bluuebunny/crossref_metadata_2025_split huggingface dataset:
D-Dimer-Driven Anticoagulation Reduces Mortality in Intubated COVID-19 Patients: A Cohort Study With a Propensity-Matched Analysis
Authors: Tassiopoulos Apostolos K. , Mofakham Sima , Rubano Jerry A. , Labropoulos Nicos , Bannazadeh Mohsen , Drakos Panagiotis , Volteas Panagiotis , Cleri Nathaniel A. , Alkadaa Leor N. , Asencio Anthony A. , Oganov Anthony , Hou Wei , Rutigliano Daniel N. , Singer Adam J. , Vosswinkel James , Talamini Mark , Mikell Charles B. , Kaushansky Kenneth 
Published: February 2021

Objective: Examine the possible beneficial effects of early, D-dimer driven anticoagulation in preventing thrombotic complications and improving the overall outcomes of COVID-19 intubated patients.Methods: To address COVID-19 hypercoagulability, we developed a clinical protocol to escalate anticoagulation based on serum D-dimer levels. We retrospectively reviewed all our first 240 intubated patients with COVID-19. Of the 240, 195 were stratified into patients treated based on this protocol (ON-protocol, n = 91) and the control group, patients who received standard thromboprophylaxis (OFF-protocol, n = 104). All patients were admitted to the Stony Brook University Hospital intensive care units (ICUs) between February 7th, 2020 and May 17, 2020 and were otherwise treated in the same manner for all aspects of COVID-19 disease.Results: We found that the overall mortality was significantly lower ON-protocol compared to OFF-protocol (27.47 vs. 58.66%, P &lt; 0.001). Average maximum D-dimer levels were significantly lower in the ON-protocol group (7,553 vs. 12,343 ng/mL), as was serum creatinine (2.2 vs. 2.8 mg/dL). Patients with poorly controlled D-dimer levels had higher rates of kidney dysfunction and mortality. Transfusion requirements and serious bleeding events were similar between groups. To address any possible between-group differences, we performed a propensity-matched analysis of 124 of the subjects (62 matched pairs, ON-protocol and OFF-protocol), which showed similar findings (31 vs. 57% overall mortality in the ON-protocol and OFF-protocol group, respectively).Conclusions: D-dimer-driven anticoagulation appears to be safe in patients with COVID-19 infection and is associated with improved survival.What This Paper Adds: It has been shown that hypercoagulability in patients with severe COVID-19 infection leads to thromboembolic complications and organ dysfunction. Anticoagulation has been variably administered to these patients, but it is unknown whether routine or escalated thromboprophylaxis provides a survival benefit. Our data shows that escalated D-dimer driven anticoagulation is associated with improved organ function and overall survival in intubated COVID-19 ICU patients at our institution. Importantly, we found that timely escalation of this anticoagulation is critical in preventing organ dysfunction and mortality in patients with severe COVID-19 infection.
Aspirin Use on Incident Dementia and Mild Cognitive Decline: A Systematic Review and Meta-Analysis
Authors: Li Hui , Li Wan , Zhang Xun , Ma Xiao-Chuan , Zhang Rong-Wei 
Published: February 2021

Background:More people with cognitive dysfunction and dementia also fall into the category of high vascular risk, for which aspirin is one of the most frequently used drugs. However, previous studies reporting that aspirin buffers against mild cognitive decline (MCI) and dementia remain controversial. We thus conducted an updated systematic review and meta-analysis to evaluate the association of aspirin use with the risk of MCI and dementia in older adults.Methods:Data sources from PubMed, Embase, Web of Science, and the Cochrane Database for randomized controlled trails (RCTs) and cohort studies (published between January 1, 2000 and April 11, 2020). Relative risks (RRs) and 95% confidence intervals (95% CIs) were used to pool data on the occurrence of dementia and MCI with random-effects models.Results:Of 3,193 identified articles, 15 studies (12 cohort studies and three RCTs) were eligible and were included in our analysis, which involved a total of 100,909 participants without cognitive dysfunctions or dementia at baseline. In pooled cohort studies, aspirin use did not reduce the incidence of MCI and dementia (the pooled RR = 0.97; 95% CI = 0.85–1.11;Ifor heterogeneity2= 65%) compared with non-users. However, low-dose aspirin (75–100 mg/day) was associated with a decreased likelihood of developing dementia or MCI (the pooled RR = 0.75; 95% CI = 0.63–0.9;Ifor heterogeneity2= 50.5%). This association existed in studies including all-cause dementia (the pooled RR = 0.82; 95% CI = 0.71–0.96) and Alzheimer's disease (AD) (the pooled RR = 0.54; 95% CI = 0.33–0.89), but not in MCI (the pooled RR = 0.58; 95% CI = 0.31–1.08). In RCTs, low-dose aspirin use was not significantly associated with less prevalence of dementia or MCI (RR = 0.94; 95% CI = 0.84–1.05;Ifor heterogeneity2= 0.0%).Conclusions:In cohort studies, we found that low-dose aspirin use had a higher likelihood of reducing the incidence of dementia, which was not supported by RCTs. The evidence was insufficient to fully evaluate the effect of aspirin on cognitive function and dementia. Well-designed studies and innovative approaches are therefore needed to clarify whether the use of aspirin improves cognitive function and reduces the risk of dementia.
One Hour-Post-load Plasma Glucose ≥155 mg/dl in Healthy Glucose Normotolerant Subjects Is Associated With Subcortical Brain MRI Alterations and Impaired Cognition: A Pilot Study
Authors: Perticone Maria , Di Lorenzo Cherubino , Arabia Gennarina , Arturi Franco , Caroleo Benedetto , Tassone Bruno , Pujia Roberta , Fiorentino Teresa Vanessa , Chiriaco Carmelina , Sesti Giorgio , Quattrone Aldo , Perticone Francesco 
Published: February 2021

Background: Glucose alterations are associated with impaired cognition. The 1-h-post-load plasma glucose ≥155 mg/dl in non-diabetic subjects confers an increased risk of cardiovascular events and diabetes. This pilot study aimed to investigate whether the 1-h-post-load plasma glucose ≥155 mg/dl negatively affects the subcortical regions of the brain and the cognitive functions.Methods: We enrolled 32 non-diabetic subjects. Patients were divided into two groups based on 1-h- post-load plasma glucose value &gt; or &lt; 155 mg/dl: normal glucose tolerance (NGT) 1-h-high and NGT 1-h-low subjects. All subjects underwent 3 Tesla MRI and standard neuropsychological tests.Results: NGT 1-h-high subjects showed significantly lower values of both right (4.9 ± 0.9 vs. 5.1 ± 0.9 ml) and left (4.8 ± 1.1 vs. 5.1 ± 1.1 ml) hippocampal hemisphere volume, while right hemisphere hippocampal diffusivity was lower in the NGT 1-h-high group (10.0 ± 0.6 vs. 10.6 ± 0.5 10−4 mm2s−1). NGT 1-h-high subjects also showed a poorer memory performance. In particular, for both Rey Auditory Verbal Learning Task (RAVLT)—immediate-recall and Free and Cued Selective Reminding Test (FCSRT)—delayed total recall, we found lower cognitive test scores in the NGT-1 h-high group (26.5 ± 6.3 and 10.4 ± 0.3, respectively).Conclusions: One-hour-post-load hyperglycemia is associated with morpho-functional subcortical brain alterations and poor memory performance tests.
Grip Strength and the Risk of Cognitive Decline and Dementia: A Systematic Review and Meta-Analysis of Longitudinal Cohort Studies
Authors: Cui Mengzhao , Zhang Siwen , Liu Yujia , Gang Xiaokun , Wang Guixia 
Published: February 2021

Purpose: Loss of grip strength and cognitive impairment are prevalent in the elderly, and they may share the pathogenesis in common. Several original studies have investigated the association between them, but the results remained controversial. In this systematic review and meta-analysis, we aimed to quantitatively determine the relationship between baseline grip strength and the risk of cognitive impairment and provide evidence for clinical work.Methods: We performed a systematic review using PubMed, EMBASE, Cochrane, and Web of Science up to March 23, 2020, and focused on the association between baseline grip strength and onset of cognitive impairment. Next, we conducted a meta-analysis using a hazard ratio (HR) and 95% confidence interval (CI) as effect measures. Heterogeneity between the studies was examined using I2 and p-value. Sensitivity analyses and subgroup analyses were also performed, and publication bias was assessed by Begg's and Egger's tests.Results: Fifteen studies were included in this systematic review. After sensitivity analyses, poorer grip strength was associated with more risk of cognitive decline and dementia (HR = 1.99, 95%CI: 1.71–2.32; HR = 1.54, 95%CI: 1.32–1.79, respectively). Furthermore, subgroup analysis indicated that people with poorer strength had more risk of Alzheimer's disease (AD) and non-AD dementia (HR = 1.41, 95%CI: 1.09–1.81; HR = 1.45, 95%CI: 1.10–1.91, respectively).Conclusions: Lower grip strength is associated with more risk of onset of cognitive decline and dementia despite of subtype of dementia. We should be alert for the individuals with poor grip strength and identify cognitive dysfunction early.
Genomic Association Study for Cognitive Impairment in Parkinson's Disease
Authors: Park Kye Won , Jo Sungyang , Kim Mi Sun , Jeon Sang Ryong , Ryu Ho-Sung , Kim Jinhee , Park Young-Min , Koh Seong-Beom , Lee Jae-Hong , Chung Sun Ju 
Published: February 2021

Background: Cognitive impairment is very common in Parkinson's disease (PD) and constitutes the most debilitating complication of this disease. However, to date, few studies have investigated a genome-wide association in the development of cognitive impairment of PD. We aimed to identify the genetic loci associated with cognitive impairment in patients with sporadic PD by ethnicity-specific genotyping.Materials and methods: We recruited 1,070 patients with PD and performed a genome-wide association study using the Korean Chip, a microarray chip containing 827,400 single-nucleotide polymorphisms (SNPs) optimized for the Korean population. Multiple logistic regression models adjusting for age, sex, years of education, and disease duration were used to compare between patients with and without cognitive impairment, which was defined using the Mini-Mental Status Examination (MMSE) score (MMSE score ≥ 26 vs. &lt; 26) or the Montreal Cognitive Assessment (MoCA) score (MoCA score ≥24 vs. &lt; 24).Results:RYR2 SNP rs10495397 was most significantly associated with cognitive impairment based on the MMSE scores (OR = 3.21; 95% CI = 1.96–5.25, P = 3.36 × 10−6) and CASC17 showed the strongest association with cognitive impairment based on the MoCA scores. However, none of the SNPs were statistically significant after Bonferroni correction.Conclusion:RYR2 may play a role in cognitive impairment in PD by the pathogenic mechanism of neuroinflammation. However, more studies are needed to replicate and validate the results of our functional study.
Timing and Outcomes of Intracranial Stenting in the Post-SAMMPRIS Era: A Systematic Review
Authors: Yu Yanying , Wang Tao , Yang Kun , Zhang Xiao , Yu Simon Chun Ho , Luo Jichang , Yang Bin , Wang Yabing , Ma Yan , Gao Peng , Jiao Liqun 
Published: February 2021

Objective: To investigate the impact of timing on the safety and efficacy of stenting for ICAS, we reviewed high-volume randomized controlled trials or prospective cohort studies of stenting for intracranial atherosclerotic artery stenosis (ICAS) after the SAMMPRIS trial.Methods: We included randomized controlled trials or prospective cohort studies since 2011 (the publication of the SAMMPRIS trial), evaluating the outcomes of intracranial stenting for ICAS patients. The primary outcomes were perioperative and 1-year stroke or death rate. The interaction of timing and outcomes were shown on trend plots. Overall meta-analysis and subgroup analysis by timing of intracranial stenting were conducted.Results: Fourteen studies with a total of 1,950 patients were included. The perioperative and post-operative stroke or death rates decreased with the time of stenting to the qualifying events. The perioperative stroke rate was significantly higher in patients treated within 21 days after the qualifying events, compared to those beyond 21 days (IRR = 1.60, 95%CI: 1.10–2.33; p = 0.014), similar relationships were obtained for both post-procedural (IRR = 1.61, 95%CI: 1.02–2.55; p = 0.042) and 1-year (IRR = 1.51, 95%CI: 1.10–2.08; p = 0.012) stroke or death rate.Conclusions: The timing of intracranial stenting may influence the safety and efficacy outcomes of stenting. Intracranial stenting within 21 days from the qualifying events may confer a higher risk of stroke or death. More studies are needed to confirm the impact of timing and the proper cut-off value.
Neural Correlates of Knee Extension and Flexion Force Control: A Kinetically-Instrumented Neuroimaging Study
Authors: Grooms Dustin R. , Criss Cody R. , Simon Janet E. , Haggerty Adam L. , Wohl Timothy R. 
Published: February 2021

Background: The regulation of muscle force is a vital aspect of sensorimotor control, requiring intricate neural processes. While neural activity associated with upper extremity force control has been documented, extrapolation to lower extremity force control is limited. Knowledge of how the brain regulates force control for knee extension and flexion may provide insights as to how pathology or intervention impacts central control of movement.Objectives: To develop and implement a neuroimaging-compatible force control paradigm for knee extension and flexion.Methods: A magnetic resonance imaging (MRI) safe load cell was used in a customized apparatus to quantify force (N) during neuroimaging (Philips Achieva 3T). Visual biofeedback and a target sinusoidal wave that fluctuated between 0 and 5 N was provided via an MRI-safe virtual reality display. Fifteen right leg dominant female participants (age = 20.3 ± 1.2 years, height = 1.6 ± 0.10 m, weight = 64.8 ± 6.4 kg) completed a knee extension and flexion force matching paradigm during neuroimaging. The force-matching error was calculated based on the difference between the visual target and actual performance. Brain activation patterns were calculated and associated with force-matching error and the difference between quadriceps and hamstring force-matching tasks were evaluated with a mixed-effects model (z &gt; 3.1, p &lt; 0.05, cluster corrected).Results: Knee extension and flexion force-matching tasks increased BOLD signal among cerebellar, sensorimotor, and visual-processing regions. Increased knee extension force-matching error was associated with greater right frontal cortex and left parietal cortex activity and reduced left lingual gyrus activity. Increased knee flexion force-matching error was associated with reduced left frontal and right parietal region activity. Knee flexion force control increased bilateral premotor, secondary somatosensory, and right anterior temporal activity relative to knee extension. The force-matching error was not statistically different between tasks.Conclusion: Lower extremity force control results in unique activation strategies depending on if engaging knee extension or flexion, with knee flexion requiring increased neural activity (BOLD signal) for the same level of force and no difference in relative error. These fMRI compatible force control paradigms allow precise behavioral quantification of motor performance concurrent with brain activity for lower extremity sensorimotor function and may serve as a method for future research to investigate how pathologies affect lower extremity neuromuscular function.
Relationship of Visceral Adipose Tissue With Dilated Perivascular Spaces
Authors: Qi Yunli , Lin Mengqi , Yang Yunjun , Li Yanxuan 
Published: February 2021

BackgroundDilated perivascular spaces (dPVS) are considered to be a type of cerebral small vessel disease (CSVD) as well as an important part of the glymphatic system. Although obesity has been shown to play a significant role in the development of CSVD, there are no studies addressing the correlation between obesity and dPVS. We aimed to study the relationship between abdominal fat distribution and dPVS in neurologically healthy cohorts.MethodsA total of 989 subjects, who were examined during a health examination project, were included in this study. We measured both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas using abdominal computed tomography. The dPVS scores were also evaluated in the basal ganglia (BG) and the centrum semiovale (CSO).ResultsIn a multivariate ordinal regression analysis, the relationship between VAT area and CSO-dPVS scores remained significant (β [95% confidence interval {CI} = 0.00003395] [0.00001074–0.00005716], P = 0.004), especially in male cohorts (β [95% CI] = 0.00004325 [0.00001772–0.00006878], P = 0.001) after adjusting for age; sex; and glucose, creatinine, uric acid, high-density lipoprotein, and low-density lipoprotein levels, while no association was found between SAT area and dPVS scores. The effects of quartile VAT area on CSO-dPVS were also significant in male cohorts (odds ratio [95% CI] = 1.33 [1.139 – 1.557], P &lt; 0.001).ConclusionWe demonstrated a positive association between VAT and CSO-dPVS scores in a healthy cohort, which was more prominent in males.
Background Parenchymal Enhancement on Breast MRI as a Prognostic Surrogate: Correlation With Breast Cancer Oncotype Dx Score
Authors: Zhang Michelle , Sadinski Meredith , Haddad Dana , Bae Min Sun , Martinez Danny , Morris Elizabeth A. , Gibbs Peter , Sutton Elizabeth J. 
Published: February 2021

PurposeBreast MRI background parenchymal enhancement (BPE) can potentially serve as a prognostic marker, by possible correlation with molecular subtype. Oncotype Dx, a gene assay, is a prognostic and predictive surrogate for tumor aggressiveness and treatment response. The purpose of this study was to investigate the association between contralateral non-tumor breast magnetic resonance imaging (MRI) background parenchymal enhancement and tumor oncotype score.MethodsIn this retrospective study, patients with ER+ and HER2− early stage invasive ductal carcinoma who underwent preoperative breast MRI, oncotype risk scoring, and breast conservation surgery from 2008–2010 were identified. After registration, BPE from the pre and three post-contrast phases was automatically extracted using a k-means clustering algorithm. Four metrics were calculated: initial enhancement (IE) relative to the pre-contrast signal, late enhancement, overall enhancement (OE), and area under the enhancement curve (AUC). Histogram analysis was performed to determine first order metrics which were compared to oncotype risk score groups using Mann–Whitney tests and Spearman rank correlation analysis.ResultsThis study included 80 women (mean age = 51.1 ± 10.3 years); 46 women were categorized as low risk (≤17) and 34 women were categorized as intermediate/high risk (≥18) according to Oncotype Dx. For the mean of the top 10% pixels, significant differences were noted for IE (p = 0.032), OE (p = 0.049), and AUC (p = 0.044). Using the risk score as a continuous variable, correlation analysis revealed a weak but significant correlation with the mean of the top 10% pixels for IE (r = 0.26, p = 0.02), OE (r = 0.25, p = 0.02), and AUC (r = 0.27, p = 0.02).ConclusionBPE metrics of enhancement in the non-tumor breast are associated with tumor Oncotype Dx recurrence score, suggesting that the breast microenvironment may relate to likelihood of recurrence and magnitude of chemotherapy benefit.
Prediction of Pathological Upgrading at Radical Prostatectomy in Prostate Cancer Eligible for Active Surveillance: A Texture Features and Machine Learning-Based Analysis of Apparent Diffusion Coefficient Maps
Authors: Xie Jinke , Li Basen , Min Xiangde , Zhang Peipei , Fan Chanyuan , Li Qiubai , Wang Liang 
Published: February 2021

ObjectiveTo evaluate a combination of texture features and machine learning-based analysis of apparent diffusion coefficient (ADC) maps for the prediction of Grade Group (GG) upgrading in Gleason score (GS) ≤6 prostate cancer (PCa) (GG1) and GS 3 + 4 PCa (GG2).Materials and methodsFifty-nine patients who were biopsy-proven to have GG1 or GG2 and underwent MRI examination with the same MRI scanner prior to transrectal ultrasound (TRUS)-guided systemic biopsy were included. All these patients received radical prostatectomy to confirm the final GG. Patients were divided into training cohort and test cohort. 94 texture features were extracted from ADC maps for each patient. The independent sample t-test or Mann−Whitney U test was used to identify the texture features with statistically significant differences between GG upgrading group and GG non-upgrading group. Texture features of GG1 and GG2 were compared based on the final pathology of radical prostatectomy. We used the least absolute shrinkage and selection operator (LASSO) algorithm to filter features. Four supervised machine learning methods were employed. The prediction performance of each model was evaluated by area under the receiver operating characteristic curve (AUC). The statistical comparison between AUCs was performed.ResultsSix texture features were selected for the machine learning models building. These texture features were significantly different between GG upgrading group and GG non-upgrading group (P &lt; 0.05). The six features had no significant difference between GG1 and GG2 based on the final pathology of radical prostatectomy. All machine learning methods had satisfactory predictive efficacy. The diagnostic performance of nearest neighbor algorithm (NNA) and support vector machine (SVM) was better than random forests (RF) in the training cohort. The AUC, sensitivity, and specificity of NNA were 0.872 (95% CI: 0.750−0.994), 0.967, and 0.778, respectively. The AUC, sensitivity, and specificity of SVM were 0.861 (95%CI: 0.732−0.991), 1.000, and 0.722, respectively. There had no significant difference between AUCs in the test cohort.ConclusionA combination of texture features and machine learning-based analysis of ADC maps could predict PCa GG upgrading from biopsy to radical prostatectomy non-invasively with satisfactory predictive efficacy.
Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature
Authors: Hooglugt Aukie , van der Stoel Miesje M. , Boon Reinier A. , Huveneers Stephan 
Published: February 2021

Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. The tumor vessels promote tumor metastasis and complicate delivery of anti-cancer therapies. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis. In addition, endothelial YAP/TAZ activation is important for the formation of new blood and lymphatic vessels during development. Oncogenic activation of YAP/TAZ in tumor cell growth and invasion has been studied in great detail, however the role of YAP/TAZ within the tumor endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting YAP/TAZ in cancer. Here, we overview the upstream signals from the tumor microenvironment that control endothelial YAP/TAZ activation and explore the role of their downstream targets in driving tumor angiogenesis. We further discuss the potential for anti-cancer treatments and vascular normalization strategies to improve tumor therapies.