bluuebunny/crossref_metadata_2025 huggingface dataset:
Lineage and Spatial Mapping of Glioblastoma-associated Immunity
Authors: Ravi Vidhya M. , Neidert Nicolas , Will Paulina , Joseph Kevin , Maier Julian P. , Kückelhaus Jan , Vollmer Lea , Goeldner Jonathan M , Behringer Simon P. , Scherer Florian , Boerries Melanie , Follo Marie , Weiss Tobias , Delev Daniel , Kernbach Julius , Franco Pamela , Schallner Nils , Dierks Christine , Carro Maria Stella , Hofmann Ulrich G. , Fung Christian , Beck Jürgen , Sankowski Roman , Prinz Marco , Schnell Oliver , Henrik Heiland Dieter
Published: June 2020

The diversity of molecular states and cellular plasticity of immune cells in the glioblastoma environment is still poorly understood. Here, we performed scRNA sequencing of the immune compartment and mapped potential cellular interactions leading to an immunosuppressive microenvironment and dysfunction of T cells. Through inferring the dynamic adaptation during T cell activation, we identified three different terminal states with unique transcriptional programs. Modeling of driver genes for terminal T cell fate identified IL-10 signaling alterations in a subpopulation of HAVCR2(+) T cells. To explore in depth cellular interactions, we established anin-silicomodel by the integration of spatial transcriptomic and scRNA-sequencing, and identified a subset of HMOX1+myeloid cells defined by IL10 release leading to T cell exhaustion. We found a spatial overlap between HMOX(+) myeloid and HAVCR2(+) T cells, suggesting that myeloid-lymphoid interaction causes immunosuppression present in tumor regions with enriched mesenchymal gene expression. Using human neocortical GBM model, coupled with patient-derived T cells, we confirmed that the functional interaction between myeloid and lymphoid cells, leads to a dysfunctional state of T cells. This IL-10 driven T cell exhaustion was found to be rescued by JAK/STAT inhibition. A comprehensive understanding of the cellular states and plasticity of lymphoid cells in GBM will aid towards successful immunotherapeutic approaches.
Brain Tumor IDH, 1p/19q, and MGMT Molecular Classification Using MRI-based Deep Learning: Effect of Motion and Motion Correction
Authors: Nalawade Sahil S. , Yu Fang F. , Bangalore Yogananda Chandan Ganesh , Murugesan Gowtham K. , Shah Bhavya R. , Pinho Marco C. , Wagner Benjamin C. , Mickey Bruce , Patel Toral R. , Fei Baowei , Madhuranthakam Ananth J. , Maldjian Joseph A.
Published: June 2020

Deep learning has shown promise for predicting glioma molecular profiles using MR images. Before clinical implementation, ensuring robustness to real-world problems, such as patient motion, is crucial. We sought to evaluate the effects of motion artifact on glioma marker classifier performance and develop a deep learning motion correction network to restore classification accuracies. T2w images and molecular information were retrieved from the TCIA and TCGA databases. Three-fold cross-validation was used to train and test the motion correction network on artifact-corrupted images. We then compared the performance of three glioma marker classifiers (IDH mutation, 1p/19q codeletion, and MGMT methylation) using motion-corrupted and motion-corrected images. Glioma marker classifier performance decreased markedly with increasing motion corruption. Applying motion correction effectively restored classification accuracy for even the most motion-corrupted images. For IDH classification, an accuracy of 99% was achieved, representing a new benchmark in non-invasive image-based IDH classification and exceeding the original performance of the network. Robust motion correction can enable high accuracy in deep learning MRI-based molecular marker classification rivaling tissue-based characterization.

STATEMENT OF SIGNIFICANCE

Deep learning networks have shown promise for predicting molecular profiles of gliomas using MR images. We demonstrate that patient motion artifact, which is frequently encountered in the clinic, can significantly impair the performance of these algorithms. The application of robust motion correction algorithms can restore the performance of these networks, rivaling tissue-based characterization.
Haplotype-Resolved Assembly for Synthetic Long Reads Using a Trio-Binning Strategy
Authors: Xu Mengyang , Guo Lidong , Du Xiao , Li Lei , Deng Li , Wang Ou , Ni Ming , Yang Huanming , Xu Xun , Liu Xin , Huang Jie , Fan Guangyi
Published: June 2020

The accuracy and completeness of genome haplotyping are crucial for characterizing the relationship between human disease susceptibility and genetic variations, especially for the heterozygous variations. However, most of current variations are unphased genotypes, and the construction of long-range haplotypes remains challenging. We introduced ade novohaplotype-resolved assembly tool, HAST that exports two haplotypes of a diploid species for synthetic long reads with trio binning. It generates parental distinguishingk-mer libraries, partitions reads from the offspring according to the unique markers, and individually assembles them to resolve the haplotyping problem. Based on the stLFR co-barcoding data of an Asian as well as his parental massive parallel sequencing data, we utilized HAST to recover both haplotypes with a scaffold N50 of >11 Mb and an assembly accuracy of 99.99995% (Q63). The complete and accurate employment of long-range haplotyping information provided sub-chromosome level phase blocks (N50 ∼13 Mb) with 99.6% precision and 94.1% recall on average. We suggest that the accurate and efficient approach accomplishes the regeneration of the haplotype chromosomes with trio binning, thus promoting the determination of haplotype phase, the heterosis of crossbreeding, and the formation of autopolyploid and allopolyploid.
Trends and gaps in the use of citizen science derived data as input for species distribution models: a quantitative review
Authors: Feldman Mariano J. , Imbeau Louis , Marchand Philippe , Mazerolle Marc J. , Darveau Marcel , Fenton Nicole J.
Published: June 2020

Citizen science (CS) currently refers to some level of volunteer participation in any discipline of scientific research. Over the last two decades, nature-based CS has flourished due to innovative technology, novel devices, and widespread digital platforms used to collect and classify species occurrence data. For scientists, CS offers a low-cost approach of collecting species occurrence information at large spatial scales that otherwise would be prohibitively expensive. We examined the trends and gaps linked to the use of CS as a source of data for species distribution models (SDMs), in order to propose guidelines and highlight solutions. We conducted a quantitative literature review of 224 peer-reviewed articles to measure how the representation of different taxa, regions, and data types have changed in SDM publications since the 2010s. Our review shows that the number of papers using CS for SDMs has increased at approximately double the rate of the overall number of SDM papers. However, disparities in taxonomic and geographic coverage remain in studies using CS. Western Europe and North America were the regions with the most coverage (71.2%). Papers on birds (51.2%) and mammals (26.2%) outnumbered other taxa. Among invertebrates, flying insects including Lepidoptera and Odonata received the most attention. Compared to studies on animal taxa, papers on plants using CS data remain rare. Although the aims and scope of SDM papers are diverse, conservation remained the central theme of SDM using CS data. We present examples of the use of CS and highlight recommendations to motivate further research, such as combining multiple data sources and promoting local and traditional knowledge. We hope our findings will strengthen citizen-researchers partnerships to better inform SDMs, especially for less-studied taxa and regions. Researchers stand to benefit from the large quantity of data available from CS sources to improve global predictions of species distributions.
Hemodynamic and electromechanical effects of paraquat in rat heart
Authors: Lin Chih-Chuan , Hsu Kuang-Hung , Chang Gwo-Jyh
Published: June 2020

Paraquat (PQ) is a highly lethal herbicide. Ingestion of large quantities of PQ usually results in cardiovascular collapse and eventually death. However, the mechanism of acute PQ poisoning induced cardiotoxicity is poorly understood. Therefore, the purpose of the present study was to aim to investigate the mechanisms of PQ induced cardiotoxicity by examining the effects of PQ on hemodynamics in vivo, as well as in vitro on isolated hearts and ventricular myocytes in rats. Intravenous administration of PQ (100 or 180 mg/kg) in anesthetized rats induced dose-dependent decreases in heart rate, blood pressure, and cardiac contractility (left ventricular [LV] dP/dtmax). Furthermore, it prolonged the rate-corrected QT (QTc) interval. In Langendorff-perfused isolated hearts, PQ (33 or 60 μM) decreased LV pressure and contractility (LV dP/dtmaxin isolated ventricular myocytes), PQ (10–60 μM) decreased the amplitude of Ca2+transients and cell shortening in a concentration-dependent manner. Patch-clamp experiments demonstrated that PQ decreased the amplitude and availability of the transient outward K+channel (Ito) and altered its gating kinetics. These results suggest that PQ-induced cardiotoxicity results mainly from diminished Ca2+transients and inhibited K+channels, which lead to the suppression of LV contractile force and prolongation of the QTc interval.
Autophagy in T cells from aged donors is maintained by spermidine, and correlates with function and vaccine responses
Authors: Alsaleh Ghada , Panse Isabel , Swadling Leo , Zhang Hanlin , Meyer Alain , Lord Janet , Barnes Eleanor , Klenerman Paul , Green Christopher , Simon Anna Katharina
Published: June 2020

Older adults are at high risk for infectious diseases such as the recent COVID-19 and vaccination seems to be the only long-term solution to the pandemic. While most vaccines are less efficacious in older adults, little is known about the molecular mechanisms that underpin this. Autophagy, a major degradation pathway and one of the few processes known to prevent aging, is critical for the maintenance of immune memory in mice. Here, we show induction of autophagy is specifically induced in human vaccine-induced antigen-specific T cellsin vivo. Reduced IFNγ secretion by vaccine-induced T cells in older vaccinees correlates with low autophagy. We demonstrate in human cohorts that levels of the endogenous autophagy-inducing metabolite spermidine, fall with age and supplementing itin vitrorecovers autophagy and T cell function. Finally, our data show that endogenous spermidine maintains autophagy via the translation factor eIF5A and transcription factor TFEB. With these findings we have uncovered novel targets and biomarkers for the development of anti-aging drugs for human T cells, providing evidence for the use of spermidine in improving vaccine immunogenicity in the aged human population.
Modelling parameter uncertainty reveals bushmeat yields versus survival trade-offs in heavily-hunted duikerCephalophusspp.
Authors: Barychka Tatsiana , Purves Drew W. , Milner-Gulland E.J. , Mace Georgina M.
Published: June 2020

Reliably predicting sustainable exploitation levels for many tropical species subject to hunting remains a difficult task, largely because of the inherent uncertainty associated with estimating parameters related to both population dynamics and hunting pressure. Here, we investigate a modelling approach to support decisions in bushmeat management which explicitly considers parameter uncertainty. We apply the approach to duikerCephalophusspp., assuming either a constant quota-based, or a constant proportional harvesting, strategy. Within each strategy, we evaluate different hunting levels in terms of both average yield and survival probability, over different time horizons. Under quota-based harvesting, considering uncertainty revealed a trade-off between yield and extinction probability that was not evident when ignoring uncertainty. The highest yield was returned by a quota that implied a 40% extinction risk, whereas limiting extinction risk to 10% reduced yield by 50%-70%. By contrast, under proportional harvesting, there was no trade-off between yield and extinction probability. The maximum proportion returned a yield comparable with the maximum possible under quota-based harvesting, but with extinction risk below 10%. However, proportional harvesting can be harder to implement in practice because it depends on an estimate of population size. In both harvesting approaches, predicted yields were highly right-skewed with median yields differing from mean yields, implying that decision outcomes depend on attitude to risk. The analysis shows how an explicit consideration of all available information, including uncertainty, can, as part of a wider process involving multiple stakeholders, help inform harvesting policies.
Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations
Authors: Hemez Colin , Clarelli Fabrizio , Palmer Adam C. , Chindelevitch Leonid , Cohen Theodore , Abel zur Wiesch Pia
Published: June 2020

Antibiotic-resistant pathogens are a major public health threat. A deeper understanding of how an antibiotic’s mechanism of action influences the emergence of resistance would aid in the design of new drugs and help to preserve the effectiveness of existing ones. To this end, we developed a model that links bacterial population dynamics with antibiotic-target binding kinetics. Our approach allows us to derive mechanistic insights on drug activity from population-scale experimental data and to quantify the interplay between drug mechanism and resistance selection. We find that whether a drug acts as a bacteriostatic or bactericidal agent has little influence on resistance selection. We also show that heterogeneous drug-target binding within a population enables resistant bacteria to evolve fitness-improving secondary mutations even when drug doses remain above the resistant strain’s minimum inhibitory concentration. Our work suggests that antibiotic doses beyond this “secondary mutation selection window” could safeguard against the emergence of high-fitness resistant strains during treatment.
Reconstructed signaling and regulatory networks identify potential drugs for SARS-CoV-2 infection
Authors: Ding Jun , Lugo-Martinez Jose , Yuan Ye , Huang Jessie , Hume Adam J. , Suder Ellen L. , Mühlberger Elke , Kotton Darrell N. , Bar-Joseph Ziv
Published: June 2020

Several molecular datasets have been recently compiled to characterize the activity of SARS-CoV-2 within human cells. Here we extend computational methods to integrate several different types of sequence, functional and interaction data to reconstruct networks and pathways activated by the virus in host cells. We identify key proteins in these networks and further intersect them with genes differentially expressed at conditions that are known to impact viral activity. Several of the top ranked genes do not directly interact with virus proteins. We experimentally tested treatments for a number of the predicted targets. We show that blocking one of the predicted indirect targets significantly reduces viral loads in stem cell-derived alveolar epithelial type II cells (iAT2s).

Software and interactive visualization

https://github.com/phoenixding/sdremsc
Neonatal hyperoxia inhibits proliferation of atrial cardiomyocytes by suppressing fatty acid synthesis
Authors: Cohen Ethan David , Yee Min , Porter George A. , McDavid Andrew N. , Brookes Paul S. , Pryhuber Gloria S. , O’Reilly Michael A.
Published: June 2020

Preterm birth increases the risk for pulmonary hypertension and heart failure in adulthood. Oxygen therapy can damage the immature cardiopulmonary system and may be partially responsible for the cardiovascular disease in adults born preterm. We previously showed that exposing newborn mice to hyperoxia causes pulmonary hypertension by 1 year of age that is preceded by a poorly understood loss of pulmonary vein cardiomyocyte proliferation. We now show that hyperoxia also inhibits the proliferation of left atrial cardiomyocytes and causes diastolic heart failure by thinning the walls of the left atrium and disrupting its ability to pump effectively. Transcriptomic profiling showed that neonatal hyperoxia permanently suppressed fatty acid synthase (Fasn), stearoyl-CoA desaturase 1 (Scd1) and other fatty acid synthesis genes in the atria of mice, the HL-1 line of mouse atrial cardiomyocytes and left atrial tissue explanted from human infants. SuppressingFasnorScd1reduced HL-1 cell proliferation while overexpressing these genes maintained their expansion in hyperoxic conditions, suggesting hyperoxia directly inhibits atrial cardiomyocyte proliferation by repressingFasnandScd1. Pharmacologic interventions that restoreFasn, Scd1and other fatty acid synthesis genes in atrial cardiomyocytes may thus provide a way of ameliorating the adverse effects of supplemental oxygen on preterm infants.
Transport mechanism of the neuronal excitatory amino acid transporter
Authors: Qiu Biao , Matthies Doreen , Fortea Eva , Yu Zhiheng , Boudker Olga
Published: June 2020

Human excitatory amino acid transporter 3 (hEAAT3) mediates glutamate uptake in neurons, intestine, and kidney. Here, we report Cryo-EM structures of hEAAT3 in several functional states where the transporter is empty, bound to coupled sodium ions only, or fully loaded with three sodium ions, a proton, and the substrate aspartate. The structures suggest that hEAAT3 operates by an elevator mechanism involving three functionally independent subunits. When the substrate-binding site is near the cytoplasm, it has a remarkably low affinity for the substrate, perhaps facilitating its release and allowing for the rapid transport turnover. The mechanism of the coupled uptake of the sodium ions and the substrate is conserved across evolutionarily distant families and is augmented by coupling to protons in EAATs. The structures further suggest a mechanism by which conserved glutamate mediates proton symport.
Neural population dynamics underlying expected value computation
Authors: Yamada Hiroshi , Imaizumi Yuri , Matsumoto Masayuki
Published: June 2020

Computation of expected values, i.e., probability times magnitude, seems to be a dynamic integrative process performed in the brain for efficient economic behavior. However, neural dynamics underlying this computation remain largely unknown. We examined (1) whether four core reward-related regions detect and integrate the probability and magnitude cued by numerical symbols and (2) whether these regions have distinct dynamics in the integrative process. Extractions of mechanistic structure of neural population signal demonstrated that expected-value signals simultaneously arose in central part of orbitofrontal cortex (cOFC, area 13m) and ventral striatum (VS). These expected-value signals were incredibly stable in contrast to weak and/or fluctuated signals in dorsal striatum and medial OFC. Notably, temporal dynamics of these stable expected-value signals were unambiguously distinct: sharp and gradual signal evolutions in cOFC and VS, respectively. These intimate dynamics suggest that cOFC and VS compute the expected-values with unique time constants, as distinct, partially overlapping processes.
Scale-dependent influences of distance and vegetation on the composition of aboveground and belowground tropical fungal communities
Authors: Boraks Andre , Plunkett Gregory M. , Doro Thomas , Alo Frazer , Sam Chanel , Tuiwawa Marika , Ticktin Tamara , Amend Anthony S.
Published: June 2020

Fungi provide essential ecosystem services and engage in a variety of symbiotic relationships with trees. In this study, we investigate the spatial relationship of trees and fungi at a community level. We characterized the spatial dynamics for above- and belowground fungi using a series of forest monitoring plots, at nested spatial scales, located in the tropical South Pacific. Fungal communities exhibited strong distance decay of similarity across our entire sampling range (3–110,000 m), and also at small spatial scales (< 50 m). Unexpectedly, this pattern was inverted at an intermediate scale (3.7–26 km). At large scales (80–110 km), belowground and aboveground fungal communities responded inversely to increasing geographic distance.Aboveground fungal communityturnover (beta diversity) was best explained, at all scales, by geographic distance. In contrast,belowground fungal communityturnover was best explained by geographic distance at small scales, and tree community composition at large scales. We demonstrate scale-dependent spatial dynamics of fungal communities, synchronous spatial dynamics for trees and fungi, and the varying influence of habitat versus geographic distance in structuring Soil,Selaginella sp.,and Understory fungal communities.
Global Impacts of Climate Change on Avian Functional Diversity
Authors: Stewart Peter S. , Voskamp Alke , Biber Matthias F. , Hof Christian , Willis Stephen G. , Tobias Joseph A.
Published: June 2020

Climate change is predicted to drive geographical range shifts in many taxa, leading to the formation of novel species assemblages and fluctuations in species richness worldwide. However, the effect of these changes on functional diversity is not yet fully understood, in part because comprehensive species-level trait data are generally lacking at global scales. Here we use morphometric and ecological trait data for 8269 terrestrial bird species to compare functional diversity (FD) of current and future bird assemblages under a medium emissions scenario. We show that future assemblages are likely to undergo substantial shifts in trait structure, with the direction and magnitude of these shifts varying with geographical location and trophic guild. Specifically, invertivore FD is projected to increase at higher latitudes with concurrent losses at mid-latitudes, reflecting poleward shifts in range, whereas frugivore FD is projected to fluctuate in many tropical regions with major declines in much of South America and New Guinea. We show that these projected changes in FD are generally greater than expected from changing species richness alone, indicating that projected FD changes are primarily driven by the loss or gain of functionally distinct species. Our findings suggest that climate change will drive continental-scale shifts in avian functional diversity, with potentially far-reaching implications for ecosystem functions and resilience.
High-density, targeted monitoring of tyrosine phosphorylation reveals activated signaling networks in human tumors
Authors: Stopfer Lauren E. , Flower Cameron T. , Gajadhar Aaron S. , Patel Bhavin , Gallien Sebastien , Lopez-Ferrer Daniel , White Forest M.
Published: June 2020

Tyrosine phosphorylation (pTyr) plays a pivotal role in signal transduction and is commonly dysregulated in cancer. As a result, profiling tumor pTyr levels may reveal therapeutic insights critical to combating disease. Existing discovery and targeted mass spectrometry-based methods used to monitor pTyr networks involve a tradeoff between broad coverage of the pTyr network, reproducibility in target identification across analyses, and accurate quantification. To address these limitations, we developed a targeted approach, termed “SureQuant pTyr,” coupling low input pTyr enrichment with a panel of isotopically labeled, tyrosine phosphorylated internal standard (IS) peptides. Using internal standard guided acquisition, the real-time detection of IS peptides during the analysis initiates the sensitive and selective quantitation of endogenous pTyr targets. This framework allows for reliable quantification of several hundred commonly dysregulated pTyr targets with high quantitative accuracy, enhances target detection success rates, and improves the robustness and usability of targeted acquisition. We establish the clinical applicability of SureQuant pTyr by profiling pTyr signaling levels in human colorectal tumors using minimal sample input, characterizing patient specific oncogenic driving mechanisms. While in some cases pTyr profiles align with previously reported proteomic, genomic, and transcriptomic molecular characterizations, we highlight instances of new insights gained using pTyr characterization and emphasize the complementary nature of pTyr measurements with traditional biomarkers for improving patient stratification and identifying therapeutic targets. The turn-key nature of this approach opens the door to rapid and reproducible pTyr profiling in research and clinical settings alike and enable pTyr-based measurements for applications in precision medicine.

A targeted, mass spectrometry-based method, termed “SureQuant pTyr,” enables highly sensitive and reproducible profiling of tyrosine phosphorylation levels in human colorectal tumors and reveals dysregulated signaling networks for enhanced tumor characterization and biomarker identification.
Minimal system for assembly of SARS-CoV-2 virus like particles
Authors: Swann Heather , Sharma Abhimanyu , Preece Benjamin , Peterson Abby , Eldridge Crystal , Belnap David M. , Vershinin Michael , Saffarian Saveez
Published: June 2020

SARS-CoV-2 virus is the causative agent of COVID-19. Here we demonstrate that non-infectious SARS-CoV-2 virus like particles (VLPs) can be assembled by co-expressing the viral proteins S, M and E in mammalian cells. The assembled SARS-CoV-2 VLPs possess S protein spikes on particle exterior, making them ideal for vaccine development. The particles range in shape from spherical to elongated with a characteristic size of 129 ± 32 nm. We further show that SARS-CoV-2 VLPs dried in ambient conditions can retain their structural integrity upon repeated scans with Atomic Force Microscopy up to a peak force of 1 nN.
HyPR-seq: Single-cell quantification of chosen RNAs via hybridization and sequencing of DNA probes
Authors: Marshall Jamie L. , Doughty Benjamin R. , Subramanian Vidya , Wang Qingbo , Chen Linlin M. , Rodriques Samuel G. , Zhang Kaite , Guckelberger Philine , Fulco Charles P. , Nasser Joseph , Grinkevich Elizabeth J. , Noel Teia , Mangiameli Sarah , Greka Anna , Lander Eric S. , Chen Fei , Engreitz Jesse M.
Published: June 2020

Single-cell quantification of RNAs is important for understanding cellular heterogeneity and gene regulation, yet current approaches suffer from low sensitivity for individual transcripts, limiting their utility for many applications. Here we present Hybridization of Probes to RNA for sequencing (HyPR-seq), a method to sensitively quantify the expression of up to 100 chosen genes in single cells. HyPR-seq involves hybridizing DNA probes to RNA, distributing cells into nanoliter droplets, amplifying the probes with PCR, and sequencing the amplicons to quantify the expression of chosen genes. HyPR-seq achieves high sensitivity for individual transcripts, detects nonpolyadenylated and low-abundance transcripts, and can profile more than 100,000 single cells. We demonstrate how HyPR-seq can profile the effects of CRISPR perturbations in pooled screens, detect time-resolved changes in gene expression via measurements of gene introns, and detect rare transcripts and quantify cell type frequencies in tissue using low-abundance marker genes. By directing sequencing power to genes of interest and sensitively quantifying individual transcripts, HyPR-seq reduces costs by up to 100-fold compared to whole-transcriptome scRNA-seq, making HyPR-seq a powerful method for targeted RNA profiling in single cells.
Immune molecular profiling of a multiresistant primary prostate cancer with a neuroendocrine-like phenotype
Authors: Williams Scott G , Caramia Franco , Yeang Han Xian Aw , Mitchell Catherine , Byrne David J , Fox Stephen B , Neeson Paul J , Haupt Sue , Haupt Ygal , Keam Simon P
Published: June 2020

Understanding the drivers of recurrence in aggressive prostate cancers requires detailed molecu-lar and genomic understanding in order to aid therapeutic interventions. Here we present a case study of a 70 year old male with high-grade clinically-localised acinar adenocarcinoma treated with definitive hormone therapy and radiotherapy. The patient progressed rapidly with rising PSA and succumbed without metastasis 52 months after diagnosis. We provide here a descrip-tion of histological, transcriptional, proteomic, immunological, and genomic features associated with this disease - identifying hallmarks of canonical neuroendocrine PC disease and other nov-el molecular features.
Pulmonary Thromboembolic Disease in Patients with COVID-19 Undergoing Computed Tomography Pulmonary Angiography (CTPA): Incidence and Relationship with Pulmonary Parenchymal Abnormalities
Authors: Fang Cheng , Garzillo Giorgio , Batohi Bhavna , Teo James T H , Berovic Marko , Sidhu Paul S , Robbie Hasti
Published: June 2020

Purpose

This study aims to report the incidence, severity and extent of pulmonary thromboembolic disease (PTD) in patients with confirmed COVID-19 who have undergone CT pulmonary angiography (CTPA) in a tertiary centre.

Materials and Methods

This is a retrospective analysis of all patients undergoing CTPA between 23rd March 2020 and 19th April 2020 in a tertiary centre. The presence of PTD, location and involved pulmonary lobes were documented. The pattern and extent of pulmonary parenchymal abnormalities including the presence of fibrosis, lymph node enlargement and pleural effusion were evaluated by two experienced observers independently and consensus was achieved for the most disparate results. Inter-observer agreement was assessed using Kappa statistics. Student t-test, Chi square and Mann-Whitney U tests were used to compare imaging features between PTD and non-PTD sub-groups.

Results

During the study period, 2157 patients were confirmed with COVID-19, 297/2157 (13.8%) had CT imaging, 100/2157 (4.6%) were CTPA studies, 93 studies were analysed, excluding suboptimal studies. Overall incidence of PTD was 41/93 (44%) with a third of patients showing segmental and subsegmental PTD (n = 28/93, 30%,). D-dimer was elevated in 90/93 (96.8%) of cases. High Wells’ score did not differentiate between PE and non-PE groups (p = 0.801). The inter-observer agreement was fair (Kappa = 0.659) for parenchymal pattern and excellent (Kappa = 0.816) for severity. Lymph node enlargement was found in 34/93 of cases (36.6%) with 29/34 (85.3%) showing no additional source of infection. Fibrosis was seen in 16/93 (17.2%) of cases, mainly demonstrating fibrotic organising pneumonia.

Conclusion

There is a high incidence of PTD in COVID-19 patients undergoing CTPA, complicated by lack of a valid risk stratification tool. Our data indicates a much higher suspicion of PTD is needed in severe COVID-19 patients. The concomitant presence of fibrotic features on CT indicates the need for follow-up for evaluation of chronic pulmonary complications.
Trauma-spectrum symptoms among the Italian general population in the time of the COVID-19 outbreak
Authors: Rossi Rodolfo , Socci Valentina , Talevi Dalila , Niolu Cinzia , Pacitti Francesca , Di Marco Antinisca , Rossi Alessandro , Siracusano Alberto , Di Lorenzo Giorgio , Olff Miranda
Published: June 2020

Background

Recent evidence showed substantial negative mental health outcomes associated with the current COVID-19 pandemic, including trauma-related symptoms although the effects on the Italian population who were subjected to unprecedented nationwide lockdown measure remains unknown. The Global Psychotrauma Screen (GPS) is a brief instrument designed to assess a broad range of trauma-related symptoms with no available validation in the Italian population.

Aims

This study aimed at examining the factor structure of the Italian version of the GPS in a general population sample exposed to the COVID-19 pandemic and at evaluating trauma-related symptoms in the Italian population in the context of specific COVID-19 related risk factors associated with the implementation of lockdown measures and social distancing.

Methods

Cross-sectional web-based observational study, as part of a long-term monitoring programme of mental health outcomes in the general population. 18147 participants completed a self-report online questionnaire to collect key demographic data and to evaluate trauma-related symptoms using the GPS, PHQ-9, GAD-7, ISI and PSS. Validation analyses included both exploratory and confirmatory factor analysis, and correlation analyses.

Results

Exploratory factor analyses supported both a two-factor and a three-factor model. Confirmatory factor analysis showed that a one-factor solution that was used as a baseline comparison showed acceptable fit indices, the two-factor solution showed good fit indices, but the best fitting model was a three-factor solution, with Negative Affect (symptoms of depressed mood, anxiety, irritability), core Post-traumatic Stress Symptoms (PTSS) (avoidance, re-experiencing, hyperarousal and insomnia) and Dissociative symptoms. GPS Risk factors as well as specific COVID-19 related stressful events, were associated with GPS total as well as the three factor scores.

Conclusions

Our data suggest that a wide range of trauma-spectrum symptoms were reported by a large Italian sample during the COVID-19 pandemic. The GPS symptoms clustered best in three factors: Negative Affect symptoms, Core PTSS, and Dissociative symptoms. In particular high rates of core PTSS and negative affect symptoms were associated with the COVID-19 pandemic in Italy and should be routinely assessed in clinical practice.
CLINICAL BLEEDING PATTERNS AND MANAGEMENT TECHNIQUES OF ABNORMAL UTERINE BLEEDING IN WESTERN KENYA.
Authors: Mutakha Godfrey Shichenje , Mwaliko Emily , Kirwa Philip
Published: June 2020

Background

Abnormal uterine bleeding (AUB) affects 30% of reproductive age women globally. However, there are limited local studies evaluating the management of these women. The diagnostic guideline using structural and functional causes of AUB adopts the PALM-COEIN criteria, namely: Polyp; Adenomyosis; Leiomyoma; Malignancy and Hyperplasia; Coagulopathy; Ovulatory dysfunction; Endometrial; Iatrogenic; and Not yet classified. This study aimed to determine the clinical bleeding patterns and management of AUB among women in their reproductive age.

Methods

A cross-sectional study among 108 women with AUB aged 18-45 years was conducted at the gynaecology department of Moi Teaching and Referral Hospital in Western Kenya between April 2018 and April 2019. Their sociodemographic and clinical characteristics were collected using interviewer administered structured questionnaire and chart reviews. Adherence to diagnosis recommendations was assessed using PALM COEIN classification. Descriptive and inferential data analysis was conducted at 95% confidence interval.

Results

The median age was 30 (IQR: 22, 41) years with prolonged bleeding as the most predominant pattern at 41.7%. Bleeding patterns were significantly associated with age (p = 0.04). Only 16.7% were diagnosed as per the PALM-COEIN criteria with PALM and COEIN accounting for 60% and 40% respectively. Leiomyoma (44.5%) was the common cause of AUB. Laboratory evaluation included: pregnancy tests, full Haemogram, hormonal profile and biopsy. Most (79.6%) of the women had abdominopelvic ultrasound done. Medical management was provided for 78.7% of women.

Conclusion

Prolonged bleeding was the most common pattern with medical management preferred. There is need for in-hospital algorithms to ensure adherence to PALM-COEIN guidelines.
SCALE19: A scalable and cost-efficient method for testing Covid-19 based on hierarchical group testing
Authors: Kim Jeremie S. , Kim Justine S. , Kim Hyong S.
Published: June 2020

Containment of Covid-19 requires an extensive testing of the affected population. Some propose global testing to effectively contain Covid-19. Current tests for Covid-19 are administered individually. These tests for Covid-19 are expensive and are limited due to the lack of resources and time. We propose a simple and efficient group testing method for Covid-19. We propose a group testing method where test subjects are grouped and tested. Depending on the result of the group test, subsequent sub groups are formed and tested recursively based on a quartery search algorithm. We designed and built an evaluation model that simulates test subject population, infected test subjects according to available Covid-19 statistics, and the group testing processes in SCALE19. We considered several population models including USA and the world. Our results show that we can significantly reduce the required number of tests up to 89% without sacrificing the accuracy of the individual test of the entire population. For USA, up to 280 million tests can be reduced from the total US population of 331 million and it would be equivalent saving of $28 billion assuming a cost of $100 per test. For the world, 6.96 billion tests can be reduced from the total population of 7.8 billion and it would be equivalent to saving $696 billion. We propose SCALE19 can significantly reduce the total required number of tests compared to individual tests of the entire population. We believe SCALE19 is efficient and simple to be deployed in containment of Covid-19.
Public’s Knowledge and Practices regarding COVID-19: A cross-sectional survey from Pakistan
Authors: Saqlain Muhmmad , Ahmed Ali , Gulzar Aqsa , Naz Sahar , Munir Muhammad Muddasir , Ahmed Zaheer , Kamran Sohail
Published: June 2020

Effective mitigation of coronavirus diseases (COVID-19) pandemic required true adoption of precautionary measures by the masses, that primarily depends upon their knowledge and practices behaviors. The current study aimed to evaluate the knowledge; practices of Pakistani residents regarding COVID-19 and factors associated with good knowledge and positive practices. A cross-sectional online survey was conducted from 15-April 2020 to 20 May 2020 among 689 Pakistanis by using a validated self-administered questionnaire. Regression analysis was applied to find potential predictor of knowledge and practices. Of 689 participants, more than half had good knowledge; 80% had good practices regarding COVID-19 and majority seek knowledge from social media. Knowledge was significantly higher (OR>1.00, p< 0.05) among educated and higher income participants. Positive practices were significantly (OR>1.00, p< 0.05) related to the older age (≥50 years), higher education, higher income and good knowledge regarding COVID-19. The study concluded that Pakistani residents had good knowledge and practices towards COVID-19 yet there are gaps in specific aspects of knowledge, and practice that should be focused in future awareness and educational campaigns. The study recommends the ministry of health authorities to promote all precautionary and preventive measures of COVID-19-consisting of a better-organized approach-to all strata of society: less privileged people, older ones and less educated people, in order to have equilibrium of knowledge about COVID-19; hence effective implementation of precautionary measures.
Progress towards the Ending Preventable Maternal Mortality (EPMM) target for Bangladesh: The role of female education
Authors: Ahsan Karar Zunaid , Streatfield Peter Kim , Jamil Kanta , El Arifeen Shams
Published: June 2020

Educational attainment among women is a well-recognized predictor for maternal mortality. Data from nationally representative surveys and the United Nations are used in the analysis for estimating maternal mortality due to improved education status up to 2030. Analysis of data from 2001 and 2010 Bangladesh Maternal Mortality Survey shows that MMR varies considerably by education level. The study shows that during 2011–2030, 15% maternal deaths will be averted due to fertility change (i.e. fewer births) and 24% of the maternal deaths can be averted only by improving the female education levels. However, in order to achieve the Ending Preventable Maternal Mortality (EPMM) target of 59 maternal deaths per 100,000 live births by 2030 for Bangladesh, a further 64% reduction will be required. Factors outside the health sector, like female education, will continue to have an impact maternal mortality in Bangladesh. However, reaching the EPMM target for Bangladesh by 2030 will also require significant investments in maternal health programs, in particular those to increase access to and quality of services.
Application accuracy of the sleep decision tree to standardized patient cases by physiotherapists: an observational study
Authors: Siengsukon Catherine F. , He Jianghua , Miller Kenneth , Jewell Dianne
Published: June 2020

Background

Physiotherapists assess lifestyle factors, including sleep health, that contribute to poor health outcomes. Recommendations of sleep screening assessments have been provided; however, physical therapists’ ability to successfully identify which patients would benefit from additional consultation has not been established.

Objective

To determine if physiotherapists can accurately apply an evidence-based sleep decision tree to four hypothetical standardized patient cases.

Methods

Participants applied the sleep decision tree to the four standardized cases via an online platform. Likert scales were used to assess perception of ease of use, likelihood of use, and how helpful they thought the sleep decision tree would be. Descriptive analyses and multiple linear regression models were conducted.

Results

Eighty-eight individuals participated in the study. Eighty-one respondents (92%) correctly answered the least complex case while 12 (14%) correctly answered the most complex case. Seventy-four (84%) respondents indicated the sleep decision tree was easy to use, 57 (65%) answered they were likely to use the sleep decision tree in clinical practice, and 66 (75%) said the sleep decision tree would be helpful to their clients.

Conclusions

Physiotherapists were able to accurately apply a sleep decision tree to simpler patient cases but were frequently unable to apply it to more complex patient cases. This may be due to lack of education, perceived ease of using, and relevance of the sleep decision tree to their clinical practice. The sleep decision tree may aid physiotherapists in assessing sleep health, screening for sleep disturbances, and referring for further assessment.
Comparison of Glycemic Control between Intensive Insulin Regimen and Continuous Subcutaneous Insulin infusion: A Meta-Analysis Report of Type-1 Diabetics from Randomized Controlled Trials
Authors: Aziz Kamran Mahmood Ahmed , Othman Abdullah
Published: June 2020

Achieving glycemic control and targets are challenging in type-1 diabetes management. To achieve this, intensive insulin therapy or multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) or pump therapy have been used in various health care settings. However, there has been a debate on their superiority. Some of researchers have recommended MDI, while others SCII. We compared MDI with CSII by a literature search. We have conducted mata-analysis for MDI and CSII on ten randomized controlled trials on 809 type-1 diabetics 809, MDI (N = 394) or CSII (N = 415). Heterogeneity between trials was quantified by conventional Q-statistic (Cochran’s heterogeneity statistic) and Higgins I2 statistic with 0-40% representing negligible heterogeneity, 30-60% moderate heterogeneity, 50-90% substantial heterogeneity and 75-100% considerable heterogeneity. tau-squared (τ2) was used to observe between-study random-effects variance. Meta Analyst software was used to analyze the data and to conduct meta-analysis. SPSS was used to analyze HbA1c student’s t-test for MDI and CSII. A random-effect analysis ((DerSimonian-Laird method) performed on ten studies found that the percentage of HbA1c was lower in patients receiving CSII compared with those receiving MDI; standardized mean difference (SMD) was 0.441, 95% confidence interval 0.267 to 0.616, p < 0.001; equivalent to a difference of 0.39%, favoring CSII. I2 statistic was 20.9; τ2 = 0.016; Q = 11.378 with df = 9, indicating that heterogeneity was not significant (heterogeneity p-value = 0.251). Patients on CSII demonstrated significantly lower values (8.2±0.72 versus 7.73±0.72; p-value < 0.001 respectively). This statistical and meta-analysis favors the usage of insulin pump therapy. We concluded that patient centered approach should be used while selecting the patients for insulin pump (CSII) or MDI.
Cardiac Adverse Events of Immune Checkpoint Inhibitors in Oncology Patients: A Systematic Review and Meta-Analysis
Authors: Vialli Nso Nso , Antwi-Amoabeng Daniel , Beutler Bryce D. , Ulanja Mark B. , Ghuman Jasmine , Hanfy Ahmed , Nimo-Boampong Joyce , Atanga Sirri , Doshi Rajkumar , Enoru Sostanie , Gullapalli Nageshwara
Published: June 2020

Background

Immune checkpoint inhibitors (ICIs) are novel therapeutic agents used for various types of cancer. ICIs have revolutionized cancer treatment and improved clinical outcomes among cancer patients. However, immune-related adverse effects of ICI therapy are common. Cardiovascular immune-related adverse events (irAEs) are rare but potentially life-threatening complications. We aimed to estimate the incidence of cardiovascular irAEs among patients undergoing ICI therapy for various malignancies.

Methods

We conducted this systematic review and meta-analysis by searching PubMed, Cochrane CENTRAL, Web of Science, and SCOPUS databases for relevant interventional trials reporting cardiovascular irAEs. We performed a single-arm meta-analysis using OpenMeta [Analyst] software of the following outcomes: myocarditis, pericardial effusion, heart failure, cardiomyopathy, atrial fibrillation, myocardial infarction, and cardiac arrest. We assessed the heterogeneity using the I2test and managed to solve it with Cochrane’s leave-one-out method. The risk of bias was performed with the Cochrane’s risk of bias tool.

Results

A total of 26 studies were included. The incidence of irAEs follows: myocarditis: 0.5% (95% CI [0.1%-0.9%]); pericardial effusion: 0.5% (95% CI [0.1%-1.0%]); heart failure: 0.3% (95% CI [0.0%-0.5%]); cardiomyopathy: 0.3% (95% CI [-0.1%-0.6%]); atrial fibrillation: 7.6% (95% CI [1.0%-14.1%]); myocardial infarction: 0.4% (95% CI [0.0%-0.7%]); and cardiac arrest: 0.4% (95% CI [0.1%-0.8%]).

Conclusion

The most common cardiovascular irAEs were atrial fibrillation, myocarditis, and pericardial effusion. Although rare, data from post market surveillance will provide estimates of the long-term prevalence and prognosis in patients with ICI-associated cardiovascular complications.
Systematic characterization of somatic mutation-mediated microRNA regulatory network perturbations
Authors: Hua Xu , Li Yongsheng , Guo Li , Xu Min , Qi Dan , Huang Jason H. , Bhat Akshay , Zhou Yunyun , Wu Erxi , Yi S. Stephen
Published: June 2020

Somatic mutations are a major source of cancer development. Many driver mutations have been identified in protein coding regions. However, the function of mutations located in microRNAs (miRNAs) and their target binding sites along the human genome remains largely unknown. Here, we built comprehensive cancer-specific miRNA regulatory networks across 30 cancer types to systematically analyze the effect of mutations on miRNA related pathways. 3,518,261 mutations from 9,819 samples were mapped to miRNA-gene interactions (mGI), and mutations in miRNAs versus in their target genes show a mutually exclusive pattern in almost all cancer types. Using a linear regression method, we further identified 89 driver mutations in 14 cancer types that can significantly perturb miRNA regulatory networks. We find that driver mutations play their roles by altering RNA binding energy and the expression of target genes. Finally, we demonstrate that mutated driver gene targets are significantly down-regulated in cancer and function as tumor suppressors during cancer progression, suggesting potential miRNA candidates with significant clinical implications. We provide this data resource (CanVar-mGI) through a user-friendly, open-access web portal. Together, our results will facilitate novel non-coding biomarker identification and therapeutic drug design.