bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPS: automated feature selection in case–control studies using extreme pseudo-sampling
Authors: Shemirani Ruhollah , Wenric Stephane , Kenny Eimear , Ambite José Luis 
Published: March 2021

Abstract

Summary
Finding informative predictive features in high-dimensional biological case–control datasets is challenging. The Extreme Pseudo-Sampling (EPS) algorithm offers a solution to the challenge of feature selection via a combination of deep learning and linear regression models. First, using a variational autoencoder, it generates complex latent representations for the samples. Second, it classifies the latent representations of cases and controls via logistic regression. Third, it generates new samples (pseudo-samples) around the extreme cases and controls in the regression model. Finally, it trains a new regression model over the upsampled space. The most significant variables in this regression are selected. We present an open-source implementation of the algorithm that is easy to set up, use and customize. Our package enhances the original algorithm by providing new features and customizability for data preparation, model training and classification functionalities. We believe the new features will enable the adoption of the algorithm for a diverse range of datasets.

Availability and implementation
The software package for Python is available online at https://github.com/roohy/eps.

Supplementary information
Supplementary data are available at Bioinformatics online.
Actual malignancy risk of either operated or non-operated presumed mucinous cystic neoplasms of the pancreas under surveillance
Authors: Marchegiani G , Andrianello S , Crippa S , Pollini T , Belfiori G , Gozzini L , Cassalia F , Caravati A , Luchini C , Doglioni C , Bassi C , Falconi M , Salvia R 
Published: March 2021

Abstract

Background
Despite the low malignant potential of pancreatic mucinous cystic neoplasms (MCNs), surgery is still performed. The aim of this pragmatic study was to assess the outcome of surgery and surveillance for patients presenting with a presumed MCN at the first evaluation.

Methods
Data for patients with a presumed MCN observed from 2000 to 2016 at the Verona Pancreas Institute and San Raffaele Hospital were extracted from prospective databases. The endpoints were risk of malignancy at pathology and rate of misdiagnosis for the surgical series, expressed as an odds ratio (OR) with 95 per cent confidence interval, and disease-specific survival (DSS) for the surveillance cohort investigated by the Kaplan–Meier method.

Results
A total of 424 patients were identified. In the surgical series (229 patients), the rate of misdiagnosis was 19.2 per cent. The rate of malignant MCNs was 10.9 per cent (25 patients). The overall rate of malignancy, including misdiagnoses, was 11.3 per cent (26 patients). Predictors of malignancy were mural nodules (OR 27.75, 95 per cent c.i. 4.44–173.61; P &lt; 0.001), size at least 50 mm (OR 13.39, 2.01 to 89.47; P = 0.007), and carbohydrate antigen 19.9 level (OR 3.98, 1.19 to 13.30; P = 0.025). In the absence of mural nodules and enhancing walls, none of the resected presumed MCNs smaller than 50 mm were malignant. Only patients with high-risk stigmata undergoing surgery experienced a significantly reduced 5-year DSS compared with all other patients (88 versus 100 per cent; P = 0.031).

Conclusion
Presumed MCNs with mural nodules, enhancing walls or cysts of 50 mm or larger should be considered for upfront surgical resection owing to the high risk of malignancy. In the absence of these features, the incidence of malignancy is negligible, favouring surveillance in selected patients given the low risk of malignancy and the high rate of misdiagnosis.
The role of educators in community resilience in natural disaster-prone communities
Authors: Edmeade Jendayi N , Buzinde Christine N 
Published: March 2021

AbstractEducators’ perceptions of community resilience have generally remained absent in scholarship on the nexus between community development, natural disasters, and resilience. Thus, building on extant research and drawing on resilience theory, the purpose of this qualitative study is to understand perceptions related to community resilience held by resident educators, located in the US Virgin Islands. In-depth interviews were conducted with educators (elementary and secondary schools) and the findings indicate that participants’ role in coping and recovery entailed the following themes: Community Alliances for Social Recovery and Learning for Social Recovery. The former speaks to the educators’ (in)direct provision of basic resources (e.g. teachers’ union offering materials), in the aftermath of the disaster. The latter deals with teachers’ provision of assistance to students experiencing psychological distress induced by the disaster as well as their work in teaching about and/or seeking educational materials related to natural disasters. In the aftermath of a hazard, access to formal counselling services is likely constrained accordingly; informal counselling services rendered by various members of the community are the most effective approach to obtain help with disaster-induced psychological distress. A key contribution of this study is that educators took on important informal counselling-like roles, in addition to their formal didactic duties, so as to better help youth with coping and recovery. Recovery requires many actors, but this study highlights educators’ integral role in effective disaster mitigation through the formal and informal roles they enact, particularly as relates to youth.
The subfornical organ drives hypertension in polycystic kidney disease via the hypothalamic paraventricular nucleus
Authors: Underwood Conor F , McMullan Simon , Goodchild Ann K , Phillips Jacqueline K , Hildreth Cara M 
Published: March 2021

AbstractAimsHypertension is a prevalent yet poorly understood feature of polycystic kidney disease. Previously, we demonstrated that increased glutamatergic neurotransmission within the hypothalamic paraventricular nucleus produces hypertension in the Lewis Polycystic Kidney (LPK) rat model of polycystic kidney disease. Here, we tested the hypothesis that augmented glutamatergic drive to the paraventricular nucleus in Lewis polycystic kidney rats originates from the forebrain lamina terminalis, a sensory structure that relays blood-borne information throughout the brain.Methods and resultsAnatomical experiments revealed that 38% of paraventricular nucleus-projecting neurons in the subfornical organ of the lamina terminalis expressed Fos/Fra, an activation marker, in LPK rats while &lt;1% of neurons were Fos/Fra+ in Lewis control rats (P = 0.01, n = 8). In anaesthetized rats, subfornical organ neuronal inhibition using isoguvacine produced a greater reduction in systolic blood pressure in LPK vs. Lewis rats (−21±4 vs. −7±2 mmHg, P &lt; 0.01; n = 10), which could be prevented by prior blockade of paraventricular nucleus ionotropic glutamate receptors using kynurenic acid. Blockade of ionotropic glutamate receptors in the paraventricular nucleus produced an exaggerated depressor response in LPK relative to Lewis rats (−23±4 vs. −2±3 mmHg, P &lt; 0.001; n = 13), which was corrected by prior inhibition of the subfornical organ with muscimol but unaffected by chronic systemic angiotensin II type I receptor antagonism or lowering of plasma hyperosmolality through high-water intake (P &gt; 0.05); treatments that both nevertheless lowered blood pressure in LPK rats (P &lt; 0.0001).ConclusionOur data reveal multiple independent mechanisms contribute to hypertension in polycystic kidney disease, and identify high plasma osmolality, angiotensin II type I receptor activation and, importantly, a hyperactive subfornical organ to paraventricular nucleus glutamatergic pathway as potential therapeutic targets.
Natural history of functional tricuspid regurgitation: impact of cardiac output
Authors: Chen Elisabeth , L’official Guillaume , Guérin Anne , Dreyfus Julien , Lavie-Badie Yoan , Sportouch Catherine , Eicher Jean-Christophe , Maréchaux Sylvestre , Le Tourneau Thierry , Oger Emmanuel , Donal Erwan 
Published: March 2021

Abstract

Aims
Tricuspid regurgitation (TR) was long forgotten until recent studies alerting on its prognostic impact. Cardiac output (CO) is the main objective of heart mechanics. We sought to compare clinical and echocardiographic data of patients with TR from inclusion to 1-year follow-up according to initial CO.

Methods and results
Patients with isolated secondary TR and left ventricular ejection fraction (LVEF) ≥40% were prospectively included. All patients had a clinical and echocardiographic evaluation at baseline and after 1 year. Echocardiographic measurements were centralized. The patients were partitioned according to their CO at baseline. The primary outcome was all-cause death. Ninety-five patients completed their follow-up. The majority of patients had normal CO (n = 64, 67.4%), whereas 16 (16.8%) patients had low-CO and 12 (12.6%) had high-CO. right ventricular function was worse in the low-CO group but with improvement at 1 year (30% increase in tricuspid annular plane systolic excursion). LVEF and global longitudinal strain were significantly worse in the low-CO group. Overall, 18 (19%) patients died during follow-up, of which 10 (55%) patients had abnormal CO. There was a U-shaped association between CO and mortality. Normal CO patients had significantly better survival (87.5% vs. 62.5% and 66.67%) in the low- and high-CO groups, respectively, even after adjustment (heart rate 2.23 for the low-CO group and 9.08 for high-CO group; P = 0.0174).

Conclusion
Significant isolated secondary TR was associated with 19% of mortality. It is also associated with higher long-term mortality if CO is abnormal, suggesting a possible role for evaluating better and selecting patients for intervention.
Tubulin-folding cofactor E deficiency promotes vascular dysfunction by increased endoplasmic reticulum stress
Authors: Efentakis Panagiotis , Molitor Michael , Kossmann Sabine , Bochenek Magdalena L , Wild Johannes , Lagrange Jeremy , Finger Stefanie , Jung Rebecca , Karbach Susanne , Schäfer Katrin , Schulz Andreas , Wild Philipp , Münzel Thomas , Wenzel Philip 
Published: March 2021

Abstract

Aims
Assessment of endothelial function in humans by measuring flow-mediated dilation (FMD) risk-stratifies individuals with established cardiovascular disease, whereas its predictive value is limited in primary prevention. We therefore aimed to establish and evaluate novel markers of FMD at the population level.

Methods and results
In order to identify novel targets that were negatively correlated with FMD and investigate their contribution to vascular function, we performed a genome-wide association study (GWAS) of 4175 participants of the population based Gutenberg Health Study. Subsequently, conditional knockout mouse models deleting the gene of interest were generated and characterized. GWAS analysis revealed that single-nucleotide polymorphisms (SNPs) in the tubulin-folding cofactor E (TBCE) gene were negatively correlated with endothelial function and TBCE expression. Vascular smooth muscle cell (VSMC)-targeted TBCE deficiency was associated with endothelial dysfunction, aortic wall hypertrophy, and endoplasmic reticulum (ER) stress-mediated VSMC hyperproliferation in mice, paralleled by calnexin up-regulation and exacerbated by the blood pressure hormone angiotensin II. Treating SMMHC-ERT2-Cre+/−TBCEfl/fl mice with the ER stress modulator tauroursodeoxycholic acid amplified Raptor/Beclin-1-dependent autophagy and reversed vascular dysfunction.

Conclusion
TBCE and tubulin homeostasis seem to be novel predictors of vascular function and offer a new drug target to ameliorate ER stress-dependent vascular dysfunction.
The enigmatic biology of rickettsiae: recent advances, open questions and outlook
Authors: McGinn Jon , Lamason Rebecca L 
Published: March 2021

ABSTRACTRickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses and are among the oldest known vector-borne pathogens. Members of this genus are extraordinarily diverse and exhibit a broad host range. To establish intracellular infection, Rickettsia species undergo complex, multistep life cycles that are encoded by heavily streamlined genomes. As a result of reductive genome evolution, rickettsiae are exquisitely tailored to their host cell environment but cannot survive extracellularly. This host-cell dependence makes for a compelling system to uncover novel host–pathogen biology, but it has also hindered experimental progress. Consequently, the molecular details of rickettsial biology and pathogenesis remain poorly understood. With recent advances in molecular biology and genetics, the field is poised to start unraveling the molecular mechanisms of these host–pathogen interactions. Here, we review recent discoveries that have shed light on key aspects of rickettsial biology. These studies have revealed that rickettsiae subvert host cells using mechanisms that are distinct from other better-studied pathogens, underscoring the great potential of the Rickettsia genus for revealing novel biology. We also highlight several open questions as promising areas for future study and discuss the path toward solving the fundamental mysteries of this neglected and emerging human pathogen.
Chromosomal-Level Genome Assembly of the Painted Sea Urchin Lytechinus pictus: A Genetically Enabled Model System for Cell Biology and Embryonic Development
Authors: Warner Jacob F , Lord James W , Schreiter Samantha A , Nesbit Katherine T , Hamdoun Amro , Lyons Deirdre C 
Published: March 2021

Abstract
The painted urchin Lytechinus pictus is a sea urchin in the family Toxopneustidae and one of several sea urchin species that are routinely used as an experimental research organism. Recently, L. pictus has emerged as a tractable model system for establishing transgenic sea urchin lines due to its amenability to long term laboratory culture. We present the first published genome of L. pictus. This chromosomal-level assembly was generated using Illumina sequencing in conjunction with Oxford Nanopore Technologies long read sequencing and HiC chromatin conformation capture sequencing. The 998.9-Mb assembly exhibits high contiguity and has a scaffold length N50 of 46.0 Mb with 97% of the sequence assembled into 19 chromosomal-length scaffolds. These 19 scaffolds exhibit a high degree of synteny compared with the 19 chromosomes of a related species Lytechinus variegatus. Ab initio and transcript evidence gene modeling, combined with sequence homology, identified 28,631 gene models that capture 92% of BUSCO orthologs. This annotation strategy was validated by manual curation of gene models for the ABC transporter superfamily, which confirmed the completeness and accuracy of the annotations. Thus, this genome assembly, in conjunction with recent high contiguity assemblies of related species, positions L. pictus as an exceptional model system for comparative functional genomics and it will be a key resource for the developmental, toxicological, and ecological biology scientific communities.
Inferring the Deep Past from Molecular Data
Authors: Williams Tom A , Schrempf Dominik , Szöllősi Gergely J , Cox Cymon J , Foster Peter G , Embley T Martin 
Published: March 2021

Abstract
There is an expectation that analyses of molecular sequences might be able to distinguish between alternative hypotheses for ancient relationships, but the phylogenetic methods used and types of data analyzed are of critical importance in any attempt to recover historical signal. Here, we discuss some common issues that can influence the topology of trees obtained when using overly simple models to analyze molecular data that often display complicated patterns of sequence heterogeneity. To illustrate our discussion, we have used three examples of inferred relationships which have changed radically as models and methods of analysis have improved. In two of these examples, the sister-group relationship between thermophilic Thermus and mesophilic Deinococcus, and the position of long-branch Microsporidia among eukaryotes, we show that recovering what is now generally considered to be the correct tree is critically dependent on the fit between model and data. In the third example, the position of eukaryotes in the tree of life, the hypothesis that is currently supported by the best available methods is fundamentally different from the classical view of relationships between major cellular domains. Since heterogeneity appears to be pervasive and varied among all molecular sequence data, and even the best available models can still struggle to deal with some problems, the issues we discuss are generally relevant to phylogenetic analyses. It remains essential to maintain a critical attitude to all trees as hypotheses of relationship that may change with more data and better methods.
Whitest City in America:A Smaller Black Community’s Experience of Gentrification, Displacement, and Aging in Place
Authors: Croff Raina , Hedmann Monique , Barnes Lisa L 
Published: March 2021

AbstractBackground and ObjectivesThe influx of people with higher socioeconomic status into large Black communities is well documented; less is known regarding smaller, aging Black communities. Older Black adults in Portland, Oregon, among America’s fastest gentrifying cities with the smallest metropolitan Black population, discussed barriers to healthy aging. Perspectives centered on the experience of gentrification, displacement, and its impact on social microsystems, place security, and aging in place.Research Design and MethodsOne-time focus groups engaged 41 Black adults aged at least 45. A demographic survey included residence area/duration. Discussions were thematically coded. Ecological Systems Theory guided interpretation.ResultsThe majority of participants resided within gentrifying historically Black neighborhoods (89.2%), were aged at least 65 (54.6%), and lived in their neighborhood for at least 21 years (24.3%). Emergent discussion themes were rise and fall of Black ownership, displacement, race-related stress, and financial burden. Gentrification contributed to the dismantling of Black property ownership curated over generations, increased financial burden, and threatened place security. Physical displacement strained social networks, diminishing intergenerational neighborhood ties that supported aging in place. Cultural and physical displacement weakened the sense of social cohesion and belonging and induced race-related stressful interactions with new residents within original and relocation neighborhoods.Discussion and ImplicationsGentrification in the Pacific Northwest echoes national trends, uprooting critical close-proximity social networks and deteriorating motivation to engage in neighborhood-based social activity. Smaller, aging Black communities may be particularly vulnerable to these effects, which critically affect aging in place. Data inform researchers and policymakers to better understand how gentrification affects smaller, aging Black communities.
Multiscale seismic imaging with inverse homogenization
Authors: Hedjazian N , Capdeville Y , Bodin T 
Published: March 2021

SummarySeismic imaging techniques such as elastic full waveform inversion (FWI) have their spatial resolution limited by the maximum frequency present in the observed waveforms. Scales smaller than a fraction of the minimum wavelength cannot be resolved, and only a smoothed, effective version of the true underlying medium can be recovered. These finite-frequency effects are revealed by the upscaling or homogenization theory of wave propagation. Homogenization aims at computing larger scale effective properties of a medium containing small-scale heterogeneities. We study how this theory can be used in the context of FWI. The seismic imaging problem is broken down in a two-stage multiscale approach. In the first step, called homogenized FWI (HFWI), observed waveforms are inverted for a smooth, fully anisotropic effective medium, that does not contain scales smaller than the shortest wavelength present in the wavefield. The solution being an effective medium, it is difficult to directly interpret it. It requires a second step, called downscaling or inverse homogenization, where the smooth image is used as data, and the goal is to recover small-scale parameters. All the information contained in the observed waveforms is extracted in the HFWI step. The solution of the downscaling step is highly non-unique as many small-scale models may share the same long wavelength effective properties. We therefore rely on the introduction of external a priori information, and cast the problem in a Bayesian formulation. The ensemble of potential fine-scale models sharing the same long wavelength effective properties is explored with a Markov chain Monte Carlo algorithm. We illustrate the method with a synthetic cavity detection problem: we search for the position, size and shape of void inclusions in a homogeneous elastic medium, where the size of cavities is smaller than the resolving length of the seismic data. We illustrate the advantages of introducing the homogenization theory at both stages. In HFWI, homogenization acts as a natural regularization helping convergence towards meaningful solution models. Working with fully anisotropic effective media prevents the leakage of anisotropy induced by the fine scales into isotropic macroparameters estimates. In the downscaling step, the forward theory is the homogenization itself. It is computationally cheap, allowing us to consider geological models with more complexity (e.g. including discontinuities) and use stochastic inversion techniques.
Perturbation in monoclinic medium with a horizontal symmetry plane
Authors: Stovas Alexey 
Published: March 2021

Summary
The perturbation method applied for the phase velocities in the monoclinic model with a horizontal symmetry plane gives insight into the seismic signatures of P, S1 and S2 wave modes associated with the monoclinic stiffness coefficients. The perturbation-based approximations are very accurate and can be used for modelling and inversion purposes.