bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generative adversarial networks for data-scarce radiative heat transfer applications
Authors: García-Esteban J J , Cuevas J C , Bravo-Abad J 
Published: March 2024

Abstract
Generative adversarial networks (GANs) are one of the most robust and versatile techniques in the field of generative artificial intelligence. In this work, we report on an application of GANs in the domain of synthetic spectral data generation for data-scarce radiative heat transfer applications, an area where their use has not been previously reported. We demonstrate the proposed approach by applying it to an illustrative problem within the realm of near-field radiative heat transfer involving a multilayered hyperbolic metamaterial. We find that a successful generation of spectral data requires two modifications to conventional GANs: (i) the introduction of Wasserstein GANs (WGANs) to avoid mode collapse, and, (ii) the conditioning of WGANs to obtain accurate labels for the generated data. We show that a simple feed-forward neural network (FFNN), when augmented with data generated by a CWGAN, enhances significantly its performance under conditions of limited data availability. In addition, we show that CWGANs can act as a surrogate model with improved performance in the low-data regime with respect to simple FFNNs. Overall, this work contributes to highlight the potential of generative machine learning algorithms in scientific applications beyond image generation and optimization.
Estimated Pulse Wave Velocity and Cognitive Outcomes: A Post hoc Analysis of SPRINT-MIND
Authors: Hao Peng , Feng Siting , Suo Min , Wang Shen , Zheng Keyang , Wu Xiaofan 
Published: March 2024

Abstract

BACKGROUND
Arterial stiffness has been confirmed to be associated with cognitive impairment. Carotid-femoral pulse wave velocity (cfPWV) is widely regarded as the gold standard for assessing arterial stiffness, yet it is not readily accessible. In response, the use of estimated pulse wave velocity (ePWV) has been proposed as a more accessible and cost-effective alternative. ePWV not only offers ease of calculation but also covers a broader spectrum of vascular aging processes, some of which may be distinct from those detected by cfPWV. The aim of our study was to investigate the association between ePWV and cognitive outcomes in SPRINT-MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension).

METHODS
This study was a post hoc analysis of the SPRINT-MIND. The primary endpoint was a composite outcome including probable dementia and mild cognitive impairment (MCI). The calculation of ePWV was based on age and mean blood pressure. The association between ePWV and cognitive outcomes was assessed Using Cox regression analysis. The response of ePWV to antihypertensive treatment at 12 months was used to define treatment efficacy.

RESULTS
8,563 patients were enrolled. The ePWV was found to be independently associated with risk of probable dementia (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.70, 1.08–2.68, P = 0.023, P for trend = 0.013), MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.35, 1.71–3.23, P &lt; 0.001, P for trend &lt; 0.001), and the composite outcome of probable dementia or MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.17, 1.65–2.86, P &lt; 0.001, P for trend &lt; 0.001). The combined effect of treatment allocation and the response of ePWV to treatment exhibited that intensive/ePWV responders had the lowest risk of the primary outcome (Log-rank P = 0.002).

CONCLUSIONS
EPWV demonstrated independent predictive value for cognitive outcomes in SPRINT-MIND.
Transgenerational plasticity to drought: contrasting patterns of non-genetic inheritance in two semi-arid Mediterranean shrubs
Authors: Ramos-Muñoz Marina , Blanco-Sánchez Mario , Pías Beatriz , Escudero Adrián , Matesanz Silvia 
Published: March 2024

Abstract

Background and Aims
Intra- and transgenerational plasticity may provide substantial phenotypic variation to cope with environmental change. Since assessing the unique contribution of the maternal environment to the offspring phenotype is challenging in perennial, outcrossing plants, little is known about the evolutionary and ecological implications of transgenerational plasticity and its persistence over the life cycle in these species. We evaluated how intra- and transgenerational plasticity interplay to shape the adaptive responses to drought in two perennial Mediterranean shrubs.

Methods
We used a novel common garden approach that reduced within-family genetic variation in both the maternal and offspring generations by growing the same maternal individual in two contrasting watering environments, well-watered and drought, in consecutive years. We then assessed phenotypic differences at the reproductive stage between offspring reciprocally grown in the same environments.

Key Results
Maternal drought had an effect on offspring performance only in Helianthemum squamatum. Offspring of drought-stressed plants showed more inflorescences, less sclerophyllous leaves and higher growth rates in both watering conditions, and heavier seeds under drought, than offspring of well-watered maternal plants. Maternal drought also induced similar plasticity patterns across maternal families, showing a general increase in seed mass in response to offspring drought, a pattern not observed in the offspring of well-watered plants. In contrast, both species expressed immediate adaptive plasticity, and the magnitude of intragenerational plasticity was larger than the transgenerational plastic responses.

Conclusions
Our results highlight that adaptive effects associated with maternal drought can persist beyond the seedling stage and provide evidence of species-level variation in the expression of transgenerational plasticity. Such differences between co-occurring Mediterranean species in the prevalence of this form of non-genetic inheritance may result in differential vulnerability to climate change.
Enhancer-MDLF: a novel deep learning framework for identifying cell-specific enhancers
Authors: Zhang Yao , Zhang Pengyu , Wu Hao 
Published: March 2024

Abstract
Enhancers, noncoding DNA fragments, play a pivotal role in gene regulation, facilitating gene transcription. Identifying enhancers is crucial for understanding genomic regulatory mechanisms, pinpointing key elements and investigating networks governing gene expression and disease-related mechanisms. Existing enhancer identification methods exhibit limitations, prompting the development of our novel multi-input deep learning framework, termed Enhancer-MDLF. Experimental results illustrate that Enhancer-MDLF outperforms the previous method, Enhancer-IF, across eight distinct human cell lines and exhibits superior performance on generic enhancer datasets and enhancer–promoter datasets, affirming the robustness of Enhancer-MDLF. Additionally, we introduce transfer learning to provide an effective and potential solution to address the prediction challenges posed by enhancer specificity. Furthermore, we utilize model interpretation to identify transcription factor binding site motifs that may be associated with enhancer regions, with important implications for facilitating the study of enhancer regulatory mechanisms. The source code is openly accessible at https://github.com/HaoWuLab-Bioinformatics/Enhancer-MDLF.
DeGenPrime provides robust primer design and optimization unlocking the biosphere
Authors: Fulghum Bryan , Tanker Sophie H , White Richard Allen 
Published: March 2024

Abstract

Motivation
Polymerase chain reaction (PCR) is the world’s most important molecular diagnostic with applications ranging from medicine to ecology. PCR can fail because of poor primer design. The nearest-neighbor thermodynamic properties, picking conserved regions, and filtration via penalty of oligonucleotides form the basis for good primer design.

Results
DeGenPrime is a console-based high-quality PCR primer design tool that can utilize MSA formats and degenerate bases expanding the target range for a single primer set. Our software utilizes thermodynamic properties, filtration metrics, penalty scoring, and conserved region finding of any proposed primer. It has degeneracy, repeated k-mers, relative GC content, and temperature range filters. Minimal penalty scoring is included according to secondary structure self-dimerization metrics, GC clamping, tri- and tetra-loop hairpins, and internal repetition. We compared PrimerDesign-M, DegePrime, ConsensusPrimer, and DeGenPrime on acceptable primer yield. PrimerDesign-M, DegePrime, and ConsensusPrimer provided 0%, 11%, and 17% yield, respectively, for the alternative iron nitrogenase (anfD) gene target. DeGenPrime successfully identified quality primers within the conserved regions of the T4-like phage major capsid protein (g23), conserved regions of molybdenum-based nitrogenase (nif), and its alternatives vanadium (vnf) and iron (anf) nitrogenase. DeGenPrime provides a universal and scalable primer design tool for the entire tree of life.

Availability and implementation
DeGenPrime is written in C++ and distributed under a BSD-3-Clause license. The source code for DeGenPrime is freely available on www.github.com/raw-lab/degenprime.
Data-driven information extraction and enrichment of molecular profiling data for cancer cell lines
Authors: Smith Ellery , Paloots Rahel , Giagkos Dimitris , Baudis Michael , Stockinger Kurt 
Published: March 2024

Abstract

Motivation
With the proliferation of research means and computational methodologies, published biomedical literature is growing exponentially in numbers and volume. Cancer cell lines are frequently used models in biological and medical research that are currently applied for a wide range of purposes, from studies of cellular mechanisms to drug development, which has led to a wealth of related data and publications. Sifting through large quantities of text to gather relevant information on cell lines of interest is tedious and extremely slow when performed by humans. Hence, novel computational information extraction and correlation mechanisms are required to boost meaningful knowledge extraction.

Results
In this work, we present the design, implementation, and application of a novel data extraction and exploration system. This system extracts deep semantic relations between textual entities from scientific literature to enrich existing structured clinical data concerning cancer cell lines. We introduce a new public data exploration portal, which enables automatic linking of genomic copy number variants plots with ranked, related entities such as affected genes. Each relation is accompanied by literature-derived evidences, allowing for deep, yet rapid, literature search, using existing structured data as a springboard.

Availability and implementation
Our system is publicly available on the web at https://cancercelllines.org.
Cellular senescence in reproduction: a two-edged sword
Authors: Pretto Luiza , Nabinger Eduarda , Filippi-Chiela Eduardo Cremonesi , Fraga Lucas Rosa 
Published: March 2024

Abstract
Cellular senescence (CS) is the state when cells are no longer capable to divide even after stimulation with grown factors. Cells that begin to undergo CS stop in the cell cycle and enter a suspended state without committing to programmed cell death. These cells assume a specific phenotype and influence their microenvironment by secreting molecules and extracellular vesicles that are part of the so-called senescent cell–associated secretory phenotype (SASP). Cellular senescence is intertwined with physiological and pathological conditions in the human organism. In terms of reproduction, senescent cells are present from reproductive tissues and germ cells to gestational tissues, and participate from fertilization to delivery, going through adverse reproductive outcomes such as pregnancy losses. Furthermore, various SASP molecules are enriched in gestational tissues throughout pregnancy. Thus, the aim of this review is to provide a basis about the features and potential roles played by CS throughout the reproductive process, encompassing its implication in each step of it and proposing a way to manage it in adverse reproductive contexts.
Repeat expansions in AR, ATXN1, ATXN2 and HTT in Norwegian patients diagnosed with amyotrophic lateral sclerosis
Authors: Novy Camilla , Busk Øyvind L , Tysnes Ole-Bjørn , Landa Sigve S , Aanjesen Tori N , Alstadhaug Karl B , Bjerknes Tale L , Bjørnå Ingrid K , Bråthen Geir , Dahl Elin , Demic Natasha , Fahlström Maria , Flemmen Heidi Ø , Hallerstig Erika , HogenEsch Ineke , Kampman Margitta T , Kleveland Grethe , Kvernmo Helene B , Ljøstad Unn , Maniaol Angelina , Morsund Aase Hagen , Nakken Ola , Olsen Cathrine G , Schlüter Katrin , Utvik May-Sissel , Yaseen Ryaz , Holla Øystein L , Holmøy Trygve , Høyer Helle 
Published: March 2024

Abstract
Genetic repeat expansions cause neuronal degeneration in amyotrophic lateral sclerosis as well as other neurodegenerative disorders such as spinocerebellar ataxia, Huntington’s disease and Kennedy’s disease. Repeat expansions in the same gene can cause multiple clinical phenotypes. We aimed to characterize repeat expansions in a Norwegian amyotrophic lateral sclerosis cohort. Norwegian amyotrophic lateral sclerosis patients (n = 414) and neurologically healthy controls adjusted for age and gender (n = 713) were investigated for repeat expansions in AR, ATXN1, ATXN2 and HTT using short read exome sequencing and the ExpansionHunter software. Five amyotrophic lateral sclerosis patients (1.2%) and two controls (0.3%) carried ≥36 repeats in HTT (P = 0.032), and seven amyotrophic lateral sclerosis patients (1.7%) and three controls (0.4%) carried ≥29 repeats in ATXN2 (P = 0.038). One male diagnosed with amyotrophic lateral sclerosis carried a pathogenic repeat expansion in AR, and his diagnosis was revised to Kennedy’s disease. In ATXN1, 50 amyotrophic lateral sclerosis patients (12.1%) and 96 controls (13.5%) carried ≥33 repeats (P = 0.753). None of the patients with repeat expansions in ATXN2 or HTT had signs of Huntington’s disease or spinocerebellar ataxia type 2, based on a re-evaluation of medical records. The diagnosis of amyotrophic lateral sclerosis was confirmed in all patients, with the exception of one patient who had primary lateral sclerosis. Our findings indicate that repeat expansions in HTT and ATXN2 are associated with increased likelihood of developing amyotrophic lateral sclerosis. Further studies are required to investigate the potential relationship between HTT repeat expansions and amyotrophic lateral sclerosis.
Healthcare utilization and clinical characteristics of genetic epilepsy in electronic health records
Authors: Boßelmann Christian M , Ivaniuk Alina , St John Mark , Taylor Sara C , Krishnaswamy Gokul , Milinovich Alex , Leu Costin , Gupta Ajay , Pestana-Knight Elia M , Najm Imad , Lal Dennis 
Published: March 2024

Abstract
Understanding the clinical characteristics and medical treatment of individuals affected by genetic epilepsies is instrumental in guiding selection for genetic testing, defining the phenotype range of these rare disorders, optimizing patient care pathways and pinpointing unaddressed medical need by quantifying healthcare resource utilization. To date, a matched longitudinal cohort study encompassing the entire spectrum of clinical characteristics and medical treatment from childhood through adolescence has not been performed. We identified individuals with genetic and non-genetic epilepsies and onset at ages 0–5 years by linkage across the Cleveland Clinic Health System. We used natural language processing to extract medical terms and procedures from longitudinal electronic health records and tested for cross-sectional and temporal associations with genetic epilepsy. We implemented a two-stage design: in the discovery cohort, individuals were stratified as being ‘likely genetic’ or ‘non-genetic’ by a natural language processing algorithm, and controls did not receive genetic testing. The validation cohort consisted of cases with genetic epilepsy confirmed by manual chart review and an independent set of controls who received negative genetic testing. The discovery and validation cohorts consisted of 503 and 344 individuals with genetic epilepsy and matched controls, respectively. The median age at the first encounter was 0.1 years and 7.9 years at the last encounter, and the mean duration of follow-up was 8.2 years. We extracted 188,295 Unified Medical Language System annotations for statistical analysis across 9659 encounters. Individuals with genetic epilepsy received an earlier epilepsy diagnosis and had more frequent and complex encounters with the healthcare system. Notably, the highest enrichment of encounters compared with the non-genetic groups was found during the transition from paediatric to adult care. Our computational approach could validate established comorbidities of genetic epilepsies, such as behavioural abnormality and intellectual disability. We also revealed novel associations for genitourinary abnormalities (odds ratio 1.91, 95% confidence interval: 1.66–2.20, P = 6.16 × 10−19) linked to a spectrum of underrecognized epilepsy-associated genetic disorders. This case-control study leveraged real-world data to identify novel features associated with the likelihood of a genetic aetiology and quantified the healthcare utilization of genetic epilepsies compared with matched controls. Our results strongly recommend early genetic testing to stratify individuals into specialized care paths, thus improving the clinical management of people with genetic epilepsies.
Differences in drug removal between standard high-flux and medium cut-off dialyzers in a case of severe vancomycin toxicity
Authors: Aberger Simon , Kolland Michael , Eller Kathrin , Rosenkranz Alexander R , Kirsch Alexander H 
Published: March 2024

ABSTRACT
Vancomycin is a widely used glycopeptide antibiotic with the need for therapeutic drug monitoring to avoid renal toxicity. We report a case of severe vancomycin-associated anuric acute kidney injury managed with successful drug-removal by hemodialysis (HD) using different types of dialyzers. Medium cut-off (MCO) and high-flux dialyzers were effective in drug removal. Higher vancomycin elimination rate and lower plasma half-life were achieved with MCO dialyzer despite low-flow vascular access and intolerance to ultrafiltration. MCO dialyzers may be reasonable for drug removal in patients with intolerance of ultrafiltration, low-flow vascular access or impracticality of hemodiafiltration. Future studies should explore the use of MCO dialyzers in comparison with high-flux HD and hemodiafiltration in both the acute and chronic setting.
Environmental Exposure to Trace Elements and Heavy Metals Preceding the Clinical Onset of Inflammatory Bowel Disease
Authors: Rodríguez-Lago Iago , Cabriada José Luis , Rodríguez Ainhoa , Barreiro-de Acosta Manuel ,   HAIR study group, Carmona Mar , de Castro Leticia , Elorza Ainara , Erdozáin Inés , Esáin Andrea , Fernández Javier , Fraga Amaya , Huerta Alain , Jiménez Itxaso , Oyón Daniel , Rodríguez Pelayo , Sampedro Blanca 
Published: March 2024

Abstract

Background
The immune dysregulation underlying inflammatory bowel disease (IBD) can start years before the diagnosis, but the role of triggering factors and environmental exposures during this period is still uncertain.

Methods
This single-center case–control study included asymptomatic subjects with an incidental diagnosis of IBD during the colorectal cancer screening program. Twenty-two minerals and 17 metals were determined at diagnosis in hair samples and compared 1:2 to healthy controls.

Results
Six patients with preclinical IBD (3 ulcerative colitis, 67% left-sided; 3 Crohn’s disease, 100% ileal, 67% inflammatory behavior) and 13 healthy non-IBD controls were included. No relevant occupational exposures were identified. We found statistically significant higher levels of sodium, potassium, and boron among cases compared to controls; while lower levels of zinc, uranium, copper, and germanium were observed.

Conclusions
A range of environmental exposures can be identified during the preclinical phase of IBD, but their relationship with the symptomatic onset and disease progression should be further explored.
Improving resolution of panoramic radiographs: super-resolution concept
Authors: Çelik Mahmut Emin , Mikaeili Mahsa , Çelik Berrin 
Published: March 2024

Abstract

Objectives
Dental imaging plays a key role in the diagnosis and treatment of dental conditions, yet limitations regarding the quality and resolution of dental radiographs sometimes hinder precise analysis. Super-resolution with deep learning refers to a set of techniques used to enhance the resolution of images beyond their original size or quality using deep neural networks instead of traditional image interpolation methods which often result in blurred or pixelated images when attempting to increase resolution. Leveraging advancements in technology, this study aims to enhance the resolution of dental panoramic radiographs, thereby enabling more accurate diagnoses and treatment planning.

Methods
About 1714 panoramic radiographs from 3 different open datasets are used for training (n = 1364) and testing (n = 350). The state of the art 4 different models is explored, namely Super-Resolution Convolutional Neural Network (SRCNN), Efficient Sub-Pixel Convolutional Neural Network, Super-Resolution Generative Adversarial Network, and Autoencoder. Performances in reconstructing high-resolution dental images from low-resolution inputs with different scales (s = 2, 4, 8) are evaluated by 2 well-accepted metrics Structural Similarity Index (SSIM) and Peak Signal-to-Noise Ratio (PSNR).

Results
SSIM spans between 0.82 and 0.98 while PSNR are between 28.7 and 40.2 among all scales and models. SRCNN provides the best performance. Additionally, it is observed that performance decreased when images are scaled with higher values.

Conclusion
The findings highlight the potential of super-resolution concepts to significantly improve the quality and detail of dental panoramic radiographs, thereby contributing to enhanced interpretability.
Left atrial shape as a marker of atrial myopathy in embolic stroke of undetermined source
Authors: Ferkh Aaisha , De Silva Kasun , Pham Jennifer , Stefani Luke , Byth Karen , Clark Amy , Trivedi Siddharth J , Nagaratnam Sai , Duggins Andrew , Kizana Eddy , Thiagalingam Aravinda , Thomas Liza 
Published: March 2024

Abstract

Aims
Embolic stroke of undetermined source (ESUS) results in significant morbidity. A left atrial (LA) myopathy is implicated in a proportion of these patients. We hypothesized that LA shape varies by cause of stroke [CE (cardioembolic) vs. ESUS].

Methods and results
A total of 236 ischaemic stroke and atrial fibrillation (AF) patients and controls were recruited prospectively. AF was classified as paroxysmal AF (PAF) or persistent AF (PersAF). Stroke patients comprised CE stroke secondary to AF and ESUS. There were 81 AF (47 PAF, 34 PersAF), 50 ESUS, 57 CE patients [subdivided into CE with PAF (CEpaf) and CE with PersAF (CEpers)], and 48 controls. Echocardiographic parameters including LA volume, function, and shape/sphericity (3D LA sphericity and 2D-derived LA circularity, ellipticity, sphericity, and eccentricity indices) were evaluated. Increased LA volume and sphericity with LA dysfunction were present in CE, AF, and ESUS groups compared with controls. K-means cluster analysis demonstrated a spectrum of LA myopathy with controls at the lowest and CEpers and PersAF at the upper extremes, with ESUS, PAF, and CEpaf being similar and falling between these extremes. After adjusting for age, sex, and left ventricular (LV) and LA parameters, LA sphericity markers differentiated ESUS from controls (P &lt; 0.01).

Conclusion
Alterations in LA shape are present in ESUS, AF, and CE patients, particularly increased spherical remodelling. The novel markers of LA sphericity proposed may identify LA myopathy in ESUS patients and potentially guide management for secondary prevention.