bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral biomarkers to assess risk, severity, and prognosis of immune checkpoint inhibitor-associated myocarditis: a retrospective clinical study
Authors: Guan Zhengkun , Yao Tiezhu , Liu Guang , Liu Jing , Guo Ling , Li Zhenli , Ma Jingtao
Published: October 2024

Background

Immune checkpoint inhibitor-associated myocarditis (ICI myocarditis) is an infrequent but potentially fatal immune-related adverse event. This study aimed to identify valuable indicators for risk prediction and evaluation of disease severity and outcomes.

Methods

A total of 79 patients with severe or mild ICI myocarditis and 158 controls without post-ICI immune-related adverse events were enrolled in this retrospective study. The clinical application value of a series of simple biomarkers were tested.

Results

Higher levels of the systemic immune-inflammation index (SII), neutrophil-to-eosinophil ratio (NER), aspartate transferase-to-albumin ratio (AAR), and lactic dehydrogenase-to-albumin ratio (LAR) at myocarditis onset were associated with severe disease conditions. In the receiver operating characteristic analysis, biomarkers areas under the curve (AUC) close to or greater than 0.8 were LAR (AUC: 0.810) and AAR (AUC: 0.806). Patients with higher SII, AAR, and LAR also exhibited poorer overall survival. The SII, NER, AAR, and LAR before the last ICI treatment increased relative to baseline in patients with ICI myocarditis, whereas no significant changes in the tested biomarkers were observed in the control group. For SII, AAR, and LAR, high ratios of the biomarker levels before the last ICI to baseline was associated with the incidence of myocarditis.

Conclusions

Surveillance of these economical biomarkers during ICI therapy might contribute to the risk prediction of ICI myocarditis, as well as the assessment of disease severity and prognosis.
Long-term Helicobacter pylori infection is associated with an increased risk of carotid plaque formation: a retrospective cohort study
Authors: Chen Yi , Ni Bingqian , Yang Chaoyu , Pan Jingjing , Zhang Jinshun
Published: October 2024

Background

Cardiovascular disease significantly impacts human health. The development of carotid plaques elevates the risk of cardiovascular disease, while the influence of Helicobacter pylori (H. pylori) on carotid plaques remains a subject of debate. This study aimed to investigate the association between H. pylori infection and carotid plaque using a cohort study.

Methods

The study included individuals who underwent multiple physical examinations at the Health Examination Center of Taizhou Hospital. The relationship between H. pylori and carotid plaque was explored using multifactorial logistic regression analysis. Participants were categorized into groups based on their H. pylori infection status at the initial and final examinations, comprising persistent infection, persistent negative, new infection, and eradication infection, to analyze variations in carotid plaque prevalence among these groups.

Results

In both univariate and multifactorial regression analyses, H. pylori was identified as a risk factor for carotid plaque development. Moreover, when compared to the persistent negative group, both the new infection and persistent infection groups showed a notable increase in the risk of carotid plaque. Additionally, individuals in the persistent infection group exhibited higher blood pressure and blood glucose levels than those in the persistent negative group. Likewise, there was a discrepancy in the impact of insulin resistance on carotid plaque between the H. pylori positive and negative groups.

Conclusion

H. pylori is a risk factor for carotid plaque, with a long-term infection associated with an increased risk of carotid plaque formation. In addition, H. pylori promoting carotid plaque formation may be related to blood pressure, blood glucose, and insulin resistance.
Unequal causality between autoimmune thyroiditis and inflammatory bowel disease: a Mendelian randomization study
Authors: Bai Siyang , Yu Yunfeng , Yang Xinyu , Hu Gang , Wu Jingyi , Tong Keke , Yin Yuman , Deng Juan , Chen Cong , Tan Chuanchuan
Published: October 2024

Objective

This study aims to analyze the causal relationship between autoimmune thyroiditis (AIT) and inflammatory bowel disease (IBD) using bidirectional Mendelian randomization (MR).

Methods

Single nucleotide polymorphisms were obtained from FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. MR-Egger intercept, Cochran’s Q, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneity, and robustness, respectively.

Results

Forward analysis revealed no significant association between AIT and the risk of ulcerative colitis (UC) (odds ratio [OR] 1.008, 95% confidence interval [CI] 0.986 to 1.03, p = 0.460) or Crohn’s disease (CD) (OR 0.972, 95% CI 0.935 to 1.010, p = 0.143). Reverse analysis showed that UC (OR 0.961, 95% CI 0.783 to 1.180, p = 0.707) was not associated with AIT risk, while CD (OR 2.371, 95% CI 1.526 to 3.683, p < 0.001) was linked to an increased risk of AIT. Intercept analysis and Cochran’s Q test indicated no horizontal pleiotropy or heterogeneity. Sensitivity analysis confirmed the robustness of the MR results.

Conclusion

This MR analysis suggests that CD, but not UC, is a risk factor for AIT, whereas AIT is not associated with the risk of IBD. Proactive prevention and treatment of CD can help mitigate the risk of AIT.
Association between the triglyceride–glucose index and left ventricular myocardial work indices in patients with coronary artery disease
Authors: Meng Xuyang , Feng Baoyu , Yang Chenguang , Li Yi , Xia Chenxi , Guo Ying , Wang Xiang , Wang Fang
Published: October 2024

Background

Triglyceride–glucose (TyG) index, as an effective surrogate marker of insulin resistance, has shown predictive value in the risk of heart failure in patients with coronary artery disease (CAD). This study aims to investigate the correlation between TyG index and myocardial work measurements in CAD, and to explore its role in detecting early subclinical cardiac dysfunction.

Methods

This cross-sectional study included 267 patients diagnosed with CAD and excluding left ventricular myocardial dysfunction in Beijing Hospital. Participants were divided into two groups according to the TyG index level, and myocardial work measurements were compared between groups. The correlation was explored between gradually increased TyG index and subclinical myocardial function in CAD patients.

Results

We observed that TyG index was significantly correlated with the global waste work (GWW), and the value of GWW increased progressively with the elevation of TyG index. After adjusting for the effects of confounding factors, TyG index was still independently associated with GWW.

Conclusion

An elevated TyG index was independently correlated with early subclinical myocardial dysfunction in CAD patients. Our study demonstrated that the strict control of TyG index may be conducive to forestall the progression of clinical heart failure in CAD patients.
An analysis of the effects of different urban park space environment construction on national health
Authors: Zhang Weijian , Yang Boyi , Wang Ruijing , Guo Xitie
Published: October 2024

Urban green spaces, including parks, plazas, and squares, are essential components of healthy and sustainable cities. These areas play a central role in enhancing the wellbeing of citizens, fostering social interactions, and promoting sustainable urban development. This study investigates the multifaceted benefits of integrating green spaces into urban environments, such as improving physical and mental health, facilitating social engagement, and supporting environmental sustainability. Despite these benefits, the development and maintenance of urban green spaces face significant challenges, including limited suitable land, financial constraints, and inadequate access, which can exclude certain populations from enjoying these green havens. The study examines specific case studies, including Linyi People’s Park, Lanshan Youth Park, and Yumin Park, to highlight the factors contributing to the success or failure of these spaces. It also draws inspiration from international examples like New York City’s High Line and Germany’s Emscher Landscape Park, which have successfully transformed neglected areas into vibrant green oases. The findings underscore the importance of adopting principles of spatial justice, resource management, urban policy revision, and access reform to ensure the equitable distribution and accessibility of urban green spaces. The study concludes with key recommendations for urban planning and public health policy, aiming to enhance the wellbeing of citizens and strengthen the harmonious relationship between urban development and the natural environment. This study explores the multifaceted benefits of urban green spaces, including parks and plazas, highlighting their critical roles in enhancing physical and mental health, fostering social interactions, and promoting environmental sustainability. Through in-depth case studies of Linyi People’s Park, Lanshan Youth Park, and Yumin Park, the research identifies key factors contributing to the success and challenges of these spaces. Innovations in the study include a holistic analysis of green space benefits, a focus on spatial justice for equitable access, and comparative insights from international examples like New York City’s High Line and Germany’s Emscher Landscape Park. The research identifies several gaps, including the need for longitudinal studies on health impacts, understanding socioeconomic and cultural variability in green space use, evaluating the effectiveness of policy interventions, exploring technological integration, assessing environmental and economic trade-offs, and developing models for community engagement and ownership. Addressing these gaps will enhance strategies for integrating green spaces into urban environments, ensuring their benefits are accessible to all citizens.
Heme catabolism and heme oxygenase-1-expressing myeloid cells in pathophysiology
Authors: Consonni Francesca Maria , Incerti Martina , Bertolotti Milena , Ballerini Giulia , Garlatti Valentina , Sica Antonio
Published: October 2024

Although the pathological significance of myeloid cell heterogeneity is still poorly understood, new evidence indicates that distinct macrophage subsets are characterized by specific metabolic programs that influence disease onset and progression. Within this scenario, distinct subsets of macrophages, endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), play critical roles in physiologic and pathological conditions. Of relevance, the substrates of HO-1 activity are the heme groups that derive from cellular catabolism and are converted into carbon monoxide (CO), biliverdin and Fe2+, which together elicit anti-apoptotic, anti-inflammatory activities and control oxidative damage. While high levels of expression of HO-1 enzyme by specialized macrophage populations (erythrophagocytes) guarantee the physiological disposal of senescent red blood cells (i.e. erythrocateresis), the action of HO-1 takes on pathological significance in various diseases, and abnormal CO metabolism has been observed in cancer, hematological diseases, hypertension, heart failure, inflammation, sepsis, neurodegeneration. Modulation of heme catabolism and CO production is therefore a feasible therapeutic opportunity in various diseases. In this review we discuss the role of HO-1 in different pathological contexts (i.e. cancer, infections, cardiovascular, immune-mediated and neurodegenerative diseases) and highlight new therapeutic perspectives on the modulation of the enzymatic activity of HO-1.
Lipidome analyses reveal radiation induced remodeling of glycerophospholipid unsaturation in lung tumor
Authors: He Jingquan , Yuan Qingqing , Gao Song , Wang Yue , Lai Haigen , Wang Kaiting , Zhou Xiaoman , Zhang Zicheng
Published: October 2024

Radiotherapy is a pivotal treatment for lung cancer, significantly impacting tumor control and patient quality of life. Despite its benefits, the molecular mechanisms underlying radiotherapy-induced biological alterations in lung cancer cells remain inadequately understood. In this study, we employed a mass spectrometry-based lipidomics approach to investigate lipid profile changes in a lung cancer mouse model post-radiation. Lewis lung carcinoma (LLC) cells were injected into C57BL/6J mice, followed by radiation treatment with varying split doses. Our results showed an increase in sterol lipids and a decrease in glycerolipids, specifically triacylglycerides, indicating disrupted lipid storage. Additionally, we observed significant changes in glycerophospholipid unsaturation, suggesting a remodeling of membrane properties that may influence cell survival. Linear regression analysis demonstrated a significant negative correlation between glycerophospholipid unsaturation index and tumor weight, indicating a potential role in radiation-induced tumor cell death. These findings provide new insights into the lipid metabolic pathways affected by radiotherapy and could inform the development of improved therapeutic strategies for lung cancer treatment.
Case report: A rare EBV-associated T/NK cell monomorphic posttransplant lymphoproliferative disorder
Authors: Jiang Xin , Zhang Yao-Yu , Li Xiao-Wei , Li Xiao-Dong , Li Zhan-Yuan , Meng Wen-Jun , Li Sha-Dan
Published: October 2024

Background

Kidney transplantation (KT) is the best treatment for patients with end-stage renal disease. However, postoperative complications remain the main issues faced during KT recovery period. Posttransplant lymphoproliferative disorders (PTLD) are one of the severe and life-threatening complications that occur after KT while the recipient is undergoing immunosuppressive therapy. PTLD risk factors include Epstein-Barr virus (EBV) infection, the cumulative degree of immunosuppression, as well as genetic aspects. PTLD is more common in the transplanted organ itself and its surroundings, and the central nervous system, while PTLD involving the pharyngeal soft tissue is relatively rare, with only a few reported case reports. Therefore, systematic experience is scarce regarding whether the treatment or the care.

Case presentation

Herein, we report a 41-year-old male, underwent a reproductive KT due to chronic renal insufficiency. Recurrent fever, pharyngeal pain, and bilateral cervical lymph node enlargement were recurred during five years’ follow-up after KT surgery. In this inpatient experience, the patient vomited a large amount of blood from the oropharynx, then the tonsil artery was ligated by emergency operation. EBV-associated T/NK cell monomorphic PTLD was eventually diagnosed by blood EBV DNA test, pharyngeal biopsy, and corresponding pathological examination. After six cycles of R-CHOP chemotherapy, the clinical symptoms and laboratory tests changed into normal. Subsequent three years’ follow-up shows no tumor recurrence and good transplant kidney function.

Conclusion

This rare case report describes a manifestation of PTLD with pharyngeal involvement. Early diagnosis using histopathological examination is crucial to prevent damage to the throat and airway, and even life-threatening conditions. Discontinuing immunosuppression and starting systemic treatment can help in disease regression. Since the low incidence of this disease, limited clinical experience, and limited data, our experience with a smooth recovery through efficacy treatment and nursing can provide a reference for the development of new clinical drugs and diagnostic and treatment plans of patients with PTLD in the future.
Medical and economic impacts of managing corneas from older donors at the tissue bank—a single-center retrospective study spanning over 12 years
Authors: Hatzfeld Anne-Sophie , Germain Nicolas , Maboudou Patrice , Dhayer Mélanie , Marchetti Philippe
Published: October 2024

Aim

To evaluate the impact of corneas from donors over 80 years of age on the activity of the North of France Tissue Bank and to determine the potential cost implications for banks using corneas from older donors.

Methods

We analyzed data from a single-center retrospective cohort study of 6,023 corneas preserved at the Lille Tissue Bank between 2012 and 2023. Donors, unrestricted by age, were divided into two groups: younger (≤ 80 years) and older (> 80 years). Corneas were categorized based on endothelial cell density (ECD). Data were collected from patients who underwent corneal transplantation. A financial impact model was created to assess the effects of using corneas from different age groups on the overall benefits of corneal transplant procedures.

Results

The average donor age was 67.5 ± 14.5 years. The median age of donors gradually increased from 66 to 73 years over the 12-year study period, with donors over 80 years old representing more than 24% since 2021. Corneas from older donors had a higher discard rate (62.53% vs. 39.66%) due to poor endothelial quality and serological concerns (both p < 0.0001). Additionally, these corneas had lower ECD, with a larger proportion deemed unsuitable for grafting due to low ECD (30% vs. 8.2%). Corneas from younger donors were more often used for endothelial transplants, which require higher ECD. The mean economic benefit per cornea showed a moderate negative correlation with donor age. The net benefit of corneal transplants decreased as the proportion of donors aged over 80 years increased. It is predicted that a net benefit of zero would be attained when the proportion of donors over 80 years is 44.4%.

Conclusion

Using corneas from donors over 80 years of age can help alleviate the shortage of donor tissue and be effective if certain quality standards are met. However, additional costs incurred by eye banks must be factored into this equation.
Home-monitoring/remote optical coherence tomography in teleophthalmology in patients with eye disorders—a systematic review
Authors: Dolar-Szczasny Joanna , Drab Agnieszka , Rejdak Robert
Published: October 2024

Introduction

Teleophthalmology uses technology to provide remote eye care services, tackling obstacles in accessing specialized care. Optical coherence tomography (OCT) represents a technical advancement, enabling high-resolution ocular imaging. The aim of this study is to evaluate the diagnostic accuracy, feasibility, safety, and clinical utility of home monitoring OCT devices and remote OCT technology compared to standard in-office OCT in teleophthalmology settings across various eye conditions.

Materials and methods

A systematic literature search was conducted in PubMed, Cochrane Library, ScienceDirect and Google Scholar for studies on home-monitoring/remote OCT published from January 2004 to February 2024. Studies utilizing home monitoring/remote OCT in teleophthalmology for patients with eye disorders and reporting on diagnostic accuracy, safety, disease monitoring (clinical utility) or treatment response were included and synthesized narratively.

Results

A total of 12 research studies involving 3,539 participants were incorporated in the analysis. The majority of home or remote OCT scans exhibited satisfactory diagnostic image quality. There was high agreement between home/remote and in-office OCT for detecting pathologies and measuring retinal thickness. Compared to in-person evaluations, home/remote OCT demonstrated excellent sensitivity and specificity, though some variability was seen across conditions and interpreters. Home OCT devices provided feasible and safe self-operation with high patient acceptability. Scan times were faster when conducted at home compared to those in the office.

Conclusion

Home/remote OCT devices can effectively provide diagnostic-grade retinal imaging outside traditional settings. High diagnostic accuracy was demonstrated compared to in-office OCT. Feasibility and patient acceptability data support home OCT for remote monitoring.
Association between the body roundness index and osteoarthritis: evidence from NHANES
Authors: Ke Tiancheng , Lai Jianqiang , Li Xianmin , Liu Fuqian , Liu Wei , Zhong Chengfan
Published: October 2024

Background

The body roundness index (BRI) is a quantitative measure used to evaluate the presence of obesity and the distribution of body fat. However, the relationship between the BRI and osteoarthritis (OA) is still unclear. This study aimed to examine the relationship between the BRI and the occurrence of OA.

Methods

This study was a cross-sectional analysis used to analyze data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. A variety of variables were included in this investigation, which employed logistic regression analysis to assess the correlation between the BRI and OA. The robustness of the results and the impact of stratification variables were evaluated using subgroup and sensitivity analyses. To evaluate the ability of the BRI to predict OA, receiver operating characteristic (ROC) analysis was performed.

Results

The analysis included 19,717 participants. Participants with OA had a significantly greater BRI than those without OA. Logistic regression analysis revealed a statistically significant positive correlation between the BRI and OA (OR = 1.18, 95% CI = 1.15–1.21, p-value <0.001). Despite the complete adjustment for covariates, this association remained stable (OR = 1.10, 95% CI = 1.04–1.17, p-value = 0.002). The results were corroborated by subgroup and sensitivity analyses, which demonstrated their robustness. Moreover, the BRI exhibited greater predictive accuracy for OA than did BMI.

Conclusion

The BRI and OA are significantly associated in adults in the United States. The risk of developing OA may be increased by elevated levels of the BRI. Monitoring levels of the BRI is essential to prevent or reduce the prevalence and advancement of OA.
Regional assessment of choroidal vascularity index in patients with pre- and early-stage diabetic retinopathy using ultra-wide-field OCTA
Authors: Chen Yulei , Xian Haoxiong , Liu Minghui , Dong Xiuqing , Du Shaolin
Published: October 2024

Purpose

To characterize the regional variations of choroidal vascularity index (CVI) in patients with diabetes mellitus (DM) using ultra-wide-field optical coherence tomography angiography (UWF-OCTA) and identify their correlations with the onset of diabetic retinopathy (DR).

Methods

This cross-sectional, monocular-sampling study recruited 141 participants from four age-matched groups: no DM (NDM), no DR with early DM (EDM) and late DM (LDM), and mild–moderate non-proliferative diabetic retinopathy (mNPDR). UWF-OCTA was employed for circular scans centered on the fovea. CVI in the central region (0–1 mm) and four quadrants of the concentric rings with different ranges (1–3, 3–6, 6–9, 9–12, 12–15, 15–18 mm) was obtained for analysis together with their demographic and clinical data. The Area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic efficacy for mNPDR and compared using the DeLong test.

Results

The average CVI was lower in patients with mNPDR compared to other groups across all regions. Although there was no significant difference in DM duration between the LDM and mNPDR groups, a notable variance in CVI was observed, particularly (p = 0.0004) in the temporal quadrant of the 15–18 mm range (T18). CVI in T18 region was negatively correlated with creatinine levels, while positively correlated with body mass index and estimated glomerular filtration rate (ps < 0.05). The CVI in the T18 region demonstrated superior diagnostic efficacy (AUC = 0.755), and when combined with those in other regions and clinical data, the AUC rose to 0.907, which was significantly better (p = 0.0280) than using clinical data alone.

Conclusion

Reduced CVI was observed in the most peripheral region, highly predictive for mNPDR and associated with the declining renal function, thus enhancing the potential of UWF-OCTA to integrate into DM management and promote early DR screening.
Dissecting the rust resistance in salt tolerant wheat germplasm
Authors: Lata Charu , Prasad Pramod , Gangwar Om P. , Kallugudi Jayanth , Adhikari Sneha , Manjul Anshul Sharma , Kumar Subodh , Kumar Arvind , Kulshreshtha Neeraj , Khippal Anil , Tiwari Ratan
Published: October 2024

Wheat is one of the most important food crop cultivated across the globe which ensures sustainability and food security to massive world’s population, but its production is threatened by both biotic factors like rust (caused by Puccinia species) and abiotic stresses such as salinity. In this study, 41 salt-tolerant wheat lines were screened for rust resistance at both seedling and adult plant stages. Rust resistance genes were characterized through gene matching technique and molecular markers analysis. Yr2 was confirmed in 23 lines, while Yr9 along with Lr26/Sr31 were postulated in six lines with the help of SRT and molecular markers. Except for KRL2013, none showed complete resistance to all Puccinia striiformis f. sp. tritici (Pst). Lr24/Sr24 genes were confirmed in HD2851 and KRL2029, and Lr13 was detected in a maximum of 24 wheat lines, with varying reaction responses to different leaf rust pathotypes. Several lines carried additional resistance genes such as Sr11, Sr28, and Lr68. Lr68 an effective race non-specific APR gene identified in 15 wheat lines with the help of CsGs-STS marker. Although many salt-tolerant wheat lines were susceptible to yellow rust during the seedling stage, a few lines showed APR in the years during 2020 and 2021. Three lines (KRL213, KRL219 and KRL238) showed complete resistance at adult plant stage to leaf rust. These findings offer insights into the genetic basis of rust resistance in salt-tolerant wheat, aiding breeding strategies.
Suppression of SARS-CoV-2 nucleocapsid protein dimerization by ISGylation and its counteraction by viral PLpro
Authors: Bang Wonjin , Kim Jaehyun , Seo Kanghun , Lee Jihyun , Han Ji Ho , Park Daegyu , Cho Jae Hwan , Shin Donghyuk , Kim Kyun-Hwan , Song Moon Jung , Ahn Jin-Hyun
Published: October 2024

Protein modification by the ubiquitin-like protein ISG15 (ISGylation) plays a crucial role in the immunological defense against viral infection. During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, innate immune signaling proteins are ISGylated, facilitating innate immunity. However, whether SARS-CoV-2 proteins are direct substrates for ISGylation remains unclear. In this study, we investigated whether SARS-CoV-2 proteins undergo ISGylation and whether ISGylation affects viral protein function. Co-transfection ISGylation analysis of SARS-CoV-2 proteins showed that the nucleocapsid (N) protein is ISGylated at several sites. Herc5 promoted N ISGylation and interacted with N, indicating that Herc5 acts as an E3 ligase for N ISGylation. Lys-261 (K261) within the oligomerization domain of N was identified as a potential ISGylation site that is necessary for efficient ISGylation of N. K261 is positioned at the center of the dimer interface in the crystal structure of the C-terminal domain dimer and the ISGylated form of N showed reduced protein dimerization in pull-down analysis. Importantly, a recombinant virus expressing K261R mutant N showed enhanced resistance to interferon-β treatment compared to its parental virus. We also found that viral PLpro removes conjugated ISG15 from N. Our findings demonstrate that ISGylation of SARS-CoV-2 N inhibits protein dimerization, resulting in viral growth more susceptible to type I interferon responses, and that viral PLpro counteracts this ISG15-mediated antiviral activity by removing conjugated ISG15 from N.
Novel cuproptosis metabolism-related molecular clusters and diagnostic signature for Alzheimer’s disease
Authors: Jia Fang , Han Wanhong , Gao Shuangqi , Huang Jianwei , Zhao Wujie , Lu Zhenwei , Zhao Wenpeng , Li Zhangyu , Wang Zhanxiang , Guo Ying
Published: October 2024

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with no effective treatments available. There is growing evidence that cuproptosis contributes to the pathogenesis of this disease. This study developed a novel molecular clustering based on cuproptosis-related genes and constructed a signature for AD patients.

Methods

The differentially expressed cuproptosis-related genes (DECRGs) were identified using the DESeq2 R package. The GSEA, PPI network, GO, KEGG, and correlation analysis were conducted to explore the biological functions of DECRGs. Molecular clusters were performed using unsupervised cluster analysis. Differences in biological processes between clusters were evaluated by GSVA and immune infiltration analysis. The optimal model was constructed by WGCNA and machine learning techniques. Decision curve analysis, calibration curves, receiver operating characteristic (ROC) curves, and two additional datasets were employed to confirm the prediction results. Finally, immunofluorescence (IF) staining in AD mice models was used to verify the expression levels of risk genes.

Results

GSEA and CIBERSORT showed higher levels of resting NK cells, M2 macrophages, naïve CD4+ T cells, neutrophils, monocytes, and plasma cells in AD samples compared to controls. We classified 310 AD patients into two molecular clusters with distinct expression profiles and different immunological characteristics. The C1 subtype showed higher abundance of cuproptosis-related genes, with higher proportions of regulatory T cells, CD8+T cells, and resting dendritic cells. We subsequently constructed a diagnostic model which was confirmed by nomogram, calibration, and decision curve analysis. The values of area under the curves (AUC) were 0.738 and 0.931 for the external datasets, respectively. The expression levels of risk genes were further validated in mouse brain samples.

Conclusion

Our study provided potential targets for AD treatment, developed a promising gene signature, and offered novel insights for exploring the pathogenesis of AD.
Analyzing public discourse of dementia from Spanish and English tweets: a comparative analysis with other neurological disorders
Authors: Domingo-Espiñeira Javier , Fraile-Martínez Óscar , García Montero Cielo , Lara Abelenda Francisco Jesus , Porta-Etessam Jesús , Baras Pastor Laura , Muñoz-Manchado Leticia I. , Arrieta María , Saeidi Mahdieh , Ortega Miguel A. , Alvarez De Mon Melchor , Alvarez-Mon Miguel Angel
Published: October 2024

Introduction

Dementia comprise a broad spectrum of cognitive declines affecting 47 million people worldwide, with numbers projected to reach 131 million by 2050. Predominantly associated with older adults, dementia can also impact younger individuals, having a significant impact on daily functioning of the affected patients, relatives, caregivers and the socioeconomic system. Recent research underscores the utility of social media, particularly X (previously designed as Twitter), in understanding public perceptions and sentiments related to neurological disorders. Despite some initial studies have explored social perceptions of dementia in X, broader and deeper analysis of this condition is still warranted.

Materials and methods

In this retrospective study, we collected and examined all tweets posted in English or Spanish from 2007 to 2023 that mentioned dementia and compare the information with other highly representative neurological disorders like migraines, epilepsy, multiple sclerosis, spinal cord injury, or Parkinson's disease. We developed a codebook to analyze tweets, classifying them by themes such as trivialization, treatment perceptions, and etiopathogenesis. Manually categorized tweets trained machine learning models, BERTWEET for English and BETO for Spanish, which then classified larger datasets with high accuracy. Statistical analysis, including ANOVA, Kruskal-Wallis, and chi-square tests, was conducted to explore linguistic and cultural differences in perceptions of neurological disorders, with results visualized.

Results

Our study reveals that dementia is by far the most frequently discussed neurological disorder on X. Likewise, this condition appears to be the most trivialized neurological disorder in Spanish tweets and the second most trivialized in English tweets, with notable differences in geolocation data. Additionally, we found significant differences in perceptions of dementia treatment and associated sentiments between Spanish and English tweets. Furthermore, our study identified varying perceptions of medical content (etiology) and non-medical content (positive/negative experiences and aid requests) related to dementia and other neurological disorders, unveiling a complex landscape of these topics on X.

Conclusions

This study explores the importance of X as a social platform for addressing various critical issues related to dementia, comparing it with other neurological disorders in English and Spanish tweets. Future research could further investigate the valuable role of social media in understanding public perceptions and needs regarding dementia and neurological disorders among X users.
Improvements in no evidence of disease activity with ublituximab vs. teriflunomide in the ULTIMATE phase 3 studies in relapsing multiple sclerosis
Authors: Alvarez Enrique , Steinman Lawrence , Fox Edward J. , Hartung Hans-Peter , Qian Peiqing , Wray Sibyl , Robertson Derrick , Selmaj Krzysztof , Wynn Daniel , Mok Koby , Xu Yihuan , Bodhinathan Karthik , Miskin Hari P. , Cree Bruce A. C.
Published: October 2024

Background

Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity. The phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate, total number of gadolinium-enhancing (Gd+) T1 lesions, and total number of new or enlarging T2 at Week 96, as well as improvement in the proportion of participants with no evidence of disease activity (NEDA) from Weeks 24–96 with ublituximab vs. teriflunomide.

Methods

In ULTIMATE I (NCT03277261; www.clinicaltrials.gov) (N = 549) and II (NCT03277248; www.clinicaltrials.gov) (N = 545), participants with relapsing multiple sclerosis received ublituximab 450 mg intravenous infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks. Pooled post hoc analyses evaluated NEDA by treatment epoch and participant subtype: age ( ≤ 38 or >38 years), early or later disease (<3 or ≥3 years following diagnosis), treatment history (treatment naïve or previously treated), 0 or ≥1 Gd+ T1 lesions at baseline, and Expanded Disability Status Scale score ≤ 3.5 or >3.5 at baseline. NEDA was defined as no confirmed relapses, no Gd+ T1 lesions, no new or enlarging T2 lesions, and no disability progression confirmed for ≥12 weeks.

Results

NEDA rates in the ublituximab vs. teriflunomide cohorts by treatment epoch were: Weeks 0–96, 44.6% vs. 12.4% (3.6 × improvement); Weeks 24–96 (re-baselined), 82.1% vs. 22.5% (3.6 × improvement); and Weeks 48–96 (re-baselined), 88.2% vs. 30.4% (2.9 × improvement) (all p < 0.0001). The primary driver of disease activity in ublituximab-treated participants was new or enlarging T2 lesions during Weeks 0–24. 41.8% of ublituximab-treated participants who had evidence of disease activity in the first year (Weeks 0–48) experienced NEDA in the second year of treatment (Weeks 48–96) compared with 17.3% of teriflunomide-treated participants. At Weeks 24–96 (re-baselined), rates of NEDA were significantly higher with ublituximab than teriflunomide in all participant subtypes (all p < 0.0001).

Conclusions

ULTIMATE I and II pooled post hoc analyses demonstrated a consistent NEDA benefit among ublituximab-treated participants across treatment epochs and key participant subpopulations.
Role of non-coding RNA in exosomes for the diagnosis and treatment of osteosarcoma
Authors: Liu Xin , Wang Yaling , Wang Chenwen , Wang Xinyuan , Tang Gangqiang , Xiong Zhou , Zhou Wei
Published: October 2024

Osteosarcoma (OS) is a malignancy characterized by the proliferation of osteoblasts that predominantly affects pediatric and adolescent populations. At present, early detection of OS is significantly lacking, coupled with treatment challenges such as high recurrence rates, increased side effects, and the development of drug resistance. Therefore, developing new diagnostic and therapeutic modalities is clinically significant. Exosomes are naturally occurring nanoparticles found in the body that contain various materials, including DNA, RNA, and proteins. Owing to their numerous beneficial properties, including histocompatibility and in vivo stability, they can be useful as drug carriers. With the development of competitive endogenous non-coding RNA (ncRNA) networks, the role of ncRNA in OS cell control has been increasingly studied. This review provides a thorough summary of multiple potential biogenetic pathways of different ncRNAs in exosomes, including microRNAs, long ncRNAs, and circular RNAs. Moreover, the review highlights their effects on OS cells and their potential applications in the diagnosis, treatment, and control of OS drug resistance. The interplay between different types of ncRNAs, which collectively affect OS through the networks of competing endogenous ncRNAs, is the primary focus of this research.
Complex karyotypes in hematologic disorders: a 12-year single-center study from Lebanon
Authors: Rammal Souraya , Abou Abdallah Farid , Attieh Charbel , El Mounajjed Zeinab , Semaan Warde , Chebly Alain
Published: October 2024

Conventional cytogenetic analysis is an important tool for the diagnosis of many hematologic disorders (HD). A karyotype is designed as « complex » when several alterations are detected. However, there is no clear consensus on the exact definition of a complex karyotype (CK), and there is a lack of studies that exclusively analyze CK in the literature. Complex karyotypes were analyzed over a period of 12 years at the Jacques Loiselet Center for Medical Genetics and Genomics (CGGM) at Saint Joseph University in Beirut (USJ) in Lebanon. 255 CK were analyzed with their associated chromosomal abnormalities (CA) detected. Out of 255 patients, 59.22% were males with a mean age of 59 years. The most common anomaly associated with CK was hyperdiploidy with a prevalence of 22.41%, which is different from a previously published study. To our knowledge, this represents the largest series of CK, particularly within the Middle East region. This study underscores the critical role of conventional cytogenetics in detecting CK, ultimately contributing to improved management of HD. Further investigations focusing on CK are needed.
Risk factors for pleural effusion in children with plastic bronchitis caused by pneumonia
Authors: Lin Xiaoliang , Xu Enhui , Zhang Tan , Zhu Qiguo , Zhuang Deyi
Published: October 2024

Objective

We aimed to investigate the clinical features of children with plastic bronchitis caused by pneumonia, and assess the risk factors for pleural effusion (PE) in plastic bronchitis.

Methods

A retrospective study was conducted on children with plastic bronchitis and hospitalized in Xiamen Children’s Hospital from January 2017 to April 2023. Participants were categorized based on the presence of PE. Their clinical manifestations and laboratory findings were analyzed.

Results

Sixty-nine children with plastic bronchitis were enrolled: 34 cases (49.27%) in the non-PE group and 35 cases (50.72%) in the PE group. No significant differences were found in sex, age, and etiology between the two groups. Significant differences were found in fever duration, C-reactive protein (CRP), albumin and lactate dehydrogenase (LDH) (p<0.05). A receiver operating characteristic (ROC) curve analysis showed that the cut-off values for higher risk of PE were CRP >31.66 mg/L or LDH >551 U/L. The prediction of PE was performed with the combination of CRP >31.66 mg/L and LDH >551 U/L, using multivariate logistic regression analysis. The area under the curve (AUC) for logistic regression was 0.797. Elevated CRP increased the risk of PE (odds ratio [OR] 8.358, 95% confidence interval [CI] 2.179–42.900, p=0.0042), elevated LDH increased the risk of PE (OR 5.851 [95% CI 1.950–19.350], p=0.0023).

Conclusion

The combined detection of CRP and LDH helps predict the risk of PE in children with plastic bronchitis caused by pneumonia.
Deciphering quinazoline derivatives’ interactions with EGFR: a computational quest for advanced cancer therapy through 3D-QSAR, virtual screening, and MD simulations
Authors: Anwar Sirajudheen , Alanazi Jowaher , Ahemad Nafees , Raza Shafaq , Chohan Tahir Ali , Saleem Hammad
Published: October 2024

Introduction

The epidermal growth factor receptor (EGFR) presents a crucial target for combatting cancer mortality.

Methods

This study employs a suite of computational techniques, including 3D-QSAR, ligand-based virtual screening, molecular docking, fingerprinting analysis, ADME, and DFT-based analyses (MESP, HOMO, LUMO), supplemented by molecular dynamics simulations and MMGB/PBSA free energy calculations, to explore the binding dynamics of quinazoline derivatives with EGFR. With strong q2 and r2 values from CoMFA and CoMSIA models, our 3D- QSAR models reliably predict EGFR inhibitors’ efficacy.

Results and Discussion

Utilizing a potent model compound as a reference, an E-pharmacophore model was developed to sift through the eMolecules database, identifying 19 virtual screening hits based on ShapeTanimoto, ColourTanimoto, and TanimotoCombo scores. These hits, assessed via 3D- QSAR, showed pIC50 predictions consistent with experimental data. Our analyses elucidate key features essential for EGFR inhibition, reinforced by ADME studies that reveal favorable pharmacokinetic profiles for most compounds. Among the primary phytochemicals examined, potential EGFR inhibitors were identified. Detailed MD simulation analyses on three select ligands—1Q1, 2Q17, and VS1—demonstrated their stability and consistent interaction over 200 ns, with MM/GBSA values corroborating their docking scores and highlighting 1Q1 and VS1’s superior EGFR1 affinity. These results position VS1 as an especially promising lead in EGFR1 inhibitor development, contributing valuable insights towards crafting novel, effective EGFR1 inhibitors.
Impact of single-nucleotide variants and individual characteristics on adverse events of L-asparaginase in children with acute lymphoblastic leukemia
Authors: Gándara-Mireles Jesús Alonso , Lares-Asseff Ismael , Reyes Espinoza Elio Aarón , Loera Castañeda Verónica , Córdova Hurtado Lourdes Patricia , Reyes Gutiérrez Flor de María , Sandoval-Cabrera Antonio , Villanueva Fierro Ignacio , Grijalva Ávila Julio Cesar , Castro Arreola Claudia , Patrón-Romero Leslie , Almanza Reyes Horacio
Published: October 2024

Introduction

L-Asparaginase (L-Asp) is a key drug in the treatment of acute lymphoblastic leukemia (ALL); however, it is commonly associated with the occurrence of adverse events (AE). Risk factors such as age, sex, nutritional status, and some single nucleotide variants (SNVs) in specific genes could be related to hypersensitivity reactions to L-Asp. The objective of this study was to identify the influence of individual characteristics and three SNVs in the GRIA1 and NFATC2 genes on the occurrence of the most significant adverse events caused by the use of L-Asp in Mexican children with ALL.

Methods

Eighty-five children from ages 0–17 years old diagnosed with ALL were included. The patients were treated at two hospital centers in Mexico. The SNV genotypes of the GRI1A and NFATC2 genes studied were examined using real-time qPCR. The evaluation of AE was carried out according to the Common Terminology Criteria for adverse events, and the determination of anti-L-Asp antibodies was conducted using Western blot immunoassay.

Results

Homozygosity (AA) of the GRIA1 rs4958351 SNV was significantly associated with the occurrence of AE with the use of L-Asp (OR = 4.05; 95% CI = 1.06 to 15.40, p = 0.04) and was strongly associated with the development of anti-L-Asp antibodies (OR = 3.4375, 95% CI = 1.04 to 11.25, p = 0.04). With this, we found a significant risk association for the SNV rs4958351 of the GRIA1 gene. On the other hand, we did not find significant risk associations for the GRIA1 rs6889909 and NFATC2 rs6021191 SNVs, although other populations have shown a significant risk.

Discussion

Our study has some limitations, such as the small sample size, the heterogeneity in adverse events due to the patients’ different regions of origin, and the limited ability to conduct a more detailed follow-up on pancreatitis. Additionally, since no significant associations were found between the NFATC2 rs6021191 and GRIA1 rs6889909 SNVs and the development of adverse events or the presence of antibodies due to the use of L-Asp, it is necessary to investigate new specific SNVs that may improve the efficacy and safety of treatment in Mexican children with ALL.
Pharmacist-led hospital intervention reduces unintentional patient-generated medication discrepancies after hospital discharge
Authors: Jošt Maja , Knez Lea , Kos Mitja , Kerec Kos Mojca
Published: October 2024

Background

Medication reconciliation can significantly reduce clinically important medication errors at hospital discharge, but its impact on post-discharge medication management has not been investigated. We aimed to investigate the incidence of patient-generated medication discrepancies 30 days after hospital discharge and the impact of a pharmacist-led medication reconciliation coupled with patient counselling on clinically important discrepancies caused by patients.

Methods

A pragmatic, prospective, controlled clinical trial was conducted at the University Clinic Golnik, Slovenia. Adult patients were divided into an intervention group and a control group. The intervention group received pharmacist-led medication reconciliation at admission and discharge, plus patient counselling at discharge. Medication discrepancies were identified by comparing the therapy prescribed in the discharge letters with the therapy 30 days after discharge, obtained through telephone patient interviews. Discrepancies were classified as intentional or unintentional, and their clinical importance was assessed.

Results

The study included 254 patients (57.9% male, median age 71 years), with 136 in the intervention group and 118 in the control group. Discrepancies occurred with a quarter of the medicines (617/2,441; 25.3%) at 30 days after hospital discharge, and patients themselves caused half of the discrepancies (323/617; 52.4%), either intentionally (171/617; 27.7%) or unintentionally (152/617; 24.6%). Clinically important discrepancies occurred in 18.7% of intentional and 45.4% of unintentional patient-generated changes. The intervention significantly reduced the likelihood of clinically important unintentional patient-generated discrepancies (OR 0.204; 95%CI: 0.093–0.448), but not clinically important intentional patient-generated discrepancies (OR 2.525; 95%CI: 0.843–7.563). The latter were more frequent among younger, male patients and patients hospitalized for respiratory diseases.

Conclusion

The study emphasizes the importance of addressing discrepancies made by patients after hospital discharge, which can result in potentially harmful outcomes. It also shows that a pharmacist-led hospital intervention can significantly reduce discrepancies in the early post-discharge period. These findings can guide the development of future services to improve patient support for medication management after hospitalization.