bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac disease diagnosis based on GAN in case of missing data
Authors: Chen Xing , Zhang Na , Yang Xiaohui , Wang Chunyan , Qi Na , Luan Tianyun , Zhu Wendi , Zhang Chenjie , Yang Chao
Published: September 2023

In daily life, two common algorithms are used for collecting medical disease data: data integration of medical institutions and questionnaires. However, these statistical methods require collecting data from the entire research area, which consumes a significant amount of manpower and material resources. Additionally, data integration is difficult and poses privacy protection challenges, resulting in a large number of missing data in the dataset. The presence of incomplete data significantly reduces the quality of the published data, hindering the timely analysis of data and the generation of reliable knowledge by epidemiologists, public health authorities, and researchers.

Consequently, this affects the downstream tasks that rely on this data. To address the issue of discrete missing data in cardiac disease, this paper proposes the AGAN (Attribute Generative Adversarial Nets) architecture for missing data filling, based on generative adversarial networks. This algorithm takes advantage of the strong learning ability of generative adversarial networks. Given the ambiguous meaning of filling data in other network structures, the attribute matrix is designed to directly convert it into the corresponding data type, making the actual meaning of the filling data more evident. Furthermore, the distribution deviation between the generated data and the real data is integrated into the loss function of the generative adversarial networks, improving their training stability and ensuring consistency between the generated data and the real data distribution. This approach establishes the missing data filling mechanism based on the generative adversarial networks, which ensures the rationality of the data distribution while filling the missing data samples. The experimental results demonstrate that compared to other filling algorithms, the data matrix filled by the proposed algorithm in this paper has more evident practical significance, fewer errors, and higher accuracy in downstream classification prediction.
BAllC and BAllCools: Efficient Formatting and Operating for Single-Cell DNA Methylation Data
Authors: Tian Wei , Ding Wubin , Shen Jiawei , Li Daofeng , Wang Ting , Ecker Joseph R.
Published: September 2023

Motivation

With single-cell DNA methylation studies yielding vast datasets, existing data formats struggle with the unique challenges of storage and efficient operations, highlighting a need for improved solutions.

Results

BAllC (Binary All Cytosines) emerges as a tailored binary format for methylation data, addressing these challenges. BAllCools, its complementary software toolkit, enhances parsing, indexing, and querying capabilities, promising superior operational speeds and reduced storage needs.

Availability

https://github.com/jksr/ballcools

Contact

ecker@salk.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Estimation of Genetic Admixture Proportions via Haplotypes
Authors: Ko Seyoon , Sobel Eric M. , Zhou Hua , Lange Kenneth
Published: September 2023

Estimation of ethnic admixture is essential for creating personal genealogies, studying human history, and conducting genome-wide association studies (GWAS). Three methods exist for estimating admixture coefficients. The frequentist approach directly maximizes the binomial loglikelihood. The Bayesian approach adds a reasonable prior and samples the posterior distribution. Finally, the nonparametric approach decomposes the genotype matrix algebraically. Each approach scales successfully to data sets with a million individuals and a million single nucleotide polymorphisms (SNPs). Despite their variety, all current approaches assume independence between SNPs. To achieve independence requires performing LD (linkage disequilibrium) filtering before analysis. Unfortunately, this tactic loses valuable information and usually retains many SNPs still in LD. The present paper explores the option of explicitly incorporating haplotypes in ancestry estimation. Our program, HaploADMIXTURE, operates on adjacent SNP pairs and jointly estimates their haplotype frequencies along with admixture coefficients. This more complex strategy takes advantage of the rich information available in haplotypes and ultimately yields better admixture estimates and better clustering of real populations in curated data sets.
SurvBal: Compositional Microbiome Balances for Survival Outcomes
Authors: Li Ying , Lee Teresa , Marin Kai , Hua Xing , Srinivasan Sujatha , Fredricks David N. , Lee John R. , Ling Wodan
Published: September 2023

Identification of balances of bacterial taxa in relation to continuous and dichotomous outcomes is an increasingly frequent analytic objective in microbiome profiling experiments. SurvBal enables the selection of balances in relation to censored survival or time-to-event outcomes which are of considerable interest in many biomedical studies. The most commonly used survival models – the Cox proportional hazards and parametric survival models are included in the package, which are used in combination with step-wise selection procedures to identify the optimal associated balance of microbiome, i.e., the ratio of the geometric means of two groups of taxa’s relative abundances.

Availability and implementation

SurvBal is available as an R package and a Shiny app:https://github.com/yinglia/SurvBal,https://yinglistats.shinyapps.io/shinyapp-survbal/.
Copy number variation introduced by a massive mobile element underpins global thermal adaptation in a fungal wheat pathogen
Authors: Moser Tralamazza Sabina , Gluck-Thaler Emile , Feurtey Alice , Croll Daniel
Published: September 2023

Copy number variation (CNV) can drive rapid evolution in changing environments. In microbial pathogens, such adaptation is a key factor underpinning epidemics and colonization of new niches. However, the genomic determinants of such adaptation remain poorly understood. Here, we systematically investigate CNVs in one of the largest to date genome sequencing dataset spanning a worldwide collection of 1109 genomes from the major wheat pathogenZymoseptoria tritici. We found overall strong purifying selection acting on most CNVs. Genomic defense mechanisms likely accelerated gene loss over episodes of continental colonization. Local adaptation along climatic gradients was facilitated by CNVs affecting secondary metabolite production and gene loss in general. One of the strongest candidates for climatic adaptation is a highly conserved gene of the NAD-dependent Sirtuin family. The Sirtuin CNV locus localizes to an ∼68-kbStarshipmobile element unique to the species carrying genes highly expressed during plant infection. The element has likely lost the ability to transpose, demonstrating how the ongoing domestication of cargo-carrying selfish elements can contribute to selectable variation within populations. Our work highlights how standing variation in gene copy numbers at the global scale is a major factor driving climatic and metabolic adaptation in microbial species.
Genome-wide characterization of MLO family genes in bread wheat and Arabidopsis thaliana shed light on their role in growth and development, and resistance to powdery mildew, biotic and abiotic stresses
Authors: Hussain Babar , Ramzan Hamza , Raza Qasim , Atif Rana Muhammad , Budak Hikmet , Ghazy Abdel-Halim I.
Published: September 2023

Powdery mildew (PM), caused by the fungus, Blumeria graminis tritici is a devastating and notorious disease that is prevalent across the globe and causes up to 62% of yield losses in wheat. The well-known 68 PM resistance loci (Pm1 -Pm68) are not long-lasting and break down when new races of pathogens interact with host plants. The editing of three known MLO genes through CRISPR/Cas9 has conferred resistance against PM. However, only seven MLO genes were known in wheat to date. Taking advantage of IWGSC Ref-seq v2.1 and using the gold-standard analysis pipeline that we have designed, we expanded this number to 47 and reported 40 additional potential CRISPR targets that can be used to develop PM resistance, disease resistance, and abiotic stress tolerance in wheat. We also performed phylogenetic, gene structure, and MOTIF analysis that indicated conserved evolutionary patterns, and the phylogenetic pattern was strongly supported by gene structure and MOTIF analysis. The gene duplication and evolution analysis showed that segmental duplications were prevalent and purifying selection operated during evolution. Comparative phylogenetic analysis with Arabidopsis thaliana and Brachypodium distachyon depicted that clade IV was exclusive for monocots. Finally, MLOs are expressed under powdery mildew, rusts, head blight, abiotic stresses, growth, and development thus TraesMLOs have a potential role in wheat under these conditions. Therefore, we hope that the MLO genes identified in this study will be edited through CRISPR/Cas9 or will be overexpressed to develop PM and disease-resistant and abiotic stress-tolerant wheat. Additionally, we performed most of the above-mentioned analyses for Arabidopsis thaliana, revised its numbers as compared to the TAIR database, and updated it outdated analysis performed in 2003.
CircWaveNet: A New Conventional Neural Network Based on Combination of Circlets and Wavelets for Macular OCT Classification
Authors: Arian Roya , Vard Alireza , Kafieh Rahele , Plonka Gerlind , Rabbani Hossein
Published: September 2023

Computer-aided systems can help the ophthalmologists in early detection of most of ocular abnormalities using retinal OCT images. The need for more accurate diagnosis increases the need for modifications and innovations to current algorithms. In this paper, we investigate the effect of different X-lets on the classification of OCT B-scans of a dataset with one normal class and two abnormal classes. Different transforms of each B-scan have been fed to the designed 2D-Convolutional-Neural-Network (2D-CNN) to extract the best-suited features. We compare the performance of them with MSVM and MLP classifiers. Comparison with the accuracy of normal and abnormal classes reveals substantially better results for normal cases using 2D-Discrete-Wavelet-Transform (2D-DWT), since the structure of most normal B-scans follows a pattern with zero-degree lines, while for abnormalities with circles appearing in the retinal structure (due to the accumulation of fluid), the circlet transform performs much better. Therefore, we combine these two X-lets and propose a new transform named CircWave which uses all sub-bands of both transformations in the form of a multi-channel-matrix, with the aim to increase the classification accuracy of normal and abnormal cases, simultaneously. We show that the classification results obtained based on CircWave transform outperform those based on the original images and each individual transform. Furthermore, the Grad-CAM class activation visualization for B-scans reconstructed from half of the CircWave sub-bands indicates a greater focus on appearing circles in abnormal cases and straight lines in normal cases at the same time, while for original B-scans the focus of the heat-map is on some irrelevant regions. To investigate the generalizability of our proposed method we have applied it also to another dataset. Using the CircWave transform, we have obtained an accuracy of 94.5% and 90% for the first and second dataset, respectively, while these values were 88% and 83% using the original images. The proposed CNN based on CircWave provides not only superior evaluation parameter values but also better interpretable results with more focus on features that are important for ophthalmologists.
Comparisons of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9I) versus Ezetimibe on Major Adverse Cardiovascular Events Amongst Patients with Dyslipidaemia: A Population-Based Study
Authors: Chou Oscar Hou In , Li Lifang , Chung Cheuk To Skylar , Lu Lei , Lee Quinncy , Pui Hugo Hok Him , Leung Bosco Kwok Hei , Chang Carlin , Liu Tong , Wai Abraham Ka Chung , Lip Gregory , Cheung Bernard Man Yung , Tse Gary , Zhou Jiandong
Published: September 2023

Background

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9I) have potential benefits against cardiovascular disease. The comparative risks of new-onset major adverse cardiovascular events (MACE) between PCSK9I and ezetimibe remain unknown.

Objective

This real-world study compared the risks of MACE upon exposure to PCSK9I and ezetimibe.

Methods

This was a retrospective population-based cohort study of patients with dyslipidaemia on either PCSK9I or ezetimibe between 1stJanuary 2015 and 30thOctober 2022 using a territory-wide database from Hong Kong. The primary outcome was new-onset MACE. The secondary outcomes were myocardial infarction, heart failure, stroke/transient ischaemic attack, and all-cause mortality. Propensity score matching (1:3 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was used to identify significant associations.

Results

This cohort included 42450 dyslipidaemia patients (median age: 65.0 years old [SD: 11.1]; 64.54 % males). The PCSK9I and ezetimibe groups consisted of 1477 and 40973 patients, respectively. After matching, 67 and 235 patients suffered from MACE in the PCSK9I and ezetimibe groups, respectively, over a total of 14514.5 person-years. PCSK9I was associated with lower risks of MACE (Hazard ratio [HR]: 0.59; 95% Confidence Interval [CI]: 0.37-0.92) compared to ezetimibe use after adjusting for demographics, past comorbidities, other medications, and time-weighted means of lipid and glucose tests. Besides, while both alirocumab and evolocumab were associated with lower risks of MACE, evolocumab was associated with significantly lower risks of myocardial infarction, heart failure, and stroke/transient ischaemic attack. The results remained consistent in the competing risk and sensitivity analyses.

Conclusions

PCSK9I use amongst dyslipidaemia patients was associated with lower risks of new-onset MACE and outcomes compared to ezetimibe after adjustments. Evolocumab might perform better than Alirocumab in reducing the risks of cardiovascular diseases.

Illustrated Abstract
Transmission potential of mpox in Mainland China, June-July 2023: estimating reproduction number during the initial phase of the epidemic
Authors: Akhmetzhanov Andrei R. , Wu Pei-Hsuan
Published: September 2023

Despite reporting very few mpox cases in early 2023, Mainland China observed a surge of over 500 cases during the summer. Amid ambiguous prevention strategies and stigma surrounding mpox transmission, the epidemic silently escalated. This study aims to quantify the scale of the mpox epidemic and assess the transmission dynamics of the virus by estimating the effective reproduction number (Re) during its early phase. Publicly available data were aggregated to obtain daily mpox incidences in Mainland China, and theRewas estimated using an exponential growth model. The meanRevalue was found to be 1.76 (95% credible interval: 1.51–2.06), suggesting a case doubling time of approximately 2 weeks. This estimate was compared withRevalues from 16 other countries’ national outbreaks in 2022 that had cumulative incidences exceeding 700 symptomatic cases by the end of that year. TheReestimates for these outbreaks ranged from 1.17 for Portugal to 2.88 for Colombia. The pooled meanRewas 1.66 (95% credible interval: 1.40–1.92), which aligns closely with theRefor Mainland China. These findings underscore the need for immediate and effective control measures including targeted vaccination campaigns to mitigate the further spread and impact of the epidemic.
The Human Infertility Single-cell Testis Atlas (HISTA): An interactive molecular scRNA-Seq reference of the human testis
Authors: Mahyari Eisa , Vigh-Conrad Katinka A. , Daube Clément , Lima Ana C. , Guo Jingtao , Carrell Douglas T. , Hotaling James M. , Aston Kenneth I. , Conrad Donald F.
Published: September 2023

Background

The Human Infertility Single-cell Testis Atlas (HISTA) is an interactive web tool and a reference for navigating the transcriptome of the human testis. It was developed using joint analyses of scRNA-Seq datasets derived from a dozen donors, including healthy adult controls, juveniles, and several infertility cases. HISTA is very different than other websites of testis scRNA-seq data, providing visualization and hypothesis testing tools on a batch-removed and integrated dataset of 23429 genes measured across 26093 cells using.

Objective

The main goal of this manuscript is to describe HISTA in detail and highlight its unique and novel features.

Methods

Therefore, we used HISTA as a guide for its application and demonstrated HISTA’s translational capacity to follow up on two observations of biological relevance.

Results

Our first analytical vignette identifies novel groupings of tightly regulated long non-coding RNA (lncRNA) molecules throughout spermatogenesis, suggesting specific functional genomics of these groupings. This analysis also found highly controlled expression of pairs of sense and antisense transcripts, suggesting conjoined regulatory mechanisms. In the next investigative vignette, we examined gene patterns in undifferentiated spermatogonia (USgs). We found the NANOS family of genes function as key drivers of transcriptomic signatures involved in human spermatogonial self-renewal programming; for the first time, demonstrating the relationship of NANOS1/2/3 transcripts in humans with scRNA-seq.

Discussion and Conclusions

Using HISTA, we found new observations that contribute to unraveling the mechanisms behind transcriptional regulation and maintenance germ cells across spermatogenesis. Furthermore, our findings provide guidance on future validation studies and experimental direction. Overall, HISTA continues to be utilized in testis-related research, and thus is updated regularly with new analytical methods, visualizations, and data. We aim to have it serve as a research environment for a broad range of investigators looking to explore the testis tissue and male infertility.

Availability and Implementation

HISTA is available as an interactive web tool:https://conradlab.shinyapps.io/HISTA

Source code and documentation for HISTA are provided on GitHub:https://github.com/eisascience/HISTA
A review of fish diversity in Mediterranean seagrass habitats, with a focus on functional traits
Authors: Lattanzi A. , Bellisario B. , Cimmaruta R.
Published: September 2023

Seagrass habitats are considered essential in supporting both fish diversity and fisheries’ income. Within the Mediterranean Sea most fish species are associated to seagrasses and constitute the subject of extensive literature. However, a complete synthesis of fish species observed in different seagrass habitats is still lacking at the whole-basin Mediterranean scale, so hindering a thorough understanding of the main functional traits and mechanisms involved in determining fish diversity patterns. We performed a systematic review by implementing a semi-automated, threshold-based filtering pipeline that allowed building up a dataset concerning all fish species reported in native Mediterranean seagrasses, including specific functional traits known to be involved with the potential use of seagrasses by fish. These data allowed to carry on a narrative synthesis on fish diversity in seagrass habitats. Moreover, the functional traits analysis highlighted a significant role of trophic level, size and benthic domain in determining the distribution of fish in different seagrass habitats at whole Mediterranean basin scale. Data evidenced a pattern of segregation between large piscivorous, pelagic predators and smaller benthic prey (including juveniles) with omnivorous to herbivorous feeding habit, with aggressive predators significantly associated withPosidonia oceanicaandCymodocea nodosabeds while their putative prey tend to occupy other seagrass habitats. We identified unexpected knowledge gaps on the role of habitat heterogeneity and fish life stages in determining the presence/absence of fish in different seagrasses, for which in-depth research is needed to fully understand the links between nursery habitats and the state of exploited fish stock.
Perceptual priors add sensory detail to contextual feedback processing in V1
Authors: Lazarova Yulia , Huang Yingying , Muckli Lars , Petro Lucy S.
Published: September 2023

How do we develop models of the world? Contextualising ambiguous information with previous experience allows us to form an enriched perception. Contextual information and prior knowledge facilitate perceptual processing, improving our recognition of even distorted or obstructed visual inputs. As a result, neuronal processing elicited by identical sensory inputs varies depending on the context in which we encounter those inputs. This modulation is in line with predictive processing accounts of vision which suggest that the brain uses internal models of the world to predict sensory inputs, with cortical feedback processing in sensory areas encoding beliefs about those inputs. As such, acquiring knowledge should enhance our internal models that we use to resolve sensory ambiguities, and feedback signals should encode more accurate estimates of sensory inputs. We used partially occluded Mooney images, ambiguous two-tone images which are difficult to recognise without prior knowledge of the image content, in behavioural and 3T fMRI experiments to measure if contextual feedback signals in early visual areas are modulated by learning. We show that perceptual priors add sensory detail to contextual feedback processing in early visual areas in response to subsequent presentations of previously ambiguous images.
Embodiment in episodic memory through premotor-hippocampal coupling
Authors: Meyer Nathalie Heidi , Gauthier Baptiste , Stampacchia Sara , Boscheron Juliette , Babo Rebelo Mariana , Potheegadoo Jevita , Herbelin Bruno , Lance Florian , Alvarez Vincent , Franc Elizabeth , Esposito Fabienne , Morais Lacerda Marilia , Blanke Olaf
Published: September 2023

Episodic memory (EM) allows us to remember and relieve past events and experiences, depending on cortical-hippocampal reinstatement involved during encoding. Although it has been claimed that EM is fundamental to establish a sense of self across time, this has never been shown experimentally. Here we combine immersive virtual reality and fMRI and report stronger hippocampal reinstatement for scenes encoded under preserved sense of self, reflecting later recall performance. We further link the sense of self to EM showing that hippocampal reinstatement is coupled with reinstatement in premotor cortex, a key sense of self region. We extend these findings in a severe amnesic patient (caused by bilateral hippocampal damage), whose memory and re-experiencing lacked the normal dependency on the sense of self. Premotor-hippocampal coupling in EM describes how the self at encoding is neurally reinstated during the retrieval of past episodes, enabling a sense of self across time.

Teaser

Premotor-hippocampal coupling reveals how the self is reinstated when retrieving past episodes.
Cortical and subcortical brain networks predict prevailing heart rate
Authors: Sentis Amy Isabella , Rasero Javier , Gianaros Peter J. , Verstynen Timothy D.
Published: September 2023

Resting heart rate may confer risk for cardiovascular disease (CVD) and other adverse cardiovascular events. While the brainstem’s autonomic control over heart rate is well established, less is known about the regulatory role of higher-level cortical and subcortical brain regions, especially in humans. The present study sought to characterize the brain networks that predict variation in prevailing heart rate in otherwise healthy adults. We used machine learning approaches designed for complex, high-dimensional datasets, to predict variation in instantaneous heart period (the inter-heartbeat-interval) from whole brain hemodynamic signals measured by fMRI. Task-based and resting-state fMRI, as well as peripheral physiological recordings, were taken from two datasets that included extensive repeated measurements within individuals. Our models reliably predicted instantaneous heart period from whole brain fMRI data both within and across individuals, with prediction accuracies being highest when measured within-participants. We found that a network of cortical and subcortical brain regions, many linked to psychological stress, were reliable predictors of variation in heart period. This adds to evidence on brain-heart interactions and constitutes an incremental step towards developing clinically-applicable biomarkers of brain contributions to CVD risk.

Impact statement

Using whole brain fMRI data, we reliably predicted instantaneous heart period within and across individuals from the activity of a network of cortical and subcortical brain regions, many linked to psychological stress. This adds to existing evidence on brain-heart interactions and constitutes a step towards developing clinically-applicable biomarkers of brain contributions to CVD risk.
Psychedelic 5-HT2A receptor agonism: neuronal signatures and altered neurovascular coupling.
Authors: Padawer-Curry Jonah A. , Krentzman Oliver J. , Kuo Chao-Cheng , Wang Xiaodan , Bice Annie R. , Nicol Ginger E. , Snyder Abraham Z. , Siegel Joshua S. , McCall Jordan G. , Bauer Adam Q.
Published: September 2023

Psychedelics hold therapeutic promise for mood disorders due to rapid, sustained results. Human neuroimaging studies have reported dramatic serotonin-2A receptor-(5-HT2AR)-dependent changes in functional brain reorganization that presumably reflect neuromodulation. However, the potent vasoactive effects of serotonin have been overlooked. We found psilocybin-mediated alterations to fMRI-HRFs in humans, suggesting potentially altered NVC. To assess the neuronal, hemodynamic, and neurovascular coupling (NVC) effects of the psychedelic 5-HT2AR agonist, 2,5-Dimethoxy-4-iodoamphetamine (DOI), wide-field optical imaging (WFOI) was used in awake Thy1-jRGECO1a mice during stimulus-evoked and resting-state conditions. While DOI partially altered tasked-based NVC, more pronounced NVC alterations occurred under resting-state conditions and were strongest in association regions. Further, calcium and hemodynamic activity reported different accounts of RSFC changes under DOI. Co-administration of DOI and the 5-HT2AR antagonist, MDL100907, reversed many of these effects. Dissociation between neuronal and hemodynamic signals emphasizes a need to consider neurovascular effects of psychedelics when interpreting blood-oxygenation-dependent neuroimaging measures.
Common and Rare Variant Contributions to Bradyarrhythmias from Multi-Ancestry Meta-Analyses
Authors: Weng Lu-Chen , Rämö Joel T. , Jurgens Sean J. , Khurshid Shaan , Chaffin Mark , Hall Amelia Weber , Morrill Valerie N. , Nauffal Victor , Sun Yan V. , Beer Dominik , Lee Simon , Nadkarni Girish , Duong ThuyVy , Wang Biqi , Czuba Tomasz , Austin Thomas R. , Yoneda Zachary T. , Friedman Daniel J. , Clayton Anne , Hyman Matthew C. , Judy Renae L. , Skanes Allan C. , Orland Kate M. , Treu Timothy M. , Oetjens Matthew T. , Alonso Alvaro , Soliman Elsayed Z. , Lin Honghuang , Lunetta Kathryn L. , van der Pals Jesper , Issa Tariq Z. , Nafissi Navid A. , May Heidi T. , Leong-Sit Peter , Roselli Carolina , Choi Seung Hoan ,   FinnGen, Million Veteran Program, Regeneron Genetics Center, Khan Habib R. , Knight Stacey , Linnér Richard K. , Bezzina Connie R. , Ripatti Samuli , Gaziano J. Michael , Loos Ruth , Psaty Bruce M. , Smith J. Gustav , Benjamin Emelia J. , Arking Dan E. , Rader Daniel , Shah Svati H. , Roden Dan M. , Damrauer Scott M. , Eckhardt Lee L. , Roberts Jason D. , Cutler Michael J. , Shoemaker M. Benjamin , Haggerty Christopher M. , Cho Kelly , Palotie Aarno , Wilson Peter W.F. , Ellinor Patrick T. , Lubitz Steven A.
Published: September 2023

To broaden our understanding of bradyarrhythmias and diseases of the cardiac conduction system, we performed cross-sectional multi-ancestry genome-wide association study meta-analyses in up to 1.3 million individuals for sinus node dysfunction (SND), distal conduction disease (DCD), and pacemaker implantation (PM). We evaluated the biological relevance of bradyarrhythmia loci by analyses of transcriptomes, pleiotropy, and partitioned heritability based on cardiac single cell RNA sequencing data. Finally, we performed rare variant burden testing in 460,000 whole exome sequenced individuals from two biobanks. We identified 13, 28, and 21 common variant loci for SND, DCD, and PM, respectively. Four well-known common variant arrhythmia loci (SCN5A/SCN10A,CCDC141, TBX20, andCAMK2D)were shared for SND and DCD, while other loci were more specific for either SND or DCD. Cardiomyocyte-expressed genes were strongly enriched for contributions to DCD heritability, while SND and PM were more heterogeneous. Rare variant analyses implicatedLMNAfor all bradyarrhythmia subtypes;SMAD6andSCN5Afor DCD; andTTN,MYBPC3, andSCN5Afor PM. The genetic architectures of SND and DCD are both overlapping and distinct. Multiple genetic mechanisms involving ion channels, sarcomeric components, cellular homeostasis, and cardiac development may influence the development of bradyarrhythmias.
Maternal smoking DNA methylation risk score associated with health outcomes in offspring of European and South Asian ancestry
Authors: Deng Wei Q. , Cawte Nathan , Campbell Natalie , Azab Sandi M. , de Souza Russell J , Lamri Amel , Morrison Katherine M. , Atkinson Stephanie A. , Subbarao Padmaja , Turvey Stuart E. , Moraes Theo J. , Teo Koon K. , Mandhane Piush , Azad Meghan B. , Simons Elinor , Pare Guillaume , Anand Sonia S.
Published: September 2023

Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations. We first examined association between individual CpGs and cigarette smoking during pregnancy, smoking exposure in two White European birth cohorts (n = 744). Several previously reported genes for maternal smoking were supported, with the strongest and most consistent signal from theGFI1gene (6 CpGs withp< 5×10-5). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n = 347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent white European (n = 397) and a South Asian birth cohort (n = 504). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR=1.09 [1.07,1.10],p=5.5×10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58],p=7.8×10-9) in White Europeans, but not with self-reported exposure (p> 0.05) in South Asians. The same score was consistently associated with a smaller birth size (−0.37±0.12 cm,p=0.0023) in the South Asian cohort and a lower birth weight (−0.043±0.013kg,p=0.0011) in the combined cohorts. This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birthweight in newborns, in both white European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers.
Trends in AI-powered classification of thyroid neoplasms based on histopathology images, a systematic review
Authors: Kussaibi Haitham , Alsafwani Noor
Published: September 2023

Background

Assessment of thyroid nodules histopathology using AI is crucial for an accurate diagnosis. This systematic review analyzes recent works employing deep learning approaches for classifying thyroid nodules based on histopathology images, evaluating their performance, and identifying limitations.

Methods

Eligibility criteria focused on peer-reviewed English papers published in the last five years, applying deep learning to categorize thyroid histopathology images. The PubMed database was searched using relevant keyword combinations.

Results

Out of 103 articles, 11 studies met inclusion criteria. They used convolutional neural networks to classify thyroid neoplasm. Most studies aimed at basic tumor subtyping; however, three studies targeted the prediction of tumor-associated mutation. Accuracy ranged from 77% to 100%, with most over 90%.

Discussion

The findings from our analysis reveal the effectiveness of deep learning in identifying discriminative morphological patterns from histopathology images, thus enhancing the accuracy of thyroid nodule histopathological classification. Key limitations were small sample sizes, subjective annotation, and limited dataset diversity. Further research with larger diverse datasets, model optimization, and real-world validation is essential to translate these tools into clinical practice.

Other

Funding

This study did not receive any funding.

Registration

The procedural instructions for this systematic review were officially recorded within the PROSPERO database under registration numberRD42023457854https://www.crd.york.ac.uk/Prospero/
Coping skills, depression, and anxiety in medical students
Authors: Baldassin Sergio , Zilbermann Mônica Levit , de Toledo Ferraz Alves Tania Correa , Martins-da-Silva Anderson Sousa , Castaldelli-Maia João Maurício , Nogueira-Martins Luiz Antonio
Published: September 2023

Objective

to describe coping strategies during medical education and their relationship with course periods, with gender, and depressive and anxiety range symptoms.

Method

the Ways of Coping Questionnaire (WCQ), the Beck Depression Inventory (BDI), and the Spielberger Trait Anxiety Inventory (STAI-T) were administered to 599 medical students from basic, intermediate and internship periods.

Results

The response rate was 80.3% (279 females and 190 males aged 21.9 ± 2.4 years). Belong to internship or basic/intermediate levels make a significant difference in choosing coping factors. Female students reported greater use of factors indicating a need for social support and fantasy. In contrast, male students reported greater use of factors such as substance use and self-control.

Twenty percent of students scored high on anxiety (STAI-T>49), whereas 7.6% scored on the depression range (>20) and 8.0% on the dysphoric range (16–20) of the BDI. Students at the normal range at the BDI and the STAI-T reported greater use of factors such as of social support and problem solving. The factor analysis of the WCQ showed that dysphoric, depressive, and high anxiety students reported greater use of factors indicating fantasy, search of relief and escape.

Conclusion

Dysphoria, depressive, and highly anxious medical students choose similar strategies to deal with stress related to medical graduation. Women and men exhibit distinct coping strategies related to medical education and training. Support and counseling services for medical students should take into consideration these depressive and anxiety ranges, and gender differences in coping strategies, with potentially important preventive and therapeutic implications.
Trends of non-tuberculous mycobacterial disease in a low-tuberculosis prevalence setting
Authors: Mohanty Biplob Kumar , Eagan Tomas Mikal Lind , Aarli Bernt Bøgvald , Skutlaberg Dag Harald , Mustafa Tehmina
Published: September 2023

Background

Limited data are available regarding factors associated with initiation of treatment and treatment outcomes after diagnosis of non-tuberculous mycobacteria (NTM) pulmonary infection and disease.

Objective

To investigate trends of NTM pulmonary infections, patient characteristics and factors associated with initiation of treatment and treatment outcomes in patients with NTM pulmonary infection and disease.

Methods

We evaluated 154 patients with NTM pulmonary infection, identified by having at least one record coded with ICD-10 A31.0 at Haukeland University Hospital in Bergen, Norway, from 2000 to 2021. A univariate and multivariate binary logistic regression was carried out to find the odds of factors associated with the initiation of treatment and treatment outcomes.

Results

70% of the patients were older than 65 years. 49 % of patients had pulmonary comorbidity and the three most common symptoms were cough, dyspnoea, and weight loss. The most frequently observed mycobacterial species wasM. avium complex(MAC), followed byM. malmoense, andM. abscessus. There was a decreasing trend in NTM pulmonary infection and NTM pulmonary disease from the year 2000 to 2014, while an increase was observedfrom 2015 to 2019. A total of 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, those below the age of 65, and those with MAC infection had more than three times the odds of receiving antibiotic treatment (P = 0.006, P = 0.006, and P = .005 respectively). Of 72 patients who received treatment, 53 (74%) had a favourable response and culture conversion. 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion. 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response including the time taken to start treatment or presence of pulmonary cavities.

Conclusion

Favourable response to treatment was seen in 74% patients whereas spontaneous culture conversion was seen in 55% of non-treated patients. Factors associated with favourable treatment response were not found.
Identification of Metabolic Pathways Altered in Thyroid Cancer Progression and Metastasis
Authors: de Oliveira Andrade Luís Jesuino , Matos de Oliveira Luisa Correia , Matos de Oliveira Gabriela Correia , Vinhaes Bittencourt Alcina Maria , Peixoto Silva Catharina , Matos de Oliveira Luís
Published: September 2023

Introduction

Thyroid cancer is a common endocrine malignancy with a rising incidence. However, to improve patient outcomes, it is essential to understand the molecular mechanisms driving its progression and metastasis, and the metabolomics can unveil alterations in metabolic pathways that contribute to thyroid cancer.

Objective

To identify the metabolic pathways altered in thyroid cancer progression and metastasis.

Methods

Multiple bioinformatics tools were employed in the research. Gene expression data was obtained from the Gene Expression Omnibus and The Cancer Genome Atlas. Functional assessment of the expressed genes in thyroid cancer was performed using gene set enrichment analysis. The Kyoto Encyclopedia of Genes and Genomes database was utilized to identify the metabolic pathway involved in thyroid cancer progression and metastasis. A computational algorithm was developed to estimate the activity levels of the identified metabolic pathways and construct a signaling pathway.

Results

The altered metabolic pathways in thyroid cancer progression and metastasis were identified based on the following algorithm: activation of growth factor signaling, activation of multiple signaling pathways, regulation by transcription factors, dysregulation of downstream signaling cascades, changes in cellular metabolism, tumor progression, invasion and metastasis, and feedback regulation.

Conclusion

By applying a comprehensive algorithm, we were able to uncover key molecular events driving the aggressive behavior of thyroid cancer. These findings provide insights into the underlying mechanisms of thyroid cancer progression and metastasis.
Virulence patterns of oat crown rust in Australia - season 2022
Authors: Henningsen Eva C. , Lewis David , Nguyen Duong T. , Sperschneider Jana , Kianian Shahryar F. , Stone Eric , Dodds Peter N. , Figueroa Melania
Published: September 2023

Puccinia coronataf. sp.avenae(Pca) is an important foliar pathogen of oat which causes crown rust disease. The virulence profile of 48Pcaisolates derived from different locations in Australia was characterised using a collection of oat lines often utilised in rust surveys in the USA and Australia. This analysis indicates thatPcapopulations in Eastern Australia are broadly virulent, in contrast to the population in Western Australia (WA). Several oat lines/Pcgenes are effective against all rust samples collected from WA, suggesting they may provide useful resistance in this region if deployed in combination. We identified 19 lines from the USA oat differential set that display disease resistance toPcain WA, some in agreement with previous rust survey reports. We adopted the 10-letter nomenclature system to define oat crown rust races in Australia and compare the frequency of those virulence traits to published data from the USA. Based on this nomenclature, 42 unique races were detected among the 48 isolates, reflecting the high diversity of virulence phenotypes forPcain Australia. Nevertheless, thePcapopulation in the USA is substantially more broadly virulent than that of Australia. Close examination of resistance profiles for the oat differential set lines after infection withPcasupports hypotheses of allelism or redundancy amongPcgenes or the presence of several resistance genes in some oat differential lines. These findings illustrate the need to deconvolute the oat differential set using molecular tools.
Weakly supervised identification and generation of adaptive immune receptor sequences associated with immune disease status
Authors: Slabodkin Andrei , Sollid Ludvig M. , Sandve Geir Kjetil , Robert Philippe A. , Greiff Victor
Published: September 2023

Adaptive immune receptor (AIR) repertoires carry immune signals as sequence motif imprints of past and present encounters with antigen (immune status). Machine learning (ML)-based identification and generation of antigen-specific immune receptors is potentially immense value for public health. The ideal training data for such ML tasks would be AIR datasets, where each sequence is labeled with its cognate antigen. However, given current technological constraints, sequence-labeled datasets are scarce, contrasted by an abundance of repertoire-labeled ones – AIR repertoire datasets where only the repertoire dataset, but not the individual AIRs, are labeled. Therefore, an unmet need exists for an ML approach that enables predictive identification and generation of disease-specific novel AIR sequences using exclusively repertoire-level immune status information. To address this need, we developed AIRRTM, an end-to-end generative model using an encoder-decoder architecture and Topic Modeling (TM) that requires exclusively repertoire-labeled AIR sequencing data as input. We validated AIRRTM’s capacity to identify and generate novel disease-associated receptors on several ground truth synthetic datasets of increasingly complex immune signals and experimental data. AIRRTM broadens the discovery space for immunotherapeutics by enabling the exploitation of large-scale and broadly available immune repertoire data previously deemed largely unsuitable for this task.
DNMT3L interacts with Piwi and modulates the expression of piRNAs
Authors: Rajeev Ramisetti , Mishra Rakesh , Khosla Sanjeev
Published: September 2023

The epigenetic modulator, DNMT3L, has been shown to be involved in nuclear reprogramming. Previous work from our laboratory had shown the accumulation and inheritance of epimutations across multiple generations when DNMT3L was ectopically expressed in transgenic DNMT3L Drosophila. Here, we show interaction of DNMT3L with Piwi, a member of a family of proteins known to perform their function through their association with piRNAs. Importantly, DNMT3L expression caused a significant alteration in the piRNA profile across multiple generations in transgenic Drosophila. As piRNAs are known to be passed on from one generation to another, we believe that the DNMT3L through its interaction with Piwi act to modify the inherited pool of piRNAs, which in turn allows accumulation of aberrant epigenetic modifications in subsequent generation. Furthermore, we show the interaction of DNMT3L with Histone H1, a non-core histone involved in higher order chromatin organisation. In light of these observations, it is proposed that in addition to its role in modulating core histone modifications, DNMT3L allows for inheritance of non-genetic information through its collaboration with Piwi, piRNAs and histone H1.
Long-read genome assembly of the Japanese parasitic waspCopidosoma floridanum(Hymenoptera: Encyrtidae)
Authors: Toga Kouhei , Sakamoto Takuma , Kanda Miyuki , Tamura Keita , Okuhara Keisuke , Tabunoki Hiroko , Bono Hidemasa
Published: September 2023

Copidosoma floridanumis a cosmopolitan species and an egg-larval parasitoid of the Plusiine moth.C. floridanumhas a unique development mode called polyembryony, in which thousands of genetically identical embryos are produced from a single egg. Some embryos develop into sterile soldier larvae, and their developmental patterns differ between the US and JapaneseC. floridanumstrains. Genome sequencing can accelerate our understanding of the molecular bases underlying polyembryony, including the production of soldier castes. However, only the genome sequence of the US strain has been reported. In the present study, we determined the genome sequence of the Japanese strain using Pacific Biosciences high-fidelity reads and generating a highly contiguous assembly (552.7 Mb, N50: 17.9 Mb). Gene prediction and annotation identified 13,886 transcripts derived from 10,786 gene models. Among these, 149 transcripts were not identified in the US strain gene model. Differences in the amino acid sequence of thevasagene were observed between the US and Japanese strains. The genome assemblies constructed in this study will facilitate our understanding of intraspecific variation in the developmental patterns ofC. floridanum.
Src/Fas2-dependent Ephrin phosphorylation initiates Eph/Ephrin reverse signaling through Rac1 to shape columnar units in the fly brain
Authors: Wang Miaoxing , Han Xujun , Lee Yunfei , Takayama Rie , Sato Makoto
Published: September 2023

Columns are the morphological and functional units containing multiple neurons in the brain. The molecular mechanisms of column formation are largely unknown. Ephrin/Eph signaling mediates a variety of developmental processes. Ephrin acts as a ligand for Eph to regulate forward signaling, while Eph acts as a ligand for Ephrin to regulate reverse signaling. However, whether and how the uni- or bi-directional Ephrin/Eph signaling is involved in column formation remains elusive. In this study, we show that Ephrin and Eph regulate the morphology and location of columnar neurons through bi-directional repulsive signaling. Furthermore, Eph ligand triggers cytoplasmic tyrosine phosphorylation of Ephrin under the control of Src kinases and Fasciclin II (Fas2), forming Ephrin/Src/Fas2 complex to promote reverse signaling through a downstream regulator, Rac1. This study presents for the first time a unified picture of the molecular interactions in the defined context of column formation using the fly brain as a model.