bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient transcriptome profiling across the malaria parasite erythrocytic cycle by flow sorting
Authors: Dia Aliou , Jett Catherine , McDew-White Marina , Li Xue , Anderson Timothy J.C. , Cheeseman Ian H. 
Published: November 2020

AbstractPlasmodium falciparumis the most virulent and widespread of the human malaria parasite species. This parasite has a complex life cycle that involves sexual replication in a mosquito vector and asexual replication in a human host. During the 48-hour intraerythrocytic developmental cycle (IDC), parasites develop and multiply through the morphologically distinct ring, trophozoite and schizont stages. Stage-specific transcriptomic approaches have shown gene expression profiles continually change throughout the IDC. Cultures of tightly synchronized parasites are required to capture the transcriptome specific to a developmental stage. However, the most commonly used synchronization methods require lysis of late stages, potentially perturbing transcription, and often do not result in tightly synchronized cultures. To produce complete transcriptome profiles of the IDC a synchronous culture requires frequent sampling over a 48-hour period, this is both time consuming and labor intensive. Here we develop a method to sample the IDC densely by isolating parasites from an asynchronous culture with fluorescence activated cell sorting (FACS). We sort parasites in tight windows of IDC progression based on their DNA/RNA abundance. We confirmed the tight synchronization and stage specificity by light microscopy and RNAseq profiling. We optimized our protocol for low numbers of sorted cells allowing us to rapidly capture transcriptome profiles across the entire IDC from a single culture flask. This methodology will allow malaria stage-specific studies to perform experiments directly from asynchronous cultures with high accuracy and without the need for labor-intensive time-course experiments.
Reduced Expression ofSlc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience
Authors: Smagin Dmitry A. , Babenko Vladimir N. , Kovalenko Irina L. , Galyamina Anna G. , Redina Olga E. , Kudryavtseva Natalia N. 
Published: November 2020

ABSTRACTThere are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of theSlc*genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressedSlcgenes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressedSlcgenes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose,etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of theSlc*genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems.
A higher ratio of green spaces means a lower racial disparity in severe acute respiratory syndrome coronavirus 2 infection rates: A nationwide study of the United States
Authors: Lu Yi , Chen Long , Liu Xueming , Yang Yuwen , Xu Wenyan , Webster Chris , Sullivan William C. , Jiang Bin 
Published: November 2020

AbstractThere is striking racial disparity in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates in the United States. We hypothesize that the disparity is significantly smaller in areas with a higher ratio of green spaces at the county level. This study used the 135 most urbanized counties across the United States as sample sites. County level data on the SARS-CoV-2 infection rates of black and white individuals in each county were collected. The ratio of green spaces by land-cover type at the county level was calculated from satellite imagery. An ecological hierarchical regression analysis measured cross-sectional associations between racial disparity in infection rates and green spaces, after controlling for socioeconomic, demographic, pre-existing chronic disease, and built-up area factors. We found significantly higher infection rate among black individuals compared to white individuals. More importantly, a higher ratio of green spaces at the county level is significantly associated with a lower racial disparity in the SARS-CoV-2 infection rate. Further, we identified four green space factors that have significant negative associations with the racial disparity in SARS-CoV-2 infection rates, including open space in developed areas, forest, shrub and scrub, and grassland and herbaceous. We suggest that green spaces are an equalizing salutogenic factor, modifying infection exposure.HighlightsThe first study to identify significant relationships between green spaces and the racial disparity of SARS-CoV-2 infection rates.A nationwide study of the 135 most urbanized counties of the United States.A within-subject study: The black-white racial disparity of SARS-CoV-2 infection rates was measured within each county.A higher ratio of green spaces in a county is associated with a lower racial disparity of SARS-CoV-2 infection rates after controlling for socio-economic, demographic, pre-existing chronic disease, and built-up area factors.Four green space factors are significantly associated with a lower racial disparity of SARS-CoV-2 infection rates.
Using Convergent Sequential Design for Rapid Complex Case Study Descriptions: Example of Public Health Briefings During the Onset of the COVID-19 Pandemic
Authors: Poth Cheryl N. , Bulut Okan , Aquilina Alexandra M. , Otto Simon J. G. 
Published: November 2020

AbstractConceptualizing the public health response to the COVID-19 pandemic response as a complex adaptive system is useful to study its key features of emergence, interdependency, and adaptation yet practical guidance for mixed methods researchers remains limited. This study contributes an illustrative example and discussion for guiding how a mixed methods convergent sequential research design, informed by complexity theory and drawing upon open-access datasets, can rapidly generate complex case study descriptions. This article serves as an essential reference for identifying points of integration within a sequential convergent design using text mining to manage large data volumes and studying complex phenomena using a complexity-informed case study-mixed methods approach to generate novel public health insights.
Association of social distancing and masking with risk of COVID-19
Authors: Kwon Sohee , Joshi Amit D. , Lo Chun-Han , Drew David A. , Nguyen Long H. , Guo Chuan-Guo , Ma Wenjie , Mehta Raaj S. , Warner Erica T. , Astley Christina M. , Merino Jordi , Murray Benjamin , Wolf Jonathan , Ourselin Sebastien , Steves Claire J. , Spector Tim D. , Hart Jaime E. , Song Mingyang , VoPham Trang , Chan Andrew T. 
Published: November 2020

AbstractGiven the continued burden of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) disease (COVID-19) across the U.S., there is a high unmet need for data to inform decision-making regarding social distancing and universal masking. We examined the association of community-level social distancing measures and individual masking with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported masking was associated with a 63% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. In the current environment of relaxed social distancing mandates and practices, universal masking may be particularly important in mitigating risk of infection.
Universal Health Coverage and COVID-19 Pandemic: A Bangladesh Perspective
Authors: Ferdous Most. Zannatul , Islam Ummay Soumayia 
Published: November 2020

AbstractBackgroundLike many other countries around the world, Bangladesh adopts Universal Health Coverage (UHC) as a national aspiration. The central theme of its providing quality and affordable health services which is a significant element of social protection. This paper was aimed to provide a narrative understanding of the perspectives of UHC in Bangladesh towards COVID-19 based on the existing literature.MethodsWe conducted a review combining articles and abstracts with full HTML and PDF format. We searched Google Scholar, ScienceDirect and Google using multiple terms related to UHC, COVID-19 and Bangladesh without any date boundary and without any basis of types of studies, that is, all types of studies were scrutinized.ResultsThis short description highlights that the current pandemic COVID-19 holds lessons that health systems and economies in several countries like Bangladesh are not in enough preparation to tackle a massive public health crisis. It reports the shortage of health workers, scarcity of personal protective equipment, limited and ineffective diagnostic facilities, inadequate infrastructure of health care facilities, scarcity of drugs, and underfunded health services. Further, COVID-19 pandemic highlights the country’s health system needs an ongoing rehab post-COVID-19 with strong coordination in governance, in health economics, in health systems, in information systems, as well as in community participation in health to achieve UHC.ConclusionsAddressing the needs for UHC achievement, it is important to break down the access barriers and keeping up to date all the activities addressing public health crisis like COVID-19.
Epidemiological and immunological features of obesity and SARS-CoV-2
Authors: Nilles Eric J , Siddiqui Sameed M , Fischinger Stephanie , Bartsch Yannic C , de Saint Aubin Michael , Zhou Guohai , Gluck Matthew J , Berger Samuel , Rhee Justin , Petersen Eric , Mormann Benjamin , Loesche Michael , Chen Zhilin , Yu Jingyou , Gebre Makda , Atyeo Caroline , Gorman Matthew J , Zhu Alex Lee , Burke John , Slein Matthew , Hasdianda Mohammad A , Jambaulikar Guruprasad , Boyer Edward , Sabeti Pardis , Barouch Dan H , Julg Boris D , Kucharski Adam J , Musk Elon R , Lauffenburger Douglas A , Alter Galit , Menon Anil S 
Published: November 2020

AbstractObesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response are poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and, remarkably homogenous immune activity across BMI categories suggests natural- and vaccine-induced protection may be similar across these groups.
Immunophenotyping reveals longitudinal changes in circulating immune cells during radium-223 therapy in patients with metastatic castration-resistant prostate cancer
Authors: Creemers J.H.A. , van der Doelen M.J. , van Wilpe S. , Hermsen R. , Duiveman-de Boer T. , Somford D.M. , Janssen M.J.R. , Sedelaar J.P.M. , Mehra N. , Textor J. , Westdorp H. 
Published: November 2020

ABSTRACTPurposeRadium-223 improves overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (mCRPC). While the exact mechanism behind this survival benefit remains unclear, radium-induced immunological mechanisms might contribute to the OS advantage. We performed a comprehensive evaluation of the immunological changes in mCRPC patients by phenotyping the peripheral blood mononuclear cells (PBMCs) during radium-223 therapy.Experimental DesignIn this prospective, single-arm, exploratory study, PBMCs of 30 mCRPC patients were collected before, during, and after treatment with radium-223. Lymphocyte and monocyte counts were analyzed to get insight into general immune cell trends. Next, we analyzed changes in T cell subsets, myeloid-derived suppressor cells (MDSCs), and immune checkpoint expression using linear regression models. Per subset, the 6-month change (% of baseline) was determined. Bootstrapped 95% confidence intervals were used to measure the degree of uncertainty of our findings.ResultsWe observed a substantial decrease in absolute lymphocyte counts (−0.12 * 10^9 cells/L per injection, 95% CI: -0.143 - -0.102). Simultaneously, an increase was observed in the proportion of T cells that expressed costimulatory (ICOS) or inhibitory (TIM-3, PD-L1, and PD-1) checkpoint molecules. Moreover, the fraction of two immunosuppressive subsets – the regulatory T cells and the monocytic MDSCs – increased throughout treatment. These findings were not more pronounced in patients with an ALP response during therapy.ConclusionImmune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes.
Aggressive COVID-19 “second wave” in Italy
Authors: Zheng Hua , Bonasera Aldo 
Published: November 2020

AbstractA two-step model for the rise and decay of the COVID-19 is applied to the Fall resurgence of COVID-19 in Italy. Data starting from October 6, 2020 are compared to the same time interval in Italy starting from the complete lockdown on March 14, 2020. The model predicts more than 130,000 deceased by the end of the year 2020 if no effective measures are taken. If similar measures to the March ones are quickly adopted, the number of deceased may decrease to over 50,000. The situation is extremely serious and requires collaboration from everyone starting from wearing masks and other protections when social distancing is not feasible.
ACE2-Targeting Monoclonal Antibody as Potent and Broad-Spectrum Coronavirus Blocker
Authors: Chen Yuning , Zhang Yanan , Yan Renhong , Wang Guifeng , Zhang Yuanyuan , Zhang Zherui , Li Yaning , Ou Jianxia , Chu Wendi , Liang Zhijuan , Wang Yongmei , Chen Yili , Chen Ganjun , Wang Qi , Zhou Qiang , Zhang Bo , Wang Chunhe 
Published: November 2020

AbstractThe evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1 and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 “knock-in” mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and “alanine walk” studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and “broad-spectrum” management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.
Stepwise Bayesian Phylogenetic Inference
Authors: Höhna Sebastian , Hsiang Allison Y. 
Published: November 2020

AbstractThe ideal approach to Bayesian phylogenetic inference is to estimate all parameters of interest jointly in a single hierarchical model. However, this is often not feasible in practice due to the high computational cost that would be incurred. Instead, phylogenetic pipelines generally consist of chained analyses, whereby a single point estimate from a given analysis is used as input for the next analysis in the chain (e.g., a single multiple sequence alignment is used to estimate a gene tree). In this framework, uncertainty is not propagated from step to step in the chain, which can lead to inaccurate or spuriously certain results. Here, we formally develop and test the stepwise approach to Bayesian inference, which uses importance sampling to generate observations for the next step of an analysis pipeline from the posterior produced in the previous step. We show that this approach is identical to the joint approach given sufficient information in the data and in the importance sample. This is demonstrated using both a toy example and an analysis pipeline for inferring divergence times using a relaxed clock model. The stepwise approach presented here not only accounts for uncertainty between analysis steps, but also allows for greater flexibility in program choice (and hence model availability) and can be more computationally efficient than the traditional joint approach when multiple models are being tested.
Inhibiting corticospinal excitability by entraining ongoing mu-alpha rhythm in motor cortex
Authors: Zmeykina Elina , Turi Zsolt , Antal Andrea , Paulus Walter 
Published: November 2020

AbstractsSensorimotor mu-alpha rhythm reflects the state of cortical excitability. Repetitive transcranial magnetic stimulation (rTMS) can modulate neural synchrony by inducing periodic electric fields (E-fields) in the cortical networks. We hypothesized that the increased synchronization of mu-alpha rhythm would inhibit the corticospinal excitability reflected by decreased motor evoked potentials (MEP). In seventeen healthy participants, we applied rhythmic, arrhythmic, and sham rTMS over the left M1. The stimulation intensity was individually adapted to 35mV/mmusing prospective E-field estimation. This intensity corresponded to ca. 40% of the resting motor threshold. We found that rhythmic rTMS increased the synchronization of mu-alpha rhythm, increased mu-alpha/beta power, and reduced MEPs. On the other hand, arrhythmic rTMS did not change the ongoing mu-alpha synchronization or MEPs, though it increased the alpha/beta power. We concluded that low intensity, rhythmic rTMS can synchronize mu-alpha rhythm and modulate the corticospinal excitability in M1.HighlightsWe studied the effect of rhythmic rTMS induced E-field at 35mV/mmin the M1Prospective electric field modeling guided the individualized rTMS intensitiesRhyhtmic rTMS entrained mu-alpha rhythm and modulated mu-alpha/beta powerArrhythmic rTMS did not synchronize ongoing activity though increased mu-alpha/beta power.Rhythmic but not arrhythmic or sham rTMS inhibited the cortical excitability in M1
Visual processing speed is linked to functional connectivity between right frontoparietal and visual networks
Authors: Küchenhoff Svenja , Sorg Christian , Schneider Sebastian , Kohl Oliver , Müller Hermann J. , Finke Kathrin , Ruiz-Rizzo Adriana L. 
Published: November 2020

AbstractVisual information processing requires an efficient visual attention system. The neural theory of visual attention (TVA) proposes that visual processing speed depends on the coordinated activity between frontoparietal and occipital brain areas. Previous research has shown that the coordinated activity between (i.e., functional connectivity, ‘inter-FC’) cingulo-opercular (COn) and right-frontoparietal (RFPn) networks is linked to visual processing speed. However, evidence for how inter-FC of COn and RFPn withvisualnetworks links to visual processing speed is still missing. Forty-eight healthy human adult participants (27 females) underwent resting-state (rs-)fMRI and performed a whole-report psychophysical task. To obtain inter-FC, we analyzed the entire frequency range available in our rs-fMRI data (i.e., 0.01-0.4 Hz) to avoid discarding neural information. Following previous approaches, we analyzed the data across frequency bins (Hz): Slow-5 (0.01-0.027), Slow-4 (0.027-0.073), Slow-3 (0.073-0.198), and Slow-2 (0.198-0.4). We used the mathematical TVA framework to estimate an individual, latent-level visual processing speed parameter. We found that visual processing speed was negatively associated with inter-FC between RFPn and visual networks in Slow-5 and Slow-2, with no corresponding significant association for inter-FC between COn and visual networks. These results provide first empirical evidence that links inter-FC between RFPn and visual networks with the visual processing speed parameter. These findings suggest a direct connectivity between occipital and right frontoparietal, but not frontoinsular, regions, to support visual processing speed.Significance statementAn efficient visual processing is at the core of visual cognition. Here, we provide evidence for a brain correlate of how fast individuals process visual stimuli. We used mathematical modeling of performance in a visual report task to estimate visual processing speed. A frequency-based analysis of resting-state fMRI signals revealed that functional connectivity between the right frontoparietal network and primary and dorsal occipital networks is linked to visual processing speed. This link was present in the slowest, typical frequency of the fMRI signal but also in the higher frequencies that are routinely discarded. These findings imply that the coordinated spontaneous activity between right frontoparietal and occipital regions supports the individual potential of the visual system for efficient processing.
Biophysical characterization of two commercially available preparations of the drug containingEscherichia coliL-Asparaginase 2
Authors: de Araújo Talita Stelling , Scapin Sandra M. N. , de Andrade William , Fasciotti Maira , de Magalhães Mariana T. Q. , Almeida Marcius S. , Lima Luís Maurício T. R. 
Published: November 2020

AbstractThe hydrolysis of asparagine and glutamine by L-asparaginase has been used to treat acute lymphoblastic leukemia for over four decades. Each L-asparaginase monomer has a long loop that closes over the active site upon substrate binding, acting as a lid. Here we present a comparative study two commercially available preparations of the drug containing Escherichia coli L-Asparaginase 2, performed by a comprehensive array of biophysical and biochemical approaches. We report the oligomeric landscape and conformational and dynamic plasticity ofE. colitype 2 L-asparaginase (EcA2) present in two different formulations, and its relationship with L-aspartic acid, which is present in Aginasa, but not in Leuginase. EcA2 shows a composition of monomers and oligomers up to tetramers, which is mostly not altered in the presence of L-Asp. The N-terminal loop of Leuginase, which is part of the active site is flexibly disordered, but gets ordered as in Aginasa in the presence os L-Asp, while L-Glu only does so to a limited extent. Ion-mobility spectrometry–mass spectrometry reveals two conformers for the monomeric EcA2, one of which can selectively bind to L-Asp and L-Glu. Aginasa has higher resistance toin vitroproteolysis than Leuginase, and this is directly related to the presence of L-Asp.