bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital twin prevalence in the medical caring fields: a bibliomatrics study and visualization analysis via CiteSpace
Authors: Zhou Ting Ting , Gong Ping , Tian Yin Ying , Su Meng Ting , Chen Xing Yang
Published: June 2024

Objectives:

We conducted academic research utilizing the visualization tool CiteSpace to explore the direct relationship between digital twin technology and medical care.

Methods:

We collected data from the Web Of Science Core Collection, PubMed ScienceDirect, SpringerLink, Wiley Online Library databases from 2010-2023, displayed visualization analysis of countries, institutions, and co-occurring keywords, cluster, citation bursts and timeline, also calculated nodes, edges, centrality, modularity and silhouette via CiteSpace 5.75r version.

Results:

The data incorporated 1109 studies, graphed the yearly publication number from 2010-2023, showed a steady increase trend. The tree map displayed the top ten prominent study subjects, the first one was “Health Care Science Service”. The top three of Countries were USA, Germany and England, and the top one institution was Harvard Medical School. As for the top five keywords were “digital health”, “care”, “technology”, “digital twin”, and “telemedicine”. The rank three cluster were “Digital Health Applications”, “Digital Twin”, and “Machine Learning”. We also displayed the visualization analysis of citation bursts and timeline.

Conclusions:

Digital twins has welcomed a popular development in strong countries and top-tier institutions, and has a tight connection with mobile health and artificial intelligence. It has been widely used in clinical trials, like surgical operation and rehabilitation discipline, to predict patient treatment outcome, and estimate potential complications, we should facilitate digital twins in clinical practice conversion and application, and try to tackle the problems from privacy concern and economy challenge.
Sexually Transmitted Infection and HIV Testing and Diagnosis Among 15- to 44-Year-Old Patients With and Without Opioid Use Disorder
Authors: Patel Chirag G. , DePadilla Lara , Cuffe Kendra M. , Tao Guoyu , Gift Thomas
Published: June 2024

Background

The association between illicit opioid use and prescription opioid misuse and sexually transmitted infections (STIs) has not been examined recently. Our study aimed to explore differences in STI/HIV care, and delivery of recommended testing and diagnoses among patients with and without opioid use disorder (OUD).

Methods

Using 2019 MarketScan commercial claims data, we identified 15- to 44-year-old male and female patients, to assess the percentages of STI/HIV diagnoses (using International Classification of Diseases, Tenth Revision, Clinical Modification) and screening (using Current Procedure Terminology codes) among patients with or without OUD diagnoses codes. We further assessed STI/HIV testing and diagnoses by demographic factors.

Results

We identified 24,724 patients with OUD codes among 7.31 million patients. Both STI/HIV testing and diagnoses were significantly (P < 0.05) higher among patients with OUD codes versus without: testing percentages were 16.81% versus 12.93% for chlamydia, 22.31% versus 16.62% for gonorrhea, 15.26% versus 7.61% for syphilis, and 18.18% versus 7.60% for HIV; diagnoses were 0.80% versus 0.35% for chlamydia, 0.30% versus 0.11% for gonorrhea, 0.23% versus 0.07% for syphilis, and 0.74% versus 0.33% for HIV. Similarly, among 0.53 million 15- to 24-year-old females who received services suggestive of sexual activity, chlamydia testing was significantly (P < 0.05) higher among patients with OUD codes versus without (59.78% vs. 55.66%).

Conclusions

Patients with OUD codes have higher percentages of STI/HIV testing and diagnoses codes compared with those without OUD codes. Clinicians may want to consider a comprehensive multidisciplinary (OUD and STI prevention) approach in patient care and provide recommended STI/HIV screening among patients with OUD if not performed.
Prediction of Interactomic HUB Genes in Periodontitis With Acute Myocardial Infarction
Authors: Thilagar Sri Sivashankari , Yadalam Pradeep Kumar , Ronsivalle Vincenzo , Cicciù Marco , Minervini Giuseppe
Published: June 2024

Background:

Acute myocardial infarction (AMI) risk correlates with C-reactive protein (CRP) levels, suggesting systemic inflammation is present well before AMI. Studying different types of periodontal disease (PD), extremely common in individuals at risk for AMI, has been one important research topic. According to recent research, AMI and PD interact via the systemic production of certain proinflammatory and anti-inflammatory cytokines, small signal molecules, and enzymes that control the onset and development of both disorders’ chronic inflammatory reactions. This study uses machine learning to identify the interactome hub biomarker genes in acute myocardial infarction and periodontitis.

Methods:

GSE208194 and GSE222883 were chosen for our research after a thorough search using keywords related to the study’s goal from the gene expression omnibus (GEO) datasets. DEGs were identified from the GEOR tool, and the hub gene was identified using Cytoscape-cytohubba. Using expression values, Random Forest, Adaptive Boosting, and Naive Bayes, widgets-generated transcriptomics data, were labelled, and divided into 80/20 training and testing data with cross-validation. ROC curve, confusion matrix, and AUC were determined. In addition, Functional Enrichment Analysis of Differentially Expressed Gene analysis was performed.

Results:

Random Forest, AdaBoost, and Naive Bayes models with 99%, 100%, and 75% AUC, respectively. Compared to RF, AdaBoost, and NB classification models, AdaBoost had the highest AUC. Categorization algorithms may be better predictors than important biomarkers.

Conclusions:

Machine learning model predicts hub and non-hub genes from genomic datasets with periodontitis and acute myocardial infarction.
Comparison Between an Expert Operator an Inexperienced Operator, and Artificial Intelligence Software: A Brief Clinical Study of Cephalometric Diagnostic
Authors: Muñoz Gonzalo , Zamora Daniel , Brito Leonardo , Ravelo Victor , de Moraes Marcio , Olate Sergio
Published: June 2024

Introduction:

Artificial intelligence (AI) is constantly developing in several medical areas and has become useful to assist with treatment planning. Orthodontics and maxillofacial surgery use AI-based technology to identify and select cephalometric points for diagnostics. Although some studies have shown promising results from the use of AI, the evidence is still limited. Hence, additional investigation is justified.

Materials and Methods:

In this retrospective study, 2 human operators (1 expert and 1 inexperienced) and 1 software analyzed 30 lateral cephalograms of individuals with orthodontic treatment indications. They measured 10 cephalometric variables and then 2 weeks later, repeated measurements on 30% of the sample. We evaluated the reliability of the measurements between the 2-time points and the differences in the means between the expert operator and the AI software and between the expert and inexperienced operators.

Results:

There was high reliability for the expert operator and AI measurements, and moderate reliability for the inexperienced operator measurements. There were some significant differences in the means produced by the AI software and the inexperienced operator compared with the expert operator.

Conclusion:

Although AI is useful for cephalometric analysis, it should be used with caution because there are differences compared with analysis by humans.
Assessment Methods and Intervention Strategies for Cleft-Related Lateral Misarticulation in Chinese-Speaking Children
Authors: Zhang Susu , Wang Tingting , Tang Lihua , Li Xiao , Shang Zibo , Zhou Tianyi , Lan Na , Yang Lijun , Zhou Haiyan
Published: June 2024

The aim of this study was to analyze the characteristics and error speech features of cleft-related lateral misarticulation and provide a basis for clinical evaluation and rational intervention. Participants who were diagnosed with lateral misarticulation after cleft palate repairment were 126 children aged 4, 6 to 16, and 11, and they had complete palatopharyngeal closure, no abnormalities in their speech organs and occlusion, and no hearing or intellectual impairments. The Chinese standard pronunciation clarity word list, the American KAY CSL4500, the Beijing Yangchen YF-16 computer speech analysis workstation, soundproof rooms, Wechsler scales of intelligence—fourth edition, and audiometers were used to evaluate the cleft-related lateral misarticulation. Statistical analysis was performed on the age, gender, error rate, corner of the mouth deviation direction, comorbidity, duration of intervention, period of treatment, and therapeutic effect of concentrated or normal intervention group in different patients. Our results showed that 2 to 3 straight stripes were visible at the onset of consonants /ti:/ /tʻi:/, and 3 clear straight lines were visible in /tʂ/, indicating that the lateralized sound had 2 or 3 bursts and lasted for 1 to 2 ms. The onset age of lateralized sound was mostly below 12 years old. Chinese lateralized sound mainly occurred in vowel /i:/, and the occurrence rate of consonants with tongue surface /tɕ]/ /tɕʻ/ /ɕ/ was the highest. In addition, the corner of the mouth deviation was also an indicator of lateralization sound, and other types of speech disorders mostly accompanied it. There was a significant difference in the improvement of speech clarity between the concentrated intervention group and the normal group before and after treatment. The 2 groups’ average duration and course of treatment were not significantly different. Still, the period of concentrated intervention was shortened considerably, and the speech clarity of both groups of children after treatment exceeded 96%, reaching a normal level.
Aconite-Induced Metamorphosis From Beauty to Ugliness in a Japanese Tale
Authors: Jung Sung Gyun , Hwang Kun , Hwang Young Joong
Published: June 2024

The authors present a narrative that details the cause and process of a woman’s transformation from beauty to ugliness in a Japanese tale. In “Tokaido Yotsuya Kaidan,” the metamorphosis from a beauty to an ugly woman is analyzed. After taking medication to recover from childbirth, Oiwa’s face became disfigured and grotesque.
Oiwa: It seems to be good for my blood, but when I drink it, it causes fraying and breakdown, causing sudden pain. I feel a numbing dullness. When she looked at herself in the mirror, she was shocked.
Oiwa: What’s wrong with my face? I hate this, it’s such a disgusting thing. Neighbor: It was a lie that the medicine you drank was a helpful medicine that protects the appearance of people’s faces. Your face is that of a wicked woman (惡女). Oiwa: Is it really me? Why does she have the face of an evil woman? Her hair falls out in a gruesome combing scene, driving her mad. The poison Oiwa took was aconite, which grows wild in Japan. Both aconite tincture and raw aconite roots contain high concentrations of Aconitum alkaloids, which can penetrate the stratum corneum following the diffusion gradient. As her hair fell out during a horrific combing session, she abandoned her maternal role and sought revenge, having lost what she considered a symbol of her femininity. In treating female patients with facial disfigurement, it is important to be mindful of their psychological state, akin to that of Oiwa, who became disfigured through no fault of her own.
Factors Associated With Head and Neck Polytrauma Presentation and Admissions at Emergency Departments of Varying Sizes
Authors: Lin Joshua S. , Won Paul , Lin Matthew E. , Ayo-Ajibola Oluwatobiloba , Luu Neil N. , Markarian Alexander , Moayer Roxana
Published: June 2024

Timely diagnosis of acute head and neck polytrauma presenting to emergency departments (EDs) optimizes outcomes. Since ED capacity influences triage and admission, the authors utilized the National Electronic Injury Surveillance System database to understand how ED size and trauma characteristics affect head and neck polytrauma presentation and admissions. Demographics and injury characteristics from the National Electronic Injury Surveillance System database from 2018 to 2021 were analyzed to delineate factors contributing to polytrauma presence and admission through multivariable logistic regressions. The authors’ 207,951-patient cohort was primarily females (48.6%), non-Hispanic (62.4%), and white (51.4%) people who averaged 57.2 years old. Nonspecific head injuries were predominant (59.7%), followed by facial trauma (22.6%) with rare substance involvement (alcohol, 6.3%; drugs, 4.1%) presenting to high-volume EDs (48.5%). Of the patients, 20% were admitted, whereas 31.1% sustained polytrauma. Substance use [alcohol, odds ratio (OR) = 4.44; drugs, OR = 2.90] increased polytrauma likelihood; neck (OR = 1.35), face (OR = 1.14), and eye (OR = 1.26) associated with polytrauma more than head injuries. Burns (OR = 1.38) increased polytrauma likelihood more than internal organ injuries. Black patients sustained higher polytrauma when presented to non-small EDs (OR = 1.41–1.90) than white patients showed to small EDs. Admissions were higher for males (OR = 1.51). Relative to small EDs, large EDs demonstrated a higher increase in admissions (OR = 2.42). Neck traumas were more likely admitted than head traumas (OR = 1.71). Fractures (OR = 2.21) and burns (OR = 2.71) demonstrated an increased admission likelihood than internal organ injuries. Polytrauma presence and admissions likelihood are site, injury, and substance dependent. Understanding the impact of factors influencing polytrauma presence or admission will enhance triage to optimize outcomes.
Primary Robotic Versus Conventional Laparoscopic Roux-en-Y Gastric Bypass in Morbidly Obese Patients: A Systematic Review and Meta-Analysis
Authors: Du Xiaoyu , Shen Liwen , Xu Shumei , Xu Wei , Yang Jiaxing , Liu Yichen , Li Kun , Fan Ruifang , Yan Long
Published: June 2024

Background:

Robotic Roux-en-Y gastric bypass (RRYGB) and conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) are commonly performed as primary bariatric procedures. The aim of this article was to assess the role of RRYGB in patients undergoing primary bariatric procedures.

Methods:

All of the qualified studies were selected from the PubMed, Embase, and Web of Science databases, etc. We mainly compared the outcomes and safety between RRYGB and LRYGB. The outcomes evaluation included surgical effect and surgical safety.

Result:

In total, 35 studies containing 426,463 patients were selected. The mortalities of patients adopting these 2 bariatric procedures were similar (RRYGB: 59/28,023, 0.21%; LRYGB: 612/397,945, 0.15%). We found no significant difference between RRYGB and LRYGB in the incidence of postoperative complications (30-day: OR=1.06, P=0.18; 1-y: OR=1.06, P=0.92). The incidence of 30-day readmission after the operation was higher in RRYGB patients (OR=1.24, P=0.003). However, we found that the RRYGB group had a lower incidence of anastomotic stricture 1 year after the operation when compared with LRYGB (OR=0.35, P=0.0004). The 1-year %EBMIL of these 2 groups was similar (78.53% vs. 76.02%). There was no significant difference in length of hospital stay (LOS) (WMD=−0.03d, P=0.59), conversion rate (OR=0.84, P=0.75), or anastomotic leak (OR=1.00, P=0.99) between these 2 groups. The mean hospital charges were higher in the RRYGB group ($11234.75 vs. $9468.58). 

Conclusion:

This systematic review and meta-analysis showed no significant advantage of RRYGB in surgical effect or reduction of intraoperative complications. RRYGB may reduce the incidence of some postoperative long-term complications. The mean hospital charges of RRYGB were higher.
Alterations in dynamic regional homogeneity within default mode network in patients with thyroid-associated ophthalmopathy
Authors: Lai Ping-Hong , Hu Rui-Yang , Huang Xin
Published: June 2024

Thyroid-associated ophthalmopathy (TAO) is a significant autoimmune eye disease known for causing exophthalmos and substantial optic nerve damage. Prior investigations have solely focused on static functional MRI (fMRI) scans of the brain in TAO patients, neglecting the assessment of temporal variations in local brain activity. This study aimed to characterize alterations in dynamic regional homogeneity (dReHo) in TAO patients and differentiate between TAO patients and healthy controls using support vector machine (SVM) classification. Thirty-two patients with TAO and 32 healthy controls underwent resting-state fMRI scans. We calculated dReHo using sliding-window methods to evaluate changes in regional brain activity and compared these findings between the two groups. Subsequently, we employed SVM, a machine learning algorithm, to investigate the potential use of dReHo maps as diagnostic markers for TAO. Compared to healthy controls, individuals with active TAO demonstrated significantly higher dReHo values in the right angular gyrus, left precuneus, right inferior parietal as well as the left superior parietal gyrus. The SVM model demonstrated an accuracy ranging from 65.62 to 68.75% in distinguishing between TAO patients and healthy controls based on dReHo variability in these identified brain regions, with an area under the curve of 0.70 to 0.76. TAO patients showed increased dReHo in default mode network-related brain regions. The accuracy of classifying TAO patients and healthy controls based on dReHo was notably high. These results offer new insights for investigating the pathogenesis and clinical diagnostic classification of individuals with TAO.
Differences in brain functional connectivity between tinnitus with or without hearing loss
Authors: Song Jianxiong , Wang Yuanyuan , Ouyang Fang , Zeng Xianjun , Yang Jian
Published: June 2024

To explore the differences in brain imaging in tinnitus with or without hearing loss (HL). We acquired functional MRI scans from 26 tinnitus patients with HL (tinnitus-HL), 24 tinnitus patients with no HL (tinnitus-NHL), and 26 healthy controls (HCs) matched by age and sex. The left and right thalamus were selected as seeds to study the endogenous functional connectivity (FC) of the whole brain, and its correlation with clinical indices was analyzed. Brain regions showing FC differences among the three groups included the Heschl gyrus (HES), right Hippocampus (HIP), right Amygdala (AMYG), left Calcarine fissure and surrounding cortex (CAL). Post hoc analysis showed that the thalamus-HIP connection and thalamus-lingual gyrus (LING) connection were enhanced in the tinnitus-NHL group, as compared to tinnitus-HL. Compared with HCs, the tinnitus-NHL group showed an enhanced connection between the thalamus and the left Inferior occipital gyrus, left CAL and LING. While in the tinnitus-HL group, the connection between the thalamus and several brain regions (right HES, right AMYG, etc) was weakened. In the tinnitus-HL group, the tinnitus handicap inventory scores were positively correlated with the FC of the left thalamus and right HES, right thalamus and right Rolandic operculum. The duration of tinnitus was negatively correlated with the FC of the right thalamus and right HIP. Abnormal FC in the thalamus may play an important role in the pathogenesis of tinnitus. Tinnitus-NHL and tinnitus-HL show different connection patterns, indicating that there are some differences in their pathogenesis.
Connectome-based prediction of cognitive performance in patients with temporal lobe epilepsy
Authors: Qin Lu , Pan Liya , Chen Zirong , Zhou Qin , Zhou Xia , Zheng Jinou
Published: June 2024

Objective

Temporal lobe epilepsy (TLE) patients often exhibit varying degrees of cognitive impairments. This study aims to predict cognitive performance in TLE patients by applying a connectome-based predictive model (CPM) to whole-brain resting-state functional connectivity (RSFC) data.

Methods

A CPM was established and leave-one-out cross-validation was employed to decode the cognitive performance of patients with TLE based on the whole-brain RSFC.

Results

Our findings indicate that cognitive performance in TLE can be predicted through the internal and network connections of the parietal lobe, limbic lobe, and cerebellum systems. These systems play crucial roles in cognitive control, emotion processing, and social perception and communication, respectively. In the subgroup analysis, CPM successfully predicted TLE patients with and without focal to bilateral tonic–clonic seizures (FBCTS). Additionally, significant differences were noted between the two TLE patient groups and the normal control group.

Conclusion

This data-driven approach provides evidence for the potential of predicting brain features based on the inherent resting-state brain network organization. Our study offers an initial step towards an individualized prediction of cognitive performance in TLE patients, which may be beneficial for diagnosis, prognosis, and treatment planning.
Atrial Fibrillation Following Electroconvulsive Therapy
Authors: Baroni Mariana , Albaba Dania , Ngo Alexandra , Livingston Robin K.
Published: June 2024

Electroconvulsive therapy (ECT) is considered the gold standard treatment for many psychiatric illnesses; however, it is not without risk. There have been no systematic reviews to date on new-onset atrial fibrillation following ECT. Thus, the aim of this study is to identify reported occurrences of new-onset atrial fibrillation following ECT and the ability to safely resume ECT thereafter.

A case pertaining to the development of atrial fibrillation after ECT in a young healthy male is presented. In addition, a systematic review of the literature pertaining to atrial fibrillation after ECT was conducted through PubMed, PsycInfo, and EMBASE. Of the 233 articles screened, 15 articles were selected for in-depth review. Of the 15 articles, only 10 articles met inclusion criteria. These articles included 9 case reports and 1 retrospective review. The retrospective review included 1 patient that developed atrial fibrillation out of 13 patients receiving ECT at the site. The 10 patients included varied in age, risk factors, type of ECT conducted, and treatment of the atrial fibrillation. Of the 4 articles that discussed outcomes, all patients were able to return to ECT without further complications.

There are many potential reasons ECT may induce atrial fibrillation, and there are additional treatment considerations for atrial fibrillation in patients receiving ECT. Notably, our results indicate that many have been able to continue ECT without further complications; however, more research is needed to identify the frequency of this adverse reaction.
The mod-minimizer: a simple and efficient sampling algorithm for longk-mers
Authors: Koerkamp Ragnar Groot , Pibiri Giulio Ermanno
Published: June 2024

Motivation

Given a stringS, aminimizerscheme is an algorithm defined by a triple (k, w, 𝒪) that samples a subset ofk-mers (k-long substrings) from a stringS. Specifically, it samples the smallestk-mer according to the order 𝒪 from each window ofwconsecutivek-mers inS. Because consecutive windows can sample the samek-mer, the set of the sampledk-mers is typically much smaller thanS. More generally, we consider substring sampling algorithms that respect awindow guarantee: at least onek-mer must be sampled from every window ofwconsecutivek-mers. As a sampledk-mer is uniquely identified by its absolute position inS, we can define thedensityof a sampling algorithm as the fraction of distinct sampled positions. Good methods have low density which, by respecting the window guarantee, is lower bounded by 1/w. It is however difficult to design a sequence-agnostic algorithm with provably optimal density. In practice, the order 𝒪 is usually implemented using a pseudo-random hash function to obtain the so-calledrandomminimizer. This scheme is simple to implement, very fast to compute even in streaming fashion, and easy to analyze. However, its density is almost a factor of 2 away from the lower bound for large windows.

Methods

In this work we introducemod-sampling, a two-step sampling algorithm to obtain new minimizer schemes. Given a (small) parametert, the mod-sampling algorithm finds the positionpof the smallestt-mer in a window. It then samples thek-mer at positionpmodw. Thelr-minimizerusest=k − wand themod-minimizerusest ≡ k(modw).

Results

These new schemes have provably lower density than random minimizers and other schemes whenkis large compared tow, while being as fast to compute. Importantly, the mod-minimizer achieves optimal density whenk → ∞. Although the mod-minimizer is not the first method to achieve optimal density for largek, its proof of optimality is simpler than previous work.

We provide pseudocode for a number of other methods and compare to them. In practice, the mod-minimizer has considerably lower density than the random minimizer and other state-of-the-art methods, like closed syncmers and miniception, whenk > w. We plugged the mod-minimizer into SSHash, ak-mer dictionary based on minimizers. For default parameters (w, k) = (11, 21), space usage decreases by 15% when indexing the whole human genome (GRCh38), while maintaining its fast query time.

2012 ACM Subject Classification

Theory of computation → Sketching and sampling; Applied computing → Bioinformatics

Digital Object Identifier

10.4230/LIPIcs.WABI.2024.11

Supplementary Material

Software (C++): github.com/jermp/minimizers

Software (Rust): github.com/RagnarGrootKoerkamp/minimizers

Funding

Ragnar Groot Koerkamp: ETH Research Grant ETH-1721-1 to Gunnar Rätsch.Giulio Ermanno Pibiri: European Union’s Horizon Europe research and innovation programme (EFRA project, Grant Agreement Number 101093026). This work was also partially supported by DAIS – Ca’ Foscari University of Venice within the IRIDE program.
BakRep – A searchable large-scale web repository for bacterial genomes, characterizations and metadata
Authors: Fenske Linda , Jelonek Lukas , Goesmann Alexander , Schwengers Oliver
Published: June 2024

Bacteria are fascinating research objects in many disciplines for countless reasons, and whole-genome sequencing has become the paramount methodology to advance our microbiological understanding. Meanwhile, access to cost-effective sequencing platforms has accelerated bacterial whole-genome sequencing to unprecedented levels introducing new challenges in terms of data accessibility, computational demands, heterogeneity of analysis workflows, and thus, ultimately its scientific usability. To that end,Blackwell et al. released a uniformly processed set of 661,405 bacterial genome assemblies obtained from the European Nucleotide Archive as of November 2018. Building on these accomplishments, we conducted further genome-based analyses like taxonomic classification, MLST subtyping and annotation of all genomes. Here we present BakRep, a searchable large-scale web repository of these genomes enriched with consistent genome characterizations and original metadata. The platform provides a flexible search engine combining taxonomic, genomic and metadata information, as well as interactive elements to visualize genomic features. Furthermore, all results can be downloaded for offline analyses via an accompanying command line tool. The web repository is accessible viahttps://bakrep.computational.bio.
Evolutionary rescue of bacterial populations by heterozygosity on multicopy plasmids
Authors: Dewan Ian , Uecker Hildegard
Published: June 2024

Bacterial plasmids and other extrachromosomal DNA elements frequently carry genes with important fitness effects for their hosts. Multicopy plasmids can additionally carry distinct alleles of host-fitness-relevant genes on different plasmid copies, allowing for heterozygosity not possible for loci on haploid chromosomes. Plasmid-mediated heterozygosity may increase the fitness of bacterial cells in circumstances where there is an advantage to having multiple distinct alleles (heterozyogote advantage); however, plasmid-mediated heterozygosity is also subject to constant loss due to random segregation of plasmid copies on cell division. We analyze a multitype branching process model to study the evolution and maintenance of plasmid-mediated heterozygosity under a heterozygote advantage. We focus on an evolutionary rescue scenario in which a novel mutant allele on a plasmid must be maintained together with the wild-type allele to allow population persistance (although our results apply more generally to the maintenance of heterozygosity due to heterozygote advantage). We determine the probability of rescue and derive an analytical expression for the threshold on the fitness of heterozygotes required to overcome segregation and make rescue possible; this threshold decreases with increasing plasmids copy number. We further show that the formation of cointegrates from the fusion of plasmid copies increases the probability of rescue. Overall, our results provide a rigorous quantitative assessment of the conditions under which bacterial populations can adapt to multiple stressors through plasmid-mediated heterozygosity. Many of the results are furthermore applicable to the related problem of the maintenance of incompatible plasmids in the same cell under selection for both.

MSC Classification

92D15, 60J85
Pangenome graph analysis reveals extensive effector copy-number variation in spinach downy mildew
Authors: Skiadas Petros , Vidal Sofía Riera , Dommisse Joris , Mendel Melanie N. , Elberse Joyce , Van den Ackerveken Guido , de Jonge Ronnie , Seidl Michael F.
Published: June 2024

Plant pathogens adapt at speeds that challenge contemporary disease management strategies like the deployment of disease resistance genes. The strong evolutionary pressure to adapt, shapes pathogens’ genomes, and comparative genomics has been instrumental in characterizing this process. With the aim to capture genomic variation at high resolution and study the processes contributing to adaptation, we here leverage and expand on an innovative, multi-genome method to construct, annotate, and analyse the first pangenome graph of an oomycete plant pathogen. We generated telomere-to-telomere genome assemblies of six genetically diverse isolates of the oomycete pathogenPeronospora effusa, the economically most important disease in cultivated spinach worldwide. The pangenome graph demonstrates thatP. effusagenomes are highly conserved, both in chromosomal structure and gene content, and revealed the continued activity of transposable elements which are directly responsible for 80% of the observed variation between the isolates. While most genes are generally conserved, pathogenicity related genes are highly variable between the isolates. Most of the variation is found in large gene clusters resulting from extensive copy-number expansion. Pangenome graph-based discovery can thus be effectively used to capture genomic variation at exceptional resolution, thereby providing a framework to study the biology and evolution of plant pathogens.

Author Summary

Plant pathogens are known to evolve rapidly and overcome disease resistance of newly introduced crop varieties. This swift adaptation is visible in the genomes of these pathogens, which can be highly variable. Such genomic variation cannot be captured with contemporary comparative genomic methods that rely on a single reference genome or focus solely on protein coding genes. To overcome these limitations and compare multiple genomes in a robust and scalable method, we constructed the first pangenome graph for an oomycete filamentous plant pathogen with six telomere-to-telomere genome assemblies ofPeronospora effusa. This high-resolution pangenomic framework enabled detailed comparisons of the genomes at any level, from the nucleotide to the chromosome, and for any subset of protein-coding genes or transposable elements, to discover novel biology and potential mechanisms for the rapid evolution of this devastating pathogen.
Raman mineral-to-matrix ratios correlate with weight percentage mineral-to-matrix ratio determined by in-SEM Raman imaging of bone tissue
Authors: Mabilleau Guillaume , Boorman Dale , Diniz Jorge
Published: June 2024

Raman imaging combined with scanning electron microscopy (SEM) is a powerful technique that allows for topographical, chemical and structural correlative multi-scale imaging. It provides the perfect tool to determine which of the Raman mineral-to-matrix ratios represent the best parameter to accurately measure the degree of mineralization of the bone matrix using quantitative backscattered electron imaging (qBEI) as the reference methodology. Indeed, previous studies evidenced that the v2PO4and v4PO4vibrational modes were less sensitive to laser polarization than the v1PO4. However, using the v2PO4or v4PO4requires a longer acquisition time or lower spectral resolution. In the present study, we evaluated the correlation between mineral-to-matrix ratios computed from v1PO4and v2PO4in a human bone sample retrieved from orthopaedic surgery during hip replacement and wt% mineral / wt% organic matrix obtained from qBEI using the inLux SEM Raman interface. We reported here that all mineral-to-matrix ratios were significantly linearly correlated with wt% mineral / wt% organic matrix and that v1PO4/CH2exhibited the strongest correlation coefficient (r=0.880). This study suggests that the v1PO4is still a valid Raman peak to estimate the mineral-to-matrix ratio in bone samples and can be used to diagnose bone fragility disorders.
Integrative epigenetics and transcriptomics identify aging genes in human blood
Authors: Moqri Mahdi , Poganik Jesse , Herzog Chiara , Ying Kejun , Chen Qingwen , Emamifar Mehrnoosh , Tyshkovskiy Alexander , Eames Alec , Mur Jure , Matei-Dediu Benyamin , Goeminne Ludger , Mitchell Wayne , Mccartney Daniel , Marioni Riccardo , Lasky-Su Jessica A. , Snyder Michael P. , Gladyshev Vadim N.
Published: June 2024

Recent epigenome-wide studies have identified a large number of genomic regions that consistently exhibit changes in their methylation status with aging across diverse populations, but the functional consequences of these changes are largely unknown. On the other hand, transcriptomic changes are more easily interpreted than epigenetic alterations, but previously identified age-related gene expression changes have shown limited replicability across populations. Here, we develop an approach that leverages high-resolution multi-omic data for an integrative analysis of epigenetic and transcriptomic age-related changes and identify genomic regions associated with both epigenetic and transcriptomic age-dependent changes in blood. Our results show that these “multi-omic aging genes” in blood are enriched for adaptive immune functions, replicate more robustly across diverse populations and are more strongly associated with aging-related outcomes compared to the genes identified using epigenetic or transcriptomic data alone. These multi-omic aging genes may serve as targets for epigenetic editing to facilitate cellular rejuvenation.
Ultra-high dose oralω3 docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) block tumorigenesis in aMYCN-driven neuroblastoma model
Authors: Patel Vishwa , Li Yan Ning , Benhamou Lorraine-Rana E. , Park Hui Gyu , Raleigh Mariya , Brenna J. Thomas , Powers John T.
Published: June 2024

Background/Objectives

Neuroblastoma is a genetically diverse, highly metastatic pediatric cancer accounting for 15% of childhood cancer deaths despite only having ~8% of childhood cancer incidence. The current standard of care for high-risk disease is highly genotoxic. This, combined with less than 50% survival in high-risk disease and an abysmal 5% survival in relapsed cases, makes discovering novel, effective, and less toxic treatments essential.

Methods

A prophylactic syngeneic mouse model was used to test high-dose lipid-mediator highly unsaturated fatty acids on tumorigenesis. Wild-type mice were gavaged with 12.3-14.6 g/d (adult human equivalent) omega-3 EPA, DHA, or oxidation-resistant bis allylic deuterated DHA (D-DHA) and 4.6-6.0 g/d arachidonic acid (ARA). At seven days,MYCN-expressing murine neuro-2a cells syngeneic to the gavaged mice were injected subcutaneously. Oral gavage continued for 10-20 d post-injection when tumors and tissues were harvested.

Results

Fifty percent of control (not gavaged) animals form tumors (4/8) at about 10 d. High-dose DHA, D-DHA, and EPA block tumor formation completely in n=8 or 10 animals. In contrast, ω6 arachidonic acid (4.6-6.0 g/d) enhances tumor formation (6/10 tumors) and reduces latency (5.5 to 10 days)compared to control. Co-delivery of ARA and EPA results in a reduced tumor burden analogous to the control group, suggesting that EPA directly opposes the mechanism of ARA-mediated tumor formation. DHA acts through a non-oxidative mechanism.

Conclusions

Sustained high dose ω3 (weeks/months) is safe and well tolerated in humans. These results suggest that ω3 DHA and EPA delivery at ultra-high doses may represent a viable low-toxicity therapy for neuroblastoma.

Simple Summary

Pediatric Neuroblastoma has an overall mortality rate above 50%, and the current standard of care consists of highly genotoxic compounds. The biological actions of omega-6 (ω6) and omega-3 (ω3) highly unsaturated fatty acids (HUFA) generally oppose one another with the ω6 HUFA signaling for inflammation and angiogenesis (new blood vessel formation). Prolonged use of ultrahigh dose (15-20 g/d) ω3 HUFA has shown efficacy in catastrophic human traumatic brain injury and is well tolerated. Tumors form in about 50% of mice in our pediatric neuro-blastoma model. We show that 12-14 g/d adult human equivalent doses of ω3 EPA or DHA, as well as an oxidation-resistant form of DHA (D-DHA), completely block tumor formation, whereas a dose of about 5 g/d of ω6 ARA enhances tumorigenesis. Our data suggest that ultra-high dose ω3 therapy should be carefully investigated as a low-toxicity approach to neuroblastoma intervention.
Plio-Pleistocene decline of mesic forest underpins diversification in a clade of AustralianPanesthiacockroaches
Authors: Adams Maxim W.D. , Walker James A. , Rose Harley A. , Jones Braxton R. , Zwick Andreas , Yang Huiming , Nicholls James , Hartley Diana , Bent Stephen , Carlile Nicholas , Hutton Ian , Ho Simon Y.W. , Lo Nathan
Published: June 2024

The progressive aridification of the Australian continent, and coincident decline of mesic forest, has been a powerful driver of allopatric and environmental speciation in native species. The relictual mesic forests of the eastern seaboard now harbor a diverse group of endemic fauna, including the wood-feeding cockroaches of the genusPanesthia, which reached the continent via two separate invasions from Melanesia. The more recent of these colonization events gave rise to a group of five recognized species, occurring in mainland woodlands, sclerophylls and rainforests, as well as the forests and grasslands of the Lord Howe Island Group. Due to limited sampling in molecular studies and doubt regarding the standing taxonomy, there is little certainty about relationships among the species and poor understanding of the effects of ancient climatic changes upon their evolution. We undertook a comprehensive phylogenetic analysis of the clade, using complete mitogenomes and nuclear ribosomal markers from nearly all known morphospecies and populations. Our time-calibrated phylogenetic analyses reveal six unrecognized, highly divergent lineages, and suggest that these have arisen primarily through vicariance as rainforests fragmented during Plio-Pleistocene glacial cycles (2–5 million years ago). Ancestral niche reconstructions also evidence a tropical rainforest origin for the group, followed by at least three niche transitions into drier forest, including one associated with the singular colonization of the Lord Howe Island Group. Finally, we find evidence of frequent, parallel wing reduction, in potential association with the contraction of forest habitats into small refugia. Our results reiterate the far-reaching role of ancient aridification in driving speciation, niche expansion and morphological evolution in Australian fauna.
Parental smoking and respiratory outcomes in young childhood cancer survivors
Authors: Žarković Maša , Sommer Grit , Nigg Carina , Sláma Tomáš , Schneider Christine , Ansari Marc , von der Weid Nicolas , Schindera Christina , Kuehni Claudia E
Published: June 2024

Background

Passive exposure to cigarette smoke has negative effects on respiratory health. Childhood cancer survivors (CCS) are at an increased risk for respiratory disease due to treatment regimens that may harm the respiratory system. The objective of this study was to assess the prevalence of parental smoking among CCS and investigate its association with respiratory outcomes.

Procedure

As part of the Swiss Childhood Cancer Survivor Study, between 2007 and 2022 we sent questionnaires to parents of children aged ≤16 years who had survived ≥ 5 years after cancer diagnosis. Parents reported on their children’s respiratory outcomes including recurrent upper respiratory tract infections (otitis media and sinusitis), asthma, and lower respiratory symptoms (chronic cough persisting > 3 months, current and exercise wheeze), and on parental smoking. We used multivariable logistic regression to investigate associations between parental smoking and respiratory outcomes.

Results

Our study included 1037 CCS (response rate 66%). Median age at study was 12 years (interquartile range [IQR] 10–14). Eighteen percent of mothers and 23% of fathers reported current smoking. CCS exposed to smoking mothers were more likely to have recurrent upper respiratory tract infections (OR 2.1; 95% CI 1.1–3.7) and lower respiratory symptoms (OR 2.0; 95%CI 1.1-3.7). We found no association with paternal smoking.

Conclusions

A substantial proportion of CCS in Switzerland have parents who smoke. Exposure to maternal smoking was associated with higher prevalence of upper and lower respiratory problems. Physicians should advise and assist families of CCS in their endeavors to quit smoking.
Complete spatiotemporal quantification of cardiac motion in mice through enhanced acquisition and super-resolution reconstruction
Authors: Mukherjee Tanmay , Keshavarzian Maziyar , Fugate Elizabeth M. , Naeini Vahid , Darwish Amr , Ohayon Jacques , Myers Kyle J. , Shah Dipan J. , Lindquist Diana , Sadayappan Sakthivel , Pettigrew Roderic I. , Avazmohammadi Reza
Published: June 2024

The quantification of cardiac motion using cardiac magnetic resonance imaging (CMR) has shown promise as an early-stage marker for cardiovascular diseases. Despite the growing popularity of CMR-based myocardial strain calculations, measures of complete spatiotemporal strains (i.e., three-dimensional strains over the cardiac cycle) remain elusive. Complete spatiotemporal strain calculations are primarily hampered by poor spatial resolution, with the rapid motion of the cardiac wall also challenging the reproducibility of such strains. We hypothesize that a super-resolution reconstruction (SRR) framework that leverages combined image acquisitions at multiple orientations will enhance the reproducibility of complete spatiotemporal strain estimation. Two sets of CMR acquisitions were obtained for five wild-type mice, combining short-axis scans with radial and orthogonal long-axis scans. Super-resolution reconstruction, integrated with tissue classification, was performed to generate full four-dimensional (4D) images. The resulting enhanced and full 4D images enabled complete quantification of the motion in terms of 4D myocardial strains. Additionally, the effects of SRR in improving accurate strain measurements were evaluated using an in-silico heart phantom. The SRR framework revealed near isotropic spatial resolution, high structural similarity, and minimal loss of contrast, which led to overall improvements in strain accuracy. In essence, a comprehensive methodology was generated to quantify complete and reproducible myocardial deformation, aiding in the much-needed standardization of complete spatiotemporal strain calculations.
A passage through India: the biotic ferry model supports the build-up of Indo-Australian biodiversity of an ancient soil arthropod clade
Authors: Manivannan Maya , Gurung Nehal , Edgecombe Gregory D , Joshi Jahnavi
Published: June 2024

Aim: Scutigeromorpha is a globally distributed, ancient group of centipedes with at least 400 million years of evolutionary history. We assess the biogeographic history of the order, with a particular focus on the Peninsular Indian Plate (PIP), a Gondwanan fragment. We hypothesize that continental vicariance explains the disjunct distribution of extant scutigeromorphs, that PIP scutigeromorphs are of ancient Gondwanan origins, and that East Gondwana vicariance explains the diversification of the subfamily Thereuoneminae into its Asian and Australian clades. Location: Global. Taxa: Centipedes, Scutigeromorpha. Methods: We use a novel molecular dataset sampled across the PIP and a global sequence database representing the geographic distribution of all families and subfamilies. We employ molecular phylogenetic analyses on two mitochondrial and three nuclear markers, molecular species delimitation and ancestral range estimation to reconstruct biogeographic history. Results: Ancestral scutigeromorphs were likely widely distributed across Gondwana and diverged prior to any continental vicariance. Scutigeromorph biogeography is shaped by continental vicariance, long-distance dispersal and jump dispersal, indicating an ability to colonize areas far from their ancestral range. The PIP emerged as the ancestral range of Thereuoneminae, which started diversifying during the Cretaceous Period. Subsequent in-situ diversification within the PIP and dispersals into Asia, Australia, and the Pacific Islands best explained the extant distribution of Thereuoneminae, more so than East Gondwana vicariance. Main conclusions: The in-situ diversification of PIP species and their ancient divergence suggest they represent Gondwanan relicts in a landmass whose biota is primarily dispersal-driven. A single dispersal event from the PIP generated most of the extant diversity in Australia, another Gondwanan fragment. Furthermore, the discovery of 11 putative species from the PIP and the Andaman Islands, five times more than was known, highlights the Wallacean and Linnean shortfalls in tropical Asia.