bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haplotype-based membership inference from summary genomic data
Authors: Bu Diyue , Wang Xiaofeng , Tang Haixu 
Published: April 2021

Abstract

Motivation
The availability of human genomic data, together with the enhanced capacity to process them, is leading to transformative technological advances in biomedical science and engineering. However, the public dissemination of such data has been difficult due to privacy concerns. Specifically, it has been shown that the presence of a human subject in a case group can be inferred from the shared summary statistics of the group, e.g. the allele frequencies, or even the presence/absence of genetic variants (e.g. shared by the Beacon project) in the group. These methods rely on the availability of the target’s genome, i.e. the DNA profile of a target human subject, and thus are often referred to as the membership inference method.

Results
In this article, we demonstrate the haplotypes, i.e. the sequence of single nucleotide variations (SNVs) showing strong genetic linkages in human genome databases, may be inferred from the summary of genomic data without using a target’s genome. Furthermore, novel haplotypes that did not appear in the database may be reconstructed solely from the allele frequencies from genomic datasets. These reconstructed haplotypes can be used for a haplotype-based membership inference algorithm to identify target subjects in a case group with greater power than existing methods based on SNVs.

Availability and implementation
The implementation of the membership inference algorithms is available at https://github.com/diybu/Haplotype-based-membership-inferences.
GEInter: an R package for robust gene–environment interaction analysis
Authors: Wu Mengyun , Qin Xing , Ma Shuangge 
Published: April 2021

Abstract

Summary
For understanding complex diseases, gene–environment (G–E) interactions have important implications beyond main G and E effects. Most of the existing analysis approaches and software packages cannot accommodate data contamination/long-tailed distribution. We develop GEInter, a comprehensive R package tailored to robust G–E interaction analysis. For both marginal and joint analysis, for data without and with missingness, for continuous and censored survival responses, it comprehensively conducts identification, estimation, visualization and prediction. It can fill an important gap in the existing literature and enjoy broad applicability.

Availability and implementation
TCGA data is analyzed as demonstrating examples. It is well known that such data is publicly available https://cran.r-project.org/web/packages/GEInter/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Splenial white matter integrity is associated with memory impairments in posterior cortical atrophy
Authors: Overman Margot Juliëtte , Zamboni Giovanna , Butler Christopher , Ahmed Samrah 
Published: April 2021

Abstract
Posterior cortical atrophy is an atypical form of Alzheimer’s disease characterized by visuospatial impairments and predominant tissue loss in the posterior parieto-occipital and temporo-occipital cortex. Whilst episodic memory is traditionally thought to be relatively preserved in posterior cortical atrophy, recent work indicates that memory impairments form a common clinical symptom in the early stages of the disease. Neuroimaging studies suggest that memory dysfunction in posterior cortical atrophy may originate from atrophy and functional hypoconnectivity of parietal cortex. The structural connectivity patterns underpinning these memory impairments, however, have not been investigated. This line of inquiry is of particular interest, as changes in white matter tracts of posterior cortical atrophy patients have been shown to be more extensive than expected based on posterior atrophy of grey matter. In this cross-sectional diffusion tensor imaging MRI study, we examine the relationship between white matter microstructure and verbal episodic memory in posterior cortical atrophy. We assessed episodic memory performance in a group of posterior cortical atrophy patients (n = 14) and a group of matched healthy control participants (n = 19) using the Free and Cued Selective Reminding Test with Immediate Recall. Diffusion tensor imaging measures were obtained for 13 of the posterior cortical atrophy patients and a second control group of 18 healthy adults. Patients and healthy controls demonstrated similar memory encoding performance, indicating that learning of verbal information was preserved in posterior cortical atrophy. However, retrieval of verbal items was significantly impaired in the patient group compared with control participants. As expected, tract-based spatial statistics analyses showed widespread reductions of white matter integrity in posterior cortical regions of patients compared with healthy adults. Correlation analyses indicated that poor verbal retrieval in the patient group was specifically associated with microstructural damage of the splenium of the corpus callosum. Post-hoc tractography analyses in healthy controls demonstrated that this splenial region was connected to thalamic radiations and the retrolenticular part of the internal capsule. These results provide insight into the brain circuits that underlie memory impairments in posterior cortical atrophy. From a cognitive perspective, we propose that the association between splenial integrity and memory dysfunction could arise indirectly via disruption of attentional processes. We discuss implications for the clinical phenotype and development of therapeutic aids for cognitive impairment in posterior cortical atrophy.
Endothelial Zeb2 preserves the hepatic angioarchitecture and protects against liver fibrosis
Authors: de Haan Willeke , Dheedene Wouter , Apelt Katerina , Décombas-Deschamps Sofiane , Vinckier Stefan , Verhulst Stefaan , Conidi Andrea , Deffieux Thomas , Staring Michael W , Vandervoort Petra , Caluwé Ellen , Lox Marleen , Mannaerts Inge , Takagi Tsuyoshi , Jaekers Joris , Berx Geert , Haigh Jody , Topal Baki , Zwijsen An , Higashi Yujiro , van Grunsven Leo A , van IJcken Wilfred F J , Mulugeta Eskeatnaf , Tanter Mickael , Lebrin Franck P G , Huylebroeck Danny , Luttun Aernout 
Published: April 2021

Abstract

Aims
Hepatic capillaries are lined with specialized liver sinusoidal endothelial cells (LSECs) which support macromolecule passage to hepatocytes and prevent fibrosis by keeping hepatic stellate cells (HSCs) quiescent. LSEC specialization is co-determined by transcription factors. The zinc-finger E-box-binding homeobox (Zeb)2 transcription factor is enriched in LSECs. Here, we aimed to elucidate the endothelium-specific role of Zeb2 during maintenance of the liver and in liver fibrosis.

Methods and results
To study the role of Zeb2 in liver endothelium we generated EC-specific Zeb2 knock-out (ECKO) mice. Sequencing of liver EC RNA revealed that deficiency of Zeb2 results in prominent expression changes in angiogenesis-related genes. Accordingly, the vascular area was expanded and the presence of pillars inside ECKO liver vessels indicated that this was likely due to increased intussusceptive angiogenesis. LSEC marker expression was not profoundly affected and fenestrations were preserved upon Zeb2 deficiency. However, an increase in continuous EC markers suggested that Zeb2-deficient LSECs are more prone to dedifferentiation, a process called ‘capillarization’. Changes in the endothelial expression of ligands that may be involved in HSC quiescence together with significant changes in the expression profile of HSCs showed that Zeb2 regulates LSEC–HSC communication and HSC activation. Accordingly, upon exposure to the hepatotoxin carbon tetrachloride (CCl4), livers of ECKO mice showed increased capillarization, HSC activation, and fibrosis compared to livers from wild-type littermates. The vascular maintenance and anti-fibrotic role of endothelial Zeb2 was confirmed in mice with EC-specific overexpression of Zeb2, as the latter resulted in reduced vascularity and attenuated CCl4-induced liver fibrosis.

Conclusion
Endothelial Zeb2 preserves liver angioarchitecture and protects against liver fibrosis. Zeb2 and Zeb2-dependent genes in liver ECs may be exploited to design novel therapeutic strategies to attenuate hepatic fibrosis.
A comparative analysis of the diagnostic performances of four clinical probability models to rule out pulmonary embolism
Authors: Silva BV , Mendonca C , Silverio Antonio P , Ferreira A , Cunha N , Rodrigues T , Morais P , Alves Da Silva P , Pacheco R , Jorge C , Pinto FJ 
Published: April 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Ruling out pulmonary embolism (PE) through a combination of clinical assessment and Ddimer is crucial to avoid excessive computed tomography pulmonary angiography (CTPA), and different algorithms should be considered as an alternative to the fixed cutoff to achieve that goal.

Purpose
To compare diagnostic performance of 4 algorithms to rule out PE: fixed Ddimer cutoff, age-adjusted, YEARS and PEGeD.

Methods
Retrospective study of consecutive outpatients who presented to the emergency department and underwent CTPA for PE suspicion from April 2019 to May 2020.
In fixed and age-adjusted cut-off, high probability patients are directly selected for CTPA. Low to moderate probability patients perform CTPA if Ddimer ≥500µg/L in fixed cutoff, and in age-adjusted cutoff if Ddimer ≥500µg/L in patients who are ≤ 50 years of age, and if Ddimer level was more than 10 times the patient’s age in patients older than 50 years. YEARS includes 3 items (signs of deep vein thrombosis, haemoptysis and whether PE is the most likely diagnosis): patients without any YEARS items and Ddimer ≥1000ng/mL or with ≥1 items and Ddimer 500ng/mL perform CTPA. In the PEGeD, patients with high clinical probability or with intermediate and Ddimers &gt;500µg/L or low probability and Ddimer &gt;1000 µg/L are selected for CTPA.

Results
We enrolled 571 patients and PE was confirmed by CTPA in 172. Compared with a fixed Ddimer cutoff, age-adjusted was associated with a significant increase of specificity (p &lt; 0.001), correctly avoiding 38 CTPAs, without losing sensitivity. YEARS and PEGED resulted in a increase in specificity, compared to the fixed cutoff, but with an impairment of sensitivity (p &lt; 0.001). PEGeD had the worst sensitivity (13 more false negatives (FN) than the fixed cutoff). Despite the lack of difference between PEGed and YEARS strategies regarding sensitivity, PEGED had a significantly higher specificity (p &lt; 0.001) and allowed to correctly avoid a higher number of CTPA (95 vs 85), compared to the fixed cutoff.

Conclusion
Compared to fixed d-dimer cutoff, all algorithms were associated with an increased specificity. Age-adjusted cutoff was the only that is not associated with a significant decrease in sensitivity when compared to fixed cutoff, allowing to safely reduce the need to perform CTPA. Sen(%)Spec(%)Correctly avoid CTPAs(n)FN(n)Fixed cutoff251017Age-adjusted933513912YEARS894718619PEGED884919620
Association of CTLA4 gene polymorphism with dilated cardiomyopathy
Authors: Chernova A , Nikulina SY , Kuznecova OO 
Published: April 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Aim
To evaluate the Association of rs231775 polymorphism of the CTLA4 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI).

Subjects and methods
The study included patients with ICMP and DMI in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years.
We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years.
The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years.
The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years).
The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the 49A/G polymorphism of the CTLA4 gene (rs231775). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris.

Results
In the group with DCMP 34.2% of patients were carriers of the common homozygous 49AA genotype, the heterozygous 49AG genotype-48.6%, and the rare homozygous 49GG genotype-17.1%. In the control group 33.5% of patients were identified as carriers of a homozygous genotype by a common allele, and 49.3% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 17.2%. The analysis revealed a statistically non significant increase in the frequency of carrying the homozygous AA genotype in patients with DCMP compared to the control group of the rs231775 polymorphism of the CTLA4 gene. In the group with DMI, there was no association with the rs231775 polymorphism of the CTLA4 gene.

Conclusion
A statistically significant association of rs231775 of the CTLA4 gene with DCMP was not found. The association of DMI c rs231775 could not be confirmed.
S-reflex score: a predictor score of vaso-vagal reflex syncope
Authors: Costa H , Fernandes R , Mota T , Bispo J , Azevedo P , Santo M , Carvalho D , Marques N , Candeias R , Jesus I 
Published: April 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Reflex syncope is one of the most common causes of syncope, usually associated with unspecified triggers and prodromes. The probability of occurrence is higher when concomitant factors coexist whether inherent to individual or related to environment, and changes in conventional tests may prove useful in their diagnosis.

Objective
Identify predictive factors in the initial investigation in order to establish a predictor score of vasovagal reflex syncope (VVS).

Methods
Observational and retrospective study, with descriptive analysis and correlation of patients followed in syncope appointment at a Cardiology Center from 1 January 2015 to 31 Novembe 2019. Descriptive analysis on patient characteristics and complementary exams were carried out. The correlation test used between categorical variables was Chi-square and among continuous variables the T-Student test with a significance level of 95%. Independent predictors of VVS were identified through binary logistic regression considering a p = 0.05, with subsequent application of a discriminatory function using the lambda Wilks test to determine the discriminant score of variables under analysis. SPSS 24.0 was used for statistical analysis.

Results
Identified N694 patients, 52% male, mean age of 63 years. 15.7% of patients with suspected VVS in a first impression. At the end, 22.9% diagnosed with VVS and of these 66% had syncope recurrence. 42% had long prodromes (p = 0.013), 17% with heat prodromes (p = 0.012), in 11.3% the trigger was the meal (p = 0.031), 12.2% suffered trauma (p = 0.07) and 59.7% had ECG with pathological q wave (p = 0.00), thus showing to be independet predictors of VVS. A predictor score of VVS was determined using the formula = -0.761 + (0.529.Long_Prodromes) + (0.721.Heat_Prodromes) + (0.313.Trigger_Meal) + (2,431.ECG_q) - (0.542.Trauma), with a cutoff value of 0.258, specificity of 90.5% with discriminative power of 87%.

Conclusion
The final diagnosis of VVS was higher than suspicions during initial clinical investigation and 66% of these patients had recurrence. The independent predictors factors of VVS are long prodromes, heat prodromes, meal as a trigger, ECG with q waves and trauma. The S-Reflex score was determined with a good discriminative power with high specificity. Considering clinical variables and conventional exams, this score could be useful to guide the strategy for syncope patients after the first evaluation to a more cost-effective strategy.
Leadless pacemaker vs conventional single chamber pacemaker for urgent permanent implantation in elderly and very elderly patients
Authors: Marschall A , Del Castillo Carnevali H , Torres Lopez M , Goncalves Sanchez F , Marti Sanchez D , Delgado Calva F , Biscotti Rodil B , Alvarez Anton S , Rubio Alonso M 
Published: April 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Data on feasibility of leadless pacemaker (LPM) in the elderly and very elderly is scarce. We aimed to investigate the security and feasibility of urgent LPM implantation in elderly patients.

Methods
Observational study of a prospective register of consecutive patients that underwent LPM insertion in a single centre. Elderly (≥75 years) and very elderly patients (≥85 years) that underwent LPM implantation in a non-elective setting between June 2016 and January 2020 were eligible. We compared pacing thresholds, R wave and impedance at baseline, short- and long term follow-up. Furthermore, we compared complication rate and all-cause mortality of LPM patients to patients that underwent conventional SCP insertion.

Results
78 elderly patients (25 LPM, 53 SCP) with a mean age of 82.4 and 83.8 years, respectively (p = 0.82), were included in the study. The mean follow-up time was 11.2 months. 35 patients (11 LPM, 24 SCP) had an age of ≥ 85 years. There were no significant differences with respect to demographic and baseline clinical data between LPM patients and SCP patients. (Table) Furthermore, we did not find significant changes in pacing thresholds, R wave and impedance on short- and long-term follow-up. Complication rates at 12 months of elderly and very elderly LPM patients were similar to those that underwent conventional SCP implantation (0% vs 5.7%, p = 0.35; 0% vs 4.2%, p = 0.41, respectively). Likewise, we did not find significant differences regarding all-cause mortality (12% vs 13%, p = 0.92; 9% vs 25%, p = 0.18). Comparing Kaplan-Meier curves, no significant differences were found regarding 12 month complication rate and all-cause mortality between LPM patients and conventional SCP patients, as assessed by Log Rank test (p = 0.98 and p = 0.91, respectively). (Figure)

Conclusion
LPM implantation is a feasible and secure alternative to conventional SCP insertion in elderly and very elderly patients, even in a non-elective setting. Basline characteristicsBaseline characteristicsConventional SCP, n = 53Leadless pacemaker, n = 25p-valueAge - years83.8 (±6.4)82.4 (±6.4)N/SSex, male - n (%)28 (52)16 (64)N/SChronic kidney disease - n (%)16 (30)6 (24)N/SAtrial fibrillation - n (%)45 (85)19 (76)N/SCharlson index, (IQR)4 (3-7)5 (4-7)N/SR wave amplitude, mV (IQR)10.5 (7.4-13.3)12.2 (9.3-15.2)N/SPacing threshold, mV (IQR)0.6 (0.5-0.9)0.4 (0.3-0.7)N/SImpedance, Ohm (IQR)669 (±185)713 (±191)N/SIQR, interquartile range; N/S: Not significant; SCP: Single chamber pacemaker​Abstract Figure. Kaplan Meier curves, Mortality
Arrhythmic storm in the acute coronary care unit
Authors: Garcia-Arribas D , Rosillo S , Caro J , Armada E , Carrion I , Ferrera C , Noriega FJ , Viana A , Lopez De Sa E 
Published: April 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Beca para la Formación e Investigación en Cuidados Críticos Cardiológicos concedida por la Asociación de Cardiopatía Isquémica y Cuidados Críticos Cardiológicos de la SEC

Introduction
Available data on arrhythmic storm (AS) is usually obtained from retrospective observational studies based on series of patients (pts) with ICD or who undergo ablation. Therefore, selection bias limits the evidence regarding mortality and prognosis of this entity.
Purpose/ Methods
Describe epidemiological and clinical characteristics, as well as therapeutic strategies and in-hospital mortality as main outcome of pts admitted between 2006 and 2020 for AS in the Acute Cardiac Care Unit (ACCU) of 2 tertiary hospitals in Madrid, Spain.

Results
A total of 190 episodes of AS in 169 pts were analysed. Baseline characteristics are depicted in Figure 1. Cardiovascular targeted treatments of pts included: betablockers (68.7%), ACEi or ARB (53.2%), ARNI (6.5%), AA (38.5%), group III antiarrhythmic drugs (27.1%) and digoxin (5.9%).
Aetiology of the AS was determined in 68.6% of the episodes: myocardial ischemia 25.1%, STEMI 22.5%, acute myocarditis 0.5%, heart failure or cardiogenic shock 28.8%, infection 11%, Bradycardia and long QT interval 10%, ionic disturbances 6.3%, others 11.5%.
Antiarrhythmic drugs used for the acute episode were: amiodarone (73.3%), procainamide (27.2%), sotalol (5.7%), other beta blockers (75.9%), calcium channel blockers (3.1%), quinidine (2.1%). Other therapies were performed as follows: sedative drugs 50.3%, endotracheal intubation 39,9%, correction of electrolyte disturbances 51.8%, therapeutic hypothermia 13.6%, intravenous temporary pacemaker insertion or ICD reprogramming (9.9%). In 45% of pts coronary angiography was performed, but only 25.7% required revascularization. Vasopressors and inotropic drugs were used in 51% of pts. Regarding mechanical support intra-aortic balloon pump was implanted in 16.2% of episodes, ECMO in 3.7% and other left ventricular assist devices in 3.1%. One patient was transplanted.
Ventricular tachycardia (VT) ablation was performed in 38.7% of episodes and its efficiency was 69.4%. Three pts underwent stellate ganglion ablation and surgical sympathectomy, and in one pt sympathectomy alone was performed. ICD was implanted in 23 pts after the AS episode.
Survival at discharge was 81.1%. Mortality in STEMI related AS was 44.2%, while in the rest of aetiologies was 6.1%. Mortality among patients with an ICD was 6.3%.

Conclusion
Patients with AS requiring admission to an ACCU have predominantly ischemic background (both acute and chronic). Most common therapeutics are beta-blockers, amiodarone, sedation and VT-ablation. In-hospital mortality differs depending on the aetiology being worst in STEMI related AS. Abstract Figure 1