bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic accuracy of shock index for severe postpartum hemorrhage in high-income country: Protocol for a systematic review and meta-analysis
Authors: Makino Yuto , Miyake Kentaro , Okada Asami , Ikeda Yumie , Okada Yohei 
Published: May 2021

AbstractBackgroundThis review aims to conduct a systematic review and meta-analysis to assess the prognostic value of shock index for prediction of severe Postpartum hemorrhage (PPH) in high-income countries.MethodWe will perform a systematic review and meta-analysis for diagnostic test accuracy (DTA). We will search CENTRAL, MEDLINE (Ovid), Web of Science, and other sources and include all relevant reports on the prognostic accuracy of shock index for severe PPH. The target condition is defined as severe PPH required higher-level care. Two review authors will independently screen the study eligibility and extract data from included studies. Two authors will also assess study quality using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. We will use the hierarchical models comprising both the bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model for data synthesis if appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs).Trial registrationThis review is submitted with University hospital medical information network clinical trial registry (UMIN-CTR) [UMIN 000044230].Conflicts of interestAll authors declare to have no conflicts of interestFundingNone
Amplitude setting and dopamine response of finger tapping and gait are related in Parkinson’s disease
Authors: Syeda Hafsa Bareen , Glover Aliyah , Pillai Lakshmi , Kemp Aaron S. , Spencer Horace , Lotia Mitesh , Larson-Prior Linda , Virmani Tuhin 
Published: May 2021

AbstractObjectiveMovement amplitude setting is affected early in Parkinson’s disease (PD), clinically manifesting as bradykinesia. Our objective was to determine if amplitude setting of upper limb bimanual movements and bipedal gait are similarly modulated in PD.Methods27 PD and 24 control participants were enrolled. Participants performed a bimanual anti-phase finger tapping task wearing gloves with joint angular sensors, and an instrumented gait assessment. Motor load was varied by asking participants to perform movements at a normal and fast pace. PD participants were evaluated OFF (PD-OFF) and ON (PD-ON) levodopa.ResultsPD-OFF participants had shorter tap interval, smaller tap amplitude, and greater tap amplitude variability than controls in the more affected hands (all p<0.05). Tap amplitude and stride length (p=0.030), and tap frequency and gait cadence (p=0.011) were correlated in PD-OFF. Tap frequency and amplitude were also correlated with motor UPDRS (p<0.005) and bradykinesia motor (p<0.05) and ADL (p<0.005) UPDRS subscales. Levodopa improved mean tap amplitude and stride length during fast tapping in PD participants.ConclusionIn PD-OFF, mean finger tapping amplitude and gait stride length were correlated and showed similar dopaminergic response.SignificanceFuture studies manipulating upper limb amplitude could help provide greater understanding of the networks responsible for amplitude setting in PD.
Epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa
Authors: Okoh Olayinka Sunday , Nii-Trebi Nicholas Israel , Jakkari Abdulrokeeb , Olaniran Tosin Titus , Senbadejo Tosin Yetunde , Kafintu-kwashie Anna Aba , Dairo Emmanuel Oluwatobi , Ganiyu Tajudeen Oladunni , Akaninyene Ifiokakaninyene Ekpo , Ezediuno Louis Odinakaose , Adeosun Idowu Jesulayomi , Ockiya Michael Asebake , Jimah Esther Moradeyo , Spiro David J. , Oladipo Elijah Kolawole , Trovão Nídia S. 
Published: May 2021

AbstractCOVID-19 disease dynamics have been widely studied in different settings around the globe, but little is known about these patterns in the African continent.To investigate the epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa, more than 2400 complete genomes from 33 African countries were retrieved from the GISAID database and analyzed. We investigated their diversity using various clade and lineage nomenclature systems, reconstructed their evolutionary divergence and history using maximum likelihood inference methods, and studied the case and death trends in the continent. We also examined potential repeat patterns and motifs across the sequences.In this study, we show that after almost one year of the COVID-19 pandemic, only 143 out of the 782 Pango lineages found worldwide circulated in Africa, with five different lineages dominating in distinct periods of the pandemic. Analysis of the number of reported deaths in Africa also revealed large heterogeneity across the continent. Phylogenetic analysis revealed that African viruses cluster closely with those from all continents but more notably with viruses from Europe. However, the extent of viral diversity observed among African genomes is closest to that of the Oceania outbreak, most likely due to genomic under-surveillance in Africa. We also identified two motifs that could function as integrin-binding sites and N-glycosylation domains.These results shed light on the evolutionary dynamics of the circulating viral strains in Africa, elucidate the functions of protein motifs present in the genome sequences, and emphasize the need to expand genomic surveillance efforts in the continent to better understand the molecular, evolutionary, epidemiological, and spatiotemporal dynamics of the COVID-19 pandemic in Africa.
Economic Impact Payment, Human Mobility and the COVID-19 Mitigation in the United States
Authors: Zhang Ruohao 
Published: May 2021

AbstractThis paper studies the relationship between the individual’s income and COVID-19 mitigation effort contribution. The paper suggests that in addition to the government mandatory policies, the income compensation policy is an alternative government instrument that helps increase the individual and social aggregate COVID-19 mitigation effort. I empirically test the effect of the income compensation policy by utilizing the United States economic impact payment (EIP) in April 2020 as a quasi-natural experiment, and use the cellphone GPS measured human mobility data as the outcome indicator of the COVID-19 mitigation effort. I find that by receiving EIP, individuals on average significantly increase median home dwell time by 3% – 5% (about 26–45 minutes). This paper highlights an unintended effect of EIP: in addition to providing economic assistance, EIP also helps mitigate the COVID-19 virus transmission.JEL codesD11 D12 H41 I12 I14 I18
Socioeconomic Status and COVID-19 Related Outcomes in India: Hospital Based Study
Authors: Sharma Arvind Kumar , Gupta Rajeev , Baig Vaseem Naheed , Singh Teja Veer , Chakraborty Surabhi , Sunda Jagdish P , Dhakar Prahalad , Sharma Shiv P , Panwar Raja Babu , Katoch Vishwa Mohan 
Published: May 2021

ABSTRACTBackground & ObjectiveCOVID-19 infection has disproportionately affected ethnic minorities and deprived populations in Europe and North America. Influence of socioeconomic status on COVID-19 related outcomes has not been studied in India. To determine association of educational status, as marker of socioeconomic status, with COVID-19 related outcomes we performed a study.MethodsClinically and virologically confirmed successive patients of COVID-19 presenting at a government hospital in India were recruited. Demographic and clinical details were recorded. The cohort was classified according to educational status into Group 1-illiterate or < primary, Group 2-higher secondary, and Group 3-some college. To compare outcomes among groups we performed univariate and multivariate logistic regression and odds ratios (OR) and 95% confidence intervals (CI) were calculated.ResultsFrom March-September 2020 we recruited 4645 patients (men 3386, women 1259) with laboratory confirmed COVID-19. Mean age was 46+18y, most lived in moderate or large households and 30.5% had low educational status. Smoking or tobacco use was in 29.5%, co-morbidities in 28.6% and low oxygen concentration (SpO2<95%) at admission in 30%. Average length of hospital stay was 6.8+3.7 days, supplemental oxygen was provided in 18.4%, high flow oxygen or non-invasive ventilation 7.1%, and mechanical ventilation in 3.6%. 340 patients (7.3%) died. Group 1 patients were younger, more women, larger households, higher tobacco use and were more hypoxic at admission with lower lymphocyte counts, elevated liver enzymes and greater kidney dysfunction. In Group 1 vs Groups 2 and 3 requirement of oxygen (21.6 vs 16.7 and 17.0%), non-invasive ventilation (8.0 vs 5.9 and 7.1%), invasive ventilation (4.6 vs 3.5 and 3.1%) and deaths (10.0 vs 6.8 and 5.5%) were significantly greater (p<0.05). Compared to Group 3, OR for deaths were significantly higher in Group 1 (1.91, 1.46-2.51) and Group 2 (1.24, 0.93-1.66). Adjustment for age, sex, household size, risk factors and comorbidities led to attenuation in OR in Groups 1 (1.44, 1.07-1.93) and 2 (1.38, 1.02-1.85) that remained with adjustments for clinical and laboratory parameters and oxygen support in Groups 1 (1.38, 0.99-1.93) and 2 (1.52, 1.01-2.11).ConclusionIlliterate and less educational (socioeconomic) status patients with COVID-19 in India have significantly greater adverse in-hospital outcomes and mortality. This is related to more severe disease at presentation.
The human hepatocyte TXG-MAPr: WGCNA transcriptomic modules to support mechanism-based risk assessment
Authors: Callegaro Giulia , Kunnen Steven J. , Trairatphisan Panuwat , Grosdidier Solène , Niemeijer Marije , den Hollander Wouter , Guney Emre , Piñero Gonzalez Janet , Furlong Laura , Webster Yue W. , Saez-Rodriguez Julio , Sutherland Jeffrey J. , Mollon Jennifer , Stevens James L. , van de Water Bob 
Published: May 2021

AbstractMechanism-based risk assessment is urged to advance and fully permeate into current safety assessment practices, possibly at early phases of drug safety testing. Toxicogenomics is a promising source of comprehensive and mechanisms-revealing data, but analysis tools to interpret mechanisms of toxicity and specific for the testing systems (e.g. hepatocytes) are lacking. In this study we present the TXG-MAPr webtool (available athttps://txg-mapr.eu/WGCNA_PHH/TGGATEs_PHH/), an R-Shiny-based implementation of weighted gene co-expression networks (WGCNA) obtained from the Primary Human Hepatocytes (PHH) TG-GATEs dataset. Gene co-expression networks (modules) were annotated with functional information (pathway enrichment, transcription factor) to reveal their mechanistic interpretation. Several well-known stress response pathways were captured in the modules, are perturbed by specific stressors and show preserved in rat systems (rat primary hepatocytes and ratin vivoliver), highlighting stress responses that translate across species/testing systems. The TXG-MAPr tool was successfully applied to investigate the mechanism of toxicity of TG-GATEs compounds and using external datasets obtained from different hepatocyte cells and microarray platforms. Additionally, we suggest that module responses can be calculated from targeted RNA-seq data therefore imputing biological responses from a limited gene. By analyzing 50 different PHH donors’ responses to a common stressor, tunicamycin, we were able to suggest modules associated with donor’s traits, e.g. pre-existing disease state, therefore connected to donors’ variability. In conclusion, we demonstrated that gene co-expression analysis coupled to an interactive visualization environment, the TXG-MAPr, is a promising approach to achieve mechanistic relevant, cross-species and cross-platform evaluation of toxicogenomic data.
Cortical network structure mediates response to stimulation: an optogenetic study in non-human primates
Authors: Bloch Julien , Greaves-Tunnell Alexander , Shea-Brown Eric , Harchaoui Zaid , Shojaie Ali , Yazdan-Shahmorad Azadeh 
Published: May 2021

AbstractAs aberrant network-level functional connectivity underlies a variety of neural disorders, the ability to induce targeted functional reorganization would be a profound development towards therapies for neural disorders. Brain stimulation has been shown to alter large-scale network-wide functional connectivity, but the mapping from stimulation to the modification is unclear. Here, we leverage advances in neural interfaces, interpretable machine learning, and graph theory to arrive at a model which accurately predicts stimulation-induced network-wide functional reorganization. The model jointly considers the stimulation protocol and the cortical network structure, departing from the standard approach which only considers the stimulation protocol. We validate our approach in the primary sensorimotor cortex of non-human primates using paired optogenetic stimulation through a large-scale optogenetic interface. We observe that the stimulation protocol only predicts a small portion of the induced functional connectivity changes while the network structure predicts much more, indicating that the underlying network is the primary mediator of the response to stimulation. We extract the relationships linking the stimulation and network characteristics to the functional connectivity changes and observe that the mappings diverge over frequency bands and successive stimulations. Finally, we uncover shared processes governing real-time and longer-term effects of stimulation. Our framework represents a paradigm shift for targeted neural stimulation and can be used to interrogate, improve, and develop stimulation-based interventions for neural disorders.TeaserBrain stimulation rewires the brain, but the pre-existing network structure of the brain controls the rewiring.
Evaluation of the Family Liaison Officer (FLO) role during the COVID-19 Pandemic
Authors: Hughes Luke , Anderton Lisa , Taylor Rachel M 
Published: May 2021

AbstractObjectivesDuring the first wave of COVID-19 heavy restrictions were placed on hospital visitations in the United Kingdom. To support communication between families and patients a central London hospital introduced the role of the Family Liaison Officer. Communication within healthcare settings is often the subject of contention, particularly for patient’s families. During periods of crisis communication can become strained for patients and their families. We aimed to evaluate the rapid implementation of this role to provide guidance if it was required in the future and to explore the potential for this to become a standard role.DesignService evaluationSettingSingle National Health Service hospital in London.MethodsSemi-structured video interviews with a convenience sample of 12 participants. Data were analysed using Framework Analysis.ParticipantsFamily Liaison Officers (n=5) and colleagues who experienced working alongside them (n=7).ResultsKey themes were identified from the interviews pertaining to the role, the team, the impact and the future. Two versions of the role emerged though the process based on the Family Liaison Officer’s previous background: Clinical Family Liaison Officers (primarily nurses) and Pastoral Family Liaison Officers (primarily play specialists). Both the Family Liaison Officers and their colleagues agreed that the role had a very positive impact on the wards during this time. Negative aspects of the role, such as a lack of induction, boundaries or clear structure were also discussed.ConclusionThe Family Liaison Officer was a key role during the pandemic in facilitating communication between patient, clinical team and family. The challenges associated with the role reflect the speed in which it was implemented but it was evident to those in the role and clinicians who the role was supporting that it has potential to help improve hospital communication, and the work of healthcare staff outside of a pandemic.Strengths and limitations of this studyThis was an in-depth evaluation of the Family Liaison Officer role from the perspective of those in the role and the clinical team who they were providing support.The sample included representation of the different disciplines who worked in the FLO role.The evaluation only represents the professional perspective and not the experience of the family.
Vaccination against COVID-19 and society’s return to normality in England: a modelling study of impacts of different types of naturally acquired and vaccine induced immunity
Authors: Song Fujian , Bachmann Max O. 
Published: May 2021

ABSTRACTObjectivesTo project impacts of mass vaccination against COVID-19, and investigate possible impacts of different types of naturally acquired and vaccine-induced immunity on future dynamics of SARS-CoV-2 transmission from 2021 to 2029 in England.DesignDeterministic, discrete-time population dynamic modelling.ParticipantsPopulation in England.Interventionsmass vaccination programmes.Outcome measuresdaily and cumulative number of deaths from COVID-19.ResultsIf vaccine efficacy is ≥ 70%, the vaccine-induced sterilising immunity lasts ≥ 182 days, and the reinfectivity is greatly reduced (by ≥ 40%), mass vaccination programmes can prevent further COVID-19 outbreaks in England. Under such optimistic scenarios, the cumulative number of COVID-19 deaths is estimated to be from 113,000 to 115,000 by the end of 2029 in England. However, under plausible scenarios with lower vaccine efficacy, shorter durability of immunity, and smaller reduction in reinfectivity, repeated vaccination programmes could not prevent further COVID-19 outbreaks.ConclusionsUnder optimistic scenarios, mass immunisation using efficacious vaccines may enable society safely to return to normality. However, under plausible scenarios with low vaccine efficacy and short durability of immunity, COVID-19 could continue to cause recurrent waves of severe morbidity and mortality despite frequent vaccinations. It is crucial to monitor the vaccination effects in the real world, and to better understand characteristics of naturally acquired and vaccine induced immunity against SARS-CoV-2.ARTICLE SUMMARYStrengths and limitations of this studyWe used a population dynamic model to assess impacts of vaccination programmes on future dynamics of SARS-CoV-2 transmission dynamics, and to explicitly investigate the impacts of different types of immune responses to SARS-CoV-2 infection and vaccines on the COVID-19 epidemic in England.The model has been verified based on historically observed outcome data in England, and a large number of projection scenarios are explored.Findings from our study improves the understanding of key immunological parameters relevant to future SARS-CoV-2 transmission dynamics and vaccination strategies.This is a deterministic simulation model, and uncertainty in estimated parameters may have not been fully accommodated. There remain many uncertainties regarding durability and types of naturally acquired and vaccine-induced immunity.
Evidence for PKD2L1-positive neurons present distant from the central canal in the ventromedial spinal cord and Medulla of the adult mouse
Authors: Jurčić Nina , Michelle Caroline , Trouslard Jérôme , Wanaverbecq Nicolas , Kastner Anne 
Published: May 2021

AbstractNeurons in contact with the cerebrospinal fluid (CSF) are found around the medullo-spinal central canal (CC) in adult mice. These neurons (CSF-cNs), located within or below the ependymal cell layer known as the stem cell niche, present a characteristic morphology with a dendrite projecting to the CC and ending with a protrusion. They are GABAergic, characterized by an immature neuronal phenotype and selectively express PKD2L1, a channel member of the TRP channel superfamily with properties of sensory receptor.Using immunohistological techniques in mice, we characterize a new population of PKD2L1 positive cells that is observed around embryonic day 16 (E16), is present distant from the CC in a zone enriched with astrocytes and ependymal fibers of the ventro-medial spinal cord and medulla. With development, their number appears stable although smaller than that of CSF-cNs and they progressively become more distant from the CC with the reorganization of the CC region. These neurons share both functional and phenotypical properties with CSF-cNs, but they appear subdivided in two groups. One, present along the midline, has a bipolar morphology and extend a long dendrite along ependymal fibers and towards the CC. The second group, localized in more ventro-lateral regions, has a multipolar morphology and no apparent projection to the CCAltogether, we describe a novel population of PKD2L1+ neurons distant from the CC but with properties similar to CSF-cNs that might serve to sense modification in the composition of either CSF or interstitial liquid, a function that will need to be confirmed.
Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases
Authors: Kaduri Maya , Sela Mor , Kagan Shaked , Poley Maria , Abumanhal-Masarweh Hanan , Mora-Raimundo Patricia , Ouro Alberto , Dahan Nitsan , Shklover Jeny , Shainsky-Roitman Janna , Buganim Yosef , Schroeder Avi 
Published: May 2021

AbstractNeurons within the tumor microenvironment promote cancer progression, thus their local targeting has potential clinical benefits. We designed PEGylated lipid nanoparticles loaded with a non-opioid analgesic, bupivacaine, to target neurons within breast cancer tumors and suppress nerve-to-cancer crosstalk.In vitro, 100-nm nanoparticles were taken up readily by primary neurons, trafficking from the neuronal body and along the axons. We demonstrate that signaling between triple-negative breast cancer cells (4T1) and neurons involves secretion of cytokines stimulating neurite outgrowth. Reciprocally, neurons stimulated 4T1 proliferation, migration and survival through secretion of neurotransmitters. Bupivacaine curbs neurite growth and signaling with cancer cells, inhibiting cancer-cell viability.In vivo, bupivacaine-loaded nanoparticles administered intravenously, suppressed neurons in orthotopic triple-negative breast cancer tumors, inhibiting tumor growth and metastatic dissemination. Overall, our findings suggest that reducing nerve involvement in tumors is important for treating cancer.
Intrinsic mechanical sensitivity of auditory neurons as a contributor to sound-driven neural activity
Authors: Perez Flores Maria C. , Verschooten Eric , Lee Jeong Han , Kim Hyo Jeong , Joris Philip X. , Yamoah Ebenezer N. 
Published: May 2021

AbstractMechanosensation – by which mechanical stimuli are converted into a neuronal signal – is the basis for the sensory systems of hearing, balance, and touch. Mechanosensation is unmatched in speed and its diverse range of sensitivities, reaching its highest temporal limits with the sense of hearing; however, hair cells (HCs) and the auditory nerve (AN) serve as obligatory bottlenecks for sounds to engage the brain. Like other sensory neurons, auditory neurons use the canonical pathway for neurotransmission and millisecond-duration action potentials (APs). How the auditory system utilizes the relatively slow transmission mechanisms to achieve ultrafast speed and high audio-frequency hearing remains an enigma. Here, we address this paradox and report that the AN is mechanically sensitive, and minute mechanical displacement profoundly affects its response properties. Sound-mimicking sinusoidal mechanical and electrical current stimuli affect phase-locked responses. In a phase-dependent manner, the two stimuli can also evoke suppressive responses. We propose that mechanical sensitivity interacts with synaptic responses to shape responses in the AN, including frequency tuning and temporal phase-locking. The combination of neurotransmission and mechanical sensation to control spike patterns gives the AN a secondary receptor role, an emerging theme in primary neuronal functions.