bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Antipsychotic Drugs and Potassium Channel Modulators on Cognition-related Local Field Potential Spectral Properties in Mouse Hippocampus and Frontal Cortex
Authors: Sun Dechuan , Kermani Mojtaba , Hudson Matt , He Xin , Rajasekharan Unnithan Ranjith , French Chris
Published: May 2020

Local field potentials (LFPs) recorded intracranially display a range of location specific oscillatory spectra which have been related to cognitive processes. Although the exact mechanisms producing LFPs are not completely understood, it is likely that voltage-gated ion channels which produce action potentials and patterned discharges play a significant role. It is also known that antipsychotic drugs (APDs) affect LFPs spectra and a direct inhibitory effect on voltage-gated potassium (Kv) channels has been reported. Additionally,Kvchannels have been implicated in the pathophysiology of schizophrenia, a disorder for which APDs are primary therapies. In this study we sought to: i) better characterise the effects of two APDs on LFPs and connectivity measures and ii) examine the effects of potassium channel modulators on LFPs and potential overlap of effects with APDs. Intracranial electrodes were implanted in the hippocampus (HIP) and pre-frontal cortex (PFC) of C57BL/6 mice; power spectra, coherence and phase-amplitude cross frequency coupling were measured. Drugs tested were the APDs haloperidol and clozapine as well as voltage-gated potassium channel modulators (KVMs) 4-aminopyridine(4AP), tetraethylammonium (TEA), E-4031 and retigabine. All drugs and vehicle controls were administered intraperitoneally. Both APDs and KVMs significantly reduced gamma power with the exception of 4AP, which conversely increased slow-gamma power. Clozapine and retigabine additionally reduced coherence between HIP and PFC. Phase-amplitude coupling between theta and gamma oscillations in HIP was significantly reduced by the administration of haloperidol and retigabine. These results provide previously undescribed effects of APDs on LFP properties and demonstrate novel modulation of LFP characteristics by KVMs that intriguingly overlaps with the effects of APDs. The possibility of a common mechanism of action deserves further study.
Templating S100A9 amyloids on Aβ fibrillar surfaces revealed by charge detection mass spectrometry, microscopy, kinetic and microfluidic analyses
Authors: Pansieri Jonathan , Iashchishyn Igor A. , Fakhouri Hussein , Ostojić Lucija , Malisauskas Mantas , Musteikyte Greta , Smirnovas Vytautas , Schneider Matthias M. , Scheidt Tom , Xu Catherine K. , Meisl Georg , Knowles Tuomas P. J. , Gazit Ehud , Antoine Rodolphe , Morozova-Roche Ludmilla A.
Published: May 2020

The mechanism of amyloid co-aggregation and its nucleation process are not fully understood in spite of extensive studies. Deciphering the interactions between proinflammatory S100A9 protein and Aβ42peptide in Alzheimer’s disease is fundamental since inflammation plays a central role in the disease onset. Here we use innovative charge detection mass spectrometry (CDMS) together with biophysical techniques to provide mechanistic insight into the co-aggregation process and differentiate amyloid complexes at a single particle level. Combination of mass and charge distributions of amyloids together with reconstruction of the differences between them and detailed microscopy reveals that co-aggregation involves templating of S100A9 fibrils on the surface of Aβ42amyloids. Kinetic analysis further corroborates that the surfaces available for the Aβ42secondary nucleation are diminished due to the coating by S100A9 amyloids, while the binding of S100A9 to Aβ42fibrils is validated by a microfuidic assay. We demonstrate that synergy between CDMS, microscopy, kinetic and microfluidic analyses opens new directions in interdisciplinary research.
Scorepochs: A Computer-Aided Scoring Tool for Resting-State M/EEG Epochs
Authors: Fraschini Matteo , La Cava Simone Maurizio , Rodriguez Giuseppe , Vitale Andrea , Demuru Matteo
Published: May 2020

M/EEG resting-state analysis often requires the definition of the epoch length and the criteria to select which epochs to include in the subsequent steps. However, the effects of epoch selection remain scarcely investigated and the procedure used to (visually) inspect, label, and remove bad epochs is often not documented, thus hindering the reproducibility of the reported results. In this study, we present Scorepochs, a simple and freely available tool for the automatic scoring of resting-state M/EEG epochs that aims to provide an objective method to aid M/EEG experts during epoch selection procedure. We tested our approach on a freely available EEG dataset containing recordings from 109 subjects using the BCI2000 64-channel system.
Unique maternal immune and functional microbial profiles during prenatal stress
Authors: Antonson Adrienne M. , Evans Morgan V. , Galley Jeffrey D. , Chen Helen J. , Rajesekera Therese A. , Lammers Sydney M. , Hale Vanessa L. , Bailey Michael T. , Gur Tamar L.
Published: May 2020

Maternal stress during pregnancy is widespread and stress-induced fetal neuroinflammation is thought to derive from a disruption in intrauterine immune homeostasis, though the exact origins are incompletely defined. We aimed to identify divergent immune and microbial metagenome profiles of stressed gestating mice that may underlie detrimental inflammatory signaling at the maternal-fetal interface. In response to stress, maternal glucocorticoid circuit activation corresponded with diminished spleen mass and IL-1β production, reflecting systemic immunosuppression. At the maternal-fetal interface, density of placental mononuclear leukocytes decreased with stress. Yet maternal whole blood leukocyte analysis indicated monocytosis and classical M1 phenotypic shifts. Genome-resolved microbial metagenomic analyses revealed reductions in genes, microbial strains, and metabolic pathways in stressed dams that are primarily associated with pro-inflammatory function. Overall, these data indicate that stress disrupts maternal immunological and microbial regulation during pregnancy, characterized by concurrent anti- and pro-inflammatory signatures, which may displace immune equilibrium at the maternal-fetal interface.
Lifestyle Risk Score for aggregating multiple lifestyle factors: Handling missingness of individual lifestyle components in meta-analysis of gene-by-lifestyle interactions
Authors: Xu Hanfei , Schwander Karen , Brown Michael R , Wang Wenyi , Waken RJ , Boerwinkle Eric , Cupples L Adrienne , de las Fuentes Lisa , van Heemst Diana , Osazuwa-Peters Oyomoare , de Vries Paul S , van Dijk Ko Willems , Sung Yun Ju , Zhang Xiaoyu , Morrison Alanna C , Rao DC , Noordam Raymond , Liu Ching-Ti
Published: May 2020

Recent studies consider lifestyle risk score (LRS), an aggregation of multiple lifestyle exposures, in identifying association of gene-lifestyle interaction with disease traits. However, not all cohorts have data on all lifestyle factors, leading to increased heterogeneity in the environmental exposure in collaborative meta-analyses. We compared and evaluated four approaches (Naïve, Safe, Complete and Moderator Approaches) to handle the missingness in LRS-stratified meta-analyses under various scenarios. Compared to “benchmark” results with all lifestyle factors available for all cohorts, the Complete Approach, which included only cohorts with all lifestyle components, was underpowered, and the Naïve Approach, which utilized all available data and ignored the missingness, was slightly liberal. The Safe Approach, which used all data in LRS-exposed group and only included cohorts with all lifestyle factors available in the LRS-unexposed group, and the Moderator Approach, which handled missingness via moderator meta-regression, were both slightly conservative and yielded almost identical p-values. We also evaluated the performance of the Safe Approach under different scenarios. We observed that the larger the proportion of cohorts without missingness included, the more accurate the results compared to “benchmark” results. In conclusion, we generally recommend the Safe Approach to handle heterogeneity in the LRS based genome-wide interaction meta-analyses.
Imaging the mechanisms of anti-CD20 therapyin vivouncovers
Authors: Grandjean Capucine L. , Garcia Zacarias , Lemaître Fabrice , Bréart Béatrice , Bousso Philippe
Published: May 2020

Anti-CD20 monoclonal antibody (mAb) represents an effective strategy for the treatment of B cell malignancies that may involve complement activity, antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP). While ADP mediated by Kupffer cells is essential to deplete circulating tumors, the relative contribution of each mechanism to the elimination of non-circulating targets has yet to be clarified. Using intravital imaging in a model of MYC-driven B cell lymphoma, we establish here the dominance and limitations of ADP in the bone marrow (BM). We found that tumor cells were stably residing in the BM with little evidence for recirculation. To quantify the contribution of different cytotoxic mechanismsin situ, we designed a dual fluorescent reporter to track phagocytosis and apoptosis in real-time. ADP by BM-associated macrophages was the primary mode of tumor elimination but was no longer active after one hour, resulting only in partial depletion. Moreover, macrophage density was strongly reduced in tumor-rich regions. Given their sessile phenotype, macrophages primarily targeted neighboring tumors, resulting in a substantial spatial constraint. Overcoming spatiotemporal bottlenecks in tumor-targeting Ab therapy represents a critical path towards the design of optimized therapies.

Key points

Functional intravital imaging establishes antibody-dependent phagocytosis as the major mechanism acting at the tumor site during anti-CD20 therapy.

A transient wave of phagocytosis and a limited macrophage density restrict the efficiency of anti-CD20 anti-tumor activity.
Novel mechanistic targets of Forkhead box Q1 transcription factor in human breast cancer cells
Authors: Kim Su-Hyeong , Hahm Eun-Ryeong , Singh Krishna B. , Singh Shivendra V.
Published: May 2020

The transcription factor forkhead box Q1 (FoxQ1), which is overexpressed in different solid tumors, has emerged as a key player in the pathogenesis of breast cancer by regulating epithelial-mesenchymal transition, maintenance of cancer-stem like cells, and metastasis. However, the mechanism underlying oncogenic function of FoxQ1 is still not fully understood. In this study, we compared the RNA-seq data from FoxQ1 overexpressing SUM159 cells with that of empty vector-transfected control (EV) cells to identify novel mechanistic targets of this transcription factor. Consistent with published results in basal-like subtype, immunohistochemistry revealed upregulation of FoxQ1 protein in luminal-type human breast cancer tissue microarrays when compared to normal mammary tissues. Many previously reported transcriptional targets of FoxQ1 (e.g.,E-cadherin, N-cadherin, fibronectin 1, etc.) were verified from the RNA-Seq analysis. FoxQ1 overexpression resulted in downregulation of genes associated with cell cycle checkpoints, M phase, and cellular response to stress/external stimuli as evidenced from the Reactome pathway analysis. Consequently, FoxQ1 overexpression resulted in S, G2M and mitotic arrest in basal-like SUM159 and HMLE cells, but not in luminal-type MCF-7 cells. There were differences in expression of cell cycle-associated proteins between FoxQ1 overexpressing SUM159 and MCF-7 cells. Finally, we show for the first time that FoxQ1 is a direct transcriptional regulator of interleukin (IL)-1α, IL-8, and vascular endothelial growth factor in breast cancer cells. Chromatin immunoprecipitation revealed FoxQ1 occupancy at the promoters ofIL-1α, IL-8, andVEGF. In conclusion, the present study reports novel mechanistic targets of FoxQ1 in human breast cancer cells.
ACME dissociation: a versatile cell fixation-dissociation method for single-cell transcriptomics
Authors: García-Castro Helena , Kenny Nathan J , Álvarez-Campos Patricia , Mason Vincent , Schönauer Anna , Sleight Victoria A. , Neiro Jakke , Aboobaker Aziz , Permanyer Jon , Iglesias Marta , Irimia Manuel , Sebé-Pedrós Arnau , Solana Jordi
Published: May 2020

Single-cell sequencing technologies are revolutionizing biology, but are limited by the need to dissociate fresh samples that can only be fixed at later stages. We present ACME (ACetic-MEthanol) dissociation, a cell dissociation approach that fixes cells as they are being dissociated. ACME-dissociated cells have high RNA integrity, can be cryopreserved multiple times, can be sorted by Fluorescence-Activated Cell Sorting (FACS) and are permeable, enabling combinatorial single-cell transcriptomic approaches. As a proof of principle, we have performed SPLiT-seq with ACME cells to obtain around ∼34K single cell transcriptomes from two planarian species and identified all previously described cell types in similar proportions. ACME is based on affordable reagents, can be done in most laboratories and even in the field, and thus will accelerate our knowledge of cell types across the tree of life.
Local sensitivity analysis of the ‘Membrane shape equation’ derived from the Helfrich energy
Authors: Rangamani P. , Behzadan A. , Holst M.
Published: May 2020

The Helfrich energy is commonly used to model the elastic bending energy of lipid bilayers in membrane mechanics. The governing differential equations for certain geometric characteristics of the shape of the membrane can be obtained by applying variational methods (minimization principles) to the Helfrich energy functional and are well-studied in the axisymmetric framework. However, the Helfrich energy functional and the resulting differential equations involve a number of parameters, and there is little explanation of the choice of parameters in the literature, particularly with respect to the choice of the “spontaneous curvature” term that appears in the functional. In this paper, we present a careful analytical and numerical study of certain aspects of parametric sensitivity of Helfrich’s model. Using simulations of specific model systems, we demonstrate the application of our scheme to the formation of spherical buds and pearled shapes in membrane vesicles.
Flapping, swirling and flipping: Non-linear dynamics of pre-stressed active filaments
Authors: Fatehiboroujeni Soheil , Gopinath Arvind , Goyal Sachin
Published: May 2020

Initially straight slender elastic filaments and rods with geometrically constrained ends buckle and form stable two-dimensional shapes when compressed by bringing the ends together. It is known that beyond a critical value of this pre-stress, clamped rods transition to bent, twisted three-dimensional equilibrium shapes. Here, we analyze the three-dimensional instabilities and dynamics of such pre-stressed, initially twisted filaments subject to active follower forces and dissipative fluid drag. We find that degree of boundary constraint and the directionality of active forces determines if oscillatory instabilities can arise. When filaments are clamped at one end and pinned at the other with follower forces directed towards the clamped end, stable planar flapping oscillations result; reversing the directionality of the active forces quenches the instability. When both ends are clamped however, computations reveal a novel secondary instability wherein planar oscillations are destabilized by off-planar perturbations resulting in three-dimensional swirling patterns with periodic flips. These swirl-flip transitions are characterized by two distinct and time-scales. The first corresponds to unidirectional swirling rotation around the end-to-end axis. The second captures the time between flipping events when the direction of swirling reverses. We find that this spatiotemporal dance resembles relaxation oscillations with each cycle initiated by a sudden jump in torsional deformation and then followed by a period of gradual decrease in net torsion until the next cycle of variations. Our work reveals the rich tapestry of spatiotemporal patterns when weakly inertial strongly damped rods are deformed by non-conservative active forces. Practically, our results suggest avenues by which pre-stress, elasticity and activity may be used to design synthetic fluidic elements to pump or mix fluid at macroscopic length scales.
Forecasting COVID-19 pandemic in Poland according to government regulations and people behavior
Authors: Orzechowska Magdalena , Bednarek Andrzej K.
Published: May 2020

The coronavirus disease 2019 (COVID-19) outbreak is a worldwide pandemic problem that started in China in December 2019 and within a few months spread to all continents. Very high infectivity of SARS-CoV-2 virus and substantial disease severity caused medical care capacity shortage in many countries. Therefore, real-time epidemic forecasting of the COVID-19 is useful to plan public health strategies like country lockdown and healthcare reorganization.

We used extended susceptible-infected-removed (eSIR) model to predict the epidemic trend of COVID-19 in Poland under different scenarios of the lockdown and lockdown removal. We used time-series data of SARS-CoV-2 infection from March 4 to May 22 2020. Our forecast includes the impact of a timeline of preventive measures introduced in Poland. Using eSIR algorithm we estimated the basic reproductive number and a total number of infections under different epidemic trend scenarios.

Using eSIR modeling we estimated that the basic reproductive number in Poland concerning different scenarios of the lockdown removal is in a range of 3.91-4.79. The lowest predicted number of infected cases would be 263 900 (0 - 1 734 200, 95%CI) if the strict protective measures were maintained until the end of September. However, under different scenarios of precautions removal, a total number of infected cases may exceed one million within the next year.

Relatively early introduction of strong precautions in Poland significantly slowed down epidemic spread in Poland in comparison with other European countries like Italy or Spain. However, early removal of protective measures may result in a significant increase in infection. Data shows that the number of new COVID-19 cases in Poland beyond May 18 is linear what could be a prognosis of a duration of the epidemic exceeding 300 days.
Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter interventional trial
Authors: Perotti Cesare , Baldanti Fausto , Bruno Raffaele , Del Fante Claudia , Seminari Elena , Casari Salvatore , Percivalle Elena , Glingani Claudia , Musella Valeria , Belliato Mirko , Garuti Martina , Meloni Federica , Frigato Marilena , Di Sabatino Antonio , Klersy Catherine , De Donno Giuseppe , Franchini Massimo
Published: May 2020

BACKGROUND

Hyperimmune plasma from Covid-19 convalescent is a potential treatment for severe Covid-19.

METHODS

We conducted a multicenter one arm proof of concept interventional study. Patients with Covid-19 disease with moderate-to-severe Acute Respiratory Distress Syndrome, elevated C-reactive Protein and need for mechanical ventilation and/or CPAP were enrolled. One to three 250-300 ml unit of hyperimmune plasma (neutralizing antibodies titer ≥1:160) were administered. Primary outcome was 7-days hospital mortality. Secondary outcomes were PaO2/FiO2, laboratory and radiologic changes, as well as weaning from mechanical ventilation and safety.

RESULTS

The study observed 46 patients from March, 25 to April, 21 2020. Patients were aged 63, 61% male, 30 on CPAP and 7 intubated. PaO2/FiO2 was 128 (SD 47). Symptoms and ARDS duration were 14 (SD 7) and 6 days (SD 3). Three patients (6.5%) died within 7 days. The upper one-sided 90%CI was 13.9%, allowing to reject the null hypothesis of a 15% mortality. PaO2/FiO2 increased by 112 units (95%CI 82 to142) in survivors, the chest radiogram severity decreased in 23% (95%CI 5% to 42%); CRP, Ferritin and LDH decreased by 60, 36 and 20% respectively. Weaning from CPAP was obtained in 26/30 patients and 3/7 were extubated. Five serious adverse events occurred in 4 patients (2 likely, 2 possible treatment related).

CONCLUSIONS

Hyperimmune plasma in Covid-19 shows promising benefits, to be confirmed in a randomized controlled trial. This proof of concept study could open to future developments including hyperimmune plasma banking, development of standardized pharmaceutical products and monoclonal antibodies.
New models of transmission of COVID-19 with time under the influence of meteorological determinants
Authors: Adhikari Atin , Ghosh Shilpi , Sen Moon M. , Adhikari Rathin
Published: May 2020

Objectives

This work aimed at modeling the progressions of COVID-19 cases in time in relation to meteorological factors in large cities of Brazil, Italy, Spain, and USA, and finding the viability of SARS-CoV-2 virus in different weather conditions based on models.

Methods

New models constructed showing the relationship of the I′ (the number of infected individuals divided by the total population of a city) with the independent variables -time, temperature, relative humidity, and wind velocity. The regression models fitting in the data were statistically validated by: 1) plot of observed and predicted response; 2) standardized residual plots showing the characteristics of errors; 3) adjusted value; 4) the p value for the parameters associated with the various independent variables; and 5) the predictive power of the model beyond data points.

Results

Models indicate that 1) the transmission of COVID-19 could be relatively high either for elevated temperatures with lower relative humidity or for lower temperatures with higher relative humidity conditions; 2) disease transmission is expected to be reduced more with higher wind velocity; 3) the rate of increase in the number of COVID-19 cases increases in one model with a constant rate and in the other two with varying rates in time. These transmission features seem to have connections with the structural components of the SARS-CoV-2 virus. Under suitable meteorological conditions, the partial natural disappearance of COVID-19 pandemic could be possible.

Conclusion

New models for I′ may be considered to understand the viability of the virus in the environment and future transmission of COVID-19.
ComplementaryIn VivoApproaches Reveal Quiescent Melanocytes in Anagen Outside the Hair Follicle Bulge
Authors: Tandukar Bishal , Joshi Sandeep S. , Pan Li , Hornyak Thomas J.
Published: May 2020

Melanocyte stem cells (McSCs) are key components of the hair follicle (HF) stem cell system that are derived from neural crest during embryogenesis and are responsible for regeneration of differentiated melanocytes during successive HF cycles. Our previous research has shown presence of two subsets of phenotypically and functionally distinct McSCs exist in murine telogen HFs, CD34+ McSCs in the bulge/lower permanent portion (LPP) and CD34− McSCs in the secondary hair germ (SHG). Whether these subsets are maintained independently or exist in a developmental hierarchy is not yet known. UsingDct-H2BGFP mice, we analyzed the quiescent and proliferative properties of McSCs and melanocytes in anagen and telogen. We found unexpectedly that Kit+Nestin− quiescent melanocytes are maintained outside of the bulge/LPP region throughout anagen in addition to the Kit+Nestin+ quiescent melanocytes of the bulge/LPP. Both subpopulations express lower levels of melanocyte differentiation markers Mitf, Pax3, Dct, Tyrp1 and Tyr compared to differentiated melanocytes of the HF bulb/matrix. These results suggest that quiescent melanocytes localized in the outer root sheath, both in and below the bulge/LPP) retain the stem cell phenotype observed in quiescent McSCs during telogen. This finding has implications for maintenance of distinct subsets of McSCs throughout successive HF cycles.
Proteoform Identification by Combining RNA-Seq and Top-down Mass Spectrometry
Authors: Chen Wenrong , Liu Xiaowen
Published: May 2020

In proteogenomic studies, genomic and transcriptomic variants are incorporated into customized protein databases for the identification of proteoforms, especially proteoforms with sample-specific variants. Most proteogenomic research has been focused on combining genomic or transcriptomic data with bottom-up mass spectrometry data. In the last decade, top-down mass spectrometry has attracted increasing attention because of its capacity to identify various proteoforms with alterations. However, top-down proteogenomics, in which genomic or transcriptomic data are combined with top-down mass spectrometry data, has not been widely adopted, and there still lack of software tools for top-down proteogenomic data analysis. In this paper, we introduce TopPG, a proteogenomic tool for identifying proteoforms with genetic alterations and alternative splicing events. Experiments on top-down proteogenomic data of DLD-1 colorectal cancer cells showed that TopPG can confidently identify proteoforms with sample-specific alterations.
Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification
Authors: Fukumoto Tatsuya , Iwasaki Sumio , Fujisawa Shinichi , Hayasaka Kasumi , Sato Kaori , Oguri Satoshi , Taki Keisuke , Nakakubo Sho , Kamada Keisuke , Yamashita Yu , Konno Satoshi , Nishida Mutsumi , Sugita Junichi , Teshima Takanori
Published: May 2020

Rapid detection of SARS-CoV-2 is critical for the diagnosis of coronavirus disease 2019 (COVID-19) and preventing the spread of the virus. A novel “2019 Novel Coronavirus Detection Kit (nCoV-DK)” halves detection time by eliminating the steps of RNA extraction and purification. We evaluated concordance between the nCoV-DK and direct PCR. The virus was detected in 53/71 fresh samples by the direct method and 55/71 corresponding frozen samples by the nCoV-DK. The overall concordance rate of the virus detection between the two methods was 94.4% (95% CI, 86.2-98.4). Concordance rates were 95.2% (95% CI, 83.8-99.4), 95.5% (95% CI, 77.2-99.9), 85.7% (95% CI, 42.1-99.6) in nasopharyngeal swab, saliva, and sputum samples, respectively. These results indicate that the nCoV-DK effectively detects SARS-CoV-2 in all types of the samples including saliva, while reducing time required for detection, labor, and risk of human error.
HYPE: Predicting Blood Pressure from Photoplethysmograms in a Hypertensive Population
Authors: Sasso Ariane M. , Datta Suparno , Jeitler Michael , Steckhan Nico , Kessler Christian S. , Michalsen Andreas , Arnrich Bert , Böttinger Erwin
Published: May 2020

The state of the art for monitoring hypertension relies on measuring blood pressure (BP) using uncomfortable cuff-based devices. Hence, for increased adherence in monitoring, a better way of measuring BP is needed. That could be achieved through comfortable wearables that contain photoplethysmography (PPG) sensors. There have been several studies showing the possibility of statistically estimating systolic and diastolic BP (SBP/DBP) from PPG signals. However, they are either based on measurements of healthy subjects or on patients on intensive care units (ICUs). Thus, there is a lack of studies with patients out of the normal range of BP and with daily life monitoring out of the ICUs. To address this, we created a dataset (HYPE) composed of data from hypertensive subjects that executed a stress test and had 24-hours monitoring. We then trained and compared machine learning (ML) models to predict BP. We evaluated handcrafted feature extraction approaches vs image representation ones and compared different ML algorithms for both. Moreover, in order to evaluate the models in a different scenario, we used an openly available set from a stress test with healthy subjects (EVAL). The best results for our HYPE dataset were in the stress test and had a mean absolute error (MAE) in mmHg of 8.79 (±3.17) for SBP and 6.37 (±2.62) for DBP; for our EVAL dataset it was 14.74 (±4.06) and 7.12 (±2.32) respectively. Although having tested a range of signal processing and ML techniques, we were not able to reproduce the small error ranges claimed in the literature. The mixed results suggest a need for more comparative studies with subjects out of the intensive care and across all ranges of blood pressure. Until then, the clinical relevance of PPG-based predictions in daily life should remain an open question.
Reliability of P3 Event-Related Potential during Working Memory Across the Spectrum of Cognitive Aging
Authors: Devos Hannes , Burns Jeffrey , Liao Ke , Ahmadnezhad Pedram , Mahnken Jonathan D. , Brooks William M. , Gustafson Kathleen
Published: May 2020

Event-related potentials (ERPs) offer unparalleled temporal resolution in tracing distinct electrophysiological processes related to normal and pathological cognitive aging. The stability of ERPs in older individuals, who inherently show more intraindividual variability in cognitive functions, has not been established. In this test-retest reliability study, 39 older individuals (age 74.10 (5.4) years; 23 (59%) women; 15 non β-amyloid elevated, 16 β-amyloid elevated, 8 cognitively impaired) with scores on the Montreal Cognitive Assessment (MOCA) ranging between 3 and 30 completed a working memory (n-back) test with three levels of difficulty at baseline and two-week follow-up. Stability of the ERP was evaluated on grand averaged task effects for both visits. P3 peak amplitude and latency were measured in frontal channels. P3 peak amplitude at Fz, our main outcome variable, showed excellent reliability in 0-back (intraclass correlation coefficient (ICC), 95% confidence interval = 0.82 (0.67 – 0.90) and 1-back (ICC = 0.87 (0.76 – 0.93), however, only fair reliability in 2-back (ICC = 0.53 (0.09 – 0.75). Reliability of P3 peak latencies was substantially lower, with ICCs ranging between 0.17 for 2-back and 0.54 for 0-back. Generalized linear mixed models showed no confounding effect of age, group, or task difficulty on stability of P3 amplitude and latency of Fz. By contrast, MOCA scores tended to negatively correlate with P3 amplitude of Fz (p=0.07). We conclude that P3 peak amplitude and latency provide a stable measure of electrophysiological processes in older individuals. However, impaired cognition may affect the stability of the ERP response.
Study protocol for COvid-19 Vascular sERvice (COVER) study: The impact of the COVID-19 pandemic on the provision, practice and outcomes of vascular surgery
Authors: Benson Ruth A
Published: May 2020

Background

The novel Coronavirus Disease 2019 (COVID-19) pandemic is having a profound impact on global healthcare. Shortages in staff, operating theatre space and intensive care beds has led to a significant reduction in the provision of surgical care. Even vascular surgery, often insulated from resource scarcity due to its status as an urgent specialty, has limited capacity due to the pandemic. Furthermore, many vascular surgical patients are elderly with multiple comorbidities putting them at increased risk of COVID-19 and its complications. There is an urgent need to investigate the impact on patients presenting to vascular surgeons during the COVID-19 pandemic.

Methods and Analysis

The COvid-19 Vascular sERvice (COVER) study has been designed to investigate the worldwide impact of the COVID-19 pandemic on vascular surgery, at both service provision and individual patient level. COVER is running as a collaborative study through the Vascular and Endovascular Research Network (VERN) with the support of numerous national (Vascular Society of Great Britain and Ireland, British Society of Endovascular Therapy, British Society of Interventional Radiology, Rouleaux Club) and an evolving number of international organisations (Vascupedia, SingVasc, Audible Bleeding (USA), Australian and New Zealand Vascular Trials Network (ANZVTN)). The study has 3 ‘Tiers’: Tier 1 is a survey of vascular surgeons to capture longitudinal changes to the provision of vascular services within their hospital; Tier 2 captures data on vascular and endovascular procedures performed during the pandemic; and Tier 3 will capture any deviations to patient management strategies from prepandemic best practice. Data submission and collection will be electronic using online survey tools (Tier 1: SurveyMonkey® for service provision data) and encrypted data capture forms (Tiers 2 and 3: REDCap® for patient level data). Tier 1 data will undergo real-time serial analysis to determine longitudinal changes in practice, with country-specific analyses also performed. The analysis of Tier 2 and Tier 3 data will occur on completion of the study as per the prespecified statistical analysis plan.

Ethical Approval

Ethical approval from the UK Health Research Authority has been obtained for Tiers 2 and 3 (20/NW/0196 Liverpool Central). Participating centres in the UK will be required to seek local research and development approval. Non-UK centres will need to obtain a research ethics committee or institutional review board approvals in accordance with national and/or local requirements.

ISRCTN: 80453162 (https://doi.org/10.1186/ISRCTN80453162)

Ethical Approval: 20/NW/0196 Liverpool Central, IRAS: 282224
Lessons from movement ecology for the return to work: modeling contacts and the spread of COVID-19
Authors: Shaw Allison K. , White Lauren A. , Michalska-Smith Matthew , Borer Elizabeth T. , Craft Meggan E. , Seabloom Eric W. , Snell-Rood Emilie , Travisano Michael
Published: May 2020

Human behavior (movement, social contacts) plays a central role in the spread of pathogens like SARS- CoV-2. The rapid spread of SARS-CoV-2 was driven by global human movement, and initial lockdown measures aimed to localize movement and contact in order to slow spread. Thus, movement and contact patterns need to be explicitly considered when making reopening decisions, especially regarding return to work. Here, as a case study, we consider the initial stages of resuming research at a large research university, using approaches from movement ecology and contact network epidemiology. First, we develop a dynamical pathogen model describing movement between home and work; we show that limiting social contact, via reduced people or reduced time in the workplace are fairly equivalent strategies to slow pathogen spread. Second, we develop a model based on spatial contact patterns within a specific office and lab building on campus; we show that restricting on-campus activities to labs (rather than labs and offices) could dramatically alter (modularize) contact network structure and thus, potentially reduce pathogen spread by providing a workplace mechanism to reduce contact. Here we argue that explicitly accounting for human movement and contact behavior in the workplace can provide additional strategies to slow pathogen spread that can be used in conjunction with ongoing public health efforts.
Combining PCR and CT testing for COVID
Authors: Shen Chen , Mark Ron , Kagetsu Nolan J. , Becker Anton S. , Bar-Yam Yaneer
Published: May 2020

We analyze the effect of using a screening CT-scan for evaluation of potential COVID-19 infections in order to isolate and perform contact tracing based upon a viral pneumonia diagnosis. RT-PCR is then used for continued isolation based upon a COVID diagnosis. Both the low false negative rates and rapid results of CT-scans lead to dramatically reduced transmission. The reduction in cases after 60 days with widespread use of CT-scan screening compared to PCR by itself is as high as 50×, and the reduction of effective reproduction rate R(t) is 0.20. Our results imply that much more rapid extinction of COVID is possible by combining social distancing with CT-scans and contact tracing.
Modeling Plasmodium falciparum Diagnostic Test Sensitivity using Machine Learning with Histidine-Rich Protein 2 Variants
Authors: Ford Colby T. , Alemayehu Gezahegn , Blackburn Kayla , Lopez Karen , Dieng Cheikh Cambel , Lo Eugenia , Golassa Lemu , Janies Daniel
Published: May 2020

Malaria, predominantly caused by Plasmodium falciparum, poses one of largest and most durable health threats in the world. Previously, simplistic regression-based models have been created to characterize malaria rapid diagnostic test performance, though these models often only include a couple genetic factors. Specifically, the Baker et al., 2005 model uses two types of particular repeats in histidine-rich protein 2 (PfHRP2) to describe a P. falciparum infection [1], though the efficacy of this model has waned over recent years due to genetic mutations in the parasite. In this work, we use a dataset of 102 P. falciparum PfHRP2 genetic sequences collected in Ethiopia and derived a larger set of motif repeat matches for use in generating a series of diagnostic machine learning models. Here we show that the usage of additional and different motif repeats proves effective in predicting infection. Furthermore, we use machine learning model explanability methods to highlight which of the repeat types are most important, thereby showcasing a novel methodology for identifying potential targets for future versions of rapid diagnostic tests.
Distinctive trajectories of COVID-19 epidemic by age and gender: a retrospective modeling of the epidemic in South Korea
Authors: Yu Xinhua , Duan Jiasong , Jiang Yu , Zhang Hongmei
Published: May 2020

Objectives

Elderly people had suffered disproportional burden of COVID-19. We hypothesized that males and females in different age groups might have different epidemic trajectories.

Methods

Using publicly available data from South Korea, daily new COVID-19 cases were fitted with generalized additive models, assuming Poisson and negative binomial distributions. Epidemic dynamics by age and gender groups were explored with interactions between smoothed time terms and age and gender.

Results

A negative binomial distribution fitted the daily case counts best. Interaction between the dynamic patterns of daily new cases and age groups was statistically significant (p<0.001), but not with gender group. People aged 20-39 years led the epidemic processes in the society with two peaks: one major peak around March 1 and a smaller peak around April 7, 2020. The epidemic process among people aged 60 or above was trailing behind that of younger people with smaller magnitude. After March 15, there was a consistent decline of daily new cases among elderly people, despite large fluctuations of case counts among young adults.

Conclusions

Although young people drove the COVID-19 epidemic in the whole society with multiple rebounds, elderly people could still be protected from virus infection after the peak of epidemic.
ACE2 polymorphisms as potential players in COVID-19 outcome
Authors: Khayat André Salim , de Assumpção Paulo Pimentel , Khayat Bruna Claudia Meireles , Araújo Taíssa Maíra Thomaz , Batista-Gomes Jéssica Almeida , Imbiriba Luciana Carvalho , Ishak Geraldo , de Assumpção Paula Baraúna , Moreira Fabiano Cordeiro , Burbano Rommel Rodriguez , Ribeiro-dos-Santos André , Ribeiro-dos-Santos Ândrea Kelly , dos Santos Ney Pereira Carneiro , dos Santos Sidney Emmanuel Batista
Published: May 2020

The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, ACE2 polymorphisms should influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.
Monitoring and forecasting the number of reported and unreported cases of the COVID-19 epidemic in Brazil using Particle Filter
Authors: Dutra J. C. S. , da Silva W. B. , da Costa J. M. J.
Published: May 2020

In this paper, we combine algorithm of Liu & West for the Particle Filter (PF) with SIRU-type epidemic model to monitor and forecast cases of Covid-19 in Brazil from February up to September. We filter the number of cumulative reported cases and estimate model parameters and more importantly unreported infectious cases (asymptomatic and symptomatic infectious individuals). The parameters under study are related to the attenuation factor of the transmission rate and the fraction of asymptomatic infectious becoming reported as symptomatic infectious. Initially, the problem is analysed through Particle Swarm Optimization (PSO) based simulations to provide initial guesses, which are then refined by means of PF simulations. Subsequently, two additional steps are performed to verify the capability of the adjusted model to predict and forecast new cases. According to the results, the pandemic peak is expected to take place in mid-June 2020 with about 25,000 news cases per day. As medical and hospital resources are limited, this result shows that public health interventions are essential and should not be relaxed prematurely, so that the coronavirus pandemic is controlled and conditions are available for the treatment of the most severe cases.
Integrated sample inactivation, amplification, and Cas13-based detection of SARS-CoV-2
Authors: Arizti-Sanz Jon , Freije Catherine A. , Stanton Alexandra C. , Boehm Chloe K. , Petros Brittany A. , Siddiqui Sameed , Shaw Bennett M. , Adams Gordon , Kosoko-Thoroddsen Tinna-Solveig F. , Kemball Molly E. , Gross Robin , Wronka Loni , Caviness Katie , Hensley Lisa E. , Bergman Nicholas H. , MacInnis Bronwyn L. , Lemieux Jacob E. , Sabeti Pardis C. , Myhrvold Cameron
Published: May 2020

The COVID-19 pandemic has highlighted that new diagnostic technologies are essential for controlling disease transmission. Here, we develop SHINE (SHERLOCK and HUDSON Integration to Navigate Epidemics), a sensitive and specific integrated diagnostic tool that can detect SARS-CoV-2 RNA from unextracted samples. We combine the steps of SHERLOCK into a single-step reaction and optimize HUDSON to accelerate viral inactivation in nasopharyngeal swabs and saliva. SHINE’s results can be visualized with an in-tube fluorescent readout — reducing contamination risk as amplification reaction tubes remain sealed — and interpreted by a companion smartphone application. We validate SHINE on 50 nasopharyngeal patient samples, demonstrating 90% sensitivity and 100% specificity compared to RT-PCR with a sample-to-answer time of 50 minutes. SHINE has the potential to be used outside of hospitals and clinical laboratories, greatly enhancing diagnostic capabilities.
An anti-CRISPR protein induces strong non-specific DNA binding activity in a CRISPR-Cas complex
Authors: Lu Wang-Ting , Trost Chantel N. , Müller-Esparza Hanna , Randau Lennart , Davidson Alan R.
Published: May 2020

Phages and other mobile genetic elements express anti-CRISPR proteins (Acrs) to protect their genomes from destruction by CRISPR-Cas systems. Acrs usually block the ability of CRISPR-Cas systems to bind or cleave their nucleic acid substrates. Here, we investigate an unusual Acr, AcrIF9, that induces a gain-of-function to a type I-F CRISPR-Cas (Csy) complex, causing it to bind strongly to DNA that lacks both a PAM sequence and sequence complementarity. We show that specific and non-specific dsDNA compete for the same site on the Csy:AcrIF9 complex with rapid exchange, but specific ssDNA appears to still bind through complemetarity to the CRISPR RNA. We also demonstrate that induction of non-specific DNA-binding is a conserved property of diverse AcrIF9 homologues, implying that this activity contributes the biologically relevant function of this Acr family. AcrIF9 provides another example of the surprising variety of mechanisms by which Acrs inhibit CRISPR-Cas systems.
Conserved nicotine-activated neuroprotective pathways involve mitochondrial stress
Authors: Nourse J. Brucker , Harshefi Gilad , Marom Adi , Karmi Abdelrahaman , Caldwell Kim A. , Caldwell Guy A. , Treinin Millet
Published: May 2020

Tobacco smoking is a risk factor for several human diseases. Conversely, smoking also reduces the prevalence of Parkinson’s disease (PD), whose hallmark is degeneration ofsubstantia nigradopaminergic neurons (DNs). We useC. elegansas a model to investigate whether tobacco-derived nicotine activates nicotinic acetylcholine receptors (nAChRs) to selectively protect DNs. Using this model we demonstrate conserved functions of DN-expressed nAChRs. We find that DOP-2, a D3-receptor homolog, MCU-1, a mitochondrial calcium uniporter, and PINK-1, PTEN-induced kinase 1, are required for nicotine-mediated protection of DNs. Together, our results support involvement of calcium-dependent mitochondrial stress activation of PINK-1 in nicotine-dependent neuroprotection. This suggests that nicotine’s selective protection ofsubstantia nigraDNs is due to the confluence of two factors: first, their unique vulnerability to mitochondrial stress, which is mitigated by increased mitochondrial quality control due to PINK1 activation; and second, to their specific expression of D3 receptors.
Targeted disruption ofPparγ1promotes trophoblast endoreplication in the murine placenta
Authors: Nakano Takanari , Aochi Hidekazu , Hirasaki Masataka , Takenaka Yasuhiro , Fujita Koji , Soma Hiroaki , Kamezawa Hajime , Koizumi Takahiro , Okuda Akihiko , Murakoshi Takayuki , Shimada Akira , Inoue Ikuo
Published: May 2020

In murine placentas, peroxisome proliferator-activated receptor (PPAR) γ1, a nuclear receptor, is abundant at the late stage of pregnancy (E15–E16), but its functional roles are still elusive because PPARγ-full knockout embryos die early (E10). We generated mice disrupted in onlyPparγ1, one of the two major mRNA splicing variants of PPARγ1.Pparγ1-knockout embryos developed normally until 15.5 dpc, but their growth was retarded thereafter and they did not survive. At 15.5 dpc, in the wild-type placentas, intense PPARγ-immunostaining was detected in sinusoidal trophoblast giant cells (sTGCs), a cell lineage that coordinates the maternal blood microcirculation in the labyrinth, whereas they were absent in the knockouts. AlthoughPparγ1-knockout placentas were normal in morphology, we observed severely dilated maternal blood sinuses in the labyrinth. ThePparγ1-knockout sTGCs had abnormally large nuclei, an enhanced endocycling phenotype, indicating insufficient differentiation. RNA-sequencing of the placentas showed increased expression of genes coding for nucleosome assembly factors. Labyrinthine gene expressions for atypical E2Fs and cyclin E, key drivers for endocycling, were increased >3-fold. These findings suggested that PPARγ1 plays a key role in endocycle termination.
Gut bacteria mediate nutrient availabilityin Drosophiladiets
Authors: Lesperance Danielle N.A. , Broderick Nichole A.
Published: May 2020

Drosophila melanogastergut microbes play important roles in host nutritional physiology. However, these associations are often indirect and studies typically are in the context of specialized nutritional conditions, making it difficult to discern how microbiome-mediated impacts translate to physiologically relevant conditions, in the laboratory or nature. Here, we show that on three artificial diets and a natural diet of grapes,D. melanogastergut bacteria alter protein, carbohydrates, and moisture of the food substrate. In depth analysis on one diet revealed bacteria also increase tryptophan levels. We investigate how nutrient changes impact life history and find that, while alterations to dietary protein and carbohydrates are arguably the most significant consequence of bacterial association, other factors, such as micronutrients, likely contribute to life history traits in a diet-dependent manner. Our work demonstrates that while some bacterial impacts on nutrition occur across experimental diets, others are dictated by unique dietary environments.