bluuebunny/crossref_metadata_2025_split huggingface dataset:
On statistical tests of functional connectome fingerprinting
Authors: Wang Zeyi , Sair Haris I. , Crainiceanu Ciprian , Lindquist Martin , Landman Bennett A. , Resnick Susan , Vogelstein Joshua T. , Caffo Brian 
Published: February 2021

AbstractFingerprinting of functional connectomes is an increasingly standard measure of reproducibility in functional magnetic resonance imaging connectomics. In such studies, one attempts to match a subject's first session image with their second, in a blinded fashion, in a group of subjects measured twice. The number or percentage of correct matches is usually reported as a statistic, which is then used in permutation tests. Despite the simplicity and increasing popularity of such procedures, the soundness of the statistical tests, the power, and the factors impacting the test are unstudied. In this article, we investigate the statistical tests of matching based on exchangeability assumption in the fingerprinting analysis. We show that a nearly universal Poisson(1) approximation applies for different matching schemes. We theoretically investigate the permutation tests and explore the issue that the test is overly sensitive to uninteresting directions in the alternative hypothesis, such as clustering due to familial status or demographics. We perform a numerical study on two functional magnetic resonance imaging (fMRI) resting‐state datasets, the Human Connectome Project (HCP) and the Baltimore Longitudinal Study of Aging (BLSA). These datasets are instructive, as the HCP includes technical replications of long scans and includes monozygotic and dizygotic twins, as well as non‐twin siblings. In contrast, the BLSA study incorporates more typical length resting‐state scans in a longitudinal study. Finally, a study of single regional connections is performed on the HCP data.
Long‐term outcomes of patients undergoing coronary sinus reducer implantation ‐ A multicenter study
Authors: Konigstein Maayan , Ponticelli Francesco , Zivelonghi Carlo , Merdler Ilan , Revivo Miri , Verheye Stefan , Giannini Francesco , Banai Shmuel 
Published: February 2021

AbstractBackgroundCoronary sinus (CS) narrowing by reducer implantation has emerged as a safe and effective therapy for patients suffering from refractory angina. However, data regarding the clinical benefit of this treatment over time is lacking.MethodsPatients undergoing successful reducer implantation were enrolled prospectively to clinical registries at three medical centers. Those with more than 2‐years of follow‐up were included in the present analysis. Peri‐procedural data, data regarding adverse events, and current evaluation of angina severity (Canadian Cardiovascular Society [CCS] class) were collected.ResultsOverall, 99 consecutive patients (77% males, mean age 69.8 ± 9.4) with severe angina were enrolled between September 2010 and October 2017 and included in the present analysis. No procedure‐related complications were recorded. During a median follow up time of 3.38 years (IQR 2.95–4.40), 15.1% of the patients died, 9% experienced myocardial infarction (MI) and 21% underwent percutaneous coronary intervention (PCI). Mean CCS class was 3.1 ± 0.5 at baseline, improved to 1.66 ± 0.8 at 1 year (p < .001), and remained low through 2‐years and at last follow up (1.72 ± 0.8 and 1.71 ± 0.8, p > 0.5 for both, in comparison to 1 year). At baseline 91% of patients reported severe disabling angina (CCS class 3–4), at 1 year only 17.9% suffered from disabling angina, p < .001, and this portion remained low overtime (19% at last follow up).ConclusionLong‐term mortality of patients undergoing reducer implantation is similar to that reported for patients with stable coronary artery disease. The previously reported short‐term efficacy of the reducer, reflected by significant improvement of angina symptoms, is maintained over time.
Evaluation of the Bioequivalence of Acarbose in Healthy Chinese People
Authors: Chen Yan , Guo Fahao , Wang Xin , Liu LuYao , Yang Can , Xiong YuQing , Zhang Hong 
Published: February 2021

AbstractThe purpose of this study was to determine whether the reference formulation and test formulation of acarbose are bioequivalent among healthy Chinese subjects based on evaluation of the pharmacodynamic end point. Two clinical trials with acarbose were conducted: study A, a pilot study (n = 12; 50 and 100 mg), and study B, a pivotal study (n = 60; 50 mg). In study A, there was a dose‐dependent relationship between 50 mg acarbose and 100 mg acarbose and a significant difference compared with sucrose alone. In study B, after logarithmic conversion, a linear mixed‐effects model was used to analyze the maximum serum glucose value and area under the serum glucose‐time curve from 0 to 2 hours. The geometric mean ratios (test formulation/reference formulation) were 92.68% and 95.70%, with 90% confidence intervals of 84.08%‐102.17% and 84.21%‐108.76%, respectively, falling between 80.00% and 125.00%. According to the geometric least‐squares mean, the test formulation (or reference formulation) was statistically significantly different as a single sucrose (P < .001). The effective dose of acarbose in healthy Chinese volunteers was 50 mg. The reference and test formulations were bioequivalent.
Blood neurofilament light in remote settings: Alternative protocols to support sample collection in challenging pre‐analytical conditions
Authors: Simrén Joel , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik 
Published: February 2021

AbstractIntroductionThis study investigated alternative pre‐analytical handling of blood for neurofilament light (NfL) analysis where resources are limited.MethodPlasma NfL was measured with single molecule array after alternative blood processing procedures: dried plasma spots (DPS), dried blood spots (DBS), and delayed 48‐hour centrifugation. These were compared to standardized plasma processing (reference standard [RS]). In a discovery cohort (n = 10) and a confirmatory cohort (n = 21), whole blood was obtained from individuals with unknown clinical etiology. In the confirmatory cohort, delayed centrifugation protocol was paired with either 37°C incubation or sample shaking to test the effect of these parameters.ResultsDelayed centrifugation (R2 = 0.991) and DPS (discovery cohort, R2 = 0.954; confirmatory cohort, DPS: R2 = 0.961) methods were strongly associated with the RS. Delayed centrifugation with higher temperatures (R2 = 0.995) and shaking (R2 = 0.975) did not affect this association. DPS (P < 0.001) returned concentrations considerably lower than the RS.DiscussionDPS or delayed centrifugation are viable pre‐analytical procedures for the accurate quantification of plasma NfL.
Deep learning shows no morphological abnormalities in neutrophils in Alzheimer's disease
Authors: Chabrun Floris , Dieu Xavier , Doudeau Nicolas , Gautier Jennifer , Luque‐Paz Damien , Geneviève Franck , Ferré Marc , Mirebeau‐Prunier Delphine , Annweiler Cédric , Reynier Pascal 
Published: February 2021

AbstractIntroductionSeveral studies have provided evidence of the key role of neutrophils in the pathophysiology of Alzheimer's disease (AD). Yet, no study to date has investigated the potential link between AD and morphologically abnormal neutrophils on blood smears.MethodsDue to the complexity and subjectivity of the task by human analysis, deep learning models were trained to predict AD from neutrophil images. Control models were trained for a known feasible task (leukocyte subtype classification) and for detecting potential biases of overfitting (patient prediction).ResultsDeep learning models achieved state‐of‐the‐art results for leukocyte subtype classification but could not accurately predict AD.DiscussionWe found no evidence of morphological abnormalities of neutrophils in AD. Our results show that a solid deep learning pipeline with positive and bias control models with visualization techniques are helpful to support deep learning model results.
Differentiating traits and states identifies the importance of chronic neuropsychiatric symptoms for cognitive prognosis in mild dementia
Authors: Giil Lasse M. , Aarsland Dag , Vik‐Mo Audun Osland 
Published: February 2021

AbstractIntroductionNeuropsychiatric symptoms (NPS) in dementia are associated with poor cognitive outcomes in longitudinal studies. Whether this is due to differences in symptom burden between persons (BP) or changes within persons (WP) is unknown.MethodsPatients with mild Alzheimer's disease (AD, n = 111) and Lewy‐body dementia (LBD, n = 85) were assessed annually for 8 years. We modelled the association between NPS assessed by the Neuropsychiatric Inventory (NPI) and Mini‐Mental State Examinations (MMSE) using Tobit mixed‐effects model with NPS as individual means over time (BP) and its deviance (WP).ResultsThe association between higher NPS and poorer cognitive outcomes was mostly due to BP differences for the NPI‐total score, and in particular for delusions, hallucinations, agitation, aberrant motor behavior, and apathy scores.DiscussionThe NPS trait (BP) effect on cognitive decline is considerably stronger than the state effect (WP). Clinically, long‐term rather than episodic NPS better identifies patients with poor cognitive outcomes.
Single‐cell transcriptomics analysis of mild cognitive impairment in World Trade Center disaster responders
Authors: Kuan Pei‐Fen , Clouston Sean , Yang Xiaohua , Che Chang , Gandy Samuel , Kotov Roman , Bromet Evelyn , Luft Benjamin J. 
Published: February 2021

AbstractIntroductionRecent research has found that World Trade Center (WTC) responders in their mid‐50s have an elevated prevalence of mild cognitive impairment (MCI) that is associated with neural degeneration and subcortical thinning. This article extends our understanding of the molecular complexity of MCI through gene expression profiling of blood.MethodsThe transcriptomics of 40 male WTC responders were profiled across two cohorts (discovery: nine MCI and nine controls; replication: 11 MCI and 11 controls) using CITE‐Seq at single‐cell resolution in blood.ResultsComparing the transcriptomic signatures across seven major cell subpopulations, the largest differences were observed in monocytes in which 226 genes were differentially expressed. Pathway analysis on the genes unique to monocytes identified processes associated with cerebral immune response.DiscussionOur findings suggested monocytes may constitute a key cell type to target in blood‐based biomarker studies for early detection of risk of MCI and development of new interventions.
Insight into the genetic etiology of Alzheimer's disease: A comprehensive review of the role of rare variants
Authors: Hoogmartens Julie , Cacace Rita , Van Broeckhoven Christine 
Published: February 2021

AbstractEarly‐onset Alzheimer's disease (EOAD) is generally known as a dominant disease due to highly penetrant pathogenic mutations in the amyloid precursor protein, presenilin 1 and 2. However, they explain only a fraction of EOAD patients (5% to 10%). Furthermore, only 10% to 15% of EOAD families present with clear autosomal dominant inheritance. Studies showed that only 35% to 60% of EOAD patients have at least one affected first‐degree relative. Parent–offspring concordance in EOAD was estimated to be <10%, indicating that full penetrant dominant alleles are not the sole players in EOAD. We aim to summarize current knowledge of rare variants underlying familial and seemingly sporadic Alzheimer's disease (AD) patients. Genetic findings indicate that in addition to the amyloid beta pathway, other pathways are of importance in AD pathophysiology. We discuss the difficulties in interpreting the influence of rare variants on disease onset and we underline the value of carefully selected ethnicity‐matched cohorts in AD genetic research.
Differential blood DNA methylation across Lewy body dementias
Authors: Nasamran Chanond A. , Sachan Anubhav Nikunj Singh , Mott Jennifer , Kuras Yuliya I. , Scherzer Clemens R. , Study Harvard Biomarkers , Ricciardelli Eugenia , Jepsen Kristen , Edland Steven D. , Fisch Kathleen M. , Desplats Paula 
Published: February 2021

AbstractIntroductionDementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by cognitive alterations, visual hallucinations, and motor impairment. Diagnosis is based on type and timing of clinical manifestations; however, determination of clinical subtypes is challenging. The utility of blood DNA methylation as a biomarker for Lewy body disorders (LBD) is mostly unexplored.MethodsWe performed a cross‐sectional analysis of blood methylation in 42 DLB and 50 PDD cases applying linear models to compare groups and logistic least absolute shrinkage and selection operator regression to explore the discriminant power of methylation signals.ResultsDLB blood shows differential methylation compared to PDD. Some methylation changes associate with core features of LBD. Sets of probes show high predictive value to discriminate between variants.DiscussionOur study is the first to explore LBD blood methylation. Despite overlapping clinical presentation, we detected differential epigenetic signatures that, if confirmed in independent cohorts, could be developed into useful biomarkers.
Glioblastoma mimicking metastatic small cell carcinoma: A case report with ultrastructural findings
Authors: Maekawa Kazunari , Tokumitsu Takako , Noguchi Hiroshi , Nakamura Eriko , Gi Toshihiro , Horinouchi Shoichi , Yamashita Shinji , Takeshima Hideo , Asada Yujiro , Sato Yuichiro 
Published: February 2021

AbstractIt is often straightforward to distinguish glioblastoma (GBM) from metastatic carcinoma by cytology; however, small cell variants of GBM or GBM with primitive neuronal component (GBMPNC) can mimic metastatic small cell carcinoma (SCC). Herein, we report a case of GBMPNC mimicking metastatic SCC and present cytological and ultrastructural findings. A 65‐year‐old man with memory disturbance was hospitalized. Magnetic resonance imaging revealed the presence of a 6 cm sized tumor in the right anterior temporal lobe. Intraoperative cytology slides indicated that the tumor consisted of small‐sized cells with scant cytoplasm showing high cellularity. The initial intraoperative diagnosis was metastatic SCC; however, any primary visceral tumor was not detected clinically. Immunohistochemical and ultrastructural studies of postoperative histological sections revealed that the lesion was GBMPNC. This case shows that some GBMs may have the potential to closely mimic metastatic SCC, which expands the differential diagnosis and emphasizes the importance of clinical correlation.
Indigenous plants promote insect biodiversity in urban greenspaces
Authors: Mata Luis , Andersen Alan N. , Morán‐Ordóñez Alejandra , Hahs Amy K. , Backstrom Anna , Ives Christopher D. , Bickel Daniel , Duncan David , Palma Estibaliz , Thomas Freya , Cranney Kate , Walker Ken , Shears Ian , Semeraro Linda , Malipatil Mallik , Moir Melinda L. , Plein Michaela , Porch Nick , Vesk Peter A. , Smith Tessa R. , Lynch Yvonne 
Published: February 2021

AbstractThe contribution of urban greenspaces to support biodiversity and provide benefits for people is increasingly recognized. However, ongoing management practices favor vegetation oversimplification, often limiting greenspaces to lawns and tree canopy rather than multi‐layered vegetation that includes under‐ and midstorey, and the use of nonnative species. These practices hinder the potential of greenspaces to sustain indigenous biodiversity, particularly for taxa like insects that rely on plants for food and habitat. Yet, little is known about which plant species may maximize positive outcomes for taxonomically and functionally diverse insect communities in greenspaces. Additionally, while cities are expected to experience high rates of introductions, quantitative assessments of the relative occupancy of indigenous vs. introduced insect species in greenspace are rare, hindering understanding of how management may promote indigenous biodiversity while limiting the establishment of introduced insects. Using a hierarchically replicated study design across 15 public parks, we recorded occurrence data from 552 insect species on 133 plant species, differing in planting design element (lawn, midstorey, and tree canopy), midstorey growth form (forbs, lilioids, graminoids, and shrubs) and origin (nonnative, native, and indigenous), to assess (1) the relative contributions of indigenous and introduced insect species and (2) which plant species sustained the highest number of indigenous insects. We found that the insect community was overwhelmingly composed of indigenous rather than introduced species. Our findings further highlight the core role of multi‐layered vegetation in sustaining high insect biodiversity in urban areas, with indigenous midstorey and canopy representing key elements to maintain rich and functionally diverse indigenous insect communities. Intriguingly, graminoids supported the highest indigenous insect richness across all studied growth forms by plant origin groups. Our work highlights the opportunity presented by indigenous understory and midstorey plants, particularly indigenous graminoids, in our study area to promote indigenous insect biodiversity in urban greenspaces. Our study provides a blueprint and stimulus for architects, engineers, developers, designers, and planners to incorporate into their practice plant species palettes that foster a larger presence of indigenous over regionally native or nonnative plant species, while incorporating a broader mixture of midstorey growth forms.
Predictive scores for identifying patients with type 2 diabetes mellitus at risk of acute myocardial infarction and sudden cardiac death
Authors: Lee Sharen , Zhou Jiandong , Guo Cosmos Liutao , Wong Wing Tak , Liu Tong , Wong Ian Chi Kei , Jeevaratnam Kamalan , Zhang Qingpeng , Tse Gary 
Published: February 2021

AbstractIntroductionThe present study evaluated the application of incorporating non‐linear J/U‐shaped relationships between mean HbA1c and cholesterol levels into risk scores for predicting acute myocardial infarction (AMI) and non‐AMI‐related sudden cardiac death (SCD) respectively, amongst patients with type 2 diabetes mellitus.MethodsThis was a territory‐wide cohort study of patients with type 2 diabetes mellitus above the age 40 and free from prior AMI and SCD, with or without prescriptions of anti‐diabetic agents between January 1st, 2009 to December 31st, 2009 at government‐funded hospitals and clinics in Hong Kong. Patients recruited were followed up until 31 December 2019 or their date of death. Risk scores were developed for predicting incident AMI and non‐AMI‐related SCD. The performance of conditional inference survival forest (CISF) model compared to that of random survival forests (RSF) model and multivariate Cox model.ResultsThis study included 261 308 patients (age = 66.0 ± 11.8 years old, male = 47.6%, follow‐up duration = 3552 ± 1201 days, diabetes duration = 4.77 ± 2.29 years). Mean HbA1c and low high‐density lipoprotein‐cholesterol (HDL‐C) were significant predictors of AMI on multivariate Cox regression. Mean HbA1c was linearly associated with AMI, whilst HDL‐C was inversely associated with AMI. Mean HbA1c and total cholesterol were significant multivariate predictors with a J‐shaped relationship with non‐AMI‐related SCD. The AMI and SCD risk scores had an area under the curve (AUC) of 0.666 (95% confidence interval (CI) = [0.662, 0.669]) and 0.677 (95% CI = [0.673, 0.682]), respectively. CISF significantly improves prediction performance of both outcomes compared to RSF and multivariate Cox models.ConclusionA holistic combination of demographic, clinical and laboratory indices can be used for the risk stratification of patients with type 2 diabetes mellitus for AMI and SCD.
Temporal trends in incidence, causes, use of mechanical circulatory support and mortality in cardiogenic shock
Authors: Schrage Benedikt , Becher Peter Moritz , Goßling Alina , Savarese Gianluigi , Dabboura Salim , Yan Isabell , Beer Benedikt , Söffker Gerold , Seiffert Moritz , Kluge Stefan , Kirchhof Paulus , Blankenberg Stefan , Westermann Dirk 
Published: February 2021

AbstractAimThe management of cardiogenic shock remains a clinical challenge even in well‐developed healthcare systems, best illustrated by its high mortality despite numerous innovative proposals for management. The aim of this study was to describe temporal trends in incidence, causes, use of mechanical circulatory support, and mortality in cardiogenic shock in Germany.Methods and resultsData on all cardiogenic shock patients treated in German hospitals between 2005 and 2017 were obtained from the Federal Bureau of Statistics. The data set comprised 441 696 patients with cardiogenic shock, mean age 71 (±13.8) years, 171 383 (39%) female patients. Incidence rates increased from 33.1/100 000 population in 2005 (27 246 cases) to 51.7/100 000 population in 2017 (42 779 cases). Acute myocardial infarction was the most common cause of cardiogenic shock in 2005–07 (43 422 of 82 037 cases, 52.9%), but the proportion of cases caused by it decreased until 2014–17 (73 274 of 165 873 cases, 44.2%). Over time, intra‐aortic balloon pump (2005: 5104; 2017: 973 cases) was used less frequently, whereas use of extracorporeal‐membrane‐oxygenation (2007: 35; 2017: 2414 cases) and percutaneous left ventricular assist devices (2005: 27; 2017: 1323 cases) increased. Mortality remained high at around 60% without relevant temporal trends in patients without acute myocardial infarction and slightly decreased in patients with acute myocardial infarction.ConclusionsIn this large, nation‐wide study, annual incidence of cardiogenic shock was growing, its causes were changing, and mortality was high despite a shift towards use of novel mechanical circulatory support devices. This highlights the need to address the evidence gap in this field, in particular for cardiogenic shock caused by diseases other than acute myocardial infarction.
Risk stratification and management of women with cardiomyopathy/heart failure planning pregnancy or presenting during/after pregnancy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy
Authors: Sliwa Karen , van der Meer Peter , Petrie Mark C. , Frogoudaki Alexandra , Johnson Mark R. , Hilfiker‐Kleiner Denise , Hamdan Righab , Jackson Alice M. , Ibrahim Bassem , Mbakwem Amam , Tschöpe Carsten , Regitz‐Zagrosek Vera , Omerovic Elmir , Roos‐Hesselink Jolien , Gatzoulis Michael , Tutarel Oktay , Price Susanna , Heymans Stephane , Coats Andrew J.S. , Müller Christian , Chioncel Ovidiu , Thum Thomas , de Boer Rudolf A. , Jankowska Ewa , Ponikowski Piotr , Lyon Alexander R. , Rosano Giuseppe , Seferovic Petar M. , Bauersachs Johann 
Published: February 2021

AbstractThis position paper focusses on the pathophysiology, diagnosis and management of women diagnosed with a cardiomyopathy, or at risk of heart failure (HF), who are planning to conceive or present with (de novo or previously unknown) HF during or after pregnancy. This includes the heterogeneous group of heart muscle diseases such as hypertrophic, dilated, arrhythmogenic right ventricular and non‐classified cardiomyopathies, left ventricular non‐compaction, peripartum cardiomyopathy, Takotsubo syndrome, adult congenital heart disease with HF, and patients with right HF. Also, patients with a history of chemo‐/radiotherapy for cancer or haematological malignancies need specific pre‐, during and post‐pregnancy assessment and counselling. We summarize the current knowledge about pathophysiological mechanisms, including gene mutations, clinical presentation, diagnosis, and medical and device management, as well as risk stratification. Women with a known diagnosis of a cardiomyopathy will often require continuation of drug therapy, which has the potential to exert negative effects on the foetus. This position paper assists in balancing benefits and detrimental effects.