bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can machine learning bring cardiovascular risk assessment to the next level? A methodological study using FOURIER trial data
Authors: Rousset Adrien , Dellamonica David , Menuet Romuald , Lira Pineda Armando , Sabatine Marc S , Giugliano Robert P , Trichelair Paul , Zaslavskiy Mikhail , Ricci Lea 
Published: November 2021

Abstract

Aims
Through this proof of concept, we studied the potential added value of machine learning (ML) methods in building cardiovascular risk scores from structured data and the conditions under which they outperform linear statistical models.

Methods and results
Relying on extensive cardiovascular clinical data from FOURIER, a randomized clinical trial to test for evolocumab efficacy, we compared linear models, neural networks, random forest, and gradient boosting machines for predicting the risk of major adverse cardiovascular events. To study the relative strengths of each method, we extended the comparison to restricted subsets of the full FOURIER dataset, limiting either the number of available patients or the number of their characteristics. When using all the 428 covariates available in the dataset, ML methods significantly (c-index 0.67, P-value 2e−5) outperformed linear models built from the same variables (c-index 0.62), as well as a reference cardiovascular risk score based on only 10 variables (c-index 0.60). We showed that gradient boosting—the best performing model in our setting—requires fewer patients and significantly outperforms linear models when using large numbers of variables. On the other hand, we illustrate how linear models suffer from being trained on too many variables, thus requiring a more careful prior selection. These ML methods proved to consistently improve risk assessment, to be interpretable despite their complexity and to help identify the minimal set of covariates necessary to achieve top performance.

Conclusion
In the field of secondary cardiovascular events prevention, given the increased availability of extensive electronic health records, ML methods could open the door to more powerful tools for patient risk stratification and treatment allocation strategies.
High-intensity statin treatment is associated with reduced plaque structural stress and remodelling of artery geometry and plaque architecture
Authors: Gu Sophie Z , Costopoulos Charis , Huang Yuan , Bourantas Christos , Woolf Adam , Sun Chang , Teng Zhongzhao , Losdat Sylvain , Räber Lorenz , Samady Habib , Bennett Martin R 
Published: November 2021

AbstractAimsPlaque structural stress (PSS) is a major cause of atherosclerotic plaque rupture and major adverse cardiovascular events (MACE). We examined the predictors of changes in peak and mean PSS (ΔPSSpeak, ΔPSSmean) in three studies of patients receiving either standard medical or high-intensity statin (HIS) treatment.Methods and resultsWe examined changes in PSS, plaque size, and composition between 7348 co-registered baseline and follow-up virtual-histology intravascular ultrasound images in patients receiving standard medical treatment (controls, n = 18) or HIS (atorvastatin 80 mg, n = 20, or rosuvastatin 40 mg, n = 22). The relationship between changes in PSSpeak and plaque burden (PB) differed significantly between HIS and control groups (P &lt; 0.001). Notably, PSSpeak increased significantly in control lesions with PB &gt;60% (P = 0.04), but not with HIS treatment. However, ΔPSSpeak correlated poorly with changes in lumen and plaque area or PB, plaque composition, or lipid lowering. In contrast, ΔPSSpeak correlated significantly with changes in lumen curvature, irregularity, and roughness (P &lt; 0.05), all of which were reduced in HIS patients. ΔPSSmean correlated with changes in lumen area, PA, PB, and circumferential calcification, and was unchanged with either treatment.ConclusionOur observational study shows that PSSpeak changes over time were associated with baseline disease severity and treatment. The PSSpeak increase seen in advanced lesions with standard treatment was associated with remodelling artery geometry and plaque architecture, but this was not seen after HIS treatment. Smoothing plaques by reducing plaque/lumen roughness, irregularity, and curvature represents a novel mechanism whereby HIS may reduce PSS and, thus may protect against plaque rupture and MACE.
Intrahousehold Resource Allocation and Individual Poverty: Assessing Collective Model Predictions using Direct Evidence on Sharing
Authors: Bargain Olivier , Lacroix Guy , Tiberti Luca 
Published: November 2021

AbstractWelfare analyses conducted by policy practitioners around the world usually rely on equivalised or per capita expenditures and ignore the extent of within-household inequality. Recent advances in the estimation of collective models suggest ways to retrieve the complete sharing process within families using homogeneity assumptions (typically preference stability upon exclusive goods across individuals or household types) and the observation of exclusive goods. So far, the prediction of these models has not been validated, essentially because intrahousehold allocation is seldom observed. We provide such a validation by leveraging a unique dataset from Bangladesh, which contains information on the fully individualised expenditures of each family member. We also test the core assumption (efficiency) and homogeneity assumptions used for identification. It turns out that the collective model predicts individual resources reasonably well when using clothing, i.e., one of the rare goods commonly assignable to males, females and children in standard expenditure surveys. It also allows for identifying poor individuals in non-poor households, while the traditional approach understates poverty among the poorest individuals.
Can External Threats Foster a European Union Identity? Evidence from Russia’s Invasion of Ukraine
Authors: Gehring Kai 
Published: November 2021

Abstract
Can external threats strengthen group identity? A growing body of research in economics emphasises the importance of cultural attributes such as identity for trust and cooperation. However, where these attributes come from is not well understood. This paper examines reactions to the Russian invasion of Ukraine in 2014, looking at European Union member states. Comparing low-threat to high-threat states in a difference-in-differences design, I find a sizeable and persistent positive effect on EU identity. It is associated with higher trust in EU institutions and support for common policies. Lower-level identities remain unaffected, and proximity to Russia and Russian minority size are driving high-threat status.
Influence of residual primary entry following the tear-oriented strategy for acute type A aortic dissection
Authors: Kawahito Koji , Aizawa Kei , Kimura Naoyuki , Yamaguchi Atsushi , Adachi Hideo 
Published: November 2021

Abstract

OBJECTIVES
Although a tear-oriented strategy has contributed to improving short-term surgical outcomes of acute type A aortic dissection (ATAAD), long-term clinical influences of residual entry tear in the downstream aorta have not been fully investigated. The goal of this study was to assess the long-term surgical outcomes of ATAAD with or without a residual entry tear in the downstream aorta.

METHODS
Medical records of 1107 patients with ATAAD who underwent emergency surgery between 1990 and 2018 were retrospectively reviewed. A tear-oriented paradigm was adopted for the baseline strategy. The 837 patients in whom the entry tears were resected comprised the resected group, and the 270 patients with a residual entry tear comprised the residual group. Of these patients, 252 in each group were analysed using propensity score matching, and long-term outcomes were compared with or without residual entry.

RESULTS
Hospital deaths were lower in the resected group (3.2% vs 8.3%; P = 0.020). The survival rate was not significantly different between the groups: It was 83.8% and 68.5% in the resected group and 80.2% and 66.5% in the residual group at 5 and 10 years, respectively (P = 0.600). However, residual entry in the downstream aorta affected the distal aortic event-free survival rate (90.4% and 80.6% in the resected group and 82.3% and 67.4% in the residual group at 5 and 10 years, respectively; P = 0.003). Furthermore, multivariable risk analysis of 1107 patients confirmed that a residual entry in the downstream aorta was a risk factor for distal aortic events.

CONCLUSIONS
The tear-oriented strategy remains the gold standard for high-risk patients; however, the extensive operation might be considered for stable patients to reduce long-term aortic events.
Acromegaly and cardiovascular outcomes: a cohort study
Authors: Hong Sangmo , Kim Kyung-Soo , Han Kyungdo , Park Cheol-Young 
Published: November 2021

Abstract

Aims
Cardiovascular disease is a common complication in acromegaly. We investigated the risk of cardiovascular disease and mortality in patients with acromegaly in a large-scale population using nationwide data in Korea.

Methods and results
We performed a nationwide, retrospective, observational, cohort study of patients with acromegaly (n = 1874) and age- and sex-matched subjects without acromegaly (n = 9370) for a mean follow-up of 7.5 ± 3.2 years. The study outcomes were myocardial infarction, stroke, atrial fibrillation, congestive heart failure, and all-cause death. All outcomes were analysed by Cox proportional hazards regression analysis while controlling for age, sex, household income, place, Type 2 diabetes, hypertension, and dyslipidaemia. The incidence (per 1000 person-years) of atrial fibrillation (3.06 vs. 1.70; P = 0.001), congestive heart failure (3.11 vs. 1.63; P &lt; 0.001), and all-cause mortality (6.31 vs. 4.03; P &lt; 0.001) in patients with acromegaly was higher than in controls. However, the incidence of myocardial infarction and stroke did not differ between groups. After adjustment for covariates, the risk for atrial fibrillation [hazard ratio (HR): 1.59; 95% confidence interval (CI): 1.09–2.31], congestive heart failure (HR: 1.54; 95% CI: 1.06–2.25), and all-cause mortality (HR: 1.31; 95% CI: 1.01–1.69) was significantly higher in patients with acromegaly. In time lag sensitivity analysis, a higher risk for atrial fibrillation was observed only in the first 4 years after diagnosis in acromegaly patients compared with controls (HR: 3.05; 95% CI: 1.94–4.79).

Conclusion
Patients with acromegaly were at higher risk for atrial fibrillation, congestive heart failure, and all-cause death. The risk of atrial fibrillation had a time-dependent association with acromegaly.
Profile of patients with type 2 diabetes and glycated haemoglobin ≥ 10% followed in general practice
Authors: Fortin Frédéric , Vorilhon Philippe , Laporte Catherine , Boirie Yves , Ruivard Marc , Riquelme Marie , Pereira Bruno , Tanguy Gilles 
Published: November 2021

Abstract

Objective
To determine whether profiles of patients with unbalanced type 2 diabetes (T2DM) and glycated haemoglobin (HbA1c) ≥ 10% could be identified on the basis of socio-demographic, behavioural, clinical, and biological characteristics.

Methods
Retrospective, cross-sectional, factorial analysis study of patients with T2DM treated for at least 1 year, with HbA1c ≥ 10%. Patients were recruited via medical analysis laboratories, France. Patients were followed up in general practice with possible recourse to specialist consultations. Data were collected by means of self-administered questionnaires sent by post.

Results
A total of 104 patients were included: 69 men and 35 women, with a median age of 66 ± 12 years, body mass index 30.7 ± 6.2kg/m2 and 47% in a vulnerable socio-economic situation. Fifty patients (48%) were followed exclusively by their general practitioners and only 30% had no compliance problems. Creatinuria was measured at least once during the year in 92% of patients, but microalbuminuria was measured in only 20%. Age, socio-economic precariousness, insulin treatment, and follow-up by several health professionals had a negative influence on quality of life (QoL). Two patient profiles were defined by factor analysis: (i) young, rural, smoker, socially isolated, precarious patient with poor compliance and QoL; and (ii) elderly, urban, regular physical activity, in a couple, without precariousness and with satisfactory QoL.

Conclusions
Analysis of the characteristics of patients with T2DM and glycaemic imbalance reveals profiles that are useful in clinical practice for a personalized approach to treatment and active prevention of diabetes complications.
Taxonomic and functional characterization of the rumen microbiome of Japanese Black cattle revealed by 16S rRNA gene amplicon and metagenome shotgun sequencing
Authors: Sato Yoshiaki , Takebe Hiroaki , Tominaga Kento , Oishi Kazato , Kumagai Hajime , Yoshida Takashi , Hirooka Hiroyuki 
Published: November 2021

ABSTRACTThis study aimed to determine the taxonomic and functional characteristics of the Japanese Black (JB) steer rumen microbiome. The rumen microbiomes of six JB steers (age 14.7 ± 1.44 months) and six JB sires × Holstein dams crossbred (F1) steers (age 11.1 ± 0.39 months), fed the same diet, were evaluated. Based on 16S rRNA gene sequencing, the beta diversity revealed differences in microbial community structures between the JB and F1 rumen. Shotgun sequencing showed that Fibrobacter succinogenes and two Ruminococcus spp., which are related to cellulose degradation were relatively more abundant in the JB steer rumen than in the F1 rumen. Furthermore, the 16S rRNA gene copy number of F. succinogenes was significantly higher in the JB steer rumen than in the F1 rumen according to quantitative real-time polymerase chain reaction analysis. Genes encoding the enzymes that accelerate cellulose degradation and those associated with hemicellulose degradation were enriched in the JB steer rumen. Although Prevotella spp. were predominant both in the JB and F1 rumen, the genes encoding carbohydrate-active enzymes of Prevotella spp. may differ between JB and F1.
Pesticide-induced disturbances of bee gut microbiotas
Authors: Hotchkiss Michelle Z , Poulain Alexandre J , Forrest Jessica R K 
Published: November 2021

ABSTRACT
Social bee gut microbiotas play key roles in host health and performance. Worryingly, a growing body of literature shows that pesticide exposure can disturb these microbiotas. Most studies examine changes in taxonomic composition in Western honey bee (Apis mellifera) gut microbiotas caused by insecticide exposure. Core bee gut microbiota taxa shift in abundance after exposure but are rarely eliminated, with declines in Bifidobacteriales and Lactobacillus near melliventris abundance being the most common shifts. Pesticide concentration, exposure duration, season and concurrent stressors all influence whether and how bee gut microbiotas are disturbed. Also, the mechanism of disturbance—i.e. whether a pesticide directly affects microbial growth or indirectly affects the microbiota by altering host health—likely affects disturbance consistency. Despite growing interest in this topic, important questions remain unanswered. Specifically, metabolic shifts in bee gut microbiotas remain largely uninvestigated, as do effects of pesticide-disturbed gut microbiotas on bee host performance. Furthermore, few bee species have been studied other than A. mellifera, and few herbicides and fungicides have been examined. We call for these knowledge gaps to be addressed so that we may obtain a comprehensive picture of how pesticides alter bee gut microbiotas, and of the functional consequences of these changes.
Wing hearts in four-wingedUltrabithorax-mutant flies—the role of Hox genes in wing heart specification
Authors: Tögel Markus , Pass Günther , Paululat Achim 
Published: November 2021

AbstractWings are probably the most advanced evolutionary novelty in insects. In the fruit fly Drosophila melanogaster, proper development of wings requires the activity of so-called wing hearts located in the scutellum of the thorax. Immediately after the imaginal ecdysis, these accessory circulatory organs remove hemolymph and apoptotic epidermal cells from the premature wings through their pumping action. This clearing process is essential for the formation of functional wing blades. Mutant flies that lack intact wing hearts are flightless and display malformed wings. The embryonic wing heart progenitors originate from two adjacent parasegments corresponding to the later second and third thoracic segments. However, adult dipterian flies harbor only one pair of wings and only one pair of associated wing hearts in the second thoracic segment. Here we show that the specification of WHPs depends on the regulatory activity of the Hox gene Ultrabithorax. Furthermore, we analyzed the development of wing hearts in the famous four-winged Ultrabithorax (Ubx) mutant, which was first discovered by Ed Lewis in the 1970s. In these flies, the third thoracic segment is homeotically transformed into a second thoracic segment resulting in a second pair of wings instead of the club-shaped halteres. We show that a second pair of functional wing hearts is formed in the transformed third thoracic segment and that all wing hearts originate from the wild-type population of wing heart progenitor cells.
Multiple epistatic DNA variants in a single gene affect gene expression in trans
Authors: Lutz Sheila , Van Dyke Krisna , Feraru Matthew A , Albert Frank W 
Published: November 2021

Abstract
DNA variants that alter gene expression in trans are important sources of phenotypic variation. Nevertheless, the identity of trans-acting variants remains poorly understood. Single causal variants in several genes have been reported to affect the expression of numerous distant genes in trans. Whether these simple molecular architectures are representative of trans-acting variation is unknown. Here, we studied the large RAS signaling regulator gene IRA2, which contains variants with extensive trans-acting effects on gene expression in the yeast Saccharomyces cerevisiae. We used systematic CRISPR-based genome engineering and a sensitive phenotyping strategy to dissect causal variants to the nucleotide level. In contrast to the simple molecular architectures known so far, IRA2 contained at least seven causal nonsynonymous variants. The effects of these variants were modulated by nonadditive, epistatic interactions. Two variants at the 5′-end affected gene expression and growth only when combined with a third variant that also had no effect in isolation. Our findings indicate that the molecular basis of trans-acting genetic variation may be considerably more complex than previously appreciated.
Replication Note: What is Political Incivility?
Authors: Stryker Robin , Conway Bethany Anne , Bauldry Shawn , Kaul Vasundhara 
Published: November 2021

Abstract
Because political incivility is so consequential and those consequences depend on observers’ perceptions, we must know what Americans perceive as uncivil. Stryker, Conway, and Danielson (2016) conducted one of the first studies addressing this using confirmatory factor analysis on 23 types of potential incivility, but the authors used a local sample representing undergraduates at one southwestern university. Using 20 of their 23 measures and replicating their analyses on a national sample of more than 2000 respondents representing U.S. whites, Blacks, and Latinx, this study finds the same conceptual structure for perceived political incivility with very similar response patterns as Stryker et al. (2016). Perceived political incivility is an overarching construct with three analytically distinct, inter-correlated dimensions: insulting utterances, deception, and behaviors that tend to shut down ongoing and inclusive discussion.
Target-Based Small Molecule Drug Discovery Towards Novel Therapeutics for Inflammatory Bowel Diseases
Authors: Li Yi , Chen Jianping , Bolinger Andrew A , Chen Haiying , Liu Zhiqing , Cong Yingzi , Brasier Allan R , Pinchuk Irina V , Tian Bing , Zhou Jia 
Published: November 2021

Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a class of severe and chronic diseases of the gastrointestinal (GI) tract with recurrent symptoms and significant morbidity. Long-term persistence of chronic inflammation in IBD is a major contributing factor to neoplastic transformation and the development of colitis-associated colorectal cancer. Conversely, persistence of transmural inflammation in CD is associated with formation of fibrosing strictures, resulting in substantial morbidity. The recent introduction of biological response modifiers as IBD therapies, such as antibodies neutralizing tumor necrosis factor (TNF)-α, have replaced nonselective anti-inflammatory corticosteroids in disease management. However, a large proportion (~40%) of patients with the treatment of anti-TNF-α antibodies are discontinued or withdrawn from therapy because of (1) primary nonresponse, (2) secondary loss of response, (3) opportunistic infection, or (4) onset of cancer. Therefore, the development of novel and effective therapeutics targeting specific signaling pathways in the pathogenesis of IBD is urgently needed. In this comprehensive review, we summarize the recent advances in drug discovery of new small molecules in preclinical or clinical development for treating IBD that target biologically relevant pathways in mucosal inflammation. These include intracellular enzymes (Janus kinases, receptor interacting protein, phosphodiesterase 4, IκB kinase), integrins, G protein-coupled receptors (S1P, CCR9, CXCR4, CB2) and inflammasome mediators (NLRP3), etc. We will also discuss emerging evidence of a distinct mechanism of action, bromodomain-containing protein 4, an epigenetic regulator of pathways involved in the activation, communication, and trafficking of immune cells. We highlight their chemotypes, mode of actions, structure-activity relationships, characterizations, and their in vitro/in vivo activities and therapeutic potential. The perspectives on the relevant challenges, new opportunities, and future directions in this field are also discussed.
Characterization of Mycophenolate Mofetil Gastrointestinal Toxicity and Risk Factors for Severe Disease and Poor Prognosis
Authors: Bhattacharya Sumona , Stoleru Gianna , Patel Preet , Abutaleb Ameer , Stashek Kristen , Cross Raymond K 
Published: November 2021

Lay SummaryAuthors performed a chart review to identify cases of mycophenolate mofetil gastrointestinal toxicity at our institution. In this cohort, friability was associated with severe disease; and nausea and erythema were associated with poor prognosis.
On ℓp-Gaussian–Grothendieck Problem
Authors: Chen Wei-Kuo , Sen Arnab 
Published: November 2021

Abstract
For $p\geq 1$ and $(g_{ij})_{1\leq i,j\leq n}$ being a matrix of i.i.d. standard Gaussian entries, we study the $n$-limit of the $\ell _p$-Gaussian–Grothendieck problem defined as $$\begin{align*} & \max\Bigl\{\sum_{i,j=1}^n g_{ij}x_ix_j: x\in \mathbb{R}^n,\sum_{i=1}^n |x_i|^p=1\Bigr\}. \end{align*}$$The case $p=2$ corresponds to the top eigenvalue of the Gaussian orthogonal ensemble; when $p=\infty $, the maximum value is essentially the ground state energy of the Sherrington–Kirkpatrick mean-field spin glass model and its limit can be expressed by the famous Parisi formula. In the present work, we focus on the cases $1\leq p&lt;2$ and $2&lt;p&lt;\infty .$ For the former, we compute the limit of the $\ell _p$-Gaussian–Grothendieck problem and investigate the structure of the set of all near optimizers along with stability estimates. In the latter case, we show that this problem admits a Parisi-type variational representation and the corresponding optimizer is weakly delocalized in the sense that its entries vanish uniformly in a polynomial order of $n^{-1}$.