bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of the 2019 EULAR/ACR SLE classification criteria for predicting mortality and hospitalisation: development and cross-validation of ominosity score
Authors: Figueroa-Parra Gabriel , Hanson Andrew C , Sanchez-Rodriguez Alain , Meade-Aguilar Jose A , González-Treviño Mariana , Cuéllar-Gutiérrez María C , Barbour Kamil E , Duarte-García Alí , Crowson Cynthia 
Published: November 2024

ObjectiveThe 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria score (≥20 points) has been associated with poor outcomes. We aimed to evaluate its utility as a predictor for mortality and hospitalisation and to derive and validate an ominosity score based on the SLE classification criteria set.MethodsIncident patients with SLE in a population-based cohort were included. The association between the 2019 EULAR/ACR SLE score and mortality and hospitalisation was assessed using Cox regression adjusted for age, sex and calendar year. An ominosity score for mortality was developed based on the SLE criteria set. The least absolute shrinkage and selection operator method was used to estimate model coefficients. Concordance and calibration were assessed by cross-validation and by plotting the observed event rates against the deciles of predicted probabilities.ResultsAmong 374 patients with incident SLE, a EULAR/ACR score ≥20 points was not associated with an increased risk of mortality (HR 1.17, 95% CI 0.67 to 2.03) or first hospitalisation (HR 1.14, 95% CI 0.79 to 1.64) compared with a score ≤19 points. The derived ominosity score for mortality included age, sex, thrombocytopaenia, neuropsychiatric manifestations, subacute cutaneous or discoid lupus, non-scarring alopecia, inflammatory arthritis, renal involvement, antiphospholipid antibodies and hypocomplementaemia. This model demonstrated a concordance=0.76 with adequate calibration. Age and sex were the main predictors, as seen in the model including just age, sex and year (concordance=0.77).ConclusionThe 2019 EULAR/ACR SLE criteria score was not associated with mortality and hospitalisation. The derived ominosity score for mortality presented good prediction for mortality but was not better than age and sex alone.
Clinical outcomes of endovascular interventions for cerebral venous thrombosis in Japan: a nationwide retrospective study
Authors: Senda Atsushi , Suginaka Hiroshi , Morishita Koji , Fushimi Kiyohide 
Published: November 2024

IntroductionCerebral venous thrombosis (CVT) is a rare but serious disease. Despite anticoagulation being the cornerstone therapy, some patients experience worsening disease, necessitating alternative treatment. Endovascular treatment is an anticipated option with an uncertain clinical relevance. The aim of this study was to assess the clinical effects and efficacy of endovascular therapy and identify patient populations that may benefit from treatment.Patients and methodsThis retrospective study examined patient data from April 2014 to March 2022 that were extracted from a nationwide Japanese Diagnosis Procedure Combination database. The primary outcome was in-hospital mortality. The secondary outcomes included modified Rankin Scale (mRS) scores and post-hospitalisation complications of cerebral infarction and intracranial haemorrhage. Severity was adjusted using a generalised linear mixed model, and propensity-score matching was employed to compare outcomes between treatment groups.ResultsThe study included 2901 patients; 240 patients in the endovascular treatment group were matched with 240 patients in the standard treatment group. After adjusting for background factors, endovascular treatment did not improve in-hospital mortality (adjusted OR 1.45; 95% CI 0.74 to 2.16) or the mRS score (adjusted OR 0.89, 95% CI 0.56 to 1.23). No subpopulations that could benefit from endovascular treatment were identified. Post-hospitalisation cerebral infarction and intracranial haemorrhage did not increase with endovascular treatment (0.8% in the endovascular treatment group vs 1.2% in the standard treatment group).ConclusionEndovascular treatment showed no significant benefit for patients with CVT, indicating that treatment guidelines need to be refined. Our findings can guide clinical decisions and suggest the necessity of further research on potential benefits in specific subpopulations.
Early Hepatic Decompensation Identifies Patients with Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab or Sorafenib at Highest Risk of Death
Authors: Cabibbo Giuseppe , Celsa Ciro , Battaglia Salvatore , Enea Marco , Di Maria Gabriele , Grova Alessandro , Ciccia Roberta , Manfredi Giulia F. , Iavarone Massimo , Vogel Arndt , Singal Amit G. , Reig Maria , Pinato David J. , Cammà Calogero 
Published: November 2024

Abstract

Purpose:
The prognosis of patients with unresectable hepatocellular carcinoma (HCC) and compensated cirrhosis is influenced by cancer progression. Data on the incidence and the prognostic role of clinical hepatic decompensation (CHD) following immune checkpoint inhibitor therapy are lacking. We aimed to assess whether early CHD within 3 months from commencement of systemic therapy affects overall survival (OS) of patients treated with atezolizumab plus bevacizumab or sorafenib.

Patients and Methods:
Individual patient data from the IMbrave150 trial were analyzed. Cumulative incidence of CHD was assessed by competing risk analysis against HCC radiologic progression. Early CHD and HCC radiologic progression were assessed as predictors of OS by the time-dependent Cox model.

Results:
The 3- and 12-month rates of CHD were 7% and 12%, respectively, whereas the 3- and 12-month rates of HCC radiologic progression were 23% and 52%, respectively. Albumin–bilirubin grade 2 [subdistribution HR (sHR) = 1.79, 95% confidence interval (CI), 1.01–3.19; P = 0.049], INR (sHR = 1.97, 95% CI, 1.64–2.37; P &lt; 0.001), and presence of neoplastic macrovascular invasion (sHR = 2.01, 95% CI, 1.14–3.54; P = 0.020) were independently associated with higher risk of CHD. Early CHD (HR = 7.56, 95% CI, 4.47–12.8) and early HCC radiologic progression (HR = 5.92, 95% CI, 4.03–8.69), as first events, were independently associated with higher mortality.

Conclusions:
This study provides robust evidence that early CHD is associated with the highest risk of death in patients with unresectable HCC undergoing systemic treatment. Within well-compensated participants, albumin–bilirubin, INR, and macrovascular invasion identify a population at higher risk of decompensation. Inclusion of clinical decompensation events in future prospective clinical trials may improve characterization of OS from systemic therapy of HCC.
Temporal Genomic Analysis of Homogeneous Tumor Models Reveals Key Regulators of Immune Evasion in Melanoma
Authors: Cohen Shvefel Sapir , Pai Joy A. , Cao Yingying , Pal Lipika R. , Bartok Osnat , Levy Ronen , Zemanek Marie J. , Weller Chen , Herzog Ella , Yao Winnie , Hiam-Galvez Kamir J. , Cheng Kuoyuan , Yin Yajie , Du Peter P. , Raposo Colin J. , Gumpert Nofar , Welti Michele , Martínez Gómez Julia M. , Sella Federica , Yakubovich Elizabeta , Orr Irit , Ben-Dor Shifra , Oren Roni , Fellus-Alyagor Liat , Golani Ofra , Brenner Ori Jacob , Salame Tomer M. , Zerbib Mirie , Goliand Inna , Ranmar Dean , Savchenko Ilya , Ketrarou Nadav , Schäffer Alejandro A. , Dahan Rony , Levesque Mitchell P. , Ruppin Eytan , Satpathy Ansuman T. , Samuels Yardena 
Published: November 2024

Abstract
Low intratumor heterogeneity correlates with increased patient survival and immunotherapy response. However, even highly homogeneous tumors are variably aggressive, and the immunologic factors impacting aggressiveness remain understudied. In this study, we analyzed the mechanisms underlying immune escape in murine tumors with low intratumor heterogeneity. We used immunophenotyping and single-cell RNA sequencing to compare the temporal growth of in vivo transplanted, genetically similar, rejected and nonrejected single-cell clones. Nonrejected clones showed high infiltration of tumor-associated macrophages, lower T cell infiltration, and increased T cell exhaustion when compared with rejected clones. Comparative analysis of rejection-associated gene expression programs, combined with in vivo CRISPR knockout screens of candidate regulators, identified macrophage migration inhibitory factor (Mif) as a major contributor to preventing immune rejection. Mif knockout resulted in smaller tumors and reduced tumor-associated macrophage infiltration. These results were validated in patients with melanoma. Overall, our homogeneous tumor system can uncover factors regulating growth variability and identifies Mif as critical in aggressive melanoma.

Significance:
In this study, we find that Mif expression is associated with tumor growth and aggressiveness, specifically in tumors with low heterogeneity. These findings could facilitate the development of new strategies to treat patients with homogeneous, high MIF–expressing tumors that are unresponsive to immune checkpoint therapy.
Vascular Endothelial Growth Factor and the Pathogenesis of Intracranial Aneurysms: A Systematic Review on the Missing Link in a Complex Pathway
Authors: Nisson Peyton L. , Lawton Michael T. , Cisneros Oscar , Maeda Takuma , Gonzalez Nestor R. , Frösen Juhana , Hashimoto Tomoki 
Published: November 2024

Background
Aneurysms are one of the most common and yet devastating cerebrovascular diseases after rupture. Despite several decades of scientific advancements including the expansion of the endovascular capabilities and noninvasive imaging modalities, no medical treatment exists to date. This failure is likely largely attributed to the complex and multifactorial nature of aneurysm pathophysiology. Recent research has increasingly implicated vascular endothelial growth factor (VEGF) in the development and rupture of intracranial aneurysms. Regarded as one of the most potent inducers of angiogenesis, it is a key factor in vascular wall maintenance, inflammation, and regulation of vascular permeability. Whether abnormal VEGF expression is directly related to aneurysm development or acting merely as an acute phase reactant remains uncertain. No review of the current‐state‐of‐evidence on this topic exists yet.

Methods and Results
A systematic literature search was performed following PRISMA guidelines May 2024 that queried PubMed (1946–2024), Wiley Cochrane Library: Central Register of Controlled Trials (1898–2024), Thompson Reuters Web of Science: Citation Index (1900–2024), and Google Scholar (1946–2024). Inclusion criteria encompassed human and animal studies that investigated the relationship of intracranial aneurysm and VEGF. Several human and animal models revealed significantly elevated expression of VEGF in intracranial aneurysm tissue, along with greater levels in the cerebrospinal fluid and systemically. Overexpression has been shown to inhibit endothelial cell migration, proliferation, and induce cell apoptosis. Recently, genetic polymorphisms of VEGF have also been shown to significantly correlate with the presence of intracranial aneurysms, establishing the first genetic link between the two.

Conclusions
Despite lacking definitive evidence of a causal relationship, the wealth of supporting data substantiates VEGF as a promising topic for future investigation into aneurysm pathophysiology and as a potential therapeutic target.
Associations Between Health‐Related Social Needs and Cardiovascular Health Among US Adults
Authors: Zhang Zefeng , Jackson Sandra L. , Thompson‐Paul Angela M. , Yin Xiaoping , Merritt Robert K. , Coronado Fatima 
Published: November 2024

Background
Unfavorable health‐related social needs (HRSNs) have the potential to worsen health and well‐being and drive health disparities. Its associations with cardiovascular health (CVH), assessed by Life's Essential 8, have not been comprehensively examined among US adults.

Methods and Results
We used the National Health and Nutrition Examination Survey 2011 to March 2020 data for adults aged ≥20 years. We grouped Life's Essential 8 scores as low (0–49), moderate (50–79), and high (80–100) CVH. We identified 8 unfavorable HRSNs and assigned a value of 1 for the unfavorable status of each. The number of unfavorable HRSNs was summed and ranged from 0 to 8, with higher numbers indicating more unfavorable HRSNs. We used multivariable linear and multinomial logistic regression to examine the association between HRSNs and CVH. A total of 14 947 participants were included (n=7340 male [49.3%]; mean [SE] age, 46.4 [0.35] years). A higher number of unfavorable HRSNs were associated with worse CVH: comparing adults with unfavorable HRSNs of 1–2, 3–4, and ≥5 to those with none, the fully adjusted prevalence ratios (95% CI) for low CVH were 1.42 (1.17–1.73), 2.11 (1.69–2.63), and 2.42 (1.90–3.08), respectively. The corresponding prevalence ratios (95% CI) for high CVH were 0.77 (0.68–0.87), 0.58 (0.49–0.67), and 0.46 (0.38–0.55). The associations were consistent across subgroups and in sensitivity analyses.

Conclusions
There was a graded association between unfavorable HRSNs and a higher prevalence of low CVH or lower prevalence of high CVH. Public health interventions targeting HRSNs might reduce health disparities and promote CVH.
Lipoprotein(a) Is Elevated and Inversely Related to Coronary Endothelial Function in People With HIV
Authors: Kikuchi Daniel S. , Kwapong Yaa A. , Schär Michael , Weiss Robert G. , Sun Kevin , Brown Todd T. , Piggott Damani A. , Minhas Anum S. , Gerstenblith Gary , Soleimani‐Fard Alborz , Leucker Thorsten M. , Hays Allison G. 
Published: November 2024

Background
HIV‐associated cardiovascular disease (CVD) is increasing in prevalence. The mechanisms underlying the heightened cardiovascular risk faced by people with HIV (PWH), however, remain poorly defined. Recent studies indicate an important role of lipoprotein(a) (Lp[a]) in predicting CVD risk in the general population, but little is known regarding its role in HIV‐associated CVD. Thus, we sought to evaluate whether Lp(a) is elevated in PWH and if it is associated with impaired coronary endothelial function (CEF), a known mediator of CVD in PWH.

Methods and Results

In this cross‐sectional study, cardiac magnetic resonance imaging with isometric handgrip exercise, an endothelial dependent stressor, was performed to assess CEF in 65 PWH and 52 controls without HIV. Percent changes in coronary cross‐sectional area and coronary blood flow from rest to stress were used to quantify CEF. Lp(a) levels were assessed by immunoturbidimetric assay at the time of magnetic resonance imaging. Lp(a) levels were higher in PWH compared with controls (78 nmol/L [39–137 nmol/L] versus 45.5 nmol/L [18–102.5 nmol/L],
P
<0.01). Both percent change in coronary cross‐sectional area (0.38% [−6.1% to 5.4%] versus 7.43% [2.4%–11.2%],
P
<0.0005) and coronary blood flow (9.1% [−1.3% to 23.1%] versus 24.1% [3.3%–39.8%],
P
<0.05) were lower in PWH compared with controls. In PWH, Lp(a) was inversely associated with percent change in coronary cross‐sectional area (β=−6.18±1.01%/nmol/L,
P
<0.001) but not with percent change in coronary blood flow even after adjustment for confounding risk factors. No association between Lp(a) and measures of CEF was observed in individuals without HIV.

Conclusions
Lp(a) concentrations are elevated in PWH and inversely related to CEF in PWH.
Projections of the Stroke Burden at the Global, Regional, and National Levels up to 2050 Based on the Global Burden of Disease Study 2021
Authors: Cheng Yiran , Lin Yongqi , Shi Hujuan , Cheng Mingmei , Zhang Baoliang , Liu Xiaofeng , Shi Chuan , Wang Yanzhong , Xia Chunhua , Xie Wanqing 
Published: November 2024

Background
Stroke is a pressing public health issue worldwide. This study aimed to forecast the future temporal trends and distribution characteristics of the global stroke burden.

Methods and Results
Global data on stroke incidence, prevalence, deaths, and disability‐adjusted life years between 1990 and 2021 were obtained from the GBD (Global Burden of Disease) Study 2021. The temporal trends of stroke burden were estimated using various regression models. Gross domestic product per capita was adopted as a predictor in the model to consider the impact of economic development on stroke burden. Projections of stroke burden up to 2050 were generated using the optimal model selected based on the Akaike information criterion, encompassing global, World Bank income levels, national levels, and sex‐age groups. In 2050, we projected 21.43 million stroke cases, 159.31 million survivors, 12.05 million deaths, and 224.86 million disability‐adjusted life years due to stroke globally. From 2021 to 2050, there was a declining trend in the global age‐adjusted stroke rates, with −7% in incidence, −4% in prevalence, −28% in deaths, and −28% in disability‐adjusted life years. Upper‐middle‐income countries were projected to have the most severe stroke burden, followed by lower‐middle‐income countries, low‐income countries, and high‐income countries. The stroke burden in over half of the 204 countries and territories was expected to be alleviated from 2022 to 2050. Men and older women worldwide bear higher burden.

Conclusions
Stroke remains a serious global health challenge, especially in low‐income and middle‐income countries. Targeted implementation of prevention and interventions is imperative across diverse demographic groups.
Prospective Observational Cohort Study of Tenecteplase: Results From the Indian Registry in Ischemic Stroke‐Tenecteplase
Authors: Saraf Amit , Gilvaz Percival C. , Ramakrishnan Tirppur C. R. , Kumar R. N. Komal , Meenakshi‐Sundaram Salvadeeswaran , Sontakke Santosh M. , Alurkar Anand , Kumaravelu Somasundaram , Vijaya Pamidimukkala , Udar Mangesh , Arjundas Deepak , Desai Soaham , Sharma Mukesh , BV Suresh , Nair Rithesh R. , Pathan Sadique , Pujari Shripad S. , Kumar Sudhir , Machhavada Keyur , Kalita Jayantee , Misra Usha K. , Vaidya Bhalchandra , Churilov Leonid , Parsons Mark W. , Singh Sanjay 
Published: November 2024

Background
Tenecteplase has been approved for acute ischemic stroke at a dose of 0.2 mg/kg by the Indian licensing authority. A registry to evaluate the safety of tenecteplase was mandated by the licensing authority. The research aim was to use the Indian Registry in Ischemic Stroke‐Tenecteplase (IRIS‐TNK) to assess the safety and clinical outcomes in patients treated with tenecteplase in routine clinical practice.

Methods and Results
In this prospective, registry‐based observational, cohort study, the primary outcome was proportion of symptomatic intracerebral hemorrhages at 36±6 hours after treatment. Secondary outcomes included improvement in National Institutes of Health Stroke Scale (NIHSS) score by either ≥4 or 8 points or an NIHSS score of 0, assessment of excellent outcome (modified Rankin Scale score 0 or 1), functional independence (modified Rankin Scale score 0–2), and Barthel Index score. From October 2017 to May 2023, 1015 patients with a median age of 62 years (interquartile range [IQR, 52–71 years]) were recruited across India. The median baseline NIHSS score was 9 (IQR, 6–13). The proportion of patients with symptomatic intracerebral hemorrhage was 0.6% (95% CI, 0.2–1.3%), and 10 patients (1% [95% CI, 0.5–1.9%]) died within 3 months. Improvement in NIHSS score by ≥4 points or an NIHSS score of 0 at 24 hours was observed in 34.4% (95% CI, 31.5–37.4%) of patients. An excellent outcome (modified Rankin Scale score 0 or 1) at 3 months was achieved in 55.4% (95% CI, 52.3–58.5%) of patients.

Conclusions
These results confirm that tenecteplase at a dose of 0.2 mg/kg is safe in routine clinical practice, when administered within 4.5 hours of symptom onset.

Registration

https://ctri.nic.in/Clinicaltrials/
. Identifier: CTRI/2017/11/010380.
Mortality Risk in Patients With Cardiac Complications Following Ischemic Stroke: A Report From the Virtual International Stroke Trials Archive
Authors: Ishiguchi Hironori , Huang Bi , El‐Bouri Wahbi K. , Dawson Jesse , Lip Gregory Y. H. , Abdul‐Rahim Azmil H. , Alexandrov A. , Bath P. M. , Bluhmki E. , Bornstein N. , Chen C. , Claesson L. , Curram J. , Davis S. M. , Diener H‐C. , Donnan G. , Fisher M. , Ginsberg M. , Gregson B. , Grotta J. , Hacke W. , Hennerici M. G. , Hommel M. , Kaste M. , Lyden P. , Marler J. , Muir K. , Roffe C. , Sacco R. , Teal P. , Venketasubramanian N. , Wahlgren N. G. , Warach S. 
Published: November 2024

Background
Cardiac complications may occur in patients following ischemic stroke (stroke‐heart syndrome [SHS]). We investigated the mortality risk in patients with SHS and across the SHS manifestations.

Methods and Results
Data were sought from the VISTA (Virtual International Stroke Trials Archive), an international repository of clinical trials data. We reviewed relevant adverse events and classified patients into 2 cohorts based on the incidence of SHS. The SHS was defined as developing any cardiac complications within 30 days following stroke. Using Cox proportional hazards models, we evaluated the temporal risk dynamics of 90‐day death associated with the day of SHS onset. We also compared the risk of 90‐day death across SHS manifestations, using multivariate analysis. Among 15 054 patients with ischemic stroke (mean age, 69±12 years; 55% men), 1787 (11.8% [95% CI, 11.3–12.3]) developed SHS. The median onset time for SHS was 2 (interquartile range, 1–4) days. The most prevalent manifestation was other arrhythmia/ECG abnormalities, with the incidence rate of 6.5% (95% CI, 6.1–6.9). Patients who developed SHS between 10 and 30 days following stroke had significantly higher risks of death compared with those with SHS within the first 0 to 3 days (adjusted hazard ratio, 1.84 [95% CI, 1.36–2.49]).
In the multivariate‐adjusted analysis, SHS manifested as acute myocardial injury/myocardial injury, heart failure/left ventricular dysfunction, and atrial fibrillation/flutter were associated with the highest risk of death within 90 days after stroke across SHS manifestations excluding cardiorespiratory arrest.

Conclusions
SHS is associated with a high risk of death, with a greater risk observed with delayed SHS onset.
Complexity in speech and music listening via neural manifold flows
Authors: Runfola Claudio , Neri Matteo , Schön Daniele , Morillon Benjamin , Trébuchon Agnès , Rabuffo Giovanni , Sorrentino Pierpaolo , Jirsa Viktor 
Published: November 2024

Abstract
Understanding the complex neural mechanisms underlying speech and music perception remains a multifaceted challenge. In this study, we investigated neural dynamics using human intracranial recordings. Employing a novel approach based on low-dimensional reduction techniques, the Manifold Density Flow (MDF), we quantified the complexity of brain dynamics during naturalistic speech and music listening and during resting state. Our results reveal higher complexity in patterns of interdependence between different brain regions during speech and music listening compared with rest, suggesting that the cognitive demands of speech and music listening drive the brain dynamics toward states not observed during rest. Moreover, speech listening has more complexity than music, highlighting the nuanced differences in cognitive demands between these two auditory domains. Additionally, we validated the efficacy of the MDF method through experimentation on a toy model and compared its effectiveness in capturing the complexity of brain dynamics induced by cognitive tasks with another established technique in the literature. Overall, our findings provide a new method to quantify the complexity of brain activity by studying its temporal evolution on a low-dimensional manifold, suggesting insights that are invisible to traditional methodologies in the contexts of speech and music perception.