bluuebunny/crossref_metadata_2025 huggingface dataset:
CoSIR: Optimal control of SIR epidemic dynamics by mapping to Lotka-Volterra System
Authors: Maheshwari Harsh , Shetty Shreyas , Bannur Nayana , Merugu Srujana
Published: November 2020

Multiple macro-phenomena such as disease epidemics, online information propagation, and economic activity can be well-approximated using simple dynamical systems. Shaping these phenomena with adaptive control of key levers has long been the holy grail of policymakers. In this paper, we focus on optimal control of transmission rate in epidemic systems following the widely applicable SIR dynamics. We first demonstrate that the SIR model with infectious patients and susceptible contacts (i.e., product of transmission rate and susceptible population) interpreted as predators and prey respectively reduces to a Lotka-Volterra (LV) predator-prey model. The modified SIR system (LVSIR) has a stable equilibrium point, an “energy” conservation property, and exhibits bounded cyclic behavior. We exploit this mapping using a control-Lyapunov approach to design a novel adaptive control policy (CoSIR) that nudges the SIR model to the desired equilibrium. Combining CoSIR policy with data-driven estimation of parameters and adjustments for discrete transmission levels yields a control strategy with practical utility. Empirical comparison with periodic lockdowns on simulated and real COVID-19 data demonstrates the efficacy and adaptability of our approach.
Addressing a complicated problem: can COVID-19 asymptomatic cases be detected – and epidemics stopped− when testing is limited and the location of such cases unknown?
Authors: Rivas Ariel L. , Hoogesteijn Almira L. , Hittner James B. , Fasina Folorunso O. , van Regenmortel Marc H.V.
Published: November 2020

Can the COVID-19 pandemic be stopped when the principal disseminators −asymptomatic cases− are not easily observable? This question was addressed exploring the cumulative epidemiologic data reported by 51 countries, up to October 2, 2020. In particular, the validity of test positivity and its inverse (the ratio of tests performed per case detected) to indicate whether asymptomatic cases are being detected and isolated –even when only a minor percentage of the population is tested− was evaluated. By linking test positivity data to the number of COVID-19 related deaths reported per million inhabitants, the research question was answered: countries that expressed a high percentage of test positivity (>5%) reported, on average, 15 times more deaths than countries that exhibited <1% test positivity. It is suggested that such a large difference in outcomes is due to the exponential growth that epidemics may experience when silent (asymptomatic) cases are not detected and, consequently, the disease disseminates. Because temporal and geo-referenced data on test positivity may facilitate cost-effective, site-specific testing policies, it is postulated that the risk of uncontrolled epidemics may be ameliorated when test positivity is investigated.
Effect of Lumbar Medial Branch Nerve Radiofrequency Ablation on Lumbar Spondylolisthesis
Authors: Patel Trusharth , Watterson Christopher , McKenzie-Brown Anne Marie , Spektor Boris , Egan Katherine , Boorman David
Published: November 2020

Importance

Radiofrequency ablation (RFA) is a denervation therapy commonly performed for pain of facet etiology. Degenerative spondylolisthesis may be a co-existing condition; yet the effect of RFA on advancing listhesis is unknown.

Objective

To test the hypothesis that RFA of painful facets in the setting of spondylolisthesis may contribute to advancement of further degenerative spondylolisthesis.

Design

Retrospective and prospective, observational study conducted at a single academic center among 15 participants with pre-existing degenerative Grade I or Grade II spondylolisthesis undergoing lumbar RFA encompassing spondylolisthesis level and followed with post-RFA imaging at 12 months and beyond to measure percent change in spondylolisthesis.

Main Outcomes and Measures

The primary outcome was the percent advancement of spondylolisthesis per year measured on post-RFA lateral lumbar spine imaging compared to non-intervention baseline advancement of 2.6% per limited observational studies.

Results

Among the 15 participants enrolled, 14 completed the study (median age 66; 64.3% women; median BMI 33.5; mean follow-up time 23.9 months). The mean advancement of spondylolisthesis per year after RFA was 1.30% (95% CI −0.14 to 2.78%), with 9/14 below 1.25%.

Conclusion and Relevance

Among patients with lumbar pain originating from facets in the setting of degenerative spondylolisthesis who underwent lumbar RFA, the observed advancement of spondylolisthesis is clinically similar to the baseline of 2.6% per year change. The study findings did not find a destabilizing effect of lumbar RFA in advancing spondylolisthesis in this patient population.
Do predictors of adherence to pandemic guidelines change over time? A panel study of 21,000 UK adults during the COVID-19 pandemic
Authors: Wright Liam , Fancourt Daisy
Published: November 2020

In the absence of a vaccine, governments have focused on behaviour change (e.g. social distancing and enhanced hygiene procedures) to tackle the COVID-19 pandemic. Existing research on the predictors of compliance with pandemic measures has often produced discrepant results. One explanation for this may be that the determinants of compliance are context specific. Understanding whether this is the case is important for designing public health messaging and for evaluating the generalisability of existing research. We used data from the UCL COVID-19 Social Study; a large weekly panel of UK adults from first five months of lockdown in the UK (n = 21,000). We tested whether the extent to which demographic, socio-economic position, personality traits, pro-social motivations, and the living environment predict compliance changed across the pandemic. Low compliance was strongly related to younger age and also to risk attitudes, empathic concern, and high income, among other factors. But the size of some of these associations was larger in later months when less stringent lockdown and household mixing measures were in place, suggesting context-specific effects. The results also showed that compliance fell faster across some groups, suggesting the importance that public health communications adopt a plurality of messages to maximize broad adherence.
Using Real World Data to Understand HIV and COVID-19 in the U.S.A. and Spain: Characterizing Co-Infected Patients Across the Care Cascade
Authors: Kohler Julianna , Kostka Kristin , Makadia Rupa , Paredes Roger , Duarte-Salles Talita , Duvall Scott , Cheng Alison , Golozar Asieh , Lane Jennifer C. E. , Sena Anthony G. , Rijnbeek Peter R. , Morales Daniel R. , Ryan Patrick B. , Reich Christian , Matheny Michael E. , Lynch Kristine E. , Siberry George K. , Prieto-Alhambra Daniel
Published: November 2020

Objective

Most patients severely affected by COVID-19 have been elderly and patients with underlying chronic disease such as diabetes, cardiovascular disease, or respiratory disease. People living with HIV (PLHIV) may have greater risk of contracting or developing severe COVID-19 due to the underlying HIV infection or higher prevalence of comorbidities.

Design

This is a cohort study, including PLHIV diagnosed, hospitalized, or requiring intensive services for COVID-19.

Methods

Data sources include routine electronic medical record or claims data from the U.S. and Spain. Patient demographics, comorbidities, and medication history are described.

Result

Four data sources had a population of HIV/COVID-19 coinfected patients ranging from 288 to 4606 lives. PLHIV diagnosed with COVID-19 were younger than HIV-negative patients diagnosed with COVID-19. PLHIV diagnosed with COVID-19 diagnosis had similar comorbidities as HIV-negative COVID-19 patients with higher prevalence of those comorbidities and history of severe disease. Treatment regimens were similar between PLHIV diagnosed with COVID-19 or PLHIV requiring intensive services.

Conclusions

Our study uses routine practice data to explore HIV impact on COVID-19, providing insight into patient history prior to COVID-19. We found that HIV and COVID-19 coinfected patients have higher prevalence of underlying comorbidities such as cardiovascular and respiratory disease as compared to HIV-negative COVID-19 infected patients. We also found that, across the care cascade, co-infected patients who received intensive services were more likely to have more serious underlying disease or a history of more serious events as compared to PLHIV who were diagnosed with COVID-19.
Leprosy in wild chimpanzees
Authors: Hockings Kimberley J. , Mubemba Benjamin , Avanzi Charlotte , Pleh Kamilla , Düx Ariane , Bersacola Elena , Bessa Joana , Ramon Marina , Metzger Sonja , Patrono Livia V. , Jaffe Jenny E. , Benjak Andrej , Bonneaud Camille , Busso Philippe , Couacy-Hymann Emmanuel , Gado Moussa , Gagneux Sebastien , Johnson Roch C. , Kodio Mamoudou , Lynton-Jenkins Joshua , Morozova Irina , Mätz-Rensing Kerstin , Regalla Aissa , Said Abílio R. , Schuenemann Verena J. , Sow Samba O. , Spencer John S. , Ulrich Markus , Zoubi Hyacinthe , Cole Stewart T. , Wittig Roman M. , Calvignac-Spencer Sebastien , Leendertz Fabian H.
Published: November 2020

Humans are considered the main host forMycobacterium leprae, the aetiologic agent of leprosy, but spill-over to other mammals such as nine-banded armadillos and red squirrels occurs. Although naturally acquired leprosy has also been described in captive nonhuman primates, the exact origins of infection remain unclear. Here, we report on leprosy-like lesions in two wild populations of western chimpanzees (Pan troglodytes verus) in the Cantanhez National Park, Guinea-Bissau, and the Taï National Park, Côte d’Ivoire, West Africa. Longitudinal monitoring of both populations revealed the progression of disease symptoms compatible with advanced leprosy. Screening of faecal and necropsy samples confirmed the presence ofM. lepraeas the causative agent at each site and phylogenomic comparisons with other strains from humans and other animals show that the chimpanzee strains belong to different and rare genotypes (4N/O and 2F). The independent evolutionary origin ofM. lepraein two geographically distant populations of wild chimpanzees, with no prolonged direct contact with humans, suggests multiple introductions ofM. lepraefrom an unknown animal or environmental source.
Reductive evolution and unique infection and feeding mode in the CPR predatory bacteriumVampirococcus lugosii
Authors: Moreira David , Zivanovic Yvan , López-Archilla Ana I. , Iniesto Miguel , López-García Purificación
Published: November 2020

The Candidate Phyla Radiation (CPR) constitutes a large supergroup of mostly uncultured bacterial lineages discovered through metabarcoding and metagenomics in diverse environments. Having small cell sizes, reduced genomes, and limited biosynthetic capabilities, they are thought to be symbionts of other organisms from which they obtain essential biomolecules. However, the nature of this symbiosis (mutualistic, neutral, or parasitic) has been ascertained only for rare cultured members of the CPR phylum Saccharibacteria, which are epibiotic parasites of other bacteria. Here, we characterize the biology and the genome ofVampirococcus lugosii, which becomes the first described species ofVampirococcus, a genus of epibiotic bacteria morphologically identified decades ago.Vampirococcusbelongs to the CPR phylum Absconditabacteria. It feeds on anoxygenic photosynthetic gammaproteobacteria, fully absorbing their cytoplasmic content. The cells divide epibiotically, forming multicellular stalks whose apical cells can more easily reach new hosts.Vampirococcusgenome is small (1.3 Mbp) and highly reduced in biosynthetic metabolism genes. However, it is enriched in genes related to an elaborate, fibrous cell surface likely involved in complex interactions with the host. Comparative genomic analyses show that gene loss has been continuous during Absconditabacteria, and generally most CPR bacteria, evolution. Nonetheless, gene loss was compensated by gene acquisition by horizontal gene transfer and evolutionde novo. InVampirococcus, these innovations include new CRISPR-Cas effectors and a novel electron transport chain. Our findings confirm parasitism as a widespread lifestyle of CPR bacteria, which probably play a previously neglected virus-like ecological role in ecosystems, controlling bacterial populations by a unique form of predation.
A benchmarking study of SARS-CoV-2 whole-genome sequencing protocols using COVID-19 patient samples
Authors: Liu Tiantian , Chen Zhong , Chen Wanqiu , Chen Xin , Hosseini Maryam , Yang Zhaowei , Li Jing , Ho Diana , Turay David , Gheorghe Ciprian , Jones Wendell , Wang Charles
Published: November 2020

The COVID-19 pandemic is a once-in-a-lifetime event, exceeding mortality rates of the flu pandemics from the 1950’s and 1960’s. Whole-genome sequencing (WGS) of SARS-CoV-2 plays a critical role in understanding the disease. Performance variation exists across SARS-CoV-2 viral WGS technologies, but there is currently no benchmarking study comparing different WGS sequencing protocols. We compared seven different SARS-CoV-2 WGS library protocols using RNA from patient nasopharyngeal swab samples under two storage conditions. We constructed multiple WGS libraries encompassing three different viral inputs: 1,000,000, 250,000 and 1,000 copies. Libraries were sequenced using two distinct platforms with varying sequencing depths and read lengths. We found large differences in mappability and genome coverage, and variations in sensitivity, reproducibility and precision of single-nucleotide variant calling across different protocols. We ranked the performance of protocols based on six different metrics. Our results indicated that the most appropriate protocol depended on viral input amount and sequencing depth. Our findings offer guidance in choosing appropriate WGS protocols to characterize SARS-CoV-2 and its evolution.
Integrative Transcriptomic Analysis Reveals the Immune Mechanism for A CyHV-3-Resistant Common Carp Strain
Authors: Jia Zhiying , Wu Nan , Jiang Xiaona , Li Heng , Sun Jiaxin , Shi Mijuan , Li Chitao , Hu Xuesong , Ge Yanlong , Ye Weidong , Tang Ying , Shan Junwei , Cheng Yingyin , Xia Xiao-Qin , Shi Lianyu
Published: November 2020

Anti-disease breeding is becoming the most promising solution to cyprinid herpesvirus-3 (CyHV-3) infection, the major threat to common carp aquaculture. Virus challenging studies suggested that a breeding strain of common carp is resistant to this disease. This study illustrates the immune mechanisms involved in anti-CyHV-3 ability. An integrative analysis of the protein-coding genes and long non-coding RNAs (lncRNAs) using transcriptomic data was performed. Tissues from the head kidney of common carp were extracted at day 0 (the healthy control) and day 7 after CyHV-3 infection (the survivors), and used to analyze the transcriptome through both Illumina and PacBio sequencing. Following analysis of the GO terms and KEGG pathways involved, the immune-related terms and pathways were merged. In order to dig out details in the immune aspect, The DEGs were filtered using the current common carp immune gene library. Immune gene categories and their corresponding genes in different comparison groups were revealed. Also, the immunological Gene Ontology terms for lncRNA modulation were retained. The weighted gene co-XSexpression network analysis was used to reveal the regulation of immune genes by lncRNA. The results demonstrated that the breeding carp strain develops marked resistance to CyHV-3 through a specific innate immune mechanism. The featured biological processes were autophagy, phagocytosis, cytotoxicity, and virus blockage by lectins and MUC3. Moreover, the immune suppressive signals, such as suppression of IL21R on STAT3, PI3K mediated inhibition on inflammation by dopamine upon infection, as well as the inhibition of NLRC3 on STING during a steady state. Possible susceptible factors for CyHV-3, such as ITGB1, TLR18, and CCL4, were also revealed from the non-breeding strain. The results of this study also suggested that Nramp and PAI regulated by LncRNA could facilitate virus infection and proliferation for infected cells respectively, while T cell leukemia homeobox 3 (TLX3) as well as galectin 3 function by lncRNA may play a role in the resistance mechanism. Therefore, immune factors that are immunogenetically insensitive or susceptible to CyHV-3 infection have been revealed.
Voltage-gated calcium channels contribute to spontaneous glutamate release directly via nanodomain coupling or indirectly via calmodulin
Authors: Lee Byoung Ju , Yang Che Ho , Lee Seung Yeon , Lee Suk-Ho , Kim Yujin , Ho Won-Kyung
Published: November 2020

Neurotransmitter release occurs either synchronously with action potentials (evoked release) or spontaneously (spontaneous release). Whether the molecular mechanisms underlying evoked and spontaneous release are identical, especially whether voltage-gated Ca2+channels (VGCCs) can trigger spontaneous events, is still a matter of debate in glutamatergic synapses. To elucidate this issue, we characterized the VGCC dependence of miniature excitatory postsynaptic currents (mEPSCs) in various synapses with different coupling distances between VGCCs and synaptic vesicles, known as a critical factor in evoked release. We found that most of the extracellular calcium-dependent mEPSCs were attributable to VGCCs in cultured autaptic hippocampal neurons and the mature calyx of Held where VGCCs and vesicles were tightly coupled. Among loosely coupled synapses, mEPSCs were not VGCC-dependent at immature calyx of Held and CA1 pyramidal neuron synapses, whereas VGCCs contribution was significant at CA3 pyramidal neuron synapses. Interestingly, the contribution of VGCCs to spontaneous glutamate release in CA3 pyramidal neurons was abolished by a calmodulin antagonist, calmidazolium. These data suggest that coupling distance between VGCCs and vesicles determines VGCC dependence of spontaneous release at tightly coupled synapses, yet VGCC contribution can be achieved indirectly at loosely coupled synapses.

Highlights

Extracellular Ca2+-dependent spontaneous glutamate release is mediated by VGCCs.

Ca2+cooperativity of spontaneous and evoked release is comparable.

Synapses at different areas and ages show distinct VGCC dependence on mini events.

Nanodomain coupling between VGCCs and Ca2+sensors determines VGCC dependence.
Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation
Authors: Frank Filipp , Liu Xu , Ortlund Eric A.
Published: November 2020

The glucocorticoid receptor (GR) is a ligand-regulated transcription factor (TF) that controls the tissue- and gene-specific transactivation and transrepression of thousands of target genes. Distinct GR DNA binding sequences with activating or repressive activities have been identified, but how they modulate transcription in opposite ways is not known. We show that GR forms phase-separated condensates that specifically concentrate known co-regulators via their intrinsically disordered regions (IDRs)in vitro.A combination of dynamic, multivalent (between IDRs) and specific, stable interactions (between LxxLL motifs and the GR ligand binding domain) control the degree of recruitment. Importantly, GR DNA-binding directs the selective partitioning of co-regulators within GR condensates such that activating DNAs cause enhanced recruitment of co-activators. Our work shows that condensation controls GR function by modulating co-regulator recruitment and provides a mechanism for the up- and down-regulation of GR target genes controlled by distinct DNA recognition elements.
Attention and prediction modulations in expected and unexpected visuospatial trajectories
Authors: Baker Kristen S. , Pegna Alan J. , Yamamoto Naohide , Johnston Patrick
Published: November 2020

Humans are constantly exposed to a rich tapestry of visual information in a potentially changing environment. To cope with the computational burden this engenders, our perceptual system must use prior context to simultaneously prioritise stimuli of importance and suppress irrelevant surroundings. This study investigated the influence of prediction and attention in visual perception by investigating event-related potentials (ERPs) often associated with these processes, N170 and N2pc for prediction and attention, respectively. A contextual trajectory paradigm was used which violated visual predictions and neglected to predetermine areas of spatial interest, to account for the potentially unpredictable nature of a real-life visual scene. Participants (N=36) viewed a visual display of cued and non-cued shapes rotating in a five-step predictable trajectory, with the fifth and final position of either the cued or non-cued shape occurring in a predictable or unpredictable spatial location. To investigate the predictive coding theory of attention we used factors of attention and prediction, whereby attention was manipulated as either cued or non-cued conditions, and prediction manipulated in either predictable or unpredictable conditions. Results showed both enhanced N170 and N2pc amplitudes to unpredictable compared to predictable stimuli. Stimulus cueing status also increased N170 amplitude, but this did not interact with stimulus predictability. The N2pc amplitude was not affected by stimulus cueing status. In accordance with previous research these results suggest the N170 is in part a visual prediction error response with respect to higher-level visual processes, and furthermore the N2pc may index attention reorientation. The results demonstrate prior context influences the sensitivity of the N170 and N2pc electrophysiological responses. These findings add further support to the role of N170 as a prediction error signal and suggest that the N2pc may reflect attentional reorientation in response to unpredicted stimulus locations.
NyuWa Genome Resource: Deep Whole Genome Sequencing Based Chinese Population Variation Profile and Reference Panel
Authors: Zhang Peng , Luo Huaxia , Li Yanyan , Wang You , Wang Jiajia , Zheng Yu , Niu Yiwei , Shi Yirong , Zhou Honghong , Song Tingrui , Kang Quan ,   The Han100K Initiative, Xu Tao , He Shunmin
Published: November 2020

The lack of Chinese population specific haplotype reference panel and whole genome sequencing resources has greatly hindered the genetics studies in the world’s largest population. Here we presented the NyuWa genome resource based on deep (26.2X) sequencing of 2,999 Chinese individuals, and constructed NyuWa reference panel of 5,804 haplotypes and 19.3M variants, which is the first publicly available Chinese population specific reference panel with thousands of samples. Compared with other panels, NyuWa reference panel reduces the Han Chinese imputation error rate by the range of 30% to 51%. Population structure and imputation simulation tests supported the applicability of one integrated reference panel for both northern and southern Chinese. In addition, a total of 22,504 loss-of-function variants in coding and noncoding genes were identified, including 11,493 novel variants. These results highlight the value of NyuWa genome resource to facilitate genetics research in Chinese and Asian populations.
Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a
Authors: Nakazawa Yuta , Kanemaru Kazumasa , Nakahashi-Oda Chigusa , Shibuya Akira
Published: November 2020

Although tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased numbers of Treg cells in tumors and greater tumor growth compared with wild-type mice after transplantation of B16 melanoma. Pharmacological impairment of extracellular vesicle (EV) release decreased Treg cell numbers in CD300a-deficient mice. Coculture of DCs with tumor-derived EV (TEV) induced the internalization of CD300a and the incorporation of EVs into endosomes, in which CD300a inhibited TEV-mediated TLR3-TRIF signaling for activation of the IFN-β-Treg cells axis. We also show that higher expression of CD300A was associated with decreased tumor-infiltrating Treg cells and longer survival time in patients with melanoma. Our findings reveal the role of TEV and CD300a on DCs in Treg cell activation in the tumor microenvironment.
Bioelectrical pattern discrimination ofMiconiaplants by spectral analysis and machine learning
Authors: Gimenez Valéria M M , Pauletti Patrícia M , Silva Ana Carolina Sousa , Costa Ernane José Xavier
Published: November 2020

We have conducted anin locoinvestigation into the speciesMiconia albicans(SW.) Triana andMiconia chamissoisNaudin (Melastomataceae), distributed in different phytophysiognomies of three Cerrado fragments in the State of São Paulo, Brazil, to characterize their oscillatory bioelectrical signals and to find out whether these signals have distinct spectral density. The experiments provided a sample bank of bioelectrical amplitudes, which were analyzed in the time and frequency domain. On the basis of the power spectral density (PSD) and machine learning techniques, analyses in the frequency domain suggested that each species has a characteristic biological pattern. Comparison between the oscillatory behavior of the species clearly showed that they have bioelectrical features, that collecting data is feasible, thatMiconiadisplay a bioelectrical pattern, and that environmental factors influence this pattern. From the point of view of experimental Botany, new questions and concepts must be formulated to advance understanding of the interactions between the communicative nature of plants and the environment. The results of this on-site technique represent a new methodology to acquire non-invasive information that might be associated with physiological, chemical, and ecological aspects of plants.

Highlight

In lococharacterization of the bioelectrical signals of twoMiconiaspecies in the time and frequency domain suggests that the species have distinct biological patterns.
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

Plasmodium 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

There 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

There 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.

Highlights

The 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

Conceptualizing 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

Given 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

Background

Like 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.

Methods

We 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.

Results

This 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.

Conclusions

Addressing 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

Obesity 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

Purpose

Radium-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 Design

In 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.

Results

We 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.

Conclusion

Immune 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

A 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

The 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

The 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

Abstracts

Sensorimotor 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.

Highlights

We studied the effect of rhythmic rTMS induced E-field at 35mV/mmin the M1

Prospective electric field modeling guided the individualized rTMS intensities

Rhyhtmic rTMS entrained mu-alpha rhythm and modulated mu-alpha/beta power

Arrhythmic 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