bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity in Kawasaki disease patients with coronary artery abnormalities investigated by data-driven cluster analysis
Authors: Sunaga Yuto , Hasebe Yohei , Kikuchi Natsumi , Yoshizawa Masashi , Kono Yosuke , Katsumata Nobuyuki , Inukai Takeshi 
Published: October 2024

Abstract

Purpose: To investigate possible heterogeneity in Kawasaki disease (KD) cases that developed coronary artery abnormality (CAA) in the acute phase and to assess associated clinical characteristics.
Methods: We performed a cluster analysis in 103 KD cases that developed CAA (maximum Z score for any coronary arteries > 2.5) within 30 days after disease onset among 726 consecutive KD cases. The hierarchical cluster analysis was performed based on 20 continuous variables derived from 33 continuous variables before initial treatment.
Results: 101 out of 103 cases with CAA in the acute phase were clustered into 4 subgroups. Cluster 1 (22 cases, 21.8%) was a younger group characterized by leukocytosis and elevated serum triglyceride levels, together with frequent coronary artery dilation before treatment and good initial treatment responses. Cluster 2 (32 cases, 31.7%) was a younger group characterized by anemia and lower serum total cholesterol levels, together with average initial treatment responses. Cluster 3 (30 cases, 29.7%) was an older group lacking distinct features, together with frequent coronary artery dilation before treatment. Cluster 4 (17 cases, 16.8%) was an older group characterized by elevated levels of serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin and decreased serum sodium levels, together with poor initial treatment response and the lowest incidence of coronary artery dilatation before treatment.
Conclusion: Our cluster analysis identified four subgroups with distinct features suggesting different　backgrounds for CAA development. Consideration of possible heterogeneity might be helpful for better understanding of the pathophysiology and better treatment strategies in KD cases.
Dysplasia of cortical capillaries as the origin of Alzheimer’s disease: experimental evidence from APP/PS1
Authors: Xie Yirong , Pi Shurong , Zhong Jingyi , Lu Yao , Liu Jieyi , Li Xin , Jiang Jun , Li Hongya , Su Heng , Zhao Zhiqiang , Wei Qing , Chen Fubin , Lu Lingeng , He Yun 
Published: October 2024

Abstract

To investigate the time course changes of key pathological features of Alzheimer’s disease (AD) and relationship between vascular damage, neuro-inflammation and Aβ in AD model. VEGFR2 expression, vascular number and Aβ levels in cortex and cerebrospinal fluid, cortical and serum inflammatory factor levels, and autonomic activity/memory were analyzed in APP/PS1 mice from 1 to 12-month-old. Transcriptomic analysis of cortical capillaries in one-month-old mice and pathway analysis were performed. Validation of cortical transcriptome data in AD patients from GEO database. Soluble Aβ1−42 oligomers were treated with mouse brain vascular pericytes and endothelial cells. APP/PS1 mice had decreased cortical capillary VEGFR2 expression and vascular dysplasia at 1-month-old, increased endothelial cell apoptosis and decreased capillary density at 3-month-old, increased cortical Aβ1−42 deposition and neuron apoptosis at 6-month-old. APP/PS1 mice showed decreased autonomic activity and increased memory loss at 9-month-old. Cortical capillary transcriptome profiling indicated that a significant energy metabolism deficit was observed at 1-month-old. Increased mRNA expression of vascular-related genes in elderly surviving AD patients. 0.1µM soluble Aβ1−42 oligomers promote angiogenesis, whereas 10µM inhibit it. Cortical capillary dysplasia is a primary contributor to the onset of AD. The accumulation of Aβ in the brain exacerbates vascular hypoplasia by damaging blood vessels, and the interplay between these factors accelerates the progression of AD. Improving vascular functions and energy metabolisms may have potential in delaying or preventing AD.
Faricimab Efficacy in Type 1 Macular Neovascularization: AI-Assisted Quantification of Pigment Epithelium Detachment (PED) Volume Reduction Over 12 Months in Naïve and Switch Eyes
Authors: Cattaneo Jennifer , Forte Paolo , Forte Giovanni , Eandi Chiara M. 
Published: October 2024

Abstract

Background: This study evaluates the efficacy of intravitreal Faricimab in reducing pigment epithelium detachment (PED) and fluid volumes in both treatment-naïve eyes and eyes unresponsive to anti-VEGF mono-therapies, all diagnosed with type 1 macular neovascularization (T1 MNV) over a period of 12-month.
Methods: A retrospective, single-center cohort study was conducted at the Jules Gonin Eye Hospital, Lausanne, Switzerland. Clinical records of treatment-naïve and non-responder switch patients presenting T1 MNV secondary to neovascular age-related macular degeneration (nAMD) from September 2022 to March 2023 were reviewed. Patients received a loading dose of three monthly Faricimab injections followed by a treat-and-extend (T&E) regimen. Multimodal imaging, including structural OCT and AI-assisted analysis, was used to quantify PED volumes and related fluid biomarkers at baseline, 3-month, 6-month, and 12-month follow-up. Statistical analyses included linear mixed models to evaluate differences and trends in intraretinal (IRF), subretinal fluid (SRF) and PED volumes.
Results: 65 eyes of 65 patients were enrolled (female: 70.7%; mean age =80.7yrs, SD=6.9yrs). 80% had received anti-VEGF treatment (Switch group) and 20% were treatment-Naïve at baseline. At 12-months, intravitreal treatments were more frequent in the Switch group (mean number=8.3 vs. 6.0; p=0.009). No cases of intraocular inflammation were observed. Significant reduction in SRF and IRF volumes were noted in both groups. A significant reduction in PED volume was observed over the follow-up period in both groups (mean slope = -206 nL, 95%CL = -273/-138; p-value<0.001).
Conclusions: Intravitreal Faricimab significantly reduced PED volumes in both treatment-Naïve and non-responder Switch patients over 12 months. The study highlights Faricimab's potential as an effective treatment option for T1 MNV in nAMD, offering significant improvements in PED volume and related fluid biomarkers.
A Systematic Identification of RBPs Driving Aberrant Splicing in Cancer
Authors: Lobato-Fernández César , Gimeno Marian , Martín Ane San , Anorbe Ana , Rubio Angel , Ferrer-Bonsoms Juan A. 
Published: October 2024

Abstract

Background: Alternative Splicing (AS) is a post-transcriptional process that allows a single RNA to produce different mRNA variants and, in some cases, multiple proteins. Various processes, many yet to be discovered, regulate AS. This study focuses on regulation by RNA-binding proteins (RBPs), which are not only crucial for splicing regulation but also linked to cancer prognosis and are emerging as therapeutic targets for cancer treatment. CLIP-seq experiments help identify where RBPs bind on nascent transcripts, potentially revealing changes in splicing status that suggest causal relationships. Selecting specific RBPs for CLIP-seq experiments is often driven by a priori hypotheses.
Results: We developed an algorithm to detect RBPs likely related to splicing changes between conditions by integrating several CLIP-seq databases and a differential splicing detection algorithm. This work refines a previous study by improving splicing event prediction, testing different enrichment statistics, and performing additional validation experiments. The new method provides more accurate predictions and is included in the Bioconductor package EventPointer. We tested the algorithm in four experiments involving knockdowns of seven different RBPs. The algorithm accurately assessed the statistical significance of these RBPs using only splicing alterations. Additionally, we applied the algorithm to study sixteen cancer types from The Cancer Genome Atlas (TCGA). We identified relationships between RBPs and various cancer types, including alterations in CREBBP and MBNL2 in adenocarcinomas of the lung, liver, prostate, rectum, stomach, and colon. Some of these findings are validated in the literature, while others are novel.
Conclusions: The developed algorithm enhances the ability to predict and understand RBP-related splicing changes, offering more accurate predictions and novel insights into cancer-related splicing alterations. This work highlights the potential of RBPs as therapeutic targets and contributes to the broader understanding of their roles in cancer biology.
Dimensions of Quadriceps Tendon Autograft Are Variable Based on Patient Age and Graft Type: A Systematic Review
Authors: Glassman Isaac , Singh Harasees , Sritha Praveen , Abdel-Khalik Hassaan , Meena Amit , Hoshino Yuichi , de SA Darren 
Published: October 2024

Abstract

Purpose
The purpose of this study is to compile graft dimensions reported in quadriceps tendon anterior cruciate ligament reconstruction surgical papers.
Methods
A systematic literature search was conducted in accordance with PRISMA and R-AMSTAR guidelines. PubMed, EMBASE, MEDLINE, and Web of Science were searched from inception to June 18, 2024. All studies were searched and screened in duplicate; Cohen’s kappa was calculated at each stage. Quality assessment was conducted using MINORs for non-randomized studies and Cochrane’s RoB 2.0 for randomized studies. Descriptive statistics are presented.
Results
Thirty-one studies featuring 2,756 knees were included. Twenty-one papers used quadriceps tendon autograft with bone block (B-QT) and 10 used all-soft tissue quadriceps tendon autograft (S-QT). Included patients had a weighted mean age of 24.2 years and a range of 7–58 years. Of the papers featuring an adult population (average age ≥ 18 years), mean B-QT total graft length was 72.5mm (range: 50-90mm), bone block length was 18.5mm (range: 15-20mm), width was 9.9mm (range: 7-12mm), and diameter was 6.5mm (range: 5-9mm). For S-QT grafts in the adult population, the mean graft length was 78.8mm (range: 60-100mm), width was 10.6mm (range: 9-12mm), and diameter was 8.4mm (range: 5-10mm). In studies featuring a pediatric population (average age ≤ 18 years), the mean B-QT total graft length was 70.0mm (range: 60-80mm), bone block length was 16.7mm (range: 15-20mm), width was 9.7mm (range: 9-10mm), and diameter was 9mm (range: 8-10mm). For S-QT grafts in the pediatric population, the mean graft length was 64.2mm (range: 50-80mm), width was 10.0mm (range: 9-11mm), and diameter was 7.8mm (range: 5-10mm).
Conclusions
This review highlights the variability in graft dimensions for QT ACL-R grafts based on patient age and graft type. The paucity of consistent reporting of graft dimensions highlights the need for standardized reporting to promote the comparability of studies using QT ACL-R.
Level of evidence Level IV
Spontaneous Atlas Fracture in a Patient with Pycnodysostosis and Mandibular Osteomyelitis: A Case Report
Authors: Pablo Crespo Reinoso , Karina Ana 
Published: October 2024

Abstract

Pycnodysostosis is a rare autosomal recessive syndrome with an incidence of 1 in 1.7 million, caused by mutations in the CTSK gene, located on chromosome 1q21. We present a case of pycnodysostosis in a 30-year-old male patient who developed osteomyelitis of the jaw and an unusual fracture of the atlas, representing the first description of this complication. Patients with Pycnodysostosis, besides osteomyelitis, may seek maxillofacial attention for bone distraction assessment or orthognathic surgery. Therefore, we emphasize the importance of a thorough cervical assessment before any intervention.
Concurrent EGFR L858R and K860I mutations: PCR-negative but NGS-positive alterations that respond to EGFR inhibitors in non-small cell lung cancer
Authors: Shi Huiyang , Li Weihua , Guo Lei , Ying Jianming , Hu Xingsheng 
Published: October 2024

Abstract

Introduction: Clinical routine amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next generation sequencing (NGS) are able to identify sensitizing EGFR mutations of non-small cell lung cancer (NSCLC) patients. Nevertheless, the detection and treatment response of NSCLC patients with concurrent L858R and uncommon EGFRexon 21 mutations remain unclear.
Methods: Concurrent NGS and ARMS-PCR were performed to identify EGFR mutations in 5033 NSCLC cases.
Results: Totally, EGFRL858R mutations were identified in 1024 (20.3%) cases, among which 54 concurrent L858R and uncommon EGFR exon 21 mutations were identified by NGS but not ARMS-PCR. The most common concurrent pathogenic mutations in EGFR exon 21 were V834L, K860I and L833V. Of those, 23 patients received EGFR-TKIs as the first-line treatment with median progression-free survival (PFS) of 16.7 months (95% CI: 12.8–20.7 months) and objective response rate (ORR) of 38.9% (95% CI: 9.1% – 46.9%). Interestingly, concurrent L858R and K860I mutations were observed in 10 cases by NGS, while ARMS-PCR showed completely negative results in EGFR mutations. Of those, three patients received EGFR-TKIs as the first-line treatment, with median PFS of 11.0 months and ORR of 100.0%. Furthermore, three patients with concurrent L858R and K860I mutations identified by NGS received adjuvant targeted therapy after surgery with median disease free survival of 10.0 months.
Conclusion: NSCLC patients with concurrentEGFR L858R and K860I mutations are able to benefit from EGFR-TKIs, which can be detected by NGS but not by ARMS-PCR.
Rapid and modular workflows for same-day sequencing-based detection of bloodstream infections and antimicrobial resistance determinants
Authors: Sajib Mohammad Saiful Islam , Oravcova Katarina , Brunker Kirstyn , Everest Paul , Fuentes Manuel , Wilson Catherine , Murphy Michael E. , Forde Taya 
Published: October 2024

Abstract

Background
Bloodstream infections (BSI) are a major global health concern, and existing diagnostic methods are too slow to guide targeted antibiotic therapy for critically ill patients, risking poor clinical outcomes. Rapid metagenomic-sequencing (mNGS) can facilitate swift pathogen and antimicrobial resistance (AMR) detection, but identification is challenged by significant host versus bacterial DNA in blood. To accelerate microbiological diagnosis, we developed M-15, a rapid and modular mNGS-based host DNA depletion workflow, validated with suspected BSI blood-culture samples and rapid culture-enriched spiked blood.
Methods
To assess chemical host DNA depletion (CHDD) efficiency, M-15 was benchmarked with five commercial/published protocols. Later, M-15 was combined with rapid mNGS with/without adaptive sampling (AS) and tested on clinical blood-culture samples (n = 33) from suspected BSI cases identified on BACT/ALERT VIRTUO (30 flagged positive, three remained negative). To determine whether it is possible to utilise M-15 mNGS prior to blood-culture flagging positive, a rapid enrichment method was tested starting with 1–10 colony forming units of the top 15 bacterial species causing BSI spiked into BACTEC medium enriched with 10 mL sheep blood.
Results
All six chemical depletion protocols reduced host DNA by 2.5x100 to 4.1x106-fold, with the in-house M-15 protocol performing best, while adaptive sampling depleted host > 5-fold. With BACT/ALERT specimens, M-15 mNGS accurately identified 3/3 negative, 28/28 mono-bacterial, and 2/4 multi-bacterial species. With rapid culture-enrichment and M-15 mNGS, < 18% DNA was classified as host and all bacterial species tested (n = 10) were correctly identified. M-15 mNGS accurately predicted phenotypic AMR/susceptibility for 90.3% (232/257) of drug/bacteria combinations from BACT/ALERT positive samples.
Conclusions
This study demonstrates that M-15 mNGS can facilitate species and AMR gene detection within 5–7 hours of BACT/ALERT positivity. Including 8-hour culture enrichment, microbiological and AMR confirmation is possible within 13–15 hours of sample collection. Thus, the M-15 mNGS workflow has the potential to improve patient outcomes in BSI.
Assessment of a Risk-Based Stratified Management Strategy for Cervical Cancer Screening in Central China: A Real-World Study across Diverse Populations of 223,533 Opportunistic and 43,102 Health Check-up Participants Over a Decade
Authors: Wu Qihui , Yan Junxia , Li Peiyao , Zhang Fan , Zhang Yu 
Published: October 2024

Abstract

Background: The evolving landscape of cervical cancer screening emphasizes risk-based stratification for effective management. This study aims to assess the applicability of a risk-based cervical cancer screening and management strategy in opportunistic screening populations at outpatient clinics and regular health check-up populations in central China.
Methods: The study validated the screening management strategy recommended by the 2019 ASCCP guidelines for 1-year and 3-year follow-up intervals in opportunistic screening and health check-up populations. Data were collected from a large tertiary hospital in central China, including 223,533 outpatient records from April 2012 to April 2022 and 43,102 health check-up records from April 2017 to April 2022. High-risk human papillomavirus (hrHPV) infection rates, cytology results, and subsequent high-grade cervical intraepithelial neoplasia (CIN3+) incidences were evaluated across different age groups. Follow-up data were examined to discern the effectiveness of risk-based management.
Results: The study revealed significant prevalence of hrHPV infection, with overall positivity rates of 18.17% in opportunistic screening and 13.22% in health check-up populations. Among screened individuals, the prevalence of CIN3+ exhibited age-related differences. Specifically, among individuals meeting the follow-up criteria, only the 25-65 years old group in the 1-year follow-up cohort had CIN3+ detection, with a prevalence of 0.47% in the outpatient population and 0.09% in the health check-up population.
Conclusions: The CIN3+ detection rates align with expectations, supporting the applicability of the ASCCP approach in varied screening settings. This study provides valuable insights into the real-world implementation of risk-based cervical cancer screening, contributing to the ongoing paradigm shift towards risk-based stratification. It underscores the importance of continuous efforts to refine screening protocols on a global scale.
The Mediation Effect of Cotinine Between Depression, Inflammation, and Mortality: A National Cohort Study
Authors: Liu Yang , Wang Linbin , Xiu Jia , Zhao Jing , Voon Valerie 
Published: October 2024

Abstract

Background
Depression is a major mental health issue that affects millions globally. Inflammation is linked to depression, and smoking is prevalent among depressed individuals. Serum cotinine, a nicotine metabolite, may mediate the effects of smoking on inflammation and mortality in depression. This study aims to explore the mediating role of cotinine between depression, inflammation, and all-cause mortality.
Methods
This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2005 and 2014. A total of 24,937 participants were included after excluding individuals with missing data on depressive symptoms, serum cotinine concentration, and mortality outcomes. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and serum cotinine levels were measured by isotope-dilution HPLC-APCI MS/MS. Multivariable logistic regression was used to assess the association between depression and cotinine. Mediation analysis was conducted to evaluate the mediating role of cotinine in the relationship between depression and WBC count, as well as between WBC count and mortality. Cox proportional hazards models were employed to determine the associations between cotinine, WBC count, and all-cause mortality.
Results
The analysis showed that individuals with depression had significantly higher serum cotinine levels (95.615 ng/mL vs. 53.546 ng/mL, P < 0.001) and WBC counts (7.665 vs. 7.203, P < 0.001) compared to those without depression. Multivariable logistic regression revealed that serum cotinine was positively associated with depression (OR = 1.002, 95% CI: 1.002–1.002, P < 0.001). Mediation analysis indicated that cotinine significantly mediated the association between depression and WBC count, accounting for 37.01% of the total effect after adjusting for confounders. Higher cotinine levels were also associated with increased all-cause mortality (HR = 1.889, 95% CI: 1.691–2.111, P < 0.001). Furthermore, cotinine mediated the relationship between WBC count and mortality, contributing to 27.39% of the total effect after adjustment.
Conclusion
This study highlights cotinine's role as a dual mediator in the relationships between depression, inflammation, and all-cause mortality. These findings underscore the need for targeted interventions, including smoking cessation and inflammation management, to improve health outcomes in individuals with depression.
Associations Between Lipid Traits and Breast Cancer Risk: A Mendelian Randomization Study in African Women
Authors: Ansah¹ Emmanuel Owusu , Kyei¹ Foster , Opoku Caleb Frimpong , Danquah¹ Andrews , Fosu Kwadwo , Agyenim⁵ Emmanuel Boateng , Agyirifo Daniel Sakyi 
Published: October 2024

Abstract

Backgrounds
Blood lipids are associated with breast cancer. An increasing number of reports have attempted to explore the genetic connection between blood lipids and the risk of developing breast cancer. However, observational studies can be affected by confounding factors and reverse causation, which can compromise the reliability of the findings.
Methods We used univariate and multivariable two-sample mendelian randomization to explore the causal association between blood lipids and breast cancer. Summary-level data for lipid traits were obtained from the Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) (N = 10,603, 58.5% of women). For breast cancer, we leveraged summary statistics from the most comprehensive Genome-wide Association Studies (GWAS) on breast cancer consisting of 18,034 cases and 22,104 controls of women of African ancestry.
Results Our analysis suggests that genetically predicted triglycerides had a potential protective effect on breast carcinoma (OR = 0.73, 95% CI = 0.56, 0.95, FDR = 0.001). We found no evidence that genetically elevated levels of TC, HDL, and LDL may be associated with the risk of breast cancer TC (OR = 1.04; 95% CI, 0.93, 1.18; FDR = 0.029); HDL (OR = 1.29, 95% CI = 0.93, 1.79, FDR = 0.008); LDL (OR = 1.04, 95% CI = 0.90, 1.20, FDR = 0.036). Multivariate mendelian randomization analysis, which adjusted for the effects of TG, TC, LDL, and HDL, attenuated the observation of TG and breast cancer and also found no relationship between TC, HDL, LDL, and breast cancers. Furthermore, there was no evidence for a causal association between lipid traits and breast cancer subtypes. Our findings were robust in several sensitivity analyses.
Conclusions This study provides strong evidence that circulating TG may be associated with a decreased risk of breast cancer, while TC, LDL and HDL may not be related to the risk of breast cancer among African women. Our findings align with both observational and MR studies conducted in European populations. However, in contrast to our results, some studies suggest that TG, LDL, and HDL may increase breast cancer risk in Europeans, indicating potential ethnic differences in the lipid profiles of breast cancer patients.