bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis between Side-to-end and End-to-end LVA for secondary lower limb lymphedema
Authors: Kwon Jin Geun , Jeong Seongsu , Pak Changsik John , Suh Hyunsuk Peter , Hong Joon Pio
Published: September 2022

Introduction

The purpose of this retrospective study is to describe, evaluate and compare the outcome between end-to-end (ETE) and side-to-end (STE) LVA for all stages of lymphedema.

Material and Method:

Total of 123 patients were divided into ETE (n=63) or STE (n=60) group. The demographics, intraoperative and postoperative findings were evaluated. In addition, subcategory evaluation was performed for early and advance phase lymphedema.

Result:

The demographic findings were insignificant. The intraoperative findings showed significantly higher number of LVAs performed for the ETE group (4.1±1.7) over the STE group (3.2±1.2) (p<0.001) while the number of different lymphatic vessels used per patients was not significant (3.4±1.4 vs 3.2±1.2, p=0.386). The diameter of the lymphatic vessels were not significant (0.43±0.06 vs 0.45±0.09mm, p=0.136). While both groups showed significant postoperative volume reduction, STE group had a significantly better reduction in all time intervals (p<0.03) and for longitudinal outcome (p=0.004). However, the subcategory evaluation for early phase patients showed no difference between the two groups while significantly better volume reduction ratio noted for the STE group at all time intervals (p<0.025) and overall longitudinal outcome (p=0.004) in advanced lymphedema patients.

Conclusion:

This is the first study to report the efficacy of ETE versus STE LVA in difference phases of lymphedema. Although both ETE and STE LVAs are significantly effective in volume reduction, there was a significantly better reduction for the STE group in advanced phase lymphedema patients with stage II late and III while no difference was noted for early phase lymphedema patients.
Cholecystectomy Increases the Risk of Type 2 Diabetes in the Korean Population
Authors: Huh Ji Hye , Lee Kyong Joo , Cho Yun Kyung , Moon Shinje , Kim Yoon Jung , Roh Eun , Han Kyung-do , Koh Dong Hee , Kang Jun Goo , Lee Seong Jin , Ihm Sung-Hee
Published: September 2022

Objective:

This study assessed whether cholecystectomy is a risk factor for newly developed type 2 diabetes mellitus (T2DM) in the Korean population.

Background:

There is a lack of evidence that cholecystectomy is independently associated with insulin resistance and T2DM.

Methods:

This study included all patients aged more than 20 years who had undergone cholecystectomy from 2010 to 2015 (n=55,166) and age-matched and sex-matched control subjects without cholecystectomy (n=110,332) using the National Health Insurance Service database. They were followed up until the date of newly developed T2DM or study end and the incidence of T2DM was traced over a maximum observation period of 7 years.

Results:

Overall, 55,166 patients who underwent cholecystectomy and 110,332 age-matched and sex-matched controls were followed up for ∼4.7 years, during which, incident T2DM occurred in 5982 (3.61%) patients. Cholecystectomy was associated with 20% higher risk of T2DM after adjustment for all covariates. The cumulative incidence of T2DM also significantly increased in the cholecystectomy group for ∼7 years (P<0.001). The adjusted hazard ratio (HR) for T2DM was the highest in the group with both cholecystectomy and obesity using the control without both cholecystectomy and obesity as a reference [HR=1.41, 95% confidence interval (CI): 1.29–1.56]. The group with cholecystectomy without obesity showed the comparable risk of incident T2DM compared with the group without cholecystectomy with obesity (HR=1.29, 95% CI: 1.20–1.40 for cholecystectomy without obesity and HR=1.24, 95% CI: 1.14–1.36 for control with obesity).

Conclusions:

These results provide evidence that cholecystectomy is associated with an increased risk of newly developed T2DM in the Korean population. Further research is required to elucidate the mechanism of the association between cholecystectomy and incident diabetes.
Operative Time is Associated With Postoperative Complications After Pulmonary Lobectomy
Authors: de Angelis Paolo , Tan Kay See , Chudgar Neel P. , Dycoco Joseph , Adusumilli Prasad S. , Bains Manjit S. , Bott Matthew J. , Downey Robert J. , Huang James , Isbell James M. , Molena Daniela , Park Bernard J. , Rusch Valerie W. , Sihag Smita , Jones David R. , Rocco Gaetano
Published: September 2022

Objective:

To investigate the association between operative time and postoperative outcomes.

Background:

The association between operative time and morbidity after pulmonary lobectomy has not been characterized fully.

Methods:

Patients who underwent pulmonary lobectomy for primary lung cancer at our institution from 2010 to 2018 were reviewed. Exclusion criteria included clinical stage ≥IIb disease, conversion to thoracotomy, and previous ipsilateral lung treatment. Operative time was measured from incision to closure. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with surgeon-level random effects.

Results:

In total, 1651 patients were included. The median age was 68 years (interquartile range, 61–74), and 63% of patients were women. Median operative time was 3.2 hours (interquartile range, 2.7–3.8) for all cases, 3.0 hours for open procedures, 3.3 hours for video-assisted thoracoscopies, and 3.3 hours for robotic procedures (P=0.0002). Overall, 488 patients (30%) experienced a complication; 77 patients (5%) had a major complication (grade ≥3), and 5 patients (0.3%) died within 30 days of discharge. On multivariable analysis, operative time was associated with higher odds of any complication [odds ratio per hour, 1.37; 95% confidence interval (CI), 1.20–1.57; P<0.0001] and major complication (odds ratio per hour, 1.41; 95% CI, 1.21–1.64; P<0.0001). Operative time was also associated with longer hospital length of stay (β, 1.09; 95% CI, 1.04–1.14; P=0.001).

Conclusions:

Longer operative time was associated with worse outcomes in patients who underwent lobectomy. Operative time is a potential risk factor to consider in the perioperative phase.
Resveratrol Treatment of Autism Spectrum Disorder—A Pilot Study
Authors: Marchezan Josemar , Deckmann Iohanna , da Fonseca Guilherme Cordenonsi , Margis Rogerio , Riesgo Rudimar , Gottfried Carmem
Published: September 2022

Objectives

Considering autism spectrum disorder (ASD) as a neurodevelopmental condition associated with immune system impairments, we aimed to evaluate the potential benefits, efficacy, tolerability, and safety of the anti-inflammatory, antioxidant, and neuroprotective trans-resveratrol (RSV) in behavioral impairments and in a set of 8 microRNAs (miR) related to the immune system in pediatric subjects with ASD.

Methods

This is an open-label pilot trial over a 3 months (90 days) study follow-up period designed to assess the effect of 200 mg/d RSV on 5 boys aged 10 to 13 (11.8 ± 1.1) years diagnosed with ASD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Results

The RSV treatment significantly reduced the Aberrant Behavior Checklist total score (P = 0.042) and Irritability (P = 0.041), with no alteration in Stereotypical Behavior (P = 0.066), Hyperactivity (P = 0.068), and Lethargy/Social Withdrawal (P = 0.078) subscales. On the Clinical Global Impression scale, 3 individuals showed marked improvement in behavior; one showed mild improvement, and the other had no changes. The RSV treatment increased the miR-195-5p (P = 0.043), an important modulator of targets related to inflammatory and immunological pathways. RSV administration did not present adverse effects and did not alter clinical laboratory results.

Conclusions

RSV is a safe molecule for administrating in the pediatric population, able to modulate behavior alterations and molecules associated with the immune system, becoming a promising therapeutic strategy for large-scale studies in ASD, to investigate both behavioral and molecular approaches.
Moraxella nasovis sp. nov., isolated from a sheep with respiratory disease
Authors: Li Fuxiang , Zhu Pei , Li Zhanhong , Zhao Wenhua , Gao Huafeng , Hong Qionghua , Song Jianling , Yang Shibiao
Published: September 2022

A novel Gram-stain-negative, aerobic, coccus-shaped bacteria, designated ZY201115T, was isolated from the nasal cavity of a sheep with respiratory disease in Yunnan Province, south-west China, and its taxonomic affiliation was studied by applying a polyphasic approach. The strain grew at 18–41 °C (optimum, 37 °C), at pH 6.0–9.0 (optimum, pH 8.0) and in 0.5–3.0% (w/v) NaCl (optimum, 1.0 % NaCl). Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain is affiliated to the genus

Moraxella

with highest similarity to

Moraxella bovis

ATCC 10900T (96.6 %). Phylogenomic analysis based on 811 single-copy genes also indicated that the strain represents a novel species in the genus

Moraxella

and formed a deep and separated clade with

Moraxella caviae

NCTC 10293T. The highest genomic orthologous average nucleotide identity and digital DNA–DNA hybridization values between the strain and the type strains in the genus

Moraxella

were 73.7% (

M. caviae

NCTC 10293T) and 25.3% (

Moraxella osloensis

CCUG 350T), respectively. The G+C content of the complete genome sequence was 42.1 mol%. The predominant fatty acids (>5 %) were C18:1 ω9c, C17:1 ω8c, C12:03OH and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The major polar lipids were phosphatidylglycerol, cardiolipin, monolysocardiolipin, phosphatidylethanolamine and hemibismonoacylglycerophosphate. The major respiratory quinone was CoQ-8. On the basis of the results of phylogenetic, phenotypic and chemotaxonomic characterizations, strain ZY201115T clearly represents a novel species of the genus

Moraxella

, for which the name Moraxella nasovis sp. nov. is proposed. The type strain is ZY201115T (=CCTCC AB 2021473T=CCUG 75922T).
The Association between Emotional Intelligence and Depression among Medical Students in Suez Canal University
Authors: El Garhy Nada M. , Hegazy Ghada , Shata Merna , Ibrahim Mohamed , Kariem Hadeel Abdel , Eleleedy Alaa , Magdy Soliman , Mohamed Kareem
Published: September 2022

Background

Emotional intelligence is defined as the capacity to be aware of, control, and express one’s emotions, and to handle interpersonal relationships judiciously and empathetically while depression is the loss of interest in daily activities that may be associated with altered dietary and sleep patterns, lowered self-esteem, feelings of guilt and worthlessness and recurrent thoughts of suicide.

Previous studies that assess depression among medical students show variable results, which makes it difficult to conclude whether depression rates are higher exclusively in medical students. Moreover, previous studies have shown that emotion management leads to less stress and may allow for adaptation by allowing subjects to induce a more positive mood and may even prevent development of a mal-adaptive emotional state.

Aim

To improve mental health of medical students by identifying and modifying risk factors that may contribute to its deterioration

Methods

Our sample size is 149 students which were picked by stratified random sampling, where stratification was done on gender and study year. Students’ names of all six years were collected and then split according to study year, each study year was further splitt into two groups of males and females, which were selected from, based on a computerized random sampling. Two questionnaires were used; “Trait Emotional Intelligence Questionnaire” (TEIQue) developed by K. V. Petrides, PhD, for emotional intelligence and Beck’s Inventory for depression measurement.

Results

Our sample is composed of 82 (response rate is 55%) students. Depression prevalence in our sample is 39%. And it significantly correlated negatively with emotional intelligence, where the most significant factor is well-being.

Conclusion

Stressful lifestyle of medical students and lack of extracurricular activities and skill training programs lead to lowered emotional intelligence levels and depression. We recommend that their should be psychiatric counselling available for medical students, to lower depression prevalence among them, and introduce to curriculum life skill training programs to increase levels of emotional intelligence. We also recommend further studies about risks and causes of depression in Suez Canal University medical students to lower its prevalence, contributing to a better quality of life for the future physicians and thus of the patients.
bootRanges: Flexible generation of null sets of genomic ranges for hypothesis testing
Authors: Mu Wancen , Davis Eric , Lee Stuart , Dozmorov Mikhail , Phanstiel Douglas H. , Love Michael I.
Published: September 2022

bootRanges provides fast functions for generation of bootstrapped genomic ranges representing the null sets in enrichment analysis. We show that shuffling or permutation schemes may result in overly narrow test statistics null distributions, while creating new ranges sets with a block bootstrap preserves local genomic correlation structure and generates more reliable null distributions. It can also be used in more complex analyses, such as accessing correlations between cis-regulatory elements (CREs) and genes across cell types or providing optimized thresholds, e.g. log fold change (logFC) from differential analysis. The bootRanges functions are available in the R/Bioconductor package nullranges at https://bioconductor.org/packages/nullranges.
Multichannel neural spike sorting with spike reduction and positional feature
Authors: Mohammadi Zeinab , Denman Daniel , Klug Achim , Lei Tim C.
Published: September 2022

Sorting neural voltages measured from a multichannel neural probe to extract the single unit activities of neuronal firing, especially in real-time, remains a significant technical challenge, largely due to the large amount of acquired data and the technical difficulties involved in processing and classifying these neural spikes promptly. Most neural spike sorting algorithms focus on sorting neural spikes post hoc for high sorting accuracy, and reducing the processing time generally is not the chief concern. Here we report on two signal processing modifications to our previously developed single-channel real-time spike sorting (Enhanced Growing Neural Gas) algorithm, which is largely based on graph network. Duplicated neural spikes were eliminated and represented by the neural spike with the strongest signal profile, significantly reducing the amount of neural data to be processed. In addition, the channel from which the representing neural spike was recorded was used as an additional feature to differentiate between neural spikes recorded from different neurons having similar temporal features. With these two modifications, the Graph nEtwork Multichannel (GEMsort) neural spike sorting algorithm can rapidly sort neural spikes without requiring significant computer processing power and system memory storage. The parallel processing architecture of GEMsort is particularly suitable for digital hardware implementation to improve processing speed and recording channel scalability. Multichannel synthetic neural spikes and actual neural recordings with Neuropixels probes were used to evaluate the sorting accuracies of the GEMsort algorithm.
Anxiety-like behaviors in mice unmasked: Revealing sex differences in anxiety using a novel light-heat conflict test
Authors: Lee Sydney E. , Park Sung-Hoon , Aldrich John C. , Fonken Laura K. , Gaudet Andrew D.
Published: September 2022

Anxiety and chronic pain afflict hundreds of millions worldwide. Both anxiety and pain are more prevalent in females compared to males. Unfortunately, robust sex differences in human anxiety are not recapitulated in rodent tests, and results from rodent pain studies frequently fail to translate clinically. Therefore, there is a need to develop tests that reflect the differential salience of anxiety or pain-related stimuli between the sexes. Accordingly, here we introduce the Thermal Increments Dark-Light (TIDAL) conflict test. The TIDAL test places an anxiety-relevant stimulus (dark vs. illuminated chamber) in conflict with a heat-related stimulus (incrementally heated vs. isothermic chamber); mice freely explore the dark-heating and illuminated-isothermic chambers. Here, we aim to determine whether the TIDAL conflict test reveals in mice underappreciated sex differences in anxiety and/or heat sensitivity. We establish in four distinct experiments that females on the TIDAL conflict test persist substantially longer on the dark-heated plate, suggesting that females as compared to males exhibit elevated anxiety-like behavior. Mice more strongly prefer the dark plate on the TIDAL conflict test compared to control thermal place preference with both chambers illuminated. We also reveal that an anxiety-relieving drug, paroxetine, reduces mouse preference for the heating dark plate, supporting the validity of the TIDAL test. Therefore, our new TIDAL conflict test reliably unmasks the relative salience of anxiety (vs. heat sensitivity): mice that are female exhibit robust anxiety-like behaviors not consistently observed in classical tests. Future studies should incorporate TIDAL and other conflict tests to better understand rodent behavior and to identify mechanisms underlying anxiety and pain.
Predicting predator-prey interactions in terrestrial endotherms using random forest
Authors: Llewelyn John , Strona Giovanni , Dickman Christopher R. , Greenville Aaron C. , Wardle Glenda M. , Lee Michael S. Y. , Doherty Seamus , Shabani Farzin , Saltré Frédérik , Bradshaw Corey J. A.
Published: September 2022

Species interactions play a fundamental role in ecosystems. However, few ecological communities have complete data describing such interactions, which is an obstacle to understanding how ecosystems function and respond to perturbations. Because it is often impractical to collect empirical data for all interactions in a community, various methods have been developed to infer interactions. Machine learning is increasingly being used for making interaction predictions, with random forest being one of the most frequently used of these methods. However, performance of random forest in inferring predator-prey interactions in terrestrial vertebrates and its sensitivity to training data quality remain untested. We examined predator-prey interactions in two diverse, primarily terrestrial vertebrate classes: birds and mammals. Combining data from a global interaction dataset and a specific community (Simpson Desert, Australia), we tested how well random forest predicted predator-prey interactions for mammals and birds using species’ ecomorphological and phylogenetic traits. We also tested how variation in training data quality—manipulated by removing records and switching interaction records to non-interactions—affected model performance. We found that random forest could predict predator-prey interactions for birds and mammals using ecomorphological or phylogenetic traits, correctly predicting up to 88% and 67% of interactions and non-interactions in the global and community-specific datasets, respectively. These predictions were accurate even when there were no records in the training data for focal species. In contrast, false non-interactions for focal predators in training data strongly degraded model performance. Our results demonstrate that random forest can identify predator-prey interactions for birds and mammals that have few or no interaction records. Furthermore, our study provides guidance on how to prepare training data to optimise machine-learning classifiers for predicting species interactions, which could help ecologists (i) address knowledge gaps and explore network-related questions in data-poor situations, and (ii) predict interactions for range-expanding species.
Spring growth variation in pioneer and fibrous roots inAbies sachalinensisseedlings from provenances with contrasting snow cover environments
Authors: Sugai Tetsuto , Ishizuka Wataru , Masumoto Taiga , Endo Izuki , Ide Jun’ichiro , Fujita Saki , Kobayashi Makoto , Makita Naoki
Published: September 2022

Premise of research

In boreal forests with various snow cover conditions, local adaptation can be expected in spring root exploration due to soil freezing or competition for the fundamental niche. However, few studies have investigated the adaptive strategies for acquiring soil space and resources after snow thawing. To get insights for the eco-evolutional significance of root growth dynamics in boreal regions, this study evaluated the intraspecific variation of morphology and structures in pioneer roots and fibrous roots.

Methodology

Validation model specie wasAbies sachalinensis, a representative boreal conifer species with local adaptation. Five-year-old seedlings derived from an eastern provenance with low snow cover and a northern provenance with high snow cover were grown for two years in a common garden of high snow cover region. To predict spring growth patterns of roots, seedlings were dug up in early spring just after snow thawing and late spring after one month has passed. Pioneer roots exploring soil space and fibrous roots acquiring soil resource were respectively collected, and their functions were evaluated by morphology and structures indicating its construction costs and maturity.

Pivotal results

In pioneer roots, morphological and structural difference between sampling months were significant only in northern provenance, and high construction cost and well-developed structure were observed in early spring. This represents the intraspecific variation in reaction norms of pioneer roots to spring soil environment, indicating the soil space exploration in northern provenance may start in early spring or earlier. In fibrous roots, differences of specific root length and area between sampling months were significant only in eastern provenance, and low construction cost were observed in early spring. This may reflect the plastic responses of fibrous roots to the condition of high snow cover region.

Conclusions

This study indicated that local adaptation to contrasting snow cover condition may lead to the differentiation of spring root growth dynamics for the competitive or conservative strategies. Our results address better understandings of the mechanisms of niche acquisition in evergreen conifer.
Relationship between social support and resilience among nurses: a systematic review
Authors: Galanis Petros , Katsiroumpa Aglaia , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Katsoulas Theodoros , Kaitelidou Daphne
Published: September 2022

Background

High levels of stress and anxiety in nurses negatively affect their physical and mental health and lead to poor job performance, limited job satisfaction, high levels of burnout and increased intention to leave the profession. By promoting resilience in nurses it is possible to reduce negative consequences for those working in highly stressful workplaces.

Objective

To summarize the evidence about the relationship between social support and resilience among nurses.

Methods

We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Pubmed, Medline, Scopus, Web of Science, and Cinahl from inception to August 28, 2022 using the following search strategy in all fields: ((resilience) AND (“social support”)) AND (nurses).

Results

Applying the inclusion criteria, we found six studies that investigated the relationship between social support and resilience among nurses. Two studies were conducted in China, two studies in Turkey, one study in Haiti, and one study in Taiwan. All studies were cross-sectionals and used convenience samples. All studies found a positive relationship between social support and resilience among nurses. In studies that used multivariable analysis, coefficient beta ranged from 0.13 to 0.69, while in studies that used correlation analysis, correlation coefficient ranged from 0.18 to 0.37.

Conclusions

We found that social support improves resilience among nurses. It is necessary to make systematic efforts to support nurses especially in the workplace. This need is even greater for inexperienced nurses, as it is more difficult for them to cope effectively with the difficulties of the profession. A harmonious working environment is essential to reduce the psychological pressure of nurses and improve job performance.
The Cilialyzer – a freely available open-source software for a standardised identification of impaired mucociliary activity facilitating the diagnostic testing for PCD
Authors: Schneiter Martin , Tschanz Stefan A. , Müller Loretta , Frenz Martin
Published: September 2022

Background and Objective

Primary ciliary dyskinesia (PCD) is a rare genetic disorder causing a defective ciliary structure, which predominantly leads to an impaired mucociliary clearance and associated airway disease. As there is currently no single diagnostic gold standard test, PCD is diagnosed by a combination of several methods comprising genetic testing and the examination of the ciliary structure and function. Among the approved diagnostic methods, only high-speed video microscopy (HSVM) allows to directly observe the ciliary motion and therefore, to directly assess ciliary function. In the present work, we present our recently developed freely available open-source software – termed “Cilialyzer”, which has been specifically designed to support and facilitate the analysis of the mucociliary activity in respiratory epithelial cells captured by high-speed video microscopy.

Methods

In its current state, the Cilialyzer software enables clinical PCD diagnosticians to load, preprocess and replay the image sequences with a feature-rich replaying module facilitating the commonly performed qualitative visual assessment of ciliary function. The image processing methods made accessible through an intuitive user interface allow clinical specialists to comfortably compute the ciliary beating frequency (CBF), the activity map and the “frequency correlation length” – an observable getting newly introduced. Furthermore, the Cilialyzer contains a simple-to-use particle tracking interface to determine the mucociliary transport speed.

Results

The Cilialyzer is fully written in the Python programming language and freely available under the terms of the MIT license. The proper functioning of the computational analysis methods constituting the Cilialyzer software is demonstrated by using simulated and representative sample data from clinical practice.

Conclusions

The Cilialyzer serves as a useful clinical tool for standardised PCD diagnostics and provides new quantitative information awaiting to be clinically evaluated using cohorts of PCD. As the Cilialyzer is freely available under the terms of a permissive open-source license, it serves as a ground frame for further development of computational methods aiming at the quantification and automation of the analysis of mucociliary activity captured by HSVM.
Ingres: from single-cell RNA-seq data to single-cell probabilistic Boolean networks
Authors: Victori Pedro , Buffa Francesca M.
Published: September 2022

Motivation

The current explosion of ’omics data has provided scientists with an unique opportunity to elucidate the inner workings of biological processes that remained opaque. For this, computational models are essential. Gene regulatory networks (GRN) have long been used as a way to integrate heterogeneous data into a discrete model, and are very useful to generate actionable hypotheses on the mechanisms governing these biological processes. Boolean networks are particularly popular for this kind of discrete models. When working with single-cell RNA-seq datasets a main focus of analysis is the differential expression between subpopulations of cells. Boolean networks are limited in this task, since they cannot easily represent different levels of expression, confined as they are to binary states. We set out to develop an algorithm that can fit Boolean networks with this kind of data, maintaining both the heterogeneity of the data and the simplicity and computational efficiency of these type of networks.

Results

Here we present Ingres (Inferring Probabilistic Boolean Networks of Gene Regulation Using Protein Activity Enrichment Scores) an open-source tool that uses single-cell sequencing data and prior knowledge GRNs to produce a probabilistic Boolean network (PBN) per each cell and/or cluster of cells in the dataset. Ingres allows to better capture the differences between cell phenotypes, using a continuous measure of protein activity while still confined to the simplicity of a GRN. We believe Ingres will be useful to better understand the heterogeneous makeup of cell populations, to gain insight into the specific circuits that drive certain phenotypes, and to use expression and other omics to infer computational cellular models in bulk or single-cell data.

Availability and implementation

Ingres has been implemented as an R package, and it is publicly available at https://github.com/CBigOxf/ingres. It is currently being submitted to the public repository CRAN too. works seamlessly with existing software for single-cell RNA-seq analysis, and for network analysis, modelling and visualization.

Contact

pedro.victori@oncology.ox.ac.uk; francesca.buffa@unibocconi.it; francesca.buffa@imm.ox.ac.uk

Supplementary information

Supplementary data are available online. Software documentation and an explanatory vignette are available on GitHub and as part of the R package.
Twenty-seven ZAD-ZNF genes of Drosophila melanogaster are orthologous to the embryo polarity determining mosquito gene cucoid
Authors: Li Muzi , Kasan Koray , Saha Zinnia , Yoon Yoseop , Schmidt-Ott Urs
Published: September 2022

The C2H2 zinc finger gene cucoid establishes anterior-posterior (AP) polarity in the early embryo of culicine mosquitoes. This gene is unrelated to genes that establish embryo polarity in other fly species (Diptera), such as the homeobox gene bicoid, which serves this function in the traditional model organism Drosophila melanogaster. The cucoid gene is a conserved single copy gene across lower dipterans but nothing is known about its function in other species, and its evolution in higher dipterans, including Drosophila, is unresolved. We found that cucoid is a member of the ZAD-containing C2H2 zinc finger (ZAD-ZNF) gene family and is orthologous to 27 of the 91 members of this family in D. melanogaster, including M1BP, ranshi, ouib, nom, zaf1, odj, Nnk, trem, Zif, and eighteen uncharacterized genes. Available knowledge of the functions of cucoid orthologs in Drosophila melanogaster suggest that the progenitor of this lineage specific expansion may played a role in regulating chromatin. We also describe many aspects of the gene duplication history of cucoid in the brachyceran lineage of D. melanogaster, thereby providing a framework for predicting potential redundancies among these genes in D. melanogaster.
The influence of genetic structure on phenotypic diversity in the Australian mango (Mangifera indica) gene pool
Authors: Wilkinson Melanie J. , Yamashita Risa , James Maddie E. , Bally Ian S.E. , Dillon Natalie L. , Ali Asjad , Hardner Craig M. , Ortiz-Barrientos Daniel
Published: September 2022

Genomic selection is a promising breeding technique for tree crops to accelerate the development of new cultivars. However, factors such as genetic structure can create spurious associations between genotype and phenotype due to the shared history between populations with different trait values. Genetic structure can therefore reduce the accuracy of the genotype to phenotype map, a fundamental requirement of genomic selection models. Here, we employed 272 single nucleotide polymorphisms from 208 Mangifera indica cultivars to explore whether the genetic structure of the Australian mango gene pool explained variation in tree size, fruit blush colour and intensity. Our results show that genetic structure is weak, but cultivars imported from Southeast Asia (mainly those from Thailand) were genetically differentiated across multiple population genetic analyses. We find that genetic structure was strongly associated with phenotypic diversity in M. indica, suggesting that the history of these cultivars could drive spurious associations between loci and key mango phenotypes in the Australian mango gene pool. Incorporating such genetic structure in associations between genotype and phenotype has the potential to improve the accuracy of genomic selection, which can assist the development of new cultivars.
Distinct immune signatures discriminate SARS-CoV-2 vaccine combinations
Authors: Núñez Nicolás Gonzalo , Schmid Jonas , Power Laura , Alberti Chiara , Krishnarajah Sinduya , Kreutmair Stefanie , Unger Susanne , Blanco Sebastián , Konigheim Brenda , Marín Constanza , Onofrio Luisina , Kienzler Jenny Christine , Costa Pereira Sara da , Ingelfinger Florian ,   InmunoCovidCba,   InViV working group, Pasinovich Marina E. , Castelli Juan M , Vizzotti Carla , Schaefer Maximilian , Villar-Vesga Juan , Merten Carla Helena , Sethi Aakriti , Wertheimer Tobias , Lutz Mirjam , Vanoaica Danusia , Sotomayor Claudia , Gruppi Adriana , Münz Christian , Cardozo Diego , Barbás Gabriela , Lopez Laura , Carreño Paula , Castro Gonzalo , Raboy Elias , Gallego Sandra , Morón Gabriel , Cervi Laura , Acosta Rodriguez Eva V , Maletto Belkys A , Maccioni Mariana , Becher Burkhard
Published: September 2022

Several vaccines have been found effective against COVID-19, usually administered in homologous regimens, with the same vaccine used for the prime and boost doses. However, recent studies have demonstrated improved protection via heterologous mix-and-match COVID-19 vaccine combinations, and a direct comparison among these regimens is needed to identify the best employment strategies. Here, we show a single-cohort comparison of changes to the humoral and cellular immune compartments following five different COVID-19 vaccines spanning three technologies (adenoviral, mRNA and inactivated vaccines). These vaccines were administered in a combinatorial fashion, resulting in sixteen different homologous and heterologous regimens. SARS-CoV-2-targeting antibody titres were highest when the boost dose consisted of mRNA-1273, independent of the vaccine used for priming. Priming with BBIBP-CorV induced less class-switching among spike-binding memory B cells and the highest antigen-specific T cell responses in heterologous combinations. These were generally more immunogenic in terms of specific antibodies and cellular responses compared to homologous regimens. Finally, single-cell analysis of 754 samples revealed specific B and T cell signatures of the vaccination regimens, indicating distinctive differences in the immune responses. These data provide new insights on the immunological effects of COVID-19 vaccine combinations and a framework for the design of improved vaccination strategies for other pathogens and cancer.
Persistent somatic symptoms are key to individual illness perception at one year after COVID-19
Authors: Hüfner Katharina , Tymoszuk Piotr , Sahanic Sabina , Luger Anna , Boehm Anna , Pizzini Alex , Schwabl Christoph , Koppelstätter Sabine , Kurz Katharina , Asshoff Malte , Mosheimer-Feistritzer Birgit , Pfeifer Bernhard , Rass Verena , Schroll Andrea , Iglseder Sarah , Egger Alexander , Wöll Ewald , Weiss Günter , Helbok Raimund , Widmann Gerlig , Sonnweber Thomas , Tancevski Ivan , Sperner-Unterweger Barbara , Löffler-Ragg Judith
Published: September 2022

Background

Sequelae of Coronavirus disease 2019 (COVID-19) were investigated by both patient-initiated and academic initiatives. Patient’s subjective illness perceptions might differ from physician’s clinical assessment results. Herein, we explored factors influencing patient’s perception during COVID-19 recovery.

Methods

Participants of the prospective observation CovILD study with persistent somatic symptoms or cardiopulmonary findings at the clinical follow-up one year after COVID-19 were analyzed (n = 74). Explanatory variables included baseline demographic and comorbidity data, COVID-19 course and one-year follow-up data of persistent somatic symptoms, physical performance, lung function testing (LFT), chest computed tomography (CT) and trans-thoracic echocardiography (TTE). Factors affecting illness perception (Brief Illness Perception Questionnaire, BIPQ) were identified by penalized multi-parameter regression and unsupervised clustering.

Results

In modeling, 47% of overall illness perception variance at one year after COVID-19 was attributed to fatigue intensity, reduced physical performance, hair loss and baseline respiratory comorbidity. Overall illness perception was independent of LFT results, pulmonary lesions in CT or heart abnormality in TTE. As identified by clustering, persistent somatic symptom count, fatigue, diminished physical performance, dyspnea, hair loss and sleep problems at the one-year follow-up and severe acute COVID-19 were associated with the BIPQ domains of concern, emotional representation, complaints, disease timeline and consequences.

Conclusion

Persistent somatic symptoms rather than clinical assessment results, revealing lung and heart abnormalities, impact on severity and quality of illness perception at one year after COVID-19 and may foster unhelpful coping mechanisms. Besides COVID-19 severity, individual illness perception should be taken into account when allocating rehabilitation and psychological therapy resources.

Study registration

ClinicalTrials.gov: NCT04416100.
Differences in maternally inherited and age-related de novo mitochondrial DNA variants between ART and spontaneously conceived individuals associate with low birth weight
Authors: Mertens Joke , Belva Florence , van Montfoort Aafke P.A. , Zambelli Filippo , Seneca Sara , de Deckersberg Edouard Couvreu , Bonduelle Maryse , Tournaye Herman , Stouffs Katrien , Barbé Kurt , Smeets Hubert , Van de Velde Hilde , Sermon Karen , Blockeel Christophe , Spits Claudia
Published: September 2022

Background

Children born using assisted reproductive technologies (ART) have an increased risk of a lower birth weight, the cause of which remains unclear. As a causative factor, we hypothesized that variants in the mitochondrial DNA (mtDNA) that are not associated with disease, may explain changes in birth weight.

Methods

We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or cycles with ovarian stimulation (OS). The mtDNA genotypes were compared across groups and logistic regression and discriminant analysis were used to study the impact of the different factors on birth weight percentile.

Results

ART individuals more frequently carried variants with higher heteroplasmic loads in protein and rRNA-coding regions. These differences in the mitochondrial genome were also predictive of the risk of a lower birth weight percentile, irrespective of the mode of conception but with a sex-dependent culture medium effect. The higher incidence of these variants in ART individuals results both from maternal transmission and de novo mutagenesis, which we found not to be caused by OS but to be associated to maternal ageing.

Conclusions

MtDNA variants in protein and rRNA coding regions are associated with a lower birth weight and are more frequently observed in ART children. We propose that these non-disease associated variants can result in a suboptimal mitochondrial function that impacts birth weight. Future research will establish the long-term health consequences of these changes and how these findings will impact the clinical practice and patient counselling in the future.
ChimeraTE: A pipeline to detect chimeric transcripts derived from genes and transposable elements
Authors: Oliveira Daniel S. , Fablet Marie , Larue Anaïs , Vallier Agnès , Carareto Claudia M. A. , Rebollo Rita , Vieira Cristina
Published: September 2022

Transposable elements (TEs) produce structural variants and are considered an important source of genetic diversity. Notably, TE-gene fusion transcripts,i.e.,chimeric transcripts, have been associated with adaptation in several species. However, the identification of these chimeras remains hindered due to the lack of detection tools at a transcriptome-wide scale, and to the reliance on a reference genome, even though different individuals/cells/strains have different TE insertions. Therefore, we developed ChimeraTE, a pipeline that uses paired-end RNA-seq reads to identify chimeric transcripts through two different modes. Mode 1 is the reference-guided approach that employs canonical genome alignment, and Mode 2 identifies chimeras derived from fixed or insertionally polymorphic TEs without any reference genome. We have validated both modes using RNA-seq data from fourDrosophila melanogasterwild-type strains. We found ∼1.12% of all genes generating chimeric transcripts, most of them from TE-exonized sequences. Approximately ∼23% of all detected chimeras were absent from the reference genome, indicating that TEs belonging to chimeric transcripts may be recent, polymorphic insertions. ChimeraTE is the first pipeline able to automatically uncover chimeric transcripts without a reference genome, consisting of two running Modes that can be used as a tool to investigate the contribution of TEs to transcriptome plasticity.
A unique case in whichKimoto-style fermentation was completed withLeuconostocas the dominant genus without transitioning toLactobacillus
Authors: Ito Kohei , Niwa Ryo , Yamagishi Yuta , Kobayashi Ken , Tsuchida Yuji , Hoshino Genki , Nakagawa Tomoyuki , Watanabe Takashi
Published: September 2022

TheKimoto-style fermentation starter is a traditional preparation method ofsakebrewing. In this process, specific microbial transition patterns have been observed within nitrate-reducing bacteria and lactic acid bacteria during the production process of the fermentation starter. We have characterized phylogenetic compositions and diversity of the bacterial community in asakebrewery performing theKimoto-style fermentation. Comparing the time-series changes with othersakebreweries previously reported, we found a novel type ofKimoto-style fermentation in which the microbial transition differed significantly from other breweries during the fermentation step. Specifically, the lactic acid bacteria,Leuconostocspp. was a predominant species in the late stage in the preparation process of fermentation starter, on the other hand,Lactobacillusspp., which plays a pivotal role in other breweries, was not detected in this analysis. The discovery of this new variation of microbiome transition inKimoto-style fermentation has further deepened our understanding of the diversity ofsakebrewing.
Mapping of Glutamate Metabolism using 1H FID-MRSI after oral Administration of [1-13C]Glc at 9.4 T
Authors: Ziegs Theresia , Ruhm Loreen , Wright Andrew , Henning Anke
Published: September 2022

Glutamate is the major excitatory transmitter in the brain and malfunction of the related metabolism is associated with various neurological diseases and disorders. The observation of labeling changes in the spectra after the administration of a13C labelled tracer is a common tool to gain better insights into the function of the metabolic system. But so far, only a very few studies presenting the labelling effects in more than two voxels to show the spatial dependence of metabolism.

In the present work, the labeling effects were measured in a transversal plane in the human brain using ultra-short TE and TR 1H FID-MRSI. The measurement set-up was most simple: The [1-13C]Glc was administered orally instead of intravenous and the spectra were measured with a pure 1H technique without the need of a13C channel (as Boumezbeur et al. demonstrated in 2004). Thus, metabolic maps and enrichment curves could be obtained for more metabolites and in more voxels than ever before in human brain. Labeling changes could be observed in [4-13C]glutamate, [3-13C]glutamate+glutamine, [2-13C]glutamate+glutamine, [4-13C]glutamine, [2,3-13C]aspartate and [6-13C]N-acetyl aspartate with a high temporal (3.6 min) and spatial resolution (32×32 grid with nominal voxel size of 0.33 μL) in five volunteers.
In silicoidentification of miRNAs related to mitochondrial dysfunction in amyotrophic lateral sclerosis
Authors: Gulcin Baykal , Burcin Erkal , Senay Vural Korkut
Published: September 2022

Non-coding, single-stranded RNA molecules known as microRNAs (miRNAs) regulate gene expression via mRNA degradation after transcription. As a result, they affect a number of pathways in organisms that are important for both health and disease. miRNAs can be utilized as potential diagnostic, prognostic, and therapeutic biomarkers for neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). Neuronal cells are highly dependent on mitochondria, and mitochondrial dysfunction has been linked to neurodegenerative diseases. Pathological changes in ALS are associated with disruptions in mitochondrial structure, bioenergetics, and calcium homeostasis. In this study, we used anin silicoapproach to identify miRNAs associated with mitochondrial dysfunction in ALS based on target genes that are implied in both ALS and mitochondrial dysfunction. A literature search revealed the genes SOD1, FUS, TARDBP, C9orf72, CHCHD10, OPTN, VCP, TBK1 and BCL2 that cause mitochondrial dysfunction and are involved in the pathogenesis of ALS. Pathway enrichment analyses using Enrichr, g:Profiler, and CROssBAR tools confirmed that the identified genes have significant associations with ALS, mitochondrial dysfunction, and neuron differentiation. In silico miRNA predictions have been made using the databases miRWalk, miRTargetLink, TargetScan, and miRNet. A Venn diagram tool was used to select common miRNAs, and finally 28 miRNAs were discovered. One set of 28 miRNAs were subjected to set analysis using the miRNet and TAM tools for functional and enrichment analyses, respectively. In both databases, three common miRNAs, hsa-miR-9-5p, hsa-miR-141-3p and hsa-miR-125b, were found to be linked to ALS.
Nucleotide level linkage of transcriptional elongation and polyadenylation
Authors: Geisberg Joseph V. , Moqtaderi Zarmik , Fong Nova , Erickson Benjamin , Bentley David L. , Struhl Kevin
Published: September 2022

Alternative polyadenylation yields many mRNA isoforms whose 3’ termini occur disproportionately in clusters within 3’ UTRs. Previously, we showed that profiles of poly(A) site usage are regulated by the rate of transcriptional elongation by RNA polymerase (Pol) II (Geisberg et., 2020). Pol II derivatives with slow elongation rates confer an upstream-shifted poly(A) profile, whereas fast Pol II strains confer a downstream-shifted poly(A) profile. In yeast, upstream and downstream shifts within isoform clusters occur steadily at the nucleotide level. In contrast, changes from one isoform to the next are much smaller between clusters, even when the distances between them are relatively large. GC content in a region 13-30 nt downstream from isoform clusters is linked to Pol II elongation rate. In human cells, the upstream shift caused by a slow Pol II mutant also occurs continuously at the nucleotide level within clusters, but not between them. Pol II occupancy increases just downstream of the most speed-sensitive poly(A) sites, suggesting a linkage between reduced elongation rate and cluster formation. These observations suggest that 1) Pol II elongation speed affects the nucleotide-level dwell time allowing polyadenylation to occur, 2) poly(A) site clusters are linked to the local elongation rate and hence do not arise simply by intrinsically imprecise cleavage and polyadenylation of the RNA substrate, 3) DNA sequence elements can affect Pol II elongation and poly(A) profiles, and 4) the cleavage/polyadenylation and Pol II elongation complexes are spatially, and perhaps physically, coupled so that polyadenylation occurs rapidly upon emergence of the nascent RNA from the Pol II elongation complex.