reviews, with the most reported outcomes being related to various types of pain and patient safety. Other frequently studied outcomes included appetite regulation, chemotherapy-induced nausea and vomiting, and muscle spasticity. Notably, 278 out of 489 descriptions of treatment effects for these health outcomes reported either “Positive” or “Potentially Positive” effects. When considering only high-quality systematic reviews, as evaluated by the AMSTAR 2 tool, 42 out of 67 descriptions of treatment effects for up to 20 health outcomes were classified as “Positive” or “Potentially Positive.” These outcomes included pain, insomnia, seizures, anxiety, muscle spasticity, multiple sclerosis, urinary incontinence, anorexia, and patient safety. This evidence map provides a comprehensive overview of the current clinical evidence on medical cannabis, highlighting its potential therapeutic benefits across a range of health conditions and emphasizing the need for further high-quality research.
Mitigating Paxlovid™-induced drug‒drug interaction toxicity: an in silico insight
Authors: Ta Giang H. , Leong Max K.
Published: November 2024

The clinical drug-drug interaction side-effects of Ritonavir, an ingredient in Paxlovid™, have been documented, highlighting the need to explore alternative administration methods for Nirmatrelvir, another drug in the Paxlovid™ combination. In this study, the skin permeability potential of Nirmatrelvir was assessed using various in silico models. The prediction results suggest that Nirmatrelvir could be administrated via the transdermal route, offering a promising avenue to enhance the efficacy of anti-COVID-19 agents.