bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Cognition in Temporal and Frontal Lobe Epilepsy: Systematic review, Meta-analysis, and Clinical Recommendations
Authors: Ziaei Maryam , Arnold Charlotte , Thompson Kate , Reutens David
Published: May 2021

Objective

Despite the importance of social cognitive functions to mental health and social adjustment, assessment of these functions is absent in routine assessment of epilepsy patients. Thus, this review aims to provide a comprehensive overview of the literature on four major aspects of social cognition among temporal and frontal lobe epilepsy, which is a critical step towards designing new interventions.

Method

Papers from 1990-2021 were reviewed and examined for inclusion in this study. After the deduplication process, a systematic review and meta-analysis of 44 and 40 articles, respectively, involving 113 people with frontal lobe epilepsy and 1482 people with temporal lobe epilepsy were conducted.

Results

Our results indicated that while patients with frontal or temporal lobe epilepsy have difficulties in all aspects of social cognition relative to non-clinical controls, the effect sizes were larger for theory of mind (g= 0.95), than for emotion recognition (g=0.69) among temporal lobe epilepsy group. The frontal lobe epilepsy group exhibited significantly greater impairment in emotion recognition compared to temporal lobe. Additionally, people with right temporal lobe epilepsy (g= 1.10) performed more poorly than those with a left-sided (g= 0.90) seizure focus, specifically in the theory of mind domain.

Conclusions

These data point to a potentially important difference in the severity of deficits within the emotion recognition and theory of mind abilities depending on the laterlization of seizure side. We also suggest a guide for the assessment of impairments in social cognition that can be integrated into multidisciplinary clinical evaluation for people with epilepsy
Clinical Significance of Circulating Tumor Cells in Unresectable Pancreatic Ductal Adenocarcinomas
Authors: Kim Hyemin , Heo Chan Mi , Oh Jinmyeong , Lee Eun Mi , Park Juhee , Lee Se-Hoon , Lee Kwang Hyuck , Lee Kyu Taek , Lee Jong Kyun , Cho Yoon-Kyoung , Park Joo Kyung
Published: May 2021

Background

Circulating tumour cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC).

Methods

CTCs were isolated using a centrifugal microfluidic disc from serially collected peripheral blood with clinical assessments. CTCs were enumerated with immunostaining against Epithelial cell adhesion molecule, Cytokeratin, Plectin-1 and CD45.

Results

CTCs were detected in 91.7% of 52 patients with unresectable PDAC at the time of diagnosis. CTC numbers were not statistically different across tumour sizes, stages and metastatic sites. The absolute CTC counts after chemotherapy was inversely related to survival, and the decreased number of CTCs after the first cycle of chemotherapy was significantly associated with longer survival.

Conclusions

Identifying CTCs and monitoring CTC changes after chemotherapy could be a useful prognostic marker for survivals in patients with unresectable PDACs.

Funding

This work was supported by a grant from SK Chemical Research Fund of the Korean Society of Gastroenterology (Grant No.800-20130378) and a grant from Korean Gastroenterology Fund for Future Development. This study was granted by the Korean Health Technology R&D Project, Ministry of Health & Welfare funded by the Korean Government (Grant No. HI12C1845), and work by Y.K.Cho was partially supported by IBS-R020-D1 funded by the Korean Government. This research was supported by Collaborative Genome Program for Fostering New Post-Genome industry through the National Research Foundation (NRF) funded by the Korean government (MSIT) (Grant No. NRF-2017M3C9A5031002), and also supported by National Research Foundation (NRF) grant funded by the Korean government (MSIT) (Grant No. 2019R1C1C1008646).

Clinical Trial Number

ClinicalTrials.gov Identifier No. NCT02934984
Risk factors at birth, in childhood and adolescence for the onset of musculoskeletal chronic pain in adulthood: a scoping review
Authors: Michele Margelli , Gianelli Alice , Borghi Lucia , Zanchetta Federico , Salvioli Stefano , Filippo Maselli
Published: May 2021

Background

Literature already confirmed that chronic pain is not only correlated to functional deficits, structural problems or neural alterations, but it is also strongly influenced by the presence of psychological and social factors. It was also observed that those factors can have an impact on the subject even after many years: in fact, pain experiences and traumatic events during childhood can lead to changes in stress and pain neural network area and to maladaptive behaviors that concur to develop chronic pain. The main purpose of this review is to identify the bio-psycho-social risk factors in developmental age that could lead to musculoskeletal chronic pain in adulthood.

Inclusion criteria

Every study about risk factors in developmental age (0-18) for the onset of musculoskeletal chronic pain in adulthood will be included. This scoping review will consider studies conducted in any context.

Methods

The proposed scoping review will be conducted in accordance with the Joanna Briggs Institute methodology (JBI) for scoping reviews.

The search will be carried out on 6 databases: MEDLINE, Cochrane Central, Scopus, CINHAL, Embase, and PEDro.

Selection and data extraction will be conducted by two blind independent researchers and inconsistencies will be resolved by a third reviewer.

The results will be presented in a schematic, tabular and descriptive format that will line up with the objectives and scope of the review.

Conclusions

This will be the first scoping review to provide a comprehensive overview of the topic. The results will add meaningful information for clinicians especially during the patient’s assessment. Furthermore, any knowledge gaps of the topic will be identified. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
Application of Omni-ATAC to Profile Chromatin Accessibility Before and After Ovarian Tissue Cryopreservation
Authors: Shannon Jennifer A. , Sundaresan Aishwarya , Bukulmez Orhan , Jiao Zexu , Capelouto Sarah , Carr Bruce , Banaszynski Laura A.
Published: May 2021

Ovarian tissue cryopreservation and subsequent autologous transplantation has allowed resumption of endocrine function as well as fertility in certain populations. However, graft function is short-lived due to ischemia and aberrant follicular activation post-transplantation. While many studies have focused on gene expression, we wanted to determine whether cryopreservation itself had a deleterious effect on regulatory elements that might influence transcriptional integrity and graft performance. In this study, we used Omni-ATAC to assess genome-wide chromatin accessibility in primary human follicles before and after cryopreservation. Omni-ATAC from fresh ovarian follicles identified active regulatory elements expected to be functional in oocytes and granulosa cells, and gene ontology was consistent with RNA translation/processing and DNA repair. While promoter accessibility was largely maintained in cryopreserved ovarian follicles, we observed a widespread increase in the number of accessible enhancers. Transcription factor motif analysis and gene ontology suggested that this dysregulation was focused around the epithelial-mesenchymal transition. Indeed, transcription factor binding was noted in major pathways involved in this transition: TGF-β and Wnt signaling. Overall, our work provides the first genomic analysis of active regulatory elements in matched fresh and cryopreserved ovarian follicles as they undergo the process of ovarian tissue cryopreservation. Our data suggest that the process of cryopreservation activates an epithelial-mesenchymal transition state, which may lead to graft burn-out post-transplantation. Optimizing this technique in relation to this transition may therefore be an important step towards improving graft longevity and patient outcomes in fertility preservation.

Summary sentence

Cryopreservation of ovarian cortical tissue results in activation of differentiation and EMT pathways in follicles, which may explain graft burnout after autotransplantation.
Spatial Association of Respiratory Health with Social and Environmental Factors: Case Study of Cook County, IL
Authors: Lotfata Aynaz , Hohl Alexander
Published: May 2021

Background

People who live with respiratory diseases like asthma are more likely at risk of serious illness. Spatial analytic techniques allow for discovering areas of concern and finding correlates of asthma prevalence.

Objective

There is growing interest in disentangling the impacts of socioeconomic and environmental factors on respiratory health, their spatial correlation, and the demographic profile of people at risk of respiratory diseases. It is important to know how people with asthma are geographically distributed and what social and environmental factors correlate with asthma. Thereby, the purpose of the study is to describe socioeconomic factors associated with asthma prevalence in Cook County, IL and to identify the significant risks and the protective factors to control asthma.

Data and Methods

Data obtained from CDC 2018 SVI, ACS, the City of Chicago Data Portal, HealthData.gov, and ESRI. In this paper, we illustrate the usefulness of geospatial regression analysis in the analysis and presentation of spatially distributed asthma prevalence among the population with disabilities, minorities with the language barrier, nonwhite population, age 17 and younger, and age 65 and older in the census tracts of Cook County, IL where Chicago Metropolitan Area located. In addition, we map the spatial variation of asthma prevalence with variation in the tree canopy, access to medical centers, air quality, and household quality. Lastly, we used bivariate mapping to illustrate the spatial distributions of residential land use and tree covers.

Results

Our findings show a good correlation between asthma and socioeconomic and physical factors including age 17 and younger, age 65 and older, population with disabilities, a minority with the language barrier, tree canopy, access to medical centers, air quality, and household quality. The aged 65 and older, 17 and younger, and people with disabilities are found to have a higher asthma prevalence in areas around the industrial corridors in southeast and west sides of Cook County, IL. Results may guide further decisions in planning for asthma research and intervention, especially for identifying vulnerable areas and people.
Double trouble: having two hosts reduces infection prevalence in vectored trypanosomatids
Authors: Hawra Al-Ghafli , Seth M. Barribeau
Published: May 2021

Trypanosomatids are a diverse family of protozoan parasites, some of which cause devastating human and livestock diseases. There are two distinct infection life-cycles in trypanosomatids; some species complete their entire life-cycle in a single host (monoxenous) while others infect two hosts (dixenous). Dixenous trypanosomatids are mostly vectored by insects, and the human trypanosomatid diseases are caused mainly by vectored parasites. While infection prevalence has been described for subsets of hosts and trypanosomatids, little is known about whether monoxenous and dixenous trypanosomatids differ in infection prevalence. Here, we use meta-analyses to synthesise all published evidence of trypanosomatid infection prevalence for the last two decades, encompassing 931 unique host-trypansomatid systems. In examining 581 studies that describe infection prevalence, we find, strikingly, that monoxenous species are two-fold more prevalent than dixenous species across all hosts. We also find that dixenous trypanosomatids have significantly lower infection prevalence in insects than their non-insect hosts. Within monoxenous trypanosomatids, genera infecting bees are most prevalent and infection prevalence does not vary between wild and managed bees. To our knowledge, these results reveal for the first time, a fundamental difference in infection prevalence according to host specificity where vectored species suffer from lower infection prevalence as a result of a ‘jack of all trades, master of none’ style trade-off between the vector and subsequent hosts.
Determination of HLA-DR level in cytotoxic T lymphocytes: a new validated tool to predict breast cancer response to treatment
Authors: Saraiva D.P. , Azeredo-Lopes S. , Antunes A. , Salvador R. , Borralho P. , Assis B. , Pereira I. , Seabra Z. , Negreiros I. , Jacinto A. , Braga S. , Cabral M. G.
Published: May 2021

Background

Neoadjuvant chemotherapy (NACT) is the usual treatment for locally-advanced breast cancer (BC). However, more than half of the patients lack an effective response to this treatment. Thus, it’s urgent to find predictive biomarkers. Recently, we proposed the HLA-DR expression level in cytotoxic T lymphocytes (CTLs) as a robust biomarker to select, in advance, patients that will actually benefit from NACT.

Patients and Methods

A total of 202 BC patients, 102 of which submitted to NACT, were enrolled in this study. 61 biopsies and 41 blood samples collected pre-NACT and 100 non-NACT tumor samples were immunophenotyped by flow cytometry. Both NACT and non-NACT patients were followed up for 34 months. Blood-isolated immune cells were cultured with BC cell lines in a 3D system.

Results

Here we confirmed that HLA-DR level in CTLs is a highly sensitive and specific biomarker to predict BC response to NACT, reflected in circulation and independent of the patients’ age, BC subtype and other tumor-immunological features. Therefore, we developed a predictive probability model, based on the determination of HLA-DR level in tumor-infiltrating CTLs, that could be used to guide therapeutic decisions. Interestingly, this biomarker was also associated with progression-free survival, regardless the treatment. Contrary to HLA-DRnegative CTLs, HLA-DR+ CTLs were able to reduce the viability of tumor cells, in culture, in agreement with their higher expression of activation, proliferation and cytotoxicity-related molecules. Tissue-residency and memory markers were also increased in HLA-DR+ CTLs. These anti-tumor features of HLA-DR+ CTLs may justify the clinical observations.

Conclusion

HLA-DR level in CTLs is a validated and independent biomarker to predict response to NACT which allow the establishment of a clinical meaningful tool to select in advance patients that will truly benefit from this treatment. Intriguingly, it may be further used as a biomarker of BC patients’ general prognosis.

Highlights

- HLA-DR level in cytotoxic T cells is an independent predictive factor of breast cancer response to NACT

- A predictive probability model based on this biomarker was developed as a new tool to improve treatment decisions

- HLA-DR level in cytotoxic T cells is also reflected systemically

- HLA-DR level in cytotoxic T cells is also a prognostic factor, associated with progression-free survival

- HLA-DR+ cytotoxic T cells exhibit several phenotypic and functional anti-tumor characteristics
Admixture mapping reveals loci for carcass mass in red deer x sika hybrids in Kintyre, Scotland
Authors: McFarlane S. Eryn , Pemberton Josephine M.
Published: May 2021

We deployed admixture mapping on a sample of 386 deer from a hybrid swarm between native red deer (Cervus elaphus) and introduced Japanese sika (Cervus nippon) sampled in Kintyre, Scotland to search for Quantitative Trait Loci (QTL) underpinning phenotypic differences between the species. These two species are highly diverged genetically (Fstbetween pure species, based on 50K SNPs, = 0.532) and phenotypically: pure red have on average twice the carcass mass of pure sika in our sample (38.7kg vs 19.1 kg). After controlling for sex, age and population genetic structure we found ten autosomal genomic locations with QTL for carcass mass. Effect sizes ranged from 0.191 to 1.839 Kg and as expected, in all cases the allele derived from sika conferred lower carcass mass. The sika population was fixed for all small carcass mass alleles, whereas the red deer population was typically polymorphic. GO term analysis of genes lying in the QTL regions are associated with oxygen transport. Although body mass is a likely target of selection, none of the SNPs marking QTL are introgressing faster or slower than expected in either direction.
Transcriptome-wide and Stratified Genomic Structural Equation Modeling Identify Neurobiological Pathways Underlying General and Specific Cognitive Functions
Authors: Grotzinger Andrew D. , de la Fuente Javier , Davies Gail , Nivard Michel G. , Tucker-Drob Elliot M.
Published: May 2021

Spearman’s observation in 1904 that distinct cognitive functions—such as reasoning, processing speed, and episodic memory—are positively intercorrelated has given rise to over a century of speculation and investigation into their common and domain-specific mechanisms of variation. Here we develop and validate Transcriptome-wide Structural Equation Modeling (T-SEM), a novel method for studying the effects of tissue-specific gene expression within multivariate space. We apply T-SEM to investigate the shared and unique functional genomic characteristics of seven, distinct cognitive traits (N= 11,263–331,679). We identify 184 genes associated with general cognitive function (g), including 10 novel genes not identified in univariate analysis for the individual cognitive traits. We go on to apply Stratified Genomic SEM to identify enrichment forgwithin 29 functional genomic categories. This includes categories indexing the intersection of protein-truncating variant intolerant (PI) genes and specific neuronal cell types, which we also find to be enriched for the genetic covariance betweengand a psychotic disorders factor.
A Method for Cost-Effective and Rapid Characterization of Genetic Parts
Authors: McManus John B. , Bernhards Casey B. , Sharpes Caitlin E. , Garcia David C. , Cole Stephanie D. , Murray Richard M. , Emanuel Peter A. , Lux Matthew W.
Published: May 2021

Characterizing and cataloging genetic parts are critical to the design of useful genetic circuits. Having well-characterized parts allows for the fine-tuning of genetic circuits, such that their function results in predictable outcomes. With the growth of synthetic biology as a field, there has been an explosion of genetic circuits that have been implemented in microbes to execute functions pertaining to sensing, metabolic alteration, and cellular computing. Here, we show a cost-effective and rapid method for characterizing genetic parts. Our method utilizes cell-free lysate, prepared in-house, as a medium to evaluate parts via the expression of a reporter protein. Template DNA is prepared by PCR-amplification using inexpensive primers to add variant parts to the reporter gene, and the template is added to the reaction as linear DNA without cloning. Parts that can be added in this way include promoters, operators, ribosome binding sites, insulators, and terminators. This approach, combined with the incorporation of an acoustic liquid handler and 384-well plates, allows the user to carry out high-throughput evaluations of genetic parts in a single day. By comparison, cell-based screening approaches require time-consuming cloning and have longer testing times due to overnight culture and culture density normalization steps. Further, working in cell-free lysate allows the user to exact tighter control over the expression conditions through the addition of exogenous components, or by titrating DNA concentrations rather than relying on limited plasmid copy numbers. Because this method retains a cell-like environment, the function of the genetic part will typically mimic its function in whole cells.

Well-characterized genetic parts are necessary for the design of novel genetic circuits. Here we describe a cost-effective, high-throughput method for rapidly characterizing genetic parts. Our method reduces cost and time by combining cell-free lysates, linear DNA to avoid cloning, and acoustic liquid handling to increase throughput and reduce reaction volumes.
Neutralization of B.1.1.28 P2 variant with sera of natural SARS-CoV-2 infection and recipients of BBV152 vaccine
Authors: Sapkal Gajanan , Yadav Pragya D. , Ella Raches , Abraham Priya , Patil Deepak Y. , Gupta Nivedita , Panda Samiran , Mohan V. Krishna , Bhargava Balram
Published: May 2021

The emergence of new SARS-CoV-2 variants has been a serious threat to the public health system and vaccination program. The variant of concerns have been the under investigation for their neutralizing potential against the currently available COVID-19 vaccines. Here, we have determined the neutralization efficacy of B.1.1.28.2 variant with the convalescent sera of individuals with natural infection and BBV152 vaccination. The two-dose vaccine regimen significantly boosted the IgG titer and neutralizing efficacy against both B.1.1.28.2 and D614G variants compared to that seen with natural infection. The study demonstrated 1.92 and 1.09 fold reductions in the neutralizing titer against B.1.1.28.2 variant in comparison with prototype D614G variant with sera of vaccine recipients and natural infection respectively.
Neural dynamics between anterior insular cortex and right supramarginal gyrus dissociate genuine affect sharing from automatic responses to pretended pain
Authors: Zhao Yili , Zhang Lei , Rütgen Markus , Sladky Ronald , Lamm Claus
Published: May 2021

Empathy for pain engages both shared affective responses and self-other distinction. In this study, we addressed the highly debated question of whether neural responses previously linked to affect sharing could result from the perception of salient affective displays. Moreover, we investigated how affect sharing and self-other distinction interact to determine our response to a pain that is either perceived as genuine or pretended (while in fact both were acted for reasons of experimental control). We found stronger activations in regions associated with affect sharing (anterior insula, aIns, and anterior mid-cingulate cortex, aMCC) as well as with affective self-other distinction (right supramarginal gyrus, rSMG), in participants watching video clips of genuine vs. pretended facial expressions of pain. Using dynamic causal modeling (DCM), we then assessed the neural dynamics between the right aIns and rSMG in these two conditions. This revealed a reduced inhibitory effect on the aIns to rSMG connection for genuine compared to pretended pain. For genuine pain only, brain-to-behavior regression analyses highlighted a linkage between this inhibitory effect on the one hand, and pain ratings as well as empathic traits on the other. These findings imply that if the pain of others is genuine and thus calls for an appropriate empathic response, neural responses in the aIns indeed seem related to affect sharing and self-other distinction is engaged to avoid empathic over-arousal. In contrast, if others merely pretend to be in pain, the perceptual salience of their painful expression results in neural responses that are down-regulated to avoid inappropriate affect sharing and social support.
Influenza viral particles harboring the SARS-CoV-2 spike RBD as a combination respiratory disease vaccine
Authors: Chaparian Ryan R. , Harding Alfred T. , Riebe Kristina , Karlsson Amelia , Sempowski Gregory D. , Heaton Nicholas S. , Heaton Brook E.
Published: May 2021

Vaccines targeting SARS-CoV-2 have gained emergency FDA approval, however the breadth against emerging variants and the longevity of protection remains unknown. Post-immunization boosting may be required, perhaps on an annual basis if the virus becomes an endemic pathogen. Seasonal influenza virus vaccines are already developed every year, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed a recombinant influenza A virus (IAV) genetic platform that “reprograms” the virus to package an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicits neutralizing antibodies and provides protection from lethal challenge with both pathogens. This technology may allow for leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses.
The effects of epistasis and linkage on the invasion of locally beneficial mutations and the evolution of genomic islands
Authors: Pontz Martin , Bürger Reinhard
Published: May 2021

We study local adaptation of a peripheral population by investigating the fate of new mutations using a haploid two-locus two-allele continent-island migration model. We explore how linkage, epistasis, and maladaptive gene flow affect the invasion probability of weakly beneficial de-novo mutations that arise on the island at an arbitrary physical distance to a locus that already maintains a stable migration-selection polymorphism. By assuming a slightly supercritical branching process, we deduce explicit conditions on the parameters that permit a positive invasion probability and we derive approximations for it. They show how the invasion probability depends on the additive and epistatic effects of the mutant, on its linkage to the polymorphism, and on the migration rate. We use these approximations together with empirically motivated distributions of epistatic effects to analyze the influence of epistasis on the expected invasion probability if mutants are drawn randomly from such a distribution and occur at a random physical distance to the existing polymorphism. We find that the invasion probability generally increases as the epistasis parameter increases or the migration rate decreases, but not necessarily as the recombination rate decreases. Finally, we shed light on the size of emerging genomic islands of divergence by exploring the size of the chromosomal neighborhood of the already established polymorphism in which 50% or 90% of the successfully invading mutations become established. These ‘window sizes’ always decrease in a reverse sigmoidal way with stronger migration and typically increase with increasing epistatic effect.
JNK activity modulates postsynaptic scaffold protein SAP102 and kainate receptor dynamics in dendritic spines
Authors: Kunde Stella-Amrei , Schmerl Bettina , Ahmadyar Elham , Rademacher Nils , Zieger Hanna L. , Shoichet Sarah A.
Published: May 2021

We show here that the dynamics of the synaptic scaffold molecule SAP102 are negatively regulated by JNK inhibition, that SAP102 is a direct phosphorylation target of JNK3, and that SAP102 regulation by JNK is restricted to neurons that harbour mature synapses. We further demonstrate that SAP102 and JNK3 cooperate in the regulated trafficking of kainate receptors to the cell membrane. Specifically, we observe that SAP102, JNK3, and the kainate receptor subunit GluK2 exhibit overlapping expression at synaptic sites, and that modulating JNK activity influences the surface expression of the kainate receptor subunit GluK2 in a neuronal context. We also show that SAP102 participates in this process in a JNK-dependent fashion. In summary, our data support a model in which JNK-mediated regulation of SAP102 influences the dynamic trafficking of kainate receptors to postsynaptic sites, and thus shed light on common pathophysiological mechanisms underlying the cognitive developmental defects associated with diverse mutations.
HyMM: Hybrid method for disease-gene prediction by integrating multiscale module structures
Authors: Xiang Ju , Meng Xiangmao , Wu Fang-Xiang , Li Min
Published: May 2021

Motivation

Identifying disease-related genes is important for the study of human complex diseases. Module structures or community structures are ubiquitous in biological networks. Although the modular nature of human diseases can provide useful insights, the mining of information hidden in multiscale module structures has received less attention in disease-gene prediction.

Results

We propose a hybrid method, HyMM, to predict disease-related genes more effectively by integrating the information from multiscale module structures. HyMM consists of three key steps: extraction of multiscale modules, gene rankings based on multiscale modules and integration of multiple gene rankings. The statistical analysis of multiscale modules extracted by three multiscale-module-decomposition algorithms (MO, AS and HC) shows that the functional consistency of the modules gradually improves as the resolution increases. This suggests the existence of different levels of functional relationships in the multiscale modules, which may help reveal disease-gene associations. We display the effectiveness of multiscale module information in the disease-gene prediction and confirm the excellent performance of HyMM by 5-fold cross-validation and independent test. Specifically, HyMM with MO can more effectively enhance the ability of disease-gene prediction; HyMM (MO, RWR) and HyMM (MO, RWRH) are especially preferred due to their excellent comprehensive performance, and HyMM (AS, RWRH) is also good choice due to its local performance. We anticipate that this work could provide useful insights for disease-module analysis and disease-gene prediction based on multi-scale module structures.

Availability

https://github.com/xiangiu0208/HvMM

Contact

limin@mail.csu.edu.cn

Supplementary information

Supplementary data are available atBioinformaticsonline.
Action at a distance: Defects in division plane positioning in the root meristematic zone affect cell organization in the differentiation zone
Authors: Mills Alison M. , Rasmussen Carolyn G
Published: May 2021

Cell division plane orientation is critical for plant and animal development and growth. TANGLED1 (TAN1) and AUXIN-INDUCED-IN-ROOT-CULTURES9 (AIR9) are division-site localized microtubule-binding proteins required for division plane positioning.tan1andair9 Arabidopsis thalianasingle mutants have minor or no noticeable phenotypes but thetan1 air9double mutant has synthetic phenotypes including stunted growth, misoriented divisions, and aberrant cell-file rotation in the root differentiation zone. These data suggest that TAN1 plays a role in nondividing cells. To determine whether TAN1 is required in elongating and differentiating cells in thetan1 air9double mutant, we limited its expression to actively dividing cells using the G2/M-specific promoter of the syntaxinKNOLLE(pKN:TAN1-YFP). Unexpectedly, in addition to rescuing division plane defects,pKN:TAN1-YFPrescued root growth and the root differentiation zone cell file rotation defects in thetan1 air9double mutant. This suggests that defects that occur in the meristematic zone later affect the organization of elongating and differentiating cells.

Summary Statement

Expression ofTAN1in the root meristematic zone rescues cell file rotation defects intan1 air9mutants, suggesting defects that occur in mitosis may influence organization of nondividing cells.
A gene drive does not spread easily in populations of the honey bee parasiteVarroa destructor
Authors: Faber Nicky R. , Meiborg Adriaan B. , McFarlane Gus R. , Gorjanc Gregor , Harpur Brock A.
Published: May 2021

Varroa mites (Varroa destructor) are the most significant threat to beekeeping worldwide. They are directly or indirectly responsible for millions of colony losses each year. Beekeepers are somewhat able to control Varroa populations through the use of physical and chemical treatments. However, these methods range in effectiveness, can harm honey bees, can be physically demanding on the beekeeper, and do not always provide complete protection from Varroa. More importantly, in some populations Varroa mites have developed resistance to available acaricides. Overcoming the Varroa mite problem will require novel and targeted treatment options. Here, we explore the potential of gene drive technology to control Varroa. We show that spreading a neutral gene drive in Varroa is possible but requires specific colony-level management practices to overcome the challenges of both inbreeding and haplodiploidy. Furthermore, continued treatment with acaricides is necessary to give a gene drive time to fix in the Varroa population. Unfortunately, a gene drive that impacts female or male fertility does not spread in Varroa. Therefore, we suggest that the most promising way forward is to use a gene drive which carries a toxin precursor or removes acaricide resistance alleles.
Burdwan University Thalassemia Severity (BUTS) Scoring System: A numerical Method For Defining the Clinicopathological status of Thalassaemia Patient
Authors: Basu Anupam , Chowdhury Prosanto Kumar , Chowdhuy Tamoghna , Sadhukhan Sukhendu , Chakrabarti Pabitra Kumar , Saha Dipankar , Pal Debashis
Published: May 2021

Background

β-haemoglobinopathies are the most common monogenic disorders worldwide. They present with extreme clinical heterogeneity, which makes generalized therapeutic approaches often ineffective. Currently available risk stratification approaches are either too complicated to be deployed at a primary healthcare level or are limited in their applicability across the spectrum of haemoglobinopathies. All current systems also classify patients into the three categories of mild, moderate and severe, where the moderate category is not well-characterized in terms of their expected prognosis.

Methods

The current study proposes a severity scoring scheme, utilizing five clinical parameters, viz., steady-state average pre-transfusion haemoglobin, age at presentation, transfusion interval, palpable splenomegaly and growth retardation to classify patients of various β-haemoglobinopathies into severe and non-severe categories. The study then proceeds to validate this scoring scheme on a clinically heterogeneous cohort of 224 Eastern Indian β-thalassaemia and β-haemoglobinopathy patients, and evaluate the predictive performance of the proposed scheme against a clinical standard.

Results

All of the chosen parameters except steady-state haemoglobin display strong individual contribution to the final determination of severity, though steady-state haemoglobin conferred increased discriminatory power to the overall scheme. The proposed system achieved an accuracy of 94% against the clinical standard.

Conclusions

The proposed risk stratification strategy, being almost entirely empirically-determined, should possess wider applicability across the spectrum of β-haemoglobinopathies than currently existing systems, and should also be more suitable than said systems for studying genotype-phenotype correlations especially within the Eastern Indian β-haemoglobinopathy population.
Raabin-WBC: a large free access dataset of white blood cells from normal peripheral blood
Authors: Kouzehkanan Zahra Mousavi , Saghari Sepehr , Tavakoli Eslam , Rostami Peyman , Abaszadeh Mohammadjavad , Mirzadeh Farzaneh , Satlsar Esmaeil Shahabi , Gheidishahran Maryam , Gorgi Fatemeh , Mohammadi Saeed , Hosseini Reshad
Published: May 2021

Accurate and early detection of peripheral white blood cell anomalies plays a crucial role in the evaluation of an individual’s well-being. The emergence of new technologies such as artificial intelligence can be very effective in achieving this. In this regard, most of the state-of-the-art methods use deep neural networks. Data can significantly influence the performance and generalization power of machine learning approaches, especially deep neural networks. To that end, we collected a large free available dataset of white blood cells from normal peripheral blood samples called Raabin-WBC. Our dataset contains about 40000 white blood cells and artifacts (color spots). To reassure correct data, a significant number of cells were labeled by two experts, and the ground truth of nucleus and cytoplasm were extracted by experts for some cells (about 1145), as well. To provide the necessary diversity, various smears have been imaged. Hence, two different cameras and two different microscopes were used. The Raabin-WBC dataset can be used for different machine learning tasks such as classification, detection, segmentation, and localization. We also did some primary deep learning experiments on Raabin-WBC, and we showed how the generalization power of machine learning methods, especially deep neural networks, was affected by the mentioned diversity.
Considerations for using reproduction data in toxicokinetic-toxicodynamic modelling
Authors: Jager Tjalling , Trijau Marie , Sherborne Neil , Goussen Benoit , Ashauer Roman
Published: May 2021

Toxicokinetic-toxicodynamic (TKTD) modelling is essential to make sense of the time dependence of toxic effects, and to interpret and predict consequences of time-varying exposure. These advantages have been recognised in the regulatory arena, especially for environmental risk assessment (ERA) of pesticides, where time-varying exposure is the norm. We critically evaluate the link between the modelled variables in TKTD models and the observations from laboratory ecotoxicity tests. For the endpoint reproduction, this link is far from trivial. The relevant TKTD models for sub-lethal effects are based on Dynamic-Energy Budget (DEB) theory, which specifies a continuous investment flux into reproduction. In contrast, experimental tests score egg or offspring release by the mother. The link between model and data is particularly troublesome when a species reproduces in discrete clutches, and even more so when eggs are incubated in the mother’s brood pouch (and release of neonates is scored in the test). This situation is quite common among aquatic invertebrates (e.g., cladocerans, amphipods, mysids), including many popular test species. We discuss these and other issues with reproduction data, reflect on their potential impact on DEB-TKTD analysis, and provide preliminary recommendations to correct them. Both modellers and users of model results need to be aware of these complications, as ignoring them could easily lead to unnecessary failure of DEB-TKTD models during calibration, or when validating them against independent data for other exposure scenarios.
Forest structure and degradation drive canopy gap sizes across the Brazilian Amazon
Authors: Rodrigues Reis Cristiano , Jackson Toby. D. , Gorgens Eric Bastos , Dalagnol Ricardo , Jucker Tommaso , Nunes Matheus Henrique , Ometto Jean Pierre , Aragão Luiz E. O. C. , Estraviz Rodriguez Luiz Carlos , Coomes David. A.
Published: May 2021

Canopy gaps are openings in the forest canopy resulting from branch fall and tree mortality events. Light reaches the lower layers of the canopy through these gaps, enabling understory trees to grow and maintaining the high heterogeneity and biodiversity of tropical forests. The size-frequency distribution of canopy gaps follows a power-law distribution, and the slope of this power-law (α) is a key indicator of forest structure and dynamics.

We detected canopy gaps using a unique LiDAR data set consisting of 650 transects randomly distributed across the Brazilian Amazon Forest providing an unprecedented perspective on forest structural variation over 2500 km2of forest. We then investigated how α varied with forest structure, elevation, soil fertility, water deficit, wind gust speed and lightning intensity.

We found that human modified forests had more large gaps than intact forests. Within the intact forests we observed a large-scale Northwest to Southeast pattern in α (more large gaps in the Southeast), which aligns with recent work on tree mortality rates. The two most important variables in predicting α were median canopy height and maximum modeled height, which had opposite effects on the number of large gaps. Forests with higher median canopy height contain fewer large gaps but the presence of very tall trees was associated with more large gaps. Environmental variables were of secondary importance in our model, with larger gaps occurring in drier forests with high soil fertility, wind speed, and lightning intensity.

The distribution of large gaps in the forest canopy varies substantially over the Brazilian Amazon as a result of canopy structure and mortality rates. We mapped this variation and found more large gaps in human modified forests, forests on fertile soils and those exposed to higher wind, lightning and drought stress. Increasing extreme weather events due to climate change may therefore increase the number of large gaps in currently intact forests, causing them to resemble human modified forests.
scShaper: ensemble method for fast and accurate linear trajectory inference from single-cell RNA-seq data
Authors: Smolander Johannes , Junttila Sini , Venäläinen Mikko S. , Elo Laura L.
Published: May 2021

Computational models are needed to infer a representation of the cells, i.e. a trajectory, from single-cell RNA-sequencing data that model cell differentiation during a dynamic process. Although many trajectory inference methods exist, their performance varies greatly depending on the dataset and hence there is a need to establish more accurate, better generalizable methods. We introduce scShaper, a new trajectory inference method that enables accurate linear trajectory inference. The ensemble approach of scShaper generates a continuous smooth pseudotime based on a set of discrete pseudotimes. We demonstrate that scShaper is able to infer accurate trajectories for a variety of nonlinear mathematical trajectories, including many for which the commonly used principal curves method fails. A comprehensive benchmarking with state-of-the-art methods revealed that scShaper achieved superior accuracy of the cell ordering and, in particular, the differentially expressed genes. Moreover, scShaper is a fast method with few hyperparameters, making it a promising alternative to the principal curves method for linear pseudotemporal ordering. scShaper is available as an R package athttps://github.com/elolab/scshaper.
Caspase-mediated regulation and cellular heterogeneity of the cGAS/STING pathway in Kaposi’s sarcoma-associated herpesvirus infection
Authors: Tabtieng Tate , Lent Rachel C. , Kaku Machika , Sanchez Alvaro Monago , Gaglia Marta Maria
Published: May 2021

As a result of the ongoing virus-host arms race, viruses have evolved numerous immune subversion strategies, many of which are aimed at suppressing the production of type I interferons (IFNs). Apoptotic caspases have recently emerged as important regulators of type I IFN signaling in both non-infectious contexts and during viral infection. Despite being widely considered anti-viral factors since they can trigger cell death, several apoptotic caspases promote viral replication by suppressing innate immune response. Indeed, we previously discovered that the AIDS-associated oncogenic gammaherpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV) exploits caspase activity to suppress the antiviral type I IFN response and promote viral replication. However, the mechanism of this novel viral immune evasion strategy is poorly understood, particularly how caspases antagonize IFN signaling during KSHV infection. Here we show that caspase activity inhibits the DNA sensor cGAS during KSHV lytic replication to block type I IFN induction. Furthermore, we use single-cell RNA-sequencing to reveal that the potent antiviral state conferred by caspase inhibition is mediated by an exceptionally small percentage of IFN-β-producing cells, thus uncovering further complexity of IFN regulation during viral infection. Collectively, these results provide insight into multiple levels of cellular type I IFN regulation that viruses co-opt for immune evasion. Unraveling these mechanisms can inform targeted therapeutic strategies for viral infections and reveal cellular mechanisms of regulating interferon signaling in the context of cancer and chronic inflammatory diseases.

Importance

Type I interferons are key factors that dictate the outcome of infectious and inflammatory diseases. Thus, intricate cellular regulatory mechanisms are in place to control IFN responses. While viruses encode their own immune-regulatory proteins, they can also usurp existing cellular interferon regulatory functions. We found that caspase activity during lytic infection with the AIDS-associated oncogenic gammaherpesvirus Kaposi’s sarcoma-associated herpesvirus inhibits the DNA sensor cGAS to block the antiviral type I IFN response. Moreover, single-cell RNA-sequencing analyses unexpectedly revealed that an exceptionally small subset of infected cells (<5%) produce IFN, yet this is sufficient to confer a potent antiviral state. These findings reveal new aspects of type I IFN regulation and highlight caspases as a druggable target to modulate cGAS activity.
A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance
Authors: Yang Kun , Longo Luisa , Narita Zui , Cascella Nicola , Nucifora Frederick C. , Coughlin Jennifer M. , Nestadt Gerald , Sedlak Thomas W. , Mihaljevic Marina , Wang Min , Kenkare Anshel , Nagpal Anisha , Sethi Mehk , Kelly Alexandra , Di Carlo Pasquale , Kamath Vidyulata , Faria Andreia , Barker Peter , Sawa Akira
Published: May 2021

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy, from a first episode psychosis cohort that includes 138 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a significant reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a significant reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC GSH, HP and SFG volumes, and age at onset could potentially be trait biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.
Warming sensitivity of spring phenology of deciduous species lies in their bud energy budget
Authors: Peaucelle Marc , Peñuelas Josep , Verbeeck Hans
Published: May 2021

Spring phenology is mainly driven by temperature in extratropical ecosystems. Contrasting responses of foliar phenology to climatic warming, however, have been reported in recent decades, raising important questions about the role of other environmental constraints, especially light. In fact, temperatures differ substantially between plant tissues and the air because plants absorb and lose energy. Yet, phenology studies always substitute plant tissue temperature by air temperature. Here, we explored how solar radiation, wind, and bud traits might affect spring phenology of deciduous forests through the energy budget of buds. We show that air temperature might be an imprecise and biased predictor of bud temperature. Our current interpretation of the plant phenological response to warming should be reconsidered, which will require new observations of bud traits and temperature for accurately quantifying their energy budget.