bluuebunny/crossref_metadata_2025 huggingface dataset:
Semi-automatic segmentation of the fetal brain from Magnetic Resonance Imaging
Authors: Wang Jianan , Nichols Emily S. , Mueller Megan E. , de Vrijer Barbra , Eagleson Roy , McKenzie Charles A. , de Ribaupierre Sandrine , Duerden Emma G.
Published: March 2022

Template-based segmentation techniques have been used for targeting deep brain structures in fetal MR images. In this study, two registration algorithms were compared to determine the optimal strategy of segmenting subcortical structures in T2-weighted images acquired during the third trimester of pregnancy. Adult women with singleton pregnancies (n=9) ranging from 35-39 weeks gestational age were recruited. Fetal MRI were performed on 1.5 T and 3 T scanners. Automatic fetal brain segmentation and volumetric reconstruction algorithms were performed on all subjects using the NiftyMIC software. An atlas of cortical and subcortical structures (36 weeks’ gestation) was registered into native space using ANTs (Automatic Normalization Tools) and FLIRT (FMRIB’s linear image registration tool). The cerebellum and thalamus were manually segmented. Dice coefficients were calculated to validate the reliability of automatic methods and to compare the performance between ANTs (nonlinear) and FLIRT (affine) registration algorithms compared to the gold-standard manual segmentations. The Dice-kappa values for the automated labels were compared using the Wilcoxon test. Comparing cerebellum and thalamus masks against the manually segmented masks, the median Dice-kappa coefficients for ANTs and FLIRT were 0.76 (interquartile range [IQR]= 0.56-0.83) and 0.65 (IQR=0.5-0.73), respectively. The Wilcoxon test (Z=4.9, P<0.01) indicated that the ANTs registration method performed better than FLIRT for the fetal cerebellum and thalamus. We found that a nonlinear registration method, provided improved results compared to an affine transformation. Nonlinear registration methods may be preferable for subcortical segmentations in MR images acquired in third-trimester fetuses.
Spatial patterns of excess mortality in the first year of the COVID-19 pandemic in Germany
Authors: Wieland Thomas
Published: March 2022

In order to quantify the impact of the SARS-CoV-2/COVID-19 pandemic, several studies have estimated excess mortality rather than infections or COVID-19-related deaths. The current study investigates excess mortality in Germany in 2020 at a small-scale spatial level (400 counties) and under consideration of demographic changes. Mortality is operationalized using standardized mortality ratios (SMRs), visualized on maps, and analyzed descriptively. Regional mortality and COVID-19-related morbidity are tested for spatial dependence by the Moran’s I index. It is, furthermore, tested whether all-cause mortality is associated with COVID-19-related morbidity by correlation coefficients. Excess mortality only occurrs in a minority of counties. There are large regional disparities of all-cause mortality and COVID-19-related morbidity. In older age groups, both indicators show spatial dependence. (Excess) mortality in older age groups is impacted by COVID-19, but this association is not found for young and middle age groups.
Stable Sparse Classifiers predict cognitive impairment from gait patterns
Authors: Aznielle-Rodríguez Tania , Ontivero-Ortega Marlis , Galán-García Lídice , Sahli Hichem , Valdés-Sosa Mitchell
Published: March 2022

Background

Although gait patterns disturbances are known to be related to cognitive decline, there is no consensus on the possibility of predicting one from the other. It is necessary to find the optimal gait features, experimental protocols, and computational algorithms to achieve this purpose.

Purposes

To assess the efficacy of the Stable Sparse Classifiers procedure (SSC) for discriminating young and older adults, as well as healthy and cognitively impaired elderly groups from their gait patterns. To identify the walking tasks or combinations of tasks and specific spatio-temporal gait features (STGF) that allow the best prediction with SSC.

Methods

A sample of 125 participants (40 young- and 85 older-adults) was studied. They underwent assessment with five neuropsychological tests that explore different cognitive domains. A summarized cognitive index (MDCog), based on the Mahalanobis distance from normative data, was calculated. The sample was divided into three groups (young adults, healthy and cognitively impaired elderly adults) using k-means clustering of MDCog in addition to Age. The participants executed four walking tasks (normal, fast, easy- and hard-dual tasks) and their gait patterns, measured with a body-fixed Inertial Measurement Unit, were used to calculate 16 STGF and dual-task costs. SSC was then employed to predict which group the participants belonged to. The classification’s performance was assessed using the area under the receiver operating curves (AUC). The set of STGF features and tasks producing the most accurate classifications were identified.

Results

The comparison between the three groups revealed significant differences for all STGF in all tasks, while the global AUC of the classification using SSC was 0.87. The classification between the groups of elderly people revealed that the combination of the easy dual-task and the fast walking task had the best prediction performance (AUC = 0.86). Gait variability in step and stride time and the RMS value of vertical acceleration were the features with the largest predictive power. SSC prediction accuracy was better than the accuracies obtained with linear discriminant analysis and support vector machine classifiers.

Conclusions

The study corroborated that the changes in gait patterns can be used to discriminate between young and older adults and more importantly between healthy and cognitively impaired adults. A subset of gait tasks and STGF optimal for achieving this goal with SSC were identified, with the latter method superior to other classification techniques.
Tau, β-amyloid, and glucose metabolism following service-related Traumatic Brain Injury in Vietnam war veterans: The AIBL-VETS study
Authors: Doré Vincent , Cummins Tia L. , Feizpour Azadeh , Krishnadas Natasha , Bourgeat Pierrick , Elias Alby , Lamb Fiona , Williams Robert , Hopwood Malcolm , Villemagne Victor L. , Weiner Michael , Rowe Christopher C. ,   Alzheimer’s Disease Neuroimaging Initiative,   AIBL Research Group
Published: March 2022

Traumatic Brain Injury (TBI) is common amongst military veterans and has been associated with an increased risk of dementia. It is unclear if this is due to increased risk for Alzheimer’s disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 NIA-AA research framework1, by measuring tau, β-amyloid and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI.

Seventy male Vietnam war veterans — 40 with TBI (aged 68.0±2.5 years) and 30 controls (aged 70.1±5.3 years) — with no prior diagnosis of dementia or mild cognitive impairment underwent β-amyloid (18F-Florbetaben), tau (18F-Flortaucipir) and18F-FDG PET. The TBI cohort included 15 participants with mild, 16 with moderate, and 9 with severe injury. β-amyloid level was calculated using the Centiloid (CL) method and tau was measured by Standardized Uptake Value Ratios (SUVR) using the cerebellar cortex as reference region. Analyses were adjusted for age and APOE-e4. The findings were validated in an independent cohort from the ADNI-DOD study.

There were no significant nor trending differences in β-amyloid or tau levels or18F-FDG uptake between the TBI and control groups before and after controlling for covariates. The β-amyloid and tau findings were replicated in the ADNI-DOD validation cohort and persisted when the AIBL-VETS and ADNI-DOD cohorts were combined (114 TBI vs 87 controls in total). These findings suggest that TBI is not associated with the later life accumulation of the neuropathological markers of AD.
How often do cancer researchers make their data and code available and what factors are associated with sharing?
Authors: Hamilton Daniel G. , Page Matthew J. , Finch Sue , Everitt Sarah , Fidler Fiona
Published: March 2022

Background

Various stakeholders are calling for increased availability of data and code from cancer research. However, it is unclear how commonly these products are shared, and what factors are associated with sharing. Our objective was to evaluate how frequently oncology researchers make data and code available, and explore factors associated with sharing.

Methods

A cross-sectional analysis of a random sample of 306 articles indexed in PubMed in 2019 presenting original cancer research was performed. Outcomes of interest included the prevalence of affirmative sharing declarations and the rate with which declarations connected to useable data. We also investigated associations between sharing rates and several journal characteristics (e.g., sharing policies, publication models), study characteristics (e.g., cancer rarity, study design), open science practices (e.g., pre-registration, pre-printing) and citation rates between 2020-2021.

Results

One in five studies declared data were publicly available (95% CI: 15-24%). However, when actual data availability was investigated this percentage dropped to 16% (95% CI: 12-20%), and then to less than 1% (95% CI: 0-2%) when data were checked for compliance with key FAIR principles. While only 4% of articles that used inferential statistics reported code to be available (10/274, 95% CI: 2-6%), the odds of reporting code to be available were 5.6 times higher for researchers who shared data. Compliance with mandatory data and code sharing policies was observed in 48% and 0% of articles, respectively. However, 88% of articles included data availability statements when required. Policies that encouraged data sharing did not appear to be any more effective than not having a policy at all. The only factors associated with higher rates of data sharing were studying rare cancers and using publicly available data to complement original research.

Conclusions

Data and code sharing in oncology occurs infrequently, and at a lower frequency than would be expected due to non-compliance with journal policies. There is also a large gap between those declaring data to be available, and those archiving data in a way that facilitates its reuse. We encourage journals to actively check compliance with sharing policies, and researchers consult community accepted guidelines when archiving the products of their research.
‘The Association of Scoliosis Properties with Spinal Cord Tethering: A Statistical Model for Prognostication’
Authors: Yarandi Kourosh Karimi , Mohammadi Esmaeil , Amirjamshidi Abbas , Bidabadi Mohammad Shirani , Rashidi Ahmad Pour , Azadnajafabad Sina , Maroufi Seyed Farzad , Alimohammadi Maisam
Published: March 2022

Objective

To evaluate the relationship between the structural measures of scoliosis and underlying spinal cord tethering (SCT) and proposing a statistical prognostication model.

Study design

Cross-sectional.

Setting

Academic healthcare center

Methods

128 definite scoliosis cases that were candidates for corrective surgery were enrolled. Anterior-posterior whole column digital radiographs and whole-spine MRI (supine for all samples and adjuvant prone MRI for suspected cases with tight filum terminal) were performed. Univariate and multiple logistic regression were used for the analysis of association and interaction. Association of SCT with structural features of scoliosis –Cobb angle, convexity, and type (idiopathic and congenital)– age, and sex were assessed.

Results

None of the study variables showed a statistical association with SCT in univariable and multiple logistic regressions. After inclusion of Cobb angle-convexity-type interaction, higher Cobb angle, idiopathic scoliosis, dextrosoliosis, and male gender had a significant effect. Stratification for convexity discovered a positive association of Cobb angle and SCT in idiopathic patients with dextroscoliosis (1.02 [1.01–1.03], 0.049). In contrast, in congenital cases, the rate of SCT decreased by higher left-sided Cobb angles but it was not statistically significant (0.94 [0.88–1.01], 0.104).

Conclusion

The risk of spinal cord tethering was not zero in any of the subgroups and no SCT-free group could be detected. Conventional MRI should be preoperatively performed for every case of scoliosis and thoroughly examined for signs of tethering. Clear imaging of patients at higher risk of SCT should not be decisive and further workup should be utilized before proceeding with reconstructive surgery.
Inferring Insulin Secretion Rate From Sparse Patient Glucose and Insulin Measures
Authors: Abohtyra Rammah M. , Chan Christine L. , Albers David J. , Gluckman Bruce J.
Published: March 2022

The insulin secretion rate (ISR) contains information that can provide a personal, quantitative understanding of endocrine function. The ISR, if it can be reliably inferred from sparse measurements, could be used both for understanding the source of a problem with glucose regulation system and for monitoring people with diabetes.

Objective

This study aims to develop a model-based method for inferring ISR and related physiological information among people with different glycemic conditions in a robust manner.

Methods

An algorithm for estimating and validating ISR for different compartmental models with unknown but estimable ISR function and absorption/decay rates describing the dynamics of insulin and C-peptide accumulation was developed. The algorithm was applied to data from 17 subjects with normal glucose regulatory systems and 9 subjects with cystic fibrosis related diabetes (CFRD) in which glucose, insulin and C-peptide were measured in course of oral glucose tolerance tests (OGTT).

Results

The model-based algorithm was able to successfully estimate ISR for a diverse set of patients. For CFRD subjects, due to high maximum observed glucose values, we observed better estimation for the degradation rates than for healthy patients. Even though ISR and C-peptide secretion rate (CSR) have different physiological characteristics and nonlinear relations with plasma glucose concentration, our model-based algorithm reproduced the expected linear relationship between ISR and CSR. And the estimated ISR can differentiate normal and CFRD patients: the ISR for individuals with CFRD is substantially lower compared with the ISR for individuals’ normal glucose regulatory systems.

Significance

A new estimation method is available to infer the ISR profile, plasma insulin, and C-peptide absorption rates from sparse measurements of insulin, C-peptide, and plasma glucose concentrations.
EMS prehospital response to the COVID-19 pandemic in the US: A brief literature review
Authors: Ventura Christian Angelo I. , Denton Edward E. , David Jessica A. , Schoenfelder Brianna J. , Mela Lillian , Lumia Rebecca P. , Rudi Rachel B. , Haldar Barnita
Published: March 2022

This study aimed to analyze prehospital Emergency Medical Services (EMS) response to the COVID-19 pandemic in the US through a brief systematic review of available literature in context with international prehospital counterparts. An exploration of the NCBI repository was performed using a search string of relevant keywords which returned n=5128 results; articles that met the inclusion criteria (n=77) were reviewed and analyzed in accordance with PRISMA and PROSPERO recommendations. Methodical quality was assessed using critical appraisal tools, and the Egger’s test was used for risk of bias reduction upon linear regression analysis of a funnel plot. Sources of heterogeneity as defined by P < 0.10 or I^2 > 50% were interrogated. Findings were considered within ten domains: structural/systemic; clinical outcomes; clinical assessment; treatment; special populations; dispatch/activation; education; mental health; perspectives/experiences; and transport. Findings suggest, EMS clinicians have likely made significant and unmeasured contributions to care during the pandemic via nontraditional roles, i.e., COVID-19 testing and vaccine deployment. EMS plays a critical role in counteracting the COVID-19 pandemic in addition to the worsening opioid epidemic, both of which disproportionately impact patients of color. As such, being uniquely influential on clinical outcomes, these providers may benefit from standardized education on care and access disparities such as racial identity. Access to distance learning continuing education opportunities may increase rates of provider recertification. Additionally, there is a high prevalence of vaccine hesitancy among surveyed nationally registered EMS providers. Continued rigorous investigation on the impact of COVID-19 on EMS systems and personnel is warranted to ensure informed preparation for future pandemic and infectious disease response.
Long-COVID in Children and Adolescents: A Systematic Review and Meta-analyses
Authors: Lopez-Leon Sandra , Wegman-Ostrosky Talia , Ayuzo del Valle Norma Cipatli , Perelman Carol , Sepulveda Rosalinda , Rebolledo Paulina A , Cuapio Angelica , Villapol Sonia
Published: March 2022

The objective of this systematic review and meta-analyses is to estimate the prevalence of long-COVID in children and adolescents and to present the full spectrum of symptoms present after acute COVID-19. We have used PubMed and Embase to identify observational studies published before February 10th, 2022 that included a minimum of 30 patients with ages ranging from 0 to 18 years that met the National Institute for Healthcare Excellence (NICE) definition of long-COVID, which consists of both ongoing (4 to 12 weeks) and post-COVID-19 (≥12 weeks) symptoms. Random-effects meta-analyses were performed using the MetaXL software to estimate the pooled prevalence with a 95% confidence interval (CI). Heterogeneity was assessed using I2 statistics. The Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) reporting guideline was followed (registration PROSPERO CRD42021275408). The literature search yielded 8,373 publications, of which 21 studies met the inclusion criteria, and a total of 80,071 children and adolescents were included. The prevalence of long-COVID was 25.24%, and the most prevalent clinical manifestations were mood symptoms (16.50%), fatigue (9.66%), and sleep disorders (8.42%). Children infected by SARS-CoV-2 had a higher risk of persistent dyspnea, anosmia/ageusia, and/or fever compared to controls. Limitations of the studies analyzed include lack of standardized definitions, recall, selection, misclassification, nonresponse and/or loss of follow-up, and a high level of heterogeneity.
Predicting systemic and pulmonary tissue barrier concentration of orally inhaled drug products
Authors: Singh Narender , Kannan Ravi , Arey Ryan , Walenga Ross , Babiskin Andrew , Przekwas Andrzej
Published: March 2022

The complex physiology and anatomy of the lungs and the range of processes involved in pulmonary drug transport and disposition make it challenging to predict the fate of orally inhaled drugs. This study aimed to develop an integrated computational pharmacology approach to mechanistically describe the spatio-temporal dynamics of inhaled drugs in both systemic circulation and site-specific lung tissue. The model included all the physiologically relevant pulmonary processes, such as deposition, dissolution, transport across lung barriers, and mucociliary clearance, to predict the inhaled drug pharmacokinetics. For validation test cases, the model predicted the fate of orally inhaled budesonide (highly soluble, mildly lipophilic) and fluticasone propionate (practically insoluble, highly lipophilic) in healthy subjects for: i) systemic and site-specific lung retention profiles, ii) aerodynamic particle size-dependent deposition profiles, and iii) identified the most impactful drug-specific, formulation-specific, and system-specific property factors that impact the fate of both the pulmonary and systemic concentration of the drugs. In summary, the presented multiscale computational model can guide the design of orally inhaled drug products to target specific lung areas, identify the effects of product differences on lung and systemic pharmacokinetics, and be used to better understand bioequivalence of generic orally inhaled drug products.

Author summary

Despite widespread use of available orally inhaled drug products (OIDPs), much is unknown regarding their optimal lung deposition, targeted delivery to specific lung regions, and the effects of various device, formulation, and physiological factors on deposition, absorption, transport, and clearance. In this study, we have presented a multiscale computational framework that integrates a full-scale 24 generation 3D lung model with distinct barrier regions spanning trachea, tracheobronchial, alveolar, and the terminal alveolar sacs with multiple other modules to track the OIDP levels (concentration) in both blood and pulmonary tissue regions. Along with validating the framework on two different inhaled drug types, we have also presented a sensitivity analysis to highlight the most impactful drug and formulation parameters, and therefore, potential optimization parameters to modulate lung selectivity and to better understand the pulmonary retention of drugs in distinct lung regions.
Transcutaneous electrical nerve stimulation modulates corticospinal excitability while preserving motor unit discharge properties during isometric contractions
Authors: Hernandez-Pavon Julio Cesar , Avrillon Simon , Hoo Grace , Pons Jose L.
Published: March 2022

Aim

Transcutaneous electrical nerve stimulation (TENS) aims to supplement sensory feedback to improve force steadiness or motor function. In this study, we directly assessed potential changes in corticospinal excitability and motor unit discharge characteristics from the first dorsal interosseous (FDI) muscle due to TENS by using transcranial magnetic stimulation (TMS) and high-density surface electromyography (HDsEMG).

Methods

Eleven healthy young adults performed a series of submaximal isometric index abductions. We estimated i) motor evoked potential (MEP) amplitudes, ii) persistent inward current amplitudes (PIC, i.e., delta F), iii) motor unit recruitment thresholds and discharge rates, and iv) common synaptic input to motor units before and after TENS.

Results

TENS did not affect force steadiness (2.5 ± 0.9% and 3.3 ± 1.9% (p = 0.010)). MEP amplitudes decreased at 110% of the resting motor threshold (rMT; 0.72 ± 0.66 mV vs. 0.59 ± 0.63 mV; p < 0.001), increased at 130% rMT (1.18 ± 1.10 mV vs. 1.41 ± 1.29 mV; p < 0.001). Delta F increased after TENS (3.7 ± 2.2 pps vs. 4.5 ± 2.6 pps; p = 0.010). We did not find a change in the level of common synaptic input or in the temporal variability of motor unit discharge rates after the session of TENS.

Conclusion

These results suggest that TENS can modulate corticospinal excitability through supraspinal and spinal processes and, thus act as a priming technique. At the same time, TENS does not generate short-term changes in the neural control of force in young, healthy adults.
Impact of dominance rank specification in dyadic interaction models
Authors: Mielke Alexander
Published: March 2022

Dominance rank is a vital descriptor of social dynamics in animal societies and regularly used in studies to explain observed interaction patterns. However, researchers can choose between different indices and standardizations, and can specify dyadic rank relations differently when studying interaction distributions. These researcher degrees of freedom potentially introduce biases into studies and reduce replicability. Here, I demonstrate the impact of researcher choices by comparing the performance of different combinations of rank index, standardization, and model specification when explaining dyadic interaction patterns in sooty mangabeys (Cercocebus atys atys). I show that while no combination consistently performed best across interaction types (aggression, grooming, proximity, supplants), model specifications allowing for non-linear patterns performed better than other models on average. Choices made in pre-processing and model building impacted model performance and subsequent interpretation of results. Researchers could end up describing social systems differently based on the same data. These results highlight the impact of researcher choices in the processing of behavioural data and potential limitations when using indirect species comparisons in animal behaviour research. To increase repeatability, researchers could make the impact of their processing choices more transparent and report results using a variety of indices and model specifications.
New distribution data and phylogenetic approach reveal bioregionalization of the western Palearctic ants
Authors: Wang Runxi , Kass Jamie M. , Galkowski Christophe , Garcia Federico , Hamer Matthew T. , Radchenko Alexander , Salata Sebastian , Schifani Enrico , Yusupov Zalimkhan M. , Economo Evan P. , Guénard Benoit
Published: March 2022

Aim

Biogeographic regionalization has fascinated biogeographers and ecologists for centuries and is endued with new vitality by evolutionary perspectives. However, progress is scant for most insect groups due to shortfalls in distribution and phylogenetic information, namely Wallacean and Darwinian shortfalls respectively. Here, we used the western Palearctic ants as the case to tackle these shortfalls and test their biogeographic structure through novel distribution data and phylogenetic approaches.

Location

Western Palearctic realm.

Taxon

Ants (Formicidae).

Methods

Firstly, we developed a refined database integrating the occurrences of 747 ant species across 207 regions of the western Palearctic realm, based on newly expert-validated records derived from the existing global ant biodiversity informatics. Using range estimates for these species derived from polygons and species distribution modelling, we produced species assemblages in 50 × 50 km grid cells. We calculated taxonomic and phylogenetic turnover of ant assemblages, performing hierarchical clustering analysis using the Simpson dissimilarity index to delineate biogeographic structure.

Results

At both the regional list- and grid assemblage-levels, the Mediterranean has higher turnover and more biogeographic regions than northern Europe, both taxonomically and phylogenetically. Delineations based on grid assemblages detected more detailed biogeographic transitions, while those based on regional lists showed stronger insularity in biogeographic structure. The phylogenetic regionalization suggested closer but varied affinities between assemblages in comparison to the taxonomic approach.

Main conclusions

Here, we integrated expert-validated regional lists, species distribution modelling, and a recent phylogeny to tackle Wallacean and Darwinian shortfalls for an important insect group by developing a next-generation map of biogeographic regionalization for the western Palearctic ants. The results of this study suggest strong constraints from geographic barriers and potential effects of climatic history on ant distributions and evolutionary history, and also provide baseline spatial information for future investigations of regional insect distributions.
Ecdysone signaling controls early embryogenesis in the short-germ hemimetabolous insect Blattella germanica
Authors: Cruz Josefa , Maestro Oscar , Franch-Marro Xavier , Martín David
Published: March 2022

Steroid hormone signaling is a central regulator of insect development especially during the post-embryonic period. However, its role during embryonic development is less understood, particularly in short-germ band hemimetabolous insects. Here, we used the short-germ band hemimetabolous insect Blattella germanica to analyse the functions of 20-hydroxyecdysone (20E), the most active insect steroid, signaling during the embryonic stage. We show that the heterodimeric 20E receptor, BgEcR-A and BgRXR, is present from the beginning of embryogenesis and that a stereotypical 20E-dependent cascade of nuclear receptors is first detected at the early blastoderm stage. Using parental RNAi, we show that both receptors are required for the proper formation of the germ band by controlling cell proliferation during the blastoderm stage. In addition, they are also required for the coordinated induction of the 20E-induced cascade of nuclear receptors. Finally, we show that two of these nuclear receptors, BgHR3 and BgFTZ-F1, have relevant roles in germ band formation. Whereas BgHR3 controls the formation and development of the cephalic region of the germ band, BgFTZ-F1 stripped expression suggested a role in the segmentation of the germ band. In summary, our results show that 20E-signaling is required much earlier in short-germ band hemimetabolous than in long-germ band holometabolous embryogenesis, which raises the possibility that the loss of 20E-signaling during the initial stages of embryogenesis could be a key feature in the evolution of the different types of insect development.
Dynamic evolution of recently duplicated genes in Caenorhabditis elegans
Authors: Ma Fuqiang , Lau Chun Yin , Zheng Chaogu
Published: March 2022

As a major origin of evolutionary novelties, gene duplication is a widespread phenomenon across species. However, the evolutionary force that determines the fate of duplicate genes is still under debate. Here, we studied the functional evolution of duplicate genes at both macroevolution and microevolution scales using the genomic sequences of eleven Caenorhabditis species and 773 C. elegans wild isolates. We found that compared to older duplicate genes and single-copy genes, recently duplicated gene copies showed rapid turnover, large genetic diversity, and signs of balancing and positive selection within the species. Young duplicate genes have low basal expression restricted to a few tissues but show highly responsive expression towards pathogenic infections. Recently duplicated genes are enriched in chemosensory perception, protein degradation, and innate immunity, implicating their functions in enhancing adaptability to external perturbations. Importantly, we found that young duplicate genes are rarely essential, while old duplicate genes have the same level of essentiality as singletons, suggesting that essentiality develops over a long time. Together, our work in C. elegans demonstrates that natural selection shapes the dynamic evolutionary trajectory of duplicate genes.

Significance

The “evolution by gene duplication” theory suggests that gene duplications provide the genetic materials for mutation and selection to act upon, expand the repertoire of molecular functions, and enable evolutionary novelty. Although various models were proposed to describe the fate of duplicate genes, empirical evidence for these models is limited. We analyzed gene duplications in eleven nematode Caenorhabditis species and studied the intraspecific variation of these duplicate genes among C. elegans wild strains. We found that compared to older duplicate gens and single-copy genes, recently duplicated genes show rapid turnover, large genetic diversity, and strong signs of balancing and positive selection but rarely develop essential functions. Our results describe the evolutionary trajectory of duplicate genes shaped by natural selection.
Purinergic P2X7 Receptor-mediated inflammation precedes PTSD-related Behaviors in Rats
Authors: Torres-Rodriguez Orlando , Rivera-Escobales Yesenia , Velazquez Bethzaly , Colón María , Porter James T.
Published: March 2022

Clinical evidence has linked increased peripheral pro-inflammatory cytokines with post-traumatic stress disorder (PTSD) symptoms. However, whether inflammation contributes to or is a consequence of PTSD is still unclear. Previous research shows that stress can activate P2X7 receptors (P2X7Rs) on microglia to induce inflammation and behavioral changes. In this investigation, we examined whether P2X7Rs contribute to the development of PTSD-like behaviors induced by single prolonged stress (SPS) exposure in rats. Consistent with the literature, exposing adult male and female rats to SPS produced a PTSD-like phenotype of impaired fear extinction and increased anxiety-like behavior one week after exposure. In addition, SPS-exposed animals had more Iba1-positive microglia expressing the P2X7R in the ventral hippocampus, a structure that regulates fear extinction and anxiety-like behavior. Next, we examined if inflammation precedes the behavioral manifestations. Three days after SPS exposure, increased inflammatory cytokines were found in the blood and hippocampal microglia showed increased expression of the P2X7R, IL-1β, and TNF-α, suggesting increased peripheral and central inflammation before behavioral testing. To determine whether P2X7Rs contribute to the PTSD-related behaviors induced by SPS exposure, we gave ICV infusions of the P2X7R antagonist, A-438079, for one week starting the day of SPS exposure. Blocking P2X7Rs prevented the SPS-induced impaired fear extinction and increased anxiety-like behaviors in male and female rats, suggesting that SPS activates P2X7Rs which increase inflammation to produce a PTSD-like phenotype.
Towards unsupervised classification of macromolecular complexes in cryo electron tomography: challenges and opportunities
Authors: Moebel E. , Kervrann C.
Published: March 2022

Background and Objectives

Cryo electron tomography visualizes native cells at nanometer resolution, but analysis is challenged by noise and artifacts. Recently, supervised deep learning methods have been applied to decipher the 3D spatial distribution of macromolecules. However, in order to discover unknown objects, unsupervised classification techniques are necessary. In this paper, we provide an overview of unsupervised deep learning techniques, discuss the challenges to analyze cryo-ET data, and provide a proof-of-concept on real data.

Methods

We propose an unsupervised sub-tomogram classification method based on transfer learning. We use a deep neural network to learn a clustering friendly representation able to capture 3D shapes in the presence of noise and artifacts. This representation is learned here from a synthetic data set.

Results

We show that when applying k-means clustering given a learning-based representation, it becomes possible to satisfyingly classify real sub-tomograms according to structural similarity. It is worth noting that no manual annotation is used for performing classification.

Conclusions

We describe the advantages and limitations of our proof-of-concept and raise several perspectives for improving classification performance.
Improving an rRNA depletion protocol with statistical design of experiments
Authors: David Benjamin M. , Jensen Paul A.
Published: March 2022

rRNA depletion is the most expensive step in prokaryotic RNA-seq library preparation. rRNA is so abundant that small increases in depletion efficiency lead to large changes in mRNA sequencing coverage. A variety of commercial and home-made methods exist to lower the cost or increase the efficiency of rRNA removal. Many of these techniques are suboptimal when applied to new species of bacteria or when the protocol or reagents need to be changed. Re-optimizing a protocol by trial-and-error is an expensive and laborious process. Systematic frameworks like the statistical design of experiments (DOE) can improve processes by exploring the quantitative relationship between multiple factors. DOE allows experimenters to find factor interactions that may not be apparent when factors are studied in isolation.

We used DOE to optimize an rRNA depletion protocol by updating reagents and identifying factors that maximize rRNA removal and minimize cost. The optimized protocol more efficiently removes rRNA, uses fewer reagents, and is less expensive than the original protocol. Our optimization required only 17 experiments and identified two significant interactions among three factors. Overall, our approach demonstrates the utility of a rational, DOE framework for improving complex protocols.
Variation in cytonuclear expression accommodation among allopolyploid plants
Authors: Grover Corrinne E. , Forsythe Evan S. , Sharbrough Joel , Miller Emma R. , Conover Justin L. , DeTar Rachael A. , Chavarro Carolina , Arick Mark A. , Peterson Daniel G. , Leal-Bertioli Soraya C.M. , Sloan Daniel B. , Wendel Jonathan F.
Published: March 2022

Cytonuclear coevolution is a common feature among plants, which coordinates gene expression and protein products between the nucleus and organelles. Consequently, lineage-specific differences may result in incompatibilities between the nucleus and cytoplasm in hybrid taxa. Allopolyploidy is also a common phenomenon in plant evolution. The hybrid nature of allopolyploids may result in cytonuclear incompatibilities, but the massive nuclear redundancy created during polyploidy affords additional avenues for resolving cytonuclear conflict (i.e.,cytonuclear accommodation). Here we evaluate expression changes in organelle-targeted nuclear genes for six allopolyploid lineages that represent four genera (i.e., Arabidopsis, Arachis, Chenopodium, andGossypium) and encompass a range in polyploid ages. Because incompatibilities between the nucleus and cytoplasm could potentially result in biases toward the maternal homoeolog and/or maternal expression level, we evaluate patterns of homoeolog usage, expression bias, and expression level dominance in cytonuclear genes relative to the background of non-cytonuclear expression changes and to the diploid parents. Although we find subsets of cytonuclear genes in most lineages that match our expectations of maternal preference, these observations are not consistent among either allopolyploids or categories of organelle-targeted genes. Our results indicate that cytonuclear expression accommodation may be a subtle and/or variable phenomenon that does not capture the full range of mechanisms by which allopolyploid plants resolve nuclear-cytoplasmic incompatibilities.
Candidatus Liberibacter asiaticus reduces callose and reactive oxygen species production in the phloem
Authors: Bernardini Chiara , Turner Donielle , Wang Chunxia , Welker Stacy , Achor Diann , Artiga Yosvanis Acanda , Turgeon Robert , Levy Amit
Published: March 2022

Huanglongbing (HLB) causes significant economic loss in citrus production worldwide. HLB is caused by Candidatus Liberibacter asiaticus (CLas), a gram-negative bacterium which inhabits the phloem exclusively. CLas infection results in accumulation of callose and reactive oxygen species in the phloem of infected plants, but little is known about the specific processes that take place during infection because of the sparse distribution of bacteria and the inaccessibility of the phloem inside the tree. In this study, we used the seed vasculatures, which accumulate a high number of CLas, as a model tissue to study CLas-host cellular interactions. In vasculature where CLas is abundant, sieve pore callose and H2O2 concentration were reduced compared to healthy seed vasculature. The expression of callose synthases (CalS) and respiratory burst oxidase homolog (RBOH) genes were downregulated in infected seeds compared to healthy ones. In leaves of HLB-infected plants, H2O2 concentration and CalS expression increased compared to uninfected leaves, but cells with CLas had lower levels of sieve plate callose compared to cells without CLas. Our results provide evidence that the bacteria manipulate cell metabolism to disable plant defenses and suggests that HLB disease is the result of a constant arms-race between the pathogen and a defense response, which is ultimately harmful to the host plant.
The GHB analogue HOCPCA improves sensorimotor function after MCAO via CaMKIIα
Authors: Griem-Krey Nane , Klein Anders B , Clausen Bettina H , Namini Mathias RJ , Nielsen Pernille V , Cheng Heung-Chin , Orset Cyrille , Vivien Denis , Clarkson Andrew N , Lambertsen Kate L , Wellendorph Petrine
Published: March 2022

Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) is a major contributor to physiological and pathological glutamate-mediated Ca2+signals, and its involvement in various critical cellular pathways demands specific pharmacological strategies. We recently presented GHB ligands as the first small molecules selectively targeting the CaMKIIα hub, a domain primarily responsible for holoenzyme oligomerisation, with an emerging functional role. Here, we report that the GHB ligand, HOCPCA, improves sensorimotor function after experimental stroke in mice when administered at clinically relevant time and in combination with alteplase. We observed that hub modulation by HOCPCA results in differential effects on distinct CaMKII pools, ultimately alleviating aberrant CaMKII signalling after cerebral ischemia. As such, HOCPCA normalised cytosolic Thr286 autophosphorylation after ischemia in mice and downregulated the ischemia-specific expression of a constitutively active CaMKII kinase fragment. Previous studies suggest holoenzyme stabilisation as a potential mechanism, yet a causal link toin vivofindings requires further studies. HOCPCA’s selectivity and absence of effects on physiological CaMKII signalling highlight pharmacological modulation of the CaMKIIα hub domain as an attractive neuroprotective strategy.
Snaq: A Dynamic Snakemake Pipeline for Microbiome data analysis with QIIME2
Authors: Mohsen Attayeb , Chen Yi-An , Allendes Osorio Rodolfo S. , Higuchi Chihiro , Mizuguchi Kenji
Published: March 2022

Optimizing a protocol for 16S microbiome data analysis with QIIME2 is a challenging task for biologists with no programming experience. It involves a multi-step process, and multiple parameters and options that need to be tested and determined. In this article, we describe Snaq, a snakemake pipeline that helps automate and optimize 16S data analysis using QIIME2. Snaq offers an informative file naming system and automatically performs the analysis of a data set by downloading and installing the required databases and classifiers, all through a single command-line instruction. It works natively on Linux and Mac and on Windows through the use of containers, and is potentially extendable by adding new rules. This pipeline will substantially reduce the efforts in sending commands and prevent the confusion caused by the accumulation of analysis results due to testing multiple parameters.
The impact of introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) on pneumococcal carriage in Nigeria
Authors: Adamu Aishatu L , Ojal J. , Abubakar Isa A. , Odeyemi Kofo , Bello Musa M. , Okoromah Christy A.N. , Karia Boniface , Karani Angela , Akech Donald. , Inem Victor , Scott J. Anthony G , Adetifa Ifedayo M.O.
Published: March 2022

Background

Pneumococcal Conjugate Vaccines (PCVs) reduce the burden of pneumococcal disease by reducing nasopharyngeal acquisition and transmission of serotypes in the vaccines (vaccine-serotypes). Following introduction of the 10-valent PCV (PCV10) in Nigeria, we assessed the population-level impact of PCV introduction on pneumococcal carriage.

Methods

We conducted annual cross-sectional carriage and vaccination coverage surveys between 2016 and 2020 in rural and urban sites in Nigeria. We recruited a random sample of residents and used WHO-recommended laboratory methods to identify pneumococcal serotypes. We modelled prevalence ratios for the change in annual carriage prevalence using log-binomial regression, and explored the association between vaccination coverage in children <5 years and changes in the population-level vaccine-serotype carriage.

Findings

We enrolled 4,684 and 3,653 participants for the carriage surveys and 2,135 and 1,106 children for the coverage surveys in the rural and urban sites, respectively. Carriage prevalence of vaccine-serotypes declined steadily with increasing levels of PCV10 coverage among children aged <5 years. From 2016 to 2020, coverage with three doses of PCV10 increased from 7% to 59% and from 15% to 81% in the rural and urban sites, respectively. Prevalence ratios for the annual change in vaccine-serotype carriage in participants aged <5 years and ≥5 years were 0.84 (95% CI:0.79-0.89) and 0.86 (95%CI:0.80-0.89) in the rural, and 0.69 (95% CI:0.62-0.77), and 0.83 (95% CI:0.74-0.93) in the urban sites.

Conclusions

We found significant reduction in vaccine-serotype carriage at a population level following a steady increase in PCV10 coverage, indicating direct and indirect vaccine effects.
Different Covid-19 Outcomes Among Systemic Rheumatic Diseases: A Nation-wide Cohort Study
Authors: Bournia Vasiliki-Kalliopi , Fragoulis George E. , Mitrou Panagiota , Mathioudakis Konstantinos , Tsolakidis Anastasios , Konstantonis George , Tseti Ioulia , Vourli Georgia , Tektonidou Maria G. , Paraskevis Dimitrios , Sfikakis Petros P.
Published: March 2022

Background

Nationwide data at a country level on Covid-19 in unvaccinated patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are scarce.

Methods

By interlinking data from national electronic registries, covering nearly 99% of the Greek population (approximately 11,000,000), between March 2020 and February 2021, when vaccination became available, we recorded confirmed infections and Covid-19-associated hospitalizations and deaths in essentially all adult patients with RA, AS, PsA, SLE, and SSc under treatment (n=74,970, median age of 67.5, 51.2, 58.1, 56.2, 62.2 years, respectively) and in individually matched (1:5) on age, sex, and region of domicile random comparators from the general population.

Results

Binary logistic regression analysis after adjusting for age, sex and biologic agents, revealed that RA, PsA, SLE and SSc, but not AS patients, had significantly higher risk of infection (by 43%, 25%, 20% and 49%, respectively), and hospitalization for Covid-19 (by 81%, 56%, 94%, and 111%, respectively), possibly due, at least in part, to increased testing and lower threshold for admission. Patients with RA and SSc had indeed higher Covid-19 associated mortality rates [OR:1.86 (95% CI 1.37 to 2.52) and OR:2.90 (95% CI 0.97 to 8.67), respectively] compared to the general population. Each additional year of age increased the risk of hospitalization for Covid-19 by 3% (OR 1.030, 95% CI: 1.028 to 1.034) and the risk of Covid-19 related death by 8% (OR 1.08, 95% CI: 1.07 to 1.09), independently of gender, systemic rheumatic disease, and biologic agents. A further analysis using AS patients as the reference category, adjusting again for age, sex and use of biologic agents showed that patients with SSc had increased mortality (OR: 6.90, 95% CI: 1.41 to 33.72), followed by SLE (OR: 4.05 95% CI: 0.96 to 17.12) and RA patients (OR: 3.65, 95% CI: 1.06 to 12.54), whereas PsA patients had comparable mortality risk with AS patients.

Conclusion

Comparing to the general population, Covid-19 may have a more severe impact in real-world patients with systemic rheumatic disease. Covid-19 related mortality is increased in subgroups of patients with specific rheumatic diseases, especially in older ones, underscoring the need for priority vaccination policies and access to targeted treatments.