bluuebunny/crossref_metadata_2025 huggingface dataset:
Multisystem Inflammatory Syndrome in Children: Survey of Early Hospital Evaluation and Management
Authors: Dove Matthew L. , Jaggi Preeti , Kelleman Michael , Abuali Mayssa , Ang Jocelyn Y. , Ballan Wassim , Basu Sanmit K. , Campbell M. Jay , Chikkabyrappa Sathish M , Choueiter Nadine F. , Clouser Katherine N. , Corwin Daniel , Edwards Amy , Gertz Shira J. , Ghassemzadeh Rod , Jarrah Rima J. , Katz Sophie E. , Knutson Stacie M. , Kuebler Joseph D. , Lighter Jennifer , Mikesell Christine , Mongkolrattanothai Kanokporn , Morton Ted , Nakra Natasha A. , Olivero Rosemary , Osborne Christina M. , Parsons Sarah , Panesar Laurie E. , Patel Rupal M. , Schuette Jennifer , Thacker Deepika , Tremoulet Adriana H. , Vidwan Navjyot K. , Oster Matthew E.
Published: August 2020

Background

In the absence of evidence-based therapies for Multisystem Inflammatory Syndrome in Children (MIS-C), we aimed to describe the similarities and differences in the evaluation and treatment of MIS-C at hospitals in the United States.

Methods

We conducted a cross-sectional survey from June 16 to July 16, 2020 of U.S. children’s hospitals regarding protocols for patients with MIS-C. Elements included hospital characteristics, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers that had treated >5 patients vs. those that had treated ≤5 patients.

Results

Forty centers of varying size and experience with MIS-C participated. About half (21/40) of centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely used medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols for primarily the moderate or severe cases. Aspirin was commonly used including for mild cases, whereas heparin or low molecular weight heparin were used primarily in severe cases. In severe cases, anakinra and vasopressors were frequently recommended. Nearly all centers (39/40) recommended follow up with cardiology. There were similar findings between centers that had treated >5 patients vs. those that had treated ≤5 patients. A supplement containing hospital protocols is provided.

Conclusion

There are many similarities yet some key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C patients.

Article Summary

This survey of U.S. hospitals highlights the interhospital similarities and differences in management of Multisystem Inflammatory Syndrome in Children.

What’s Known on This Subject

MIS-C is a novel and life-threatening disease in children associated with COVID-19. Early cases were treated with immunomodulatory agents similar to current guidelines for Kawasaki disease. There are currently no evidence-based guidelines for treatment of MIS-C.

What This Study Adds

This study describes the protocolized evaluation and treatment of children with MIS-C at 40 hospitals in the U.S. These findings can help other hospitals create protocols to care for these children at their centers.
Estimating the total size of coronavirus epidemic in Algeria via different approaches
Authors: Rezki Mohamed
Published: August 2020

In this paper, several techniques and models proposed the spread of coronavirus (Covid-19) and determines approximately the final number of coronavirus infected cases as well as infection point (peak time) in Algeria. To see the goodness of the predicting techniques, a comparative study was done by calculating error indicators such as Root-Mean-Square Error (RMSE) and the sum of squared estimate of errors (SSE). The main technique used in this study is the logistic growth regression model widely used in epidemiology. The results only relate to the two months from the beginning of the epidemic in Algeria, which should be readjusted by integrating the new data over time, because hazardous parameters like possible relaxations (decrease of vigilance or laxity of society) can affect these results and generally cause a time lag in the curve. Hence, a re-estimation of the curves is always requested.
The last frontier for global Non-Communicable Disease action: the Emergency Department – a cross-sectional study from East Africa
Authors: Ngaruiya Christine , Wambua Mbatha , Mutua Thomas Kedera , Owambo Daniel Rafiki , Muchemi Morgan , Rop Kipkoech , Maciejewski Kaitlin R. , Leff Rebecca , Mūtua Mūgane , Wachira Benjamin
Published: August 2020

Background

Deaths due to non-communicable diseases (NCDs) have surpassed those due to communicable diseases globally and are projected to do so in Africa by 2030. Despite demonstrated effectiveness in high-income country (HIC) settings, the ED is a primary source of NCD care that has been under-prioritized in Africa. In this study, we assess the burden of leading NCDs and NCD risk factors in Kenyan Casualty Department patients, to inform interventions targeting patients with NCDs in emergency care settings.

Methods

Using the WHO STEPwise approach to surveillance (STEPS) tool and the Personal Health Questionnaire (PHQ-9), we conducted a survey of 923 adults aged 18 and over at Kenyatta National Hospital Emergency Department (KNH ED), the largest hospital in East Africa between May-October 2018. We used descriptive statistics and covariate-adjusted logistic analysis to analyze results. We included the following socio-demographic variables in our models: age, income, household size (t-test), sex, education, marital status, work status, and poverty status (chi-squared test or fisher’s exact test).

Findings

More than a third of respondents had hypertension (35.8%, n=225/628), one in five had raised blood sugar or diabetes (18.3%, n=61/333), and more than one in ten reported having cardiovascular disease (11.7%, n=90/769). Having lower levels of education was associated with tobacco use (OR 6.0, 95% CI 2.808– 12.618, p < 0.0001), while those with higher levels of education reported increased alcohol use (OR 0.620 (95% CI 0.386– 0.994, p = 0. 0472). While a predominant proportion of respondents had had some form of screening for either hypertension (80.3%, n=630/772), blood sugar (42.6%, n=334/767) or cholesterol (13.9%, n=109/766), the proportion of those on treatment was low, with the highest proportion being half of those diagnosed with hypertension reporting taking medication(51.6%, n=116/225). Determinants of disease burden were age, sex, and income.

Interpretation

Comprehension of the unique epidemiology and characteristics of patients presenting to the ED is key to guide care in African populations. Patient-driven interventions, and collaboration with community-based stakeholders such as patient navigators, are ideal considerations to sustainably address NCDs leveraging the ED in the resource-limited setting.

Funding

Hecht-Albert Global Health Pilot Innovation Award for Junior Faculty, Global Health Leadership Institute, Yale University.
Sex-specificity of mortality risk factors among hospitalized COVID-19 patients in New York City: prospective cohort study
Authors: Jun Tomi , Nirenberg Sharon , Kovatch Patricia , Huang Kuan-lin
Published: August 2020

Objective

To identify sex-specific effects of risk factors for in-hospital mortality among COVID-19 patients admitted to a hospital system in New York City.

Design

Prospective observational cohort study with in-hospital mortality as the primary outcome.

Setting

Five acute care hospitals within a single academic medical system in New York City.

Participants

3,086 hospital inpatients with COVID-19 admitted on or before April 13, 2020 and followed through June 2, 2020. Follow-up till discharge or death was complete for 99.3% of the cohort.

Results

The majority of the cohort was male (59.6%). Men were younger (median 64 vs. 70, p<0.001) and less likely to have comorbidities such as hypertension (32.5% vs. 39.9%, p<0.001), diabetes (22.6% vs. 26%, p=0.03), and obesity (6.9% vs. 9.8%, p=0.004) compared to women. Women had lower median values of laboratory markers associated with inflammation compared to men: white blood cells (5.95 vs. 6.8 K/uL, p<0.001), procalcitonin (0.14 vs 0.21 ng/mL, p<0.001), lactate dehydrogenase (375 vs. 428 U/L, p<0.001), C-reactive protein (87.7 vs. 123.2 mg/L, p<0.001). Unadjusted mortality was similar between men and women (28.8% vs. 28.5%, p=0.84), but more men required intensive care than women (25.2% vs. 19%, p<0.001). Male sex was an independent risk factor for mortality (OR 1.26, 95% 1.04-1.51) after adjustment for demographics, comorbidities, and baseline hypoxia. There were significant interactions between sex and coronary artery disease (p=0.038), obesity (p=0.01), baseline hypoxia (p<0.001), ferritin (p=0.002), lactate dehydrogenase (p=0.003), and procalcitonin (p=0.03). Except for procalcitonin, which had the opposite association, each of these factors was associated with disproportionately higher mortality among women.

Conclusions

Male sex was an independent predictor of mortality, consistent with prior studies. Notably, there were significant sex-specific interactions which indicated a disproportionate increase in mortality among women with coronary artery disease, obesity, and hypoxia. These new findings highlight patient subgroups for further study and help explain the recognized sex differences in COVID-19 outcomes.
Shoulder MRI Findings in Manual Wheelchair Users with Spinal Cord Injury
Authors: Jahanian Omid , Van Straaten Meegan G. , Goodwin Brianna M. , Lennon Ryan J. , Barlow Jonathan D. , Murthy Naveen S. , Morrow Melissa M. B.
Published: August 2020

Objective

To investigate the prevalence of rotator cuff and long head of the biceps pathologies in manual wheelchair (MWC) users with spinal cord injury (SCI).

Design

Cross-sectional study.

Setting

Academic medical center.

Participants

MWC users with SCI.

Outcome Measures

Participants’ demographic and anthropometric information, presence of shoulder pain, wheelchair user’s pain Index (WUSPI) scores, and MRI findings of shoulder pathologies including tendinopathy, tendon tears, and muscle atrophy.

Results

Forty-four adult MWC users with SCI participated in the study. Fifty-nine percent of the participants reported some shoulder pain. The prevalence of any tendinopathy across the rotator cuff and the long head of biceps tendon was 98%. The prevalence of tendinopathy in the supraspinatus was 86%, infraspinatus was 91%, subscapularis was 75%, and biceps was 57%. The majority of tendinopathies had mild or moderate severity. The prevalence of any tears was 68%. The prevalence of tendon tears in the supraspinatus was 48%, infraspinatus was 36%, subscapularis was 43%, and biceps was 12%. The majority of the tears were partial-thickness tears. Participants without tendon tears were significantly younger (p < 0.001) and had been dependent on wheelchair for significantly shorter time (p = 0.005) than those with tendon tears.

Conclusion

Mild and moderate shoulder tendinopathy and partial-thickness tendon tears were highly prevalent in MWC users with SCI. Additionally, the findings of this study suggest that strategies for monitoring shoulder pathologies in this population should not be overly reliant on patient-reported pain, but perhaps more concerned with years of wheelchair use and age.
Clinical Outcomes From COVID-19 Following Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers Among Patients with Hypertension in South Korea: A nationwide study
Authors: Kim Ju Hwan , Baek Yeon-Hee , Lee Hyesung , Choe Young June , Shin Hyun Joon , Shin Ju-Young
Published: August 2020

There is ongoing debate as to whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) use is associated with poor prognosis of coronavirus disease-2019 (COVID-19). We sought to investigate the association between ACEI/ARB use and risk of poor clinical outcomes from COVID-19. We identified 1,290 patients with hypertension, of which 682 had recorded ACEI/ARB use and 608 without the use during 30 days preceding the date of COVID-19 diagnosis in completely enumerated COVID-19 cohort in South Korea. Our primary endpoint was the clinical outcomes comprised of all-cause mortality, use of mechanical ventilation, intensive care unit (ICU) admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and Poisson regression model to estimate the relative risks (RR) and 95% confidence intervals (CI) to compare outcomes in ACEI/ARB users with non-users. Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW adjusted RR, 0.60; 95% CI, 0.42-0.85; p=0.0046). When assessed by individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW adjusted RR, 0.62; 95% CI, 0.35-1.09; p=0.0973) and respiratory events (IPTW adjusted RR, 0.99; 95% CI, 0.84-1.17; p=0.9043). Subgroup analysis showed a trend toward protective role of ACEIs and ARBs against overall outcomes in men (IPTW adjusted RR, 0.84; 95% CI, 0.69-1.03; p-for-interaction=0.008) and with pre-existing respiratory disease (IPTW adjusted RR, 0.74; 95% CI, 0.60-0.92; p-for-interaction=0.0023). We present clinical evidence to support continuing ACE/ARB use in completely enumerated hypertensive COVID-19 cohort in South Korea.
Persistence of anti-SARS-CoV-2 antibodies in non-hospitalized COVID-19 convalescent health care workers
Authors: Bruni Margherita , Cecatiello Valentina , Diaz-Basabe Angelica , Lattanzi Georgia , Mileti Erika , Monzani Silvia , Pirovano Laura , Rizzelli Francesca , Visintin Clara , Bonizzi Giuseppina , Giani Marco , Lavitrano Marialuisa , Faravelli Silvia , Forneris Federico , Caprioli Flavio , Pelicci Pier Giuseppe , Natoli Gioacchino , Pasqualato Sebastiano , Mapelli Marina , Facciotti Federica
Published: August 2020

Background

Coronavirus disease-19 (COVID-19) is a respiratory illness caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), a novel beta-coronavirus. Although antibody response to SARS-CoV-2 can be detected early during the infection, several outstanding questions remain to be addressed regarding magnitude and persistence of antibody titer against different viral proteins and their correlation with the strength of the immune response, as measured by serum levels of pro-inflammatory mediators.

Methods

An ELISA assay has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length nucleocapsid protein (N protein). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies as well as soluble pro-inflammatory mediators in the sera.

Results

Specificity and sensitivity of the ELISA assays were high for anti-RBD IgG and IgA (92-97%) and slightly lower for IgM and the Spike and N proteins (70-85%). The ELISA allowed quantification of IgM, IgG and IgA antibody responses against all the viral antigens tested and showed a correlation between magnitude of the antibody response and disease severity. Non-hospitalized subjects showed lower antibody titers and blood pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested. Noteworthy, in non-severe COVID-19 infections, antibody titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance.

Conclusions

Rapid decline in antibody titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection, suggesting that antibody-mediated protection against re-infection with SARS-CoV-2 is of short duration. These results suggest caution in use serological testing to estimate the prevalence of SARS-CoV-2 infection in the general population.
NetQuilt: Deep Multispecies Network-based Protein Function Prediction using Homology-informed Network Similarity
Authors: Barot Meet , Gligorijević Vladimir , Cho Kyunghyun , Bonneau Richard
Published: August 2020

Transferring knowledge between species is challenging: different species contain distinct proteomes and cellular architectures, which cause their proteins to carry out different functions via different interaction networks. Many approaches to proteome and biological network functional annotation use sequence similarity to transfer knowledge between species. These similarity-based approaches cannot produce accurate predictions for proteins without homologues of known function, as many functions require cellular or organismal context for meaningful function prediction. In order to supply this context, network-based methods use protein-protein interaction (PPI) networks as a source of information for inferring protein function and have demonstrated promising results in function prediction. However, the majority of these methods are tied to a network for a single species, and many species lack biological networks. In this work, we integrate sequence and network information across multiple species by applying an IsoRank-derived network alignment algorithm to create a meta-network profile of the proteins of multiple species. We then use this integrated multispecies meta-network as input features to train a maxout neural network with Gene Ontology terms as target labels. Our multispecies approach takes advantage of more training examples, and more diverse examples from multiple organisms, and consequently leads to significant improvements in function prediction performance. Further, we evaluate our approach in a setting in which an organism’s PPI network is left out, using other organisms’ network information and sequence homology in order to make predictions for the left-out organism, to simulate cases in which a newly sequenced species has no network information available.
Representation of contralateral visual space in the human hippocampus
Authors: Silson Edward H , Zeidman Peter , Knapen Tomas , Baker Chris I
Published: August 2020

The initial encoding of visual information primarily from the contralateral visual field is a fundamental organizing principle of the primate visual system. Recently, the presence of such retinotopic sensitivity has been shown to extend well beyond early visual cortex to regions not historically considered retinotopically sensitive. In particular, human scene-selective regions in parahippocampal and medial parietal cortex exhibit prominent biases for the contralateral visual field. Here we used fMRI to test the hypothesis that the human hippocampus, which is thought to be anatomically connected with these scene-selective regions, would also exhibit a biased representation of contralateral visual space. First, population receptive field mapping with scene stimuli revealed strong biases for the contralateral visual field in bilateral hippocampus. Second, the distribution of retinotopic sensitivity suggested a more prominent representation in anterior medial portions of the hippocampus. Finally, the contralateral bias was confirmed in independent data taken from the Human Connectome Project initiative. The presence of contralateral biases in the hippocampus – a structure considered by many as the apex of the visual hierarchy - highlights the truly pervasive influence of retinotopy. Moreover, this finding has important implications for understanding how this information relates to the allocentric global spatial representations known to be encoded therein.

Significance Statement

Retinotopic encoding of visual information is an organizing principle of visual cortex. Recent work demonstrates this sensitivity in structures far beyond early visual cortex, including those anatomically connected to the hippocampus. Here, using population receptive field modelling in two independent sets of data we demonstrate a consistent bias for the contralateral visual field in bilateral hippocampus. Such a bias highlights the truly pervasive influence of retinotopy, with important implications for understanding how the presence of retinotopy relates to more allocentric spatial representations.
Topographic connectivity reveals task-dependent retinotopic processing throughout the human brain
Authors: Knapen Tomas
Published: August 2020

The human visual system is organized as a hierarchy of maps that share the topography of the retina. These retinotopic maps have been identified throughout the brain, but how much of the brain is visually organized remains unknown. Here we demonstrate widespread stable visual organization beyond the traditional visual system. We analyzed detailed topographic connectivity with primary visual cortex during moviewatching, rest, and retinotopic mapping experiments to reveal that visual-spatial representations are warped by experimental condition and cognitive state. Specifically, traditionally visual regions alternate with default mode network and hippocampus in preferentially representing the center of the visual field. This visual role of hippocampus would allow it to implement sensory predictions by interfacing between abstract memories and concrete perceptions. These results indicate that pervasive sensory coding facilitates the communication between far-flung brain regions.
Decoding visual colour from scalp electroencephalography measurements
Authors: Hajonides Jasper E. , Nobre Anna C. , van Ede Freek , Stokes Mark G.
Published: August 2020

Recent advances have made it possible to decode various aspects of visually presented stimuli from patterns of scalp EEG measurements. As of recently, such multivariate methods have been commonly used to decode visual-spatial features such as location, orientation, or spatial frequency. In the current study, we show that it is also possible to track visual colour processing by using Linear Discriminant Analysis on patterns of EEG activity. Building on other recent demonstrations, we show that colour decoding: (1) reflects sensory qualities (as opposed to, for example, verbal labelling) with a prominent contribution from posterior electrodes contralateral to the stimulus, (2) conforms to a parametric coding space, (3) is possible in multi-item displays, and (4) is comparable in magnitude to the decoding of visual stimulus orientation. Through subsampling our data, we also provide an estimate of the approximate number of trials and participants required for robust decoding. Finally, we show that while colour decoding can be sensitive to subtle differences in luminance, our colour decoding results are primarily driven by measured colour differences between stimuli. Colour decoding opens a relevant new dimension in which to track visual processing using scalp EEG measurements, while bypassing potential confounds associated with decoding approaches that focus on spatial features.
Co-evolved maternal effects selectively eliminate offspring depending on resource availability
Authors: Hsu Bin-Yan , Müller Martina S. , Gahr Christoph L. , Dijkstra Cor , Groothuis Ton G. G. G.
Published: August 2020

Many plants and animals adaptively downsize the number of already-produced propagules if resources become insufficient to raise all of them. In birds, mothers often induce hatching asynchrony by incubating first eggs before last eggs are laid, creating an age/size hierarchy within broods which selectively eliminates the smallest chicks in poor food conditions. However, mothers also deposit more testosterone into late-laid eggs, which boosts competitive abilities of younger chicks, counteracts the competitive hierarchy, and ostensibly creates a paradox. Since testosterone also carries costs, we hypothesized that benefits of maternally deposited testosterone outweigh its costs in good food conditions, but that testosterone has a net detrimental effect in poor food conditions. We found experimental evidence that elevated maternal testosterone in the egg caused higher chick mortality in poor food conditions but better chick growth in good food conditions. These context-dependent effects resolve the paradox, suggesting co-evolution of two maternal effects, and explain inconsistent results of egg hormone manipulations in the literature.
Automated prediction of the clinical impact of structural copy number variations
Authors: Gaziova Michaela , Sladecek Tomas , Pos Ondrej , Stevko Martin , Krampl Werner , Pos Zuzana , Hekel Rastislav , Hlavacka Mario , Kucharik Marcel , Radvanszky Jan , Budis Jaroslav , Szemes Tomas
Published: August 2020

Introduction: Copy number variants (CNVs) play an important role in many biological processes, including the development of genetic diseases, making them attractive targets for genetic analyses. The interpretation of the effect of structural variants is a challenging problem due to highly variable numbers of gene, regulatory or other genomic elements affected by the CNV. This led to the demand for the interpretation tools that would relieve researchers, laboratory diagnosticians, genetic counselors, and clinical geneticists from the laborious process of annotation and classification of CNVs. Materials and Methods: We designed a classifier method based on the annotations of CNVs from several publicly available databases. The attributes take into account gene elements, regulatory elements affected by the CNV, as well as other CNVs with known clinical significance that overlap the candidate CNV. We also describe the process of model selection and the construction of training, validation, and test set. Results: The presented approach achieved more than 98% prediction accuracy on both copy number loss and copy number gain variants and can be improved by imposing probability thresholds to eliminate low confidence predictions. Discussion: Method has shown considerable performance in predicting the clinical impact of CNVs and therefore has a great potential to guide users to more precise conclusions. The CNV annotation and pathogenicity prediction can be fully automated, relieving users of tedious interpretation processes. Availability and Implementation: The results can be reproduced by following instructions at {{https://github.com/tsladecek/isv}}.
Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease
Authors: Smyth LJ , Kilner J , Nair V , Liu H , Brennan E , Kerr K , Sandholm N , Cole J , Dahlström E , Syreeni A , Salem RM , Nelson RG , Looker HC , Wooster C , Anderson K , McKay GJ , Kee F , Young I ,   NICOLA Collaborative Team,   Warren 3 and Genetics of Kidneys in Diabetes (GoKinD) Study Group, Andrews D , Forsblom C , Hirschhorn JN , Godson C , Groop PH , Maxwell AP , Susztak K , Kretzler M , Florez JC , McKnight AJ ,   on behalf of the GENIE consortium
Published: August 2020

A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), which is the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina’s Infinium MethylationEPIC BeadChip arrays (n=862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p≤×10−8and fold change ±2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM.

Top-ranked genes within which several dmCpGs were located and supported byin silicofunctional data, and replication where possible, include;AFF3, ARID5B, CUX1, ELMO1,FKBP5,HDAC4, ITGAL, LY9,PIM1, RUNX3, SEPTIN9, andUPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation.

Epigenetic alterations provide a dynamic link between an individual’s genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals, has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.
Selective attention in hypothesis-driven data analysis
Authors: Yanai Itai , Lercher Martin
Published: August 2020

When analyzing the results of an experiment, the mental focus on a specific hypothesis might prevent the exploration of other aspects of the data, effectively blinding one to new ideas. To test this notion, we performed an experiment in which we asked undergraduate students to analyze a fictitious dataset. In addition to being asked what they could conclude from the dataset, half of the students were asked to also test specific hypotheses. In line with our notion, students in the hypothesis-free group were almost 5 times more likely to observe an image of a gorilla when simply plotting the data, a proxy for an initial step towards data analysis. If these findings are representative also of scientific research as a whole, they warrant concern about the current emphasis on hypothesis-driven research, especially in the context of information-rich datasets such as those now routinely created in the biological sciences. Our work provides evidence for a link between the psychological effect of selective attention and hypothesis-driven data analysis, and suggests a hidden cost to having a hypothesis when analyzing a dataset.
Repeated evolution of inactive pseudonucleases in a fungal branch of the Dis3/RNase II family of nucleases
Authors: Ballou Elizabeth R. , Cook Atlanta G. , Wallace Edward W.J.
Published: August 2020

The RNase II family of 3′-5′ exoribonucleases are present in all domains of life, and eukaryotic family members Dis3 and Dis3L2 play essential roles in RNA degradation. Ascomycete yeasts contain both Dis3 and inactive RNase II-like “pseudonucleases”. These function as RNA-binding proteins that affect cell growth, cytokinesis, and fungal pathogenicity. Here, we show how these pseudonuclease homologs, includingSaccharomyces cerevisiaeSsd1, are descended from active Dis3L2 enzymes. During fungal evolution, active site mutations in Dis3L2 homologs have arisen at least four times, in some cases following gene duplication. The N-terminal cold-shock domains and regulatory features are conserved across diverse dikarya and mucoromycota, suggesting that the non-nuclease function require this region. In the basidiomycete pathogenic yeastCryptococcus neoformans, the single Ssd1/Dis3L2 homolog is required for cytokinesis from polyploid “titan” growth stages and yet retains an active site sequence signature. We propose that that a nuclease-independent function for Dis3L2 arose in an ancestral hyphae-forming fungus. This second function has been conserved across hundreds of millions of years, while the RNase activity was lost repeatedly in independent lineages.
Cell-type-specific alternative polyadenylation (APA) genes reveal the function of dynamic APA in complex tissues
Authors: Bai Yulong , Qin Yidi , Fan Zhenjiang , Morrison Robert M. , Nam KyongNyon , Zarour Hassane Mohamed , Koldamova Radosveta , Padiath Quasar Saleem , Kim Soyeon , Park Hyun Jung
Published: August 2020

Alternative polyadenylation (APA) causes shortening or lengthening of the 3’-untranslated region (3’-UTR) of genes across multiple cell types. Bioinformatic tools have been developed to identify genes that are affected by APA (APA genes) in single-cell RNA-Seq (scRNA-Seq) data. However, they suffer from low power, and they cannot identify APA genes specific to each cell type (cell-type-specific APA) when multiple cell types are analyzed. To address these limitations, we developed scMAPA that systematically integrates two novel steps. First, scMAPA quantifies 3’-UTR long and short isoforms without requiring assumptions on the read density shape of input data. Second, scMAPA estimates the significance of the APA genes for each cell type while controlling confounders. In the analyses on our novel simulation data and human peripheral blood mono cellular data, scMAPA showed enhanced power in identifying APA genes. Further, in mouse brain data, scMAPA identifies cell-type-specific APA genes, improving interpretability for the cell-type-specific function of APA. We further showed that this improved interpretability helps to understand a novel role of APA on the interaction between neurons and blood vessels, which is critical to maintaining the operational condition of brains. With high sensitivity and interpretability, scMAPA shed novel insights into the function of dynamic APA in complex tissues.

Key Points

We developed a bioinformatic tool, scMAPA, that identifies dynamic APA across multiple cell types and a novel simulation pipeline to assess performance of such tools in APA calling.

In simulation data of various scenarios from our novel simulation pipeline, scMAPA achieves sensitivity with a minimal loss of specificity.

In human peripheral blood monocellular data, scMAPA identifies APA genes accurately and robustly, finding unique associations of APA with hematological processes.

scMAPA identifies APA genes specific to each cell type in mouse brain data while controlling confounders that sheds novel insights into the complex molecular processes.
Network variants are similar between task and rest states
Authors: Kraus Brian T. , Perez Diana , Ladwig Zach , Seitzman Benjamin A. , Dworetsky Ally , Petersen Steven E. , Gratton Caterina
Published: August 2020

Recent work has demonstrated that individual-specific variations in functional networks (that we call “network variants”) can be identified in individuals using functional magnetic resonance imaging (fMRI). These network variants exhibit reliability over time with resting-state fMRI data. These properties have suggested that network variants may be trait-like markers of individual differences in brain organization. Another test of this conclusion would be to examine if network variants are stable between task and rest states. Here, we use precision data from the Midnight Scan Club (MSC) to demonstrate that (1) task data can be used to identify network variants reliably, (2) these network variants show substantial spatial overlap with those observed in rest, although state-specific effects are present, (3) network variants assign to similar canonical functional networks in different states, and (4) single tasks or a combination of multiple tasks produce similar network variants to rest. Together, these findings further reinforce the trait-like nature of network variants and demonstrate the utility of using task data to define network variants.
Inference of ploidy by leveraging read depth from amplicon sequencing
Authors: Delomas Thomas A. , Willis Stuart C. , Schreier Andrea , Narum Shawn
Published: August 2020

Variation in ploidy occurs naturally in select plant and animal species. Ploidy variation can also occur spontaneously or be induced during artificial propagation of fish and shellfish. Studying species and systems that have variable ploidy requires techniques to infer ploidy of individuals. Massively parallel sequencing of biallelic SNPs has been used to infer ploidy, but existing techniques have several drawbacks. These include being limited to only comparing a fixed number of ploidies (diploidy, triploidy, and tetraploidy) and requiring that heterozygous genotypes in an individual be identified prior to ploidy inference. We describe a method of inferring ploidy from sequencing of biallelic SNPs based on beta-binomial mixture models. This method is generalized to apply to any ploidy and does not require prior identification of heterozygous genotypes. We demonstrate efficacy of this method for comparing ancestral octoploidy, decaploidy, and dodecaploidy (tetraploidy, pentaploidy, and hexaploidy for the sequenced SNPs) in white sturgeon and diploidy and triploidy in Chinook salmon with amplicon sequencing (GT-seq) data. Results indicated that ploidy could be reliably estimated for individuals based on distinct distribution of log-likelihood ratios (LLR) for known ploidy samples of both species that were tested. Confidence in ploidy estimates increased with sequencing depth. We encourage users to explore the sequencing depths and LLR critical values that provide reliable estimates of ploidy for a given organism and set of SNPs. We expect that the R package provided will empower studies of genetic variation and inheritance in organisms that vary in ploidy naturally or as a result of artificial propagation practices.
Spatially localized cluster solutions in inhibitory neural networks
Authors: Ryu Hwayeon , Miller Jennifer , Teymuroglu Zeynep , Wang Xueying , Booth Victoria , Campbell Sue Ann
Published: August 2020

Neurons in the inhibitory network of the striatum display cell assembly firing patterns which recent results suggest may consist of spatially compact neural clusters. Previous computational modeling of striatal neural networks has indicated that non-monotonic, distance-dependent coupling may promote spatially localized cluster firing. Here, we identify conditions for the existence and stability of cluster firing solutions in which clusters consist of spatially adjacent neurons in inhibitory neural networks. We consider simple non-monotonic, distance-dependent connectivity schemes in weakly coupled 1-D networks where cells make strong connections with theirkthnearest neighbors on each side. Using the phase model reduction of the network system, we prove the existence of cluster solutions where neurons that are spatially close together are also synchronized in the same cluster, and find stability conditions for these solutions. Our analysis predicts the long-term behavior for networks of neurons, and we confirm our results by numerical simulations of biophysical neuron network models. Additionally, we add weaker coupling between closer neighbors as a perturbation to our network connectivity. We analyze the existence and stability of cluster solutions of the perturbed network and validate our results with numerical simulations. Our results demonstrate that an inhibitory network with non-monotonic, distance-dependent connectivity can exhibit cluster solutions where adjacent cells fire together.
Built to change: dominance strategy changes with life stage in a primitively eusocial bee
Authors: Orlova Margarita , Treanore Erin , Amsalem Etya
Published: August 2020

Access to reproduction is determined by an individual dominance’s rank in many species and is achieved through aggression and/or dominance signalling. In eusocial insects one or several dominant females (queens) monopolize reproduction but to what extent queens rely on aggression and signalling remains obscure. Aggression is costly and its efficiency depends on the group size, whereas signalling may reduce the risks and costs of aggression. Both strategies are used to regulate reproduction in social taxa, with aggression being more common in small social groups, compared to signalling in larger societies.

Here, we examine the use of aggression and chemical signalling in a social species (Bombus impatiens) where the dominant queen interacts with increasing numbers of workers as she ages.

We found that the queens’ strategy to monopolize reproduction changes with life stage, shifting from overt aggression to chemical signalling as the queen gets older. Particularly, old queens exhibited a higher ratio of short to long cuticular hydrocarbons compared to young queens, an endogenous shift that was attributed to age, as all egg-laying queens were fecund and kept with the same number of workers. Our findings contribute to the understanding of reproductive dominance in the context of an individual’s life history.
Isolating Compounds that Inhibit EV 71 Virus
Authors: Murali Giridhar , Kejriwal Rishabh , Olson David , Alexandrescu Lauren , White Simon
Published: August 2020

Enterovirus 71, or EV 71, is responsible for causing Hand, Foot, and Mouth disease in humans. In particular, it is especially deadly when children and small infants are exposed. The objective of this research paper is to address the possibility of a novel antiviral drug that can be used once infection of EV 71 has occurred. The methods for this research include transformation ofE. coliwith the genetic information from Enterovirus 71, growth of theE. colicolonies in the lab setting, 2C protein purification, and ATPase assays with drug testing. Of the 364 drugs tested in the ATPase assay, a combination of two of them (Mitrofudil and N6-Benzyladenosine) indicated a stoppage in activity of ATPase, signaling no further activity of the enzyme and viral proliferation.
Fitness benefit plays a vital role in the retention of thePi-tasusceptible alleles
Authors: Liu Jia , Wang Yue , Zhang Suobing , Wu Fan , Wang Long , Xue Jiayu , Zhang Yanmei , Xie Pengfei , Hang Yueyu , Sun Xiaoqin
Published: August 2020

In plants, large numbers ofRgenes, which segregate as loci with alternative alleles conferring different resistance to pathogens, have been maintained over a long evolutionary time. In theory, there seem to be no reason for hosts to harbor these susceptible alleles in view of their null contribution to resistance. As such, why should populations support disease-susceptible individuals along with disease-resistant individuals? In rice, a single copyRgenePi-tasegregates for two expressed clades of alleles, one resistant and the other susceptible. We discovered that knockout of thePi-tasusceptible alleles induced drastic fitness decline in the absence of pathogens. Gene expression profiling and endogenous hormones quantification showed that the susceptible alleles might serve as an off-switch to the downstream immune signaling, thus contributing to fine-tuning of plant defense response. The fitness benefit of carrying a susceptiblePi-taallele provides a plausible explanation for their retention in the genome.
Memory drives the formation of animal home ranges: evidence from a reintroduction
Authors: Ranc Nathan , Cagnacci Francesca , Moorcroft Paul R.
Published: August 2020

Most animals live in a characteristic home range, a space-use pattern thought to emerge from the benefits of memory-based movements; however, a general model for characterizing and predicting their formation in the absence of territoriality has been lacking. Here, we use a mechanistic movement model to quantify the role of memory in the movements of a large mammal reintroduced into a novel environment, and to predict observed patterns of home range emergence. We show that an interplay between memory and resource preferences is the primary process influencing the movements of reintroduced roe deer (Capreolus capreolus). Our memory-based model fitted with empirical data successfully predicts the formation of home ranges, as well as emerging properties of movement and revisits observed in the reintroduced animals. These results provide a quantitative framework for combining memory-based movements, resource preference and the emergence of home ranges in nature.
Notch-Directed Germ Cell Proliferation Is Mediated by Proteoglycan-Dependent Transcription
Authors: Gopal Sandeep , Amran Aqilah , Elton Andre , Ng Leelee , Pocock Roger
Published: August 2020

Notch receptors are essential membrane-bound regulators of cell proliferation and differentiation in metazoa. In the nematodeCaenorhabditis elegans, correct expression of GLP-1 (germline proliferation-1), a germline-expressed Notch receptor, is important for germ cell maintenance. However, mechanisms that regulate GLP-1 expression are undefined. Here, we demonstrate that an AP-2 transcription factor (APTF-2) regulates GLP-1 expression through calcium-dependent binding to a conserved motif in theglp-1promoter. Our data reveals that SDN-1 (syndecan-1), a transmembrane proteoglycan, regulates a TRP calcium channel in the soma to modulate the interaction between APTF-2 andglp-1promoter - thus providing a potential communication nexus between the germline and its somatic environment to control germ cell fate decisions.
Comparative study of curvature sensing mediated by F-BAR domain and an intrinsically disordered region of FBP17
Authors: Su Maohan , Zhuang Yinyin , Miao Xinwen , Zeng Yongpeng , Gao Weibo , Zhao Wenting , Wu Min
Published: August 2020

Membrane curvature has emerged as an intriguing physical organization principle underlying biological signaling and membrane trafficking. FBP17 of the CIP4/FBP17/Toca-1 F-BAR family is unique in the BAR family because its structurally folded F-BAR domain does not contain any hydrophobic motifs that insert into lipid bilayer. While it has been widely assumed so, whether the banana-shaped F-BAR domain alone can sense curvature has never been experimentally demonstrated. Using a nanopillar-supported lipid bilayer system, we found that the F-BAR domain of FBP17 displayed minimal curvature sensingin vitro. We further identified an alternatively spliced intrinsically disordered region (IDR) of FBP17 next to its F-BAR domain that is conserved in sequence across species. The IDR senses membrane curvature and its sensing ability greatly exceeds that of F-BAR domain alone. In living cells, presence of the IDR domain changed the dynamics of FBP17 recruitment in a curvature-coupled cortical wave system. Collectively, we propose that FBP17 does sense curvature but contrary to the common belief, its curvature sensing capability largely originates from its disordered region, not F-BAR domain itself.
The genome of low-chill Chinese plum ‘Sanyueli’ (Prunus salicinaLindl.) provides insights into the regulation of the chilling requirement of flower buds
Authors: Fang Zhi-Zhen , Lin-Wang Kui , Dai He , Zhou Dan-Rong , Jiang Cui-Cui , Espley Richard V. , Lin Yan-Juan , Pan Shao-Lin , Ye Xin-Fu
Published: August 2020

Chinese plum (Prunus salicinaLindl.) is a stone fruit that belongs to thePrunusgenus and plays an important role in the global production of plum. In this study, we report the genome sequence of the Chinese plum ‘Sanyueli’, which is known to have a low-chill requirement for flower bud break. The assembled genome size was 308.06 Mb, with a contig N50 of 815.7 kb. A total of 30,159 protein-coding genes were predicted from the genome and 56.4% (173.39 Mb) of the genome was annotated as repetitive sequence. Bud dormancy is influenced by chilling requirement in plum and partly controlled byDORMANCY ASSOCIATED MADS-box(DAM) genes. Six tandemly arrayedPsDAMgenes were identified in the assembled genome. Sequence analysis ofPsDAM6in ‘Sanyueli’revealed the presence of large insertions in the intron and exon regions. Transcriptome analysis indicated that the expression ofPsDAM6in the dormant flower buds of ‘Sanyueli’ was significantly lower than that in the dormant flower buds of the high chill requiring ‘Furongli’ plum. In addition, the expression ofPsDAM6was repressed by chilling treatment. The genome sequence of ‘Sanyueli’ plum provides a valuable resource for elucidating the molecular mechanisms responsible for the regulation of chilling requirements, and is also useful for the identification of the genes involved in the control of other important agronomic traits and molecular breeding in plum.