bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of coronavirus disease 2019
Authors: Hung Ivan F.N. 
Published: September 2020

Purpose of review
Coronavirus disease 2019 (COVID-19) is a highly contagious and potentially lethal pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No specific antiviral treatment is currently available. The purpose of this review is to highlight the main repurposed drug treatments with in-vitro or in-vivo efficacy against the SARS-CoV-2.

Recent findings
Recent clinical trials suggested remdesivir, IFN-β-1b and favipiravir have potential clinical and/or virological benefits on patients with COVID-19. Short course of stress dose of corticosteroids might be used as adjunctive treatment to patients who are late presenters with cytokine storm. Convalescent plasma from recovered COVID-19 patients with high neutralizing antibody might also be beneficial in the treatment of severe disease.

Summary
Early effective antiviral therapy in COVID-19 patients will suppress the SARS-CoV-2 viral load. Adjunctive therapy with corticosteroid and convalescent plasma might further ameliorate the cytokine response. Further randomized clinical trials of combination therapy are needed.
Drug-induced maculopathy
Authors: Khan Mahmood J. , Papakostas Thanos , Kovacs Kyle , Gupta Mrinali P. 
Published: September 2020

Purpose of review
The purpose of this article is to provide an overview of drug-induced maculopathies including their clinical presentations, diagnostic findings, and treatment options. With the increasing pace of development and arrival of drugs to the market, this review aims to inform retina specialists of relevant side effects that may be encountered in a clinical practice setting.

Recent findings
The major themes visited in this article focus on relevant findings of drugs that cause pigmentary and crystalline maculopathy, photoreceptor dysfunction, cystoid macular edema, central serous choroidopathy, uveitis, and vascular damage.

Summary
The current review reports updated findings and discusses the pathophysiologic mechanisms, presentations, and treatments of drug-induced maculopathies.
Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report
Authors: Goldman Jason D. , Wang Kai , Röltgen Katharina , Nielsen Sandra C. A. , Roach Jared C. , Naccache Samia N. , Yang Fan , Wirz Oliver F. , Yost Kathryn E. , Lee Ji-Yeun , Chun Kelly , Wrin Terri , Petropoulos Christos J. , Lee Inyoul , Fallen Shannon , Manner Paula M. , Wallick Julie A. , Algren Heather A. , Murray Kim M. , Su Yapeng , Hadlock Jennifer , Jeharajah Joshua , Berrington William R. , Pappas George P. , Nyatsatsang Sonam T. , Greninger Alexander L. , Satpathy Ansuman T. , Pauk John S. , Boyd Scott D. , Heath James R. 
Published: September 2020

AbstractRecovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 140 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G. With antibody and B cell analytics, we show correlates of adaptive immunity, including a differential response to D614G. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.
Human cerebral cortex networks use expanding and contracting state dynamic to shape cortical functions
Authors: Willumsen Alex , Midtgaard Jens , Jespersen Bo , Hansen Christoffer K.K. , Lam Salina N. , Hansen Sabine , Kupers Ron , Fabricius Martin E. , Litman Minna , Pinborg Lars , Tascón-Vidarte José D. , Sabers Anne , Roland Per E. 
Published: September 2020

AbstractWe lack viable explanations of how brain functions emerge from collective activities of neurons in networks. We recorded field potentials from many local networks in the human cerebral cortex during a wide variety of brain functions. The network dynamics showed that each local cortical network produced fluctuating attractor states. The state trajectories continuously stretched and contracted during all brain functions, leaving no stable patterns. Different local networks all produced this dynamic, despite different architectures. Single trial stimuli and tasks modified the stretching and contractions. These modified fluctuations cross-correlated among particular networks during specific brain functions. Spontaneous states, rest, sensory, motor and cognitive states all emerged from this dynamic. Its mathematical structure provides a general explanation of cortical dynamics that can be tested experimentally. This universal dynamic is a simple functional organizing principle for brain functions at the mm3 scale that is distinct from existing frameworks.
Single circuit in V1 capable of switching contexts during movement using VIP population as a switch
Authors: Voina Doris , Recanatesi Stefano , Hu Brian , Shea-Brown Eric , Mihalas Stefan 
Published: September 2020

AbstractAs animals adapt to their environments, their brains are tasked with processing stimuli in different sensory contexts. Whether these computations are context dependent or independent, they are all implemented in the same neural tissue. A crucial question is what neural architectures can respond flexibly to a range of stimulus conditions and switch between them. This is a particular case of flexible architecture that permits multiple related computations within a single circuit.Here, we address this question in the specific case of the visual system circuitry, focusing on context integration, defined as the integration of feedforward and surround information across visual space. We show that a biologically inspired microcircuit with multiple inhibitory cell types can switch between visual processing of the static context and the moving context. In our model, the VIP population acts as the switch and modulates the visual circuit through a disinhibitory motif. Moreover, the VIP population is efficient, requiring only a relatively small number of neurons to switch contexts. This circuit eliminates noise in videos by using appropriate lateral connections for contextual spatio-temporal surround modulation, having superior denoising performance compared to circuits where only one context is learned. Our findings shed light on a minimally complex architecture that is capable of switching between two naturalistic contexts using few switching units.Author SummaryThe brain processes information at all times and much of that information is context-dependent. The visual system presents an important example: processing is ongoing, but the context changes dramatically when an animal is still vs. running. How is context-dependent information processing achieved? We take inspiration from recent neurophysiology studies on the role of distinct cell types in primary visual cortex (V1).We find that relatively few “switching units” — akin to the VIP neuron type in V1 in that they turn on and off in the running vs. still context and have connections to and from the main population — is sufficient to drive context dependent image processing. We demonstrate this in a model of feature integration, and in a test of image denoising. The underlying circuit architecture illustrates a concrete computational role for the multiple cell types under increasing study across the brain, and may inspire more flexible neurally inspired computing architectures.
Neutralizing activity of broadly neutralizing anti-HIV-1 antibodies against primary African isolates
Authors: Lorenzi Julio C.C. , Mendoza Pilar , Cohen Yehuda Z. , Nogueira Lilian , Lavine Christy , Sapiente Joseph , Seaman Michael S. , Wiatr Marie , Mugo Nelly R. , Mujugira Andrew , Delany Sinead , Lingappa Jairam , Celum Connie , Caskey Marina , Nussenzweig Michel C. 
Published: September 2020

AbstractNovel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Broadly neutralizing human antibodies (bNAbs) with exceptional activity against HIV-1 are currently being tested in HIV-1 prevention trials. The selection of anti-HIV-1 bNAbs for clinical development was primarily guided by theirin vitroneutralizing activity against HIV-1 Env pseudotyped viruses. Here we report on the neutralizing activity of 9 anti-HIV-1 bNAbs now in clinical development against 126 Clade A, C, D PBMC-derived primary African isolates. The neutralizing potency and breadth of the bNAbs tested was significantly reduced compared to pseudotyped viruses panels. The difference in sensitivity between pseudotyped viruses and primary isolates varied from 3-to nearly 100-fold depending on the bNAb and the HIV-1 clade. Thus, the neutralizing activity of bNAbs against primary African isolates differs and cannot be predicted from their activity against pseudovirus panels. The data have significant implications for interpreting the results of ongoing HIV-1 prevention trials.
Within-host competition modulates pneumococcal antibiotic resistance in the pre-vaccination era
Authors: Lourenço José , Daon Yair , Gori Andrea , Obolski Uri 
Published: September 2020

AbstractBackgroundAntibiotic treatment is a key tool in the fight against pneumococcal infections. However, the ongoing emergence of antibiotic resistant strains and high frequencies of antibiotic resistance of pneumococci pose a major public health challenge. How and which ecological and evolutionary mechanisms help maintain the coexistence of strains susceptible and resistant to antibiotic treatment remains largely an open question.Methods/resultsExpanding on aStreptococcus pneumoniaemodelling framework, we here explore how both between- and within-host mechanisms of transmission can sustain observed levels of pneumococcal resistance to antibiotics in the pre-vaccination era using a stochastic, individual-based model. Our framework considers that within-host competition for co-colonization between resistant and susceptible strains can arise via pre-existing immunity (immunological competition) or intrinsic fitness differences due to resistance costs (ecological competition). We find that beyond stochasticity, host-population structure or movement at the between-host level, competition at the within-host level can explain observed variation in resistance frequencies.ConclusionIn a series of simulated scenarios informed by observed pneumococcal data in the European region, we demonstrate that ecological competition for co-colonization can explain much of the variation in co-existence observed at the country level in the pre-vaccination era. This work expands our understanding of how within-host pneumococcal competition facilitates the maintenance of antibiotic resistance in the pre-vaccination era. The demonstration of the effects of such underlying, often unmeasured competition-related components of pneumococcal dynamics improves our understanding of the mechanistic drivers for the emergence and maintenance of antibiotic resistance.
Associations between ADHD symptom remission and white matter microstructure: a longitudinal analysis
Authors: Leenders A.E.M. , Damatac C.G. , Soheili-Nezhad S. , Chauvin R.J.M. , Mennes M.J.J. , Zwiers M.P. , vanRooij D. , Akkermans S.E.A. , Naaijen J. , Franke B. , Buitelaar J.K. , Beckmann C.F. , Sprooten E. 
Published: September 2020

AbstractBackgroundAttention-deficit hyperactivity disorder (ADHD) is associated with white matter (WM) microstructure. Our objective was to investigate how WM microstructure is longitudinally related to symptom remission in adolescents and young adults with ADHD.MethodsWe obtained diffusion-weighted imaging (DWI) data from 99 participants at two time points (mean age baseline: 16.91 years, mean age follow-up: 20.57 years). We used voxel-wise Tract-Based Spatial Statistics (TBSS) with permutation-based inference to investigate associations of inattention (IA) and hyperactivity-impulsivity (HI) symptom change with fractional anisotropy (FA) at baseline, follow-up, and change between time points.ResultsRemission of combined HI and IA symptoms was significantly associated with reduced FA at follow-up in the left superior longitudinal fasciculus and the left corticospinal tract (CST) (PFWE=0.038 andPFWE=0.044, respectively), mainly driven by an association between HI remission and follow-up CST FA (PFWE=0.049). There was no significant association of combined symptom decrease with FA at baseline or with changes in FA between the two assessments.ConclusionsIn this longitudinal DWI study of ADHD using dimensional symptom scores, we show that greater symptom decrease is associated with lower follow-up FA in specific WM tracts. Altered FA thus may appear to follow, rather than precede, changes in symptom remission. Our findings indicate divergent WM developmental trajectories between individuals with persistent and remittent ADHD, and support the role of prefrontal and sensorimotor tracts in the remission of ADHD.
NEBULA: a fast negative binomial mixed model for differential expression and co-expression analyses of large-scale multi-subject single-cell data
Authors: He Liang , Kulminski Alexander M. 
Published: September 2020

AbstractThe growing availability of large-scale single-cell data revolutionizes our understanding of biological mechanisms at a finer resolution. In differential expression and co-expression analyses of multi-subject single-cell data, it is important to take into account both subject-level and cell-level overdispersions through negative binomial mixed models (NBMMs). However, the application of NBMMs to large-scale single-cell data is computationally demanding. In this work, we propose an efficient NEgative Binomial mixed model Using a Large-sample Approximation (NEBULA)), which analytically solves the high-dimensional integral in the marginal likelihood instead of using the Laplace approximation. Our benchmarks show that NEBULA dramatically reduces the running time by orders of magnitude compared to existing tools. We showed that NEBULA controlled false positives in identifying marker genes, while a simple negative binomial model produced spurious associations. Leveraging NEBULA, we decomposed between-subject and within-subject overdispersions of an snRNA-seq data set in the frontal cortex comprising ∼80,000 cells from a cohort of 48 individuals for Alzheimer’s diseases (AD). We observed that subpopulations and known subject-level covariates contributed substantially to the overdispersions. We carried out cell-type-specific transcriptome-wide within-subject co-expression analysis ofAPOE. The results revealed thatAPOEwas most co-expressed with multiple AD-related genes, includingCLUandCST3in astrocytes,TREM2and C1q genes in microglia, andITM2B, an inhibitor of the amyloid-beta peptide aggregation, in both cell types. We found that the co-expression patterns were different inAPOE2+andAPOE4+cells in microglia, which suggest an isoform-dependent regulatory role in the immune system through the complement system in microglia. NEBULA opens up a new avenue for the broad application of NBMMs in the analysis of large-scale multi-subject single-cell data.
Population variability in social brain morphology: links to socioeconomic status and health disparity
Authors: Suryoputri Nathania , Kiesow Hannah , Bzdok Danilo 
Published: September 2020

AbstractHealth disparity across layers of society involves reasons beyond the healthcare system. Socioeconomic status (SES) shapes people’s daily interaction with their social environment, and is known to impact various health outcomes. Using generative probabilistic modeling, we investigated health satisfaction and complementary indicators of socioeconomic lifestyle in the human social brain. In a population cohort of ~10,000 UK Biobank participants, our first analysis probed the relationship between health status and subjective social standing (i.e., financial satisfaction). We identified volume effects in participants unhappy with their health in regions of the higher associative cortex, especially the dorsomedial prefrontal cortex (dmPFC) and bilateral temporo-parietal junction (TPJ). Specifically, participants in poor subjective health showed deviations in dmPFC and TPJ volume as a function of financial satisfaction. The second analysis on health status and objective social standing (i.e., household income) revealed volume deviations in regions of the limbic system for individuals feeling unhealthy. In particular, low-SES participants dissatisfied with their health showed deviations in volume distributions in the amygdala and hippocampus bilaterally. Thus, our population-level evidence speaks to the possibility that health status and socioeconomic position have characteristic imprints in social brain differentiation.
Novel Competition test for food rewards reveals stable dominance status in adult male rats
Authors: Costa Diana F , Moita Marta A , Márquez Cristina 
Published: September 2020

AbstractSocial hierarchy is a potent modulator of behavior, that is typically established through overt agonistic interactions between individuals in the group. Once established, social ranks are maintained through subtler interactions allowing the redirection of energy away from agonistic interactions towards other needs. The available tasks for assessing social rank in rats allow the study of the mechanisms by which social hierarches are formed in early phases but fail to assess the maintenance of established hierarchies between stable pairs of animals, which might rely on distinct neurobiological mechanisms. Here we present and validate a novel trial-based dominancy assay, the modified Food Competition test, where established social hierarchies can be identified in the home cage of non-food deprived pairs of male rats. In this task, we introduce a small conflict in the home cage, where access to a new feeder containing palatable pellets can only be gained by one animal at a time. We found that this subtle conflict triggered asymmetric social interactions and resulted in higher consumption of food by one of the animals in the pair, which reliably predicted hierarchy in other tests. Our findings reveal stable dominance status in pair-housed rats and provide a novel tool for the evaluation of established social hierarchies, the modified Food Competition test, that is robust and easy to implement.
Distinct recruitment of feed-forward and recurrent pathways across higher-order areas of mouse visual cortex
Authors: Li Jennifer Y. , Hass Charles A. , Matthews Ian , Kristl Amy C. , Glickfeld Lindsey L. 
Published: September 2020

AbstractCortical visual processing transforms features of the external world into increasingly complex and specialized neuronal representations. These transformations arise in part through target-specific routing of information; however, within-area computations may also contribute to area-specific function. Here, we sought to determine whether higher-order visual cortical areas LM, AL, PM, and AM have specialized anatomical and physiological properties by using a combination of whole-cell recordings and optogenetic stimulation of V1 axons in vitro. We discovered area-specific differences in the strength of recruitment of interneurons through feed-forward and recurrent pathways, as well as differences in cell-intrinsic properties and interneuron densities. These differences were most striking when comparing across medial and lateral areas, suggesting that these areas have distinct profiles for net excitability and integration of V1 inputs. Thus, cortical areas are not defined simply by the information they receive, but also by area-specific circuit properties that enable specialized filtering of these inputs.
Muilla lordsburgana(Asparagaceae: Brodiaeoideae), a new species found north of Lordsburg, southwestern New Mexico
Authors: Alexander Patrick J. 
Published: September 2020

AbstractMuilla lordsburganaP.J.Alexander sp. nov. is described from eastern Lordsburg Mesa in the northwestern fringe of the Chihuahuan Desert, southwestern New Mexico. It is very similar toMuilla coronata, a species known in the Mojave Desert of California and a small area of adjacent Nevada. Compared toMuilla coronata, the style and stigma combined are longer, the anthers are longer, the fruits are larger, and the seeds are larger. It has a short flowering period in March, and is difficult or impossible to find at other times of the year. It is narrowly distributed, limited to a band of deep, coarse, sandy soils derived primarily from granite. Several species that are otherwise uncommon in the area also occur in this habitat, includingLogfia depressa, Pectocarya platycarpa, andPlagiobothrys arizonicus. Invasive species, especiallyErodium cicutariumin the winter annual flora, are generally dominant.Muilla lordsburganahas probably been overlooked until now because it is not easy to observe and occurs in habitats that are not attractive to botanists.
Evidence that an HDAC2-targeted ASO persistently upregulates cortical acetylcholine and dopamine signaling via a CREB | Gs positive feedback loop
Authors: Sanders Teresa H. 
Published: September 2020

AbstractEpigenetic modulation of neural circuits facilitates learning and memory. Here, we examined specific inhibition of histone deacetylase 2 (HDAC2) expression in rats receiving a single intracerebroventricular injection ofHDAC2-targeted anti-sense oligonucleotides (ASOs) one month prior to cognitive testing. TheHDAC2ASO-injected rats displayed increased novelty preference, decreased cortical and hippocampalHDAC2mRNA and protein, and upregulated gene expression that persisted 1-month post-injection. Cortical RNA-seq revealed strongly increased transcription of a subset of cyclic adenosine monophosphate (cAMP)-response element binding (CREB) genes known to influence synaptic plasticity, along with dopamine (DRD1, DRD2) and adenosine (ADORA2A) G-protein-coupled receptors (GPCRs). Our analysis identified evidence of a positive-feedback loop that amplified expression of CREB-regulated Gs GPCRs and genes in cAMP/Gs/Gi signaling pathways. Additionally, we found differential expression of enzymes that shift neurotransmitter biosynthesis away from norepinephrine and toward dopamine and acetylcholine (DBH, CHAT). We also observed increased expression of genes important for neurotransmitter packaging (SV2C, VMAT) and release (SYT9). The data indicate that persistent inhibition ofHDAC2expression enables long-lived enhancement of aspects of cognition through increased cortical transcription of a subset of CREB-regulated genes amplified by a positive-feedback mechanism that increases synaptic plasticity and shifts neurotransmitter balance toward increased dopaminergic and cholinergic signaling.