bluuebunny/crossref_metadata_2025 huggingface dataset:
A census of coronal mass ejections on solar-like stars
Authors: Leitzinger M , Odert P , Greimel R , Vida K , Kriskovics L , Guenther E W , Korhonen H , Koller F , Hanslmeier A , Kővári Zs , Lammer H
Published: February 2020

Coronal mass ejections (CMEs) may have major importance for planetary and stellar evolution. Stellar CME parameters, such as mass and velocity, have yet not been determined statistically. So far only a handful of stellar CMEs has been detected mainly on dMe stars using spectroscopic observations. We therefore aim for a statistical determination of CMEs of solar-like stars by using spectroscopic data from the ESO phase 3 and Polarbase archives. To identify stellar CMEs, we use the Doppler signal in optical spectral lines being a signature of erupting filaments that are closely correlated to CMEs. We investigate more than 3700 h of on-source time of in total 425 dF-dK stars. We find no signatures of CMEs and only few flares. To explain this low level of activity, we derive upper limits for the non-detections of CMEs and compare those with empirically modelled CME rates. To explain the low number of detected flares, we adapt a flare power law derived from EUV data to the H α regime, yielding more realistic results for H α observations. In addition, we examine the detectability of flares from the stars by extracting Sun-as-a-star H α light curves. The extrapolated maximum numbers of observable CMEs are below the observationally determined upper limits, which indicates that the on-source times were mostly too short to detect stellar CMEs in H α. We conclude that these non-detections are related to observational biases in conjunction with a low level of activity of the investigated dF-dK stars.
Characterizing low-contrast Galactic open clusters with Gaia Data Release 2
Authors: Angelo M S , Santos J F C , Corradi W J B
Published: February 2020

In this study, we characterized 16 objects previously classified as faint or low-contrast Galactic open clusters (OCs). We employed parameters associated with the dynamical evolution of the OCs: the core (rc), tidal (rt) and half-mass (rhm) radii, age and crossing time (tcr). Relations among these parameters were exploited to draw some evolutionary connections. We also included 11 OCs with previous characterizations to provide wider coverage of the parameter space. The investigated sample spans a considerable range in age, log (t yr−1) ∼7.0–9.7, and Galactocentric distance, RG ∼ 6–11 kpc). Most of these OCs present solar metallicity. We employed Gaia Data Release 2 astrometry and photometry, and we selected member stars through a decontamination algorithm that explores the three-dimensional astrometric space (μα, μδ, ϖ) to assign membership likelihoods. Previous studies of most of these objects were based mostly on photometric information. All investigated OCs were proved to be real stellar concentrations. The relations among their parameters indicate a general disruption scenario in which OCs tend to be more concentrated as they evolve. Internal interactions sucessively drive OCs to develop more dynamically relaxed structures and make them less subject to mass loss due to tidal effects. Tidal radius tends to increase with RG in accordance with the strength of the Galactic tidal field. Besides, the correlation between rc and the dynamical ratio τdyn = age/tcr suggests two distinct evolutionary sequences, which may be a consequence of different initial formation conditions.
Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B
Authors: Lin Chien-Chu , Chen Yi-Ping , Yang Wei-Zen , Shen James C K , Yuan Hanna S
Published: February 2020

DNA methyltransferases are primary enzymes for cytosine methylation at CpG sites of epigenetic gene regulation in mammals. De novo methyltransferases DNMT3A and DNMT3B create DNA methylation patterns during development, but how they differentially implement genomic DNA methylation patterns is poorly understood. Here, we report crystal structures of the catalytic domain of human DNMT3B–3L complex, noncovalently bound with and without DNA of different sequences. Human DNMT3B uses two flexible loops to enclose DNA and employs its catalytic loop to flip out the cytosine base. As opposed to DNMT3A, DNMT3B specifically recognizes DNA with CpGpG sites via residues Asn779 and Lys777 in its more stable and well-ordered target recognition domain loop to facilitate processive methylation of tandemly repeated CpG sites. We also identify a proton wire water channel for the final deprotonation step, revealing the complete working mechanism for cytosine methylation by DNMT3B and providing the structural basis for DNMT3B mutation-induced hypomethylation in immunodeficiency, centromere instability and facial anomalies syndrome.
Structural adaptation of vertebrate endonuclease G for 5-hydroxymethylcytosine recognition and function
Authors: Vander Zanden Crystal M , Czarny Ryan S , Ho Ethan N , Robertson Adam B , Ho P Shing
Published: February 2020

Modified DNA bases functionally distinguish the taxonomic forms of life—5-methylcytosine separates prokaryotes from eukaryotes and 5-hydroxymethylcytosine (5hmC) invertebrates from vertebrates. We demonstrate here that mouse endonuclease G (mEndoG) shows specificity for both 5hmC and Holliday junctions. The enzyme has higher affinity (>50-fold) for junctions over duplex DNAs. A 5hmC-modification shifts the position of the cut site and increases the rate of DNA cleavage in modified versus unmodified junctions. The crystal structure of mEndoG shows that a cysteine (Cys69) is positioned to recognize 5hmC through a thiol-hydroxyl hydrogen bond. Although this Cys is conserved from worms to mammals, a two amino acid deletion in the vertebrate relative to the invertebrate sequence unwinds an α-helix, placing the thiol of Cys69 into the mEndoG active site. Mutations of Cys69 with alanine or serine show 5hmC-specificity that mirrors the hydrogen bonding potential of the side chain (C–H < S–H < O–H). A second orthogonal DNA binding site identified in the mEndoG structure accommodates a second arm of a junction. Thus, the specificity of mEndoG for 5hmC and junctions derives from structural adaptations that distinguish the vertebrate from the invertebrate enzyme, thereby thereby supporting a role for 5hmC in recombination processes.
Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections
Authors: Alosaimy Sara , Jorgensen Sarah C J , Lagnf Abdalhamid M , Melvin Sarah , Mynatt Ryan P , Carlson Travis J , Garey Kevin W , Allen David , Venugopalan Veena , Veve Michael , Athans Vasilios , Saw Stephen , Yost Christine N , Davis Susan L , Rybak Michael J
Published: February 2020

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.
Incidence and mortality of acute kidney injury in patients undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis
Authors: Kanduri S R , Cheungpasitporn W , Thongprayoon C , Bathini T , Kovvuru K , Garla V , Medaura J , Vaitla P , Kashani K B
Published: February 2020

Background

While acute kidney injury (AKI) is commonly reported following hematopoietic stem cell transplant (HCT), the incidence and impact of AKI on mortality among patients undergoing HCT are not well described. We conducted this systematic review to assess the incidence and impact of AKI on mortality risk among patients undergoing HCT.

Methods

Ovid MEDLINE, EMBASE and the Cochrane Databases were searched from database inceptions through August 2019 to identify studies assessing the incidence of AKI and mortality risk among adult patients who developed AKI following HCT. Random-effects and generic inverse variance method of DerSimonian–Laird were used to combine the effect estimates obtained from individual studies.

Results

We included 36 cohort studies with a total of 5144 patients undergoing HCT. Overall, the pooled estimated incidence of AKI and severe AKI (AKI Stage III) were 55.1% (95% confidence interval (CI) 46.6–63.3%) and 8.3% (95% CI 6.0–11.4%), respectively. The pooled estimated incidence of AKI using contemporary AKI definitions (RIFLE, AKIN and KDIGO criteria) was 49.8% (95% CI 41.6–58.1%). There was no significant correlation between study year and the incidence of AKI (P = 0.12) or severe AKI (P = 0.97). The pooled odds ratios of 3-month mortality and 3-year mortality among patients undergoing HCT with AKI were 3.05 (95% CI 2.07–4.49) and 2.23 (95% CI 1.06–4.73), respectively.

Conclusion

The incidence of AKI among patients who undergo HCT remains high, and it has not changed over the years despite advances in medicine. AKI after HCT is associated with increased short- and long-term mortality.
Genetics of age-related clonal hematopoiesis and atherosclerotic cardiovascular disease
Authors: Jung Changhee , Evans Megan A. , Walsh Kenneth
Published: February 2020

Purpose of review

While advanced age is the major risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), we have a poor understanding of how aging promotes the progression of this disease. Recent evidence suggests that the age-dependent accumulation of somatic mutations in hematopoietic cells may represent a new causal risk factor for ASCVD.

Recent findings

A hallmark of aging is the accumulation of somatic DNA mutations in all tissues of the body. Accordingly, evidence shows that hematopoietic stem/progenitor cells accumulate somatic mutations as a function of age in nonsymptomatic individuals. When these mutations occur in driver genes that provide a selective advantage to the hematopoietic stem/progenitor cells, they undergo a clonal expansion and progressively give rise to blood leukocytes that harbor these mutations. This phenomenon, referred to as clonal hematopoiesis, has been associated with the increased risk of mortality, hematologic malignancy, ASCVD, and related diseases. Notably, many individuals exhibiting clonal hematopoiesis carry single ‘driver’ mutations in preleukemic genes including DNA methyltransferase 3a, ten-eleven translocation 2, additional sex combs like 1, and Janus kinase 2. Experimental studies show that these mutations in some of these genes can alter the inflammatory properties of the leukocyte and contribute to the pathogenesis of ASCVD.

We review recent epidemiological and experimental findings on the association between age-related clonal hematopoiesis and ASCVD by focusing on prevalent driver gene mutations.
Provision of Utility Shut-off Protection Letters at an Urban Safety-Net Hospital, 2009-2018
Authors: Giraldo Paula , Hsu Heather E. , Ashe Erin M. , Buitron de la Vega Pablo A. , Losi Stephanie , Silverstein Michael , Lasser Karen E.
Published: February 2020

Most states prohibit utility companies from terminating service to low-income households when occupants present a medical letter confirming a household member has a chronic serious illness. It is unclear how many patients receive these letters and whether screening for health-related social needs (HRSN) identifies these patients. We analyzed characteristics of adult patients at a safety-net hospital with a utility shut-off protection letter 2009-2018. A total of 2973 patients received a letter; most were non-Hispanic black, and had government insurance. Among patients who received a letter in 2018, 70% were screened for HRSN. Among these, only 16% screened positive for difficulty paying utility bills.
Ischemia in patients with no obstructive coronary artery disease: classification, diagnosis and treatment of coronary microvascular dysfunction
Authors: Sucato Vincenzo , Novo Giuseppina , Saladino Antonino , Rubino Marianna , Caronna Nicola , Luparelli Mirko , D’Agostino Alessandro , Novo Salvatore , Evola Salvatore , Galassi Alfredo Ruggero
Published: February 2020

Patients with coronary microvascular dysfunction represent a widespread population, and despite the good prognosis, many of them, because of the angina symptoms, have a poor quality of life with strong limitations in their daily activities. In 2017, a new classification of microvascular dysfunction as well as a new definition of ischemia in patients with no obstructive coronary artery disease became available. This new definition improves Kemp’s initial work, where cardiac X syndrome was initially described. This work summarizes the last updates on the subject with particular attention to the new classification of microvascular dysfunction, with particular attention to microvascular and vasospastic angina definition and diagnostic criteria.
Triglycerides and residual risk
Authors: Vallejo-Vaz Antonio J. , Corral Pablo , Schreier Laura , Ray Kausik K.
Published: February 2020

Purpose of review

To review the recent evidence from observational/genetic/interventional studies addressing triglycerides and residual cardiovascular risk (CVRisk).

Recent findings

Large population-based and secondary prevention studies consistently show an association of higher triglycerides with increased CVRisk. This is compounded by genetic studies demonstrating an independent relationship between triglyceride raising or lowering genetic variants affecting triglyceride-rich lipoproteins (TRL) metabolism and CVRisk. Mendelian randomization analysis suggests the benefit of genetic lowering of triglycerides and LDL-cholesterol is similar per unit change in apolipoprotein-B. Among cholesterol-lowering trials, more intensive statin therapy produced greater CVRisk reductions in patients with higher TRL-cholesterol or triglycerides; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition led to similar triglycerides reduction but greater non-HDL-C or apolipoprotein-B reductions than fibrates or fish oils. Regarding n-3 fatty acids, A Study of Cardiovascular Events in Diabetes (ASCEND) and Vitamin D and Omega-3 Trial (VITAL) primary prevention trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid failed to demonstrate cardiovascular benefits, Conversely, Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) using high-dose icosapent-ethyl (purified EPA) in primary (diabetes) and secondary prevention with hypertriglyceridemia showed significant cardiovascular events reductions (greater than expected by the observed triglycerides or apolipoprotein-B reductions, suggesting potential benefits through non-lipid pathways).

Evidence suggests higher triglycerides are a marker of CVRisk and may help identify patients who benefit from intensification of therapy. Moreover, genetic studies support a causal link between TRL/triglycerides and cardiovascular disease. Treatment with high-dose EPA may be of benefit in high-risk patients with hypertriglyceridemia to reduce CVRisk.
Risk factors for myocardial infarction in very young South Asians
Authors: Gupta Mohit D. , Gupta Puneet , MP Girish , Roy Ambuj , Qamar Arman
Published: February 2020

Purpose of review

It is only over the last few decades that the impact of coronary artery disease (CAD) in very young South Asian population has been recognized. There has been a tremendous interest in elucidating the causes behind this phenomenon and these efforts have uncovered several mechanisms that might explain the early onset of CAD in this population. The complete risk profile of very young South Asians being affected by premature CAD still remains unknown.

Recent findings

The existing data fail to completely explain the burden of premature occurrence of CAD in South Asians especially in very young individuals. Results from some studies identified nine risk factors, including low consumption of fruits and vegetables, smoking, alcohol, diabetes, psychosocial factors, sedentary lifestyle, abdominal obesity, hypertension and dyslipidemia as the cause of myocardial infarction in 90% of the patients in this population. Recent large genome-wide association studies have discovered the association of several novel genetic loci with CAD in South Asians. Nonetheless, continued scientific efforts are required to further our understanding of the causal risk factors of CAD in South Asians to address the rising burden of CVD in this vulnerable population.

In this review, we discuss established and emerging risk factors of CAD in this population.
Refractory coeliac disease: what should we be doing different?
Authors: Chetcuti Zammit Stefania , Sanders David S. , Sidhu Reena
Published: February 2020

Purpose of review

The aim of this review is to provide insight into the diagnosis and management of patients with refractory coeliac disease (RCD) and highlight recent advances in this field.

Recent findings

The diagnosis of RCD can be more accurately confirmed with flow cytometry in addition to immunohistochemistry. Dietary input and excretion of gluten immunogenic peptides can help rule out gluten contamination, and therefore, substantiate a diagnosis of RCD type I. Small bowel capsule endoscopy (SBCE) is important at diagnosis and follow-up in addition to duodenal histology. Apart from ruling out complications, it can give information on extent of disease in the small bowel, and therefore, help assess response to therapy. Those patients with a poor response can have earlier intensification of therapy, which may result in an improved outcome. RCD also occurs in patients with serology negative coeliac disease but with an increased mortality compared with patients with serology-positive coeliac disease.

Patients with RCD can present with persistent symptoms of malnutrition but can also be completely asymptomatic. Serology is not a reliable marker to detect refractory disease. Immunostaining and flow cytometry are necessary for a diagnosis of RCD. Small bowel endoscopy enables disease extent to be assessed and allows for small bowel biopsies to be taken in case of suspicious lesions. Small bowel radiology can be complementary to small bowel endoscopy.
Basic principles of liver allocation and development over the years
Authors: Aby Elizabeth S. , Lake John R.
Published: February 2020

Purpose of review

Prior to the enactment of the National Organ Transplant Act in 1984, there was no organized system to allocate donor organs in the United States. The process of liver allocation has come a long way since then, including the development and implementation of the Model for End-stage Liver Disease, which is an objective estimate of risk of mortality among candidates awaiting liver transplantation.

Recent findings

The Liver Transplant Community is constantly working to optimize the distribution and allocation of scare organs, which is essential to promote equitable access to a life-saving procedure in the setting of clinical advances in the treatment of liver disease. Over the past 17 years, many changes have been made. Most recently, liver distribution changed such that deceased donor livers will be distributed based on units established by geographic circles around a donor hospital rather than the current policy, which uses donor service areas as the unit of distribution. In addition, a National Liver Review Board was created to standardize the process of determining liver transplant priority for candidates with exceptional medical conditions. The aim of these changes is to allocate and distribute organs in an efficient and equitable fashion.

The current review provides a historical perspective of liver allocation and the changing landscape in the United States.
Continuous distribution as an organ allocation framework
Authors: Kasiske Bertram L. , Pyke Joshua , Snyder Jon J.
Published: February 2020

Purpose of review

The Scientific Registry of Transplant Recipients (SRTR) supports the Organ Procurement and Transplantation Network (OPTN) efforts to better align liver allocation with the Final Rule. Here, we review recent literature related to removing place of residence or listing from organ allocation policy and describe how SRTR may help advance the OPTN policy development process.

Recent findings

In December 2018, the OPTN Board of Directors endorsed the recommendation from OPTN's ad hoc Committee on Geography to develop organ-allocation policies that do not rely on geographic boundaries, called ‘continuous distribution.’ Many objections to wider organ distribution stem from efforts to address inequities in allocation for populations within geographic regions rather than for individual patients. A continuous distribution system could equitably address the needs of individual patients, merging ethical–medical urgency with geographic feasibility.

The effort to remove geographic boundaries from organ distribution and allocation has been controversial. An integrated continuous distribution system may help focus the debate on priorities that matter most to patients.
A detailed analysis of the current status of intestinal transplantation in Latin America
Authors: Gondolesi Gabriel E. , Doeyo Mariana , Solar-Muñiz Héctor
Published: February 2020

Purpose of review

Latin America and the Caribbean represent a vast territory, with very different economic and healthcare realities, which result in significant disparities in the management of intestinal failure patients throughout the region. Since 1968, multiple attempts have been done to accomplish a successful intestinal transplant; but it was not until 2004, with the establishment of multidisciplinary programs, that large series with long-term results could be obtained. Currently, three countries (Colombia, Argentina, and Brazil) in the region are actively performing these procedures.

Recent findings

A total number of 135 intestinal transplants have been performed; 11 attempts before 2004, and 124 after that period, 66 transplants were done in Argentina (42 in children), 40 in Colombia, 15 in Brazil (1 child), 2 in Costa Rica and 1 in México; 76% have been isolated, whereas 2 were done with living donors.

Publications are still scarce, and compliance to existing registries remains limited. The challenge for the next years is to develop more ‘comprehensive units’ and extend home parenteral nutrition availability in the rest of the region. Regional cooperation and networking need to be set, in order to achieve regional self-sufficiency and improve long-term results.
Development and outcomes of the French liver allocation system
Authors: Durand François
Published: February 2020

Purpose of review

Although most countries adopted the Model for End Stage Liver Disease (MELD) score for prioritization in liver transplantation, differences exist from country to country. The purpose of the review is to present the specificity of the French allocation policy.

Recent findings

Organ allocation in France is typically based on the MELD score and the distance between the donor and the recipient at a national level. Organs are offered to patients on a national basis, not to centers. Patients with hepatocellular carcinoma and α-fetoprotein score 2 or less receive extra points to have access to transplantation similar to that of patients with cirrhosis. A third category is represented by MELD exceptions where MELD score is inaccurate at predicting outcome. MELD exceptions include complications of cirrhosis such as refractory ascites and other conditions such as polycystic liver disease. The objective is to guarantee similar waiting list mortality and similar posttransplant outcomes for each of these categories.

The French allocation system has been created with MELD as reference for prioritization, but it also takes into account distance between the donor and the recipient. Patients with hepatocellular carcinoma and patients with MELD exceptions are prioritized to have a similar access to transplantation.
High Prevalence of Vaginal and Rectal Mycoplasma genitalium Macrolide Resistance Among Female Sexually Transmitted Disease Clinic Patients in Seattle, Washington
Authors: Khosropour Christine M. , Jensen Jørgen S. , Soge Olusegun O. , Leipertz Gina , Unutzer Anna , Pascual Rushlenne , Barbee Lindley A. , Dombrowski Julia C. , Golden Matthew R. , Manhart Lisa E.
Published: February 2020

Background

Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are increasingly recognized as common infections among women. Little is known about the prevalence of rectal Mycoplasma genitalium (MG), rectal MG/CT/GC coinfection, or MG antimicrobial resistance patterns among women.

Methods

In 2017 to 2018, we recruited women at high risk for CT from Seattle's municipal sexually transmitted disease clinic. Participants self-collected vaginal and rectal specimens for CT/GC nucleic acid amplification testing. We retrospectively tested samples for vaginal and rectal MG using nucleic acid amplification testing and tested MG-positive specimens for macrolide resistance-mediating mutations (MRM) and ParC quinolone resistance-associated mutations (QRAMs).

Results

Of 50 enrolled women, 13 (26%) tested positive for MG, including 10 (20%) with vaginal MG and 11 (22%) with rectal MG; 8 (62%) had concurrent vaginal/rectal MG. Five (38%) were coinfected with CT, none with GC. Only 2 of 11 women with rectal MG reported anal sex in the prior year. Of MG-positive specimens, 100% of rectal and 89% of vaginal specimens had an MRM. There were no vaginal or rectal MG-positive specimens with ParC QRAMs previously associated with quinolone failure. Five MG-infected women received azithromycin for vaginal CT, 4 of whom had a MG MRM detected in their vaginal and/or rectal specimens.

Conclusions

We observed a high prevalence of macrolide-resistant vaginal and rectal MG among a population of women at high risk for CT. This study highlights how the use of antimicrobials designed to treat an identified infection—in this case, CT—could influence treatment outcomes and antimicrobial susceptibility in other unidentified infections.
Mapping the extent of heterogeneity of human CCR5+ CD4+ T cells in peripheral blood and lymph nodes
Authors: Zaunders John , Munier C. Mee Ling , McGuire Helen M. , Law Hannah , Howe Annett , Xu Yin , de St Groth Barbara Fazekas , Schofield Peter , Christ Daniel , Milner Brad , Obeid Solange , Dyer Wayne B. , Saksena Nitin K. , Kelleher Anthony D.
Published: February 2020

Background:

CD4+ T cells that express the chemokine receptor, CCR5, are the most important target of HIV-1 infection, but their functions, phenotypes and anatomical locations are poorly understood. We aimed to use multiparameter flow cytometry to better define the full breadth of these cells.

Methods:

High-parameter fluorescence flow and mass cytometry were optimized to analyse subsets of CCR5+ memory CD4+ T cells, including CD25highCD127dim Tregs, CXCR3+CCR6− Th1-like, CCR6+CD161+CXCR3− Th17-like, integrins α4+ß7+ gut-homing, CCR4+ skin-homing, CD62L+ lymph node-homing, CD38+HLA-DR+ activated cells, and CD27−CD28− cytotoxic T lymphocytes, in a total of 22 samples of peripheral blood, ultrasound-guided fine needle biopsies of lymph nodes and excised tonsils. CCR5+ antigen-specific CD4+ T cells were studied using the OX40 flow-based assay.

Results:

10–20% of CCR5+ memory CD4+ T cells were Tregs, 10–30% were gut-homing, 10–30% were skin-homing, 20–40% were lymph node-homing, 20–50% were Th1-like and 20–40% were Th17-like cells. Up to 30% were cytotoxic T lymphocytes in CMV-seropositive donors, including cells that were either CCR5highGranzyme K+ or CCR5dimGranzyme B+. When all possible phenotypes were exhaustively analysed, more than 150 different functional and trafficking subsets of CCR5+ CD4+ T cells were seen. Moreover, a small population of resident CD69+Granzyme K+CCR5+ CD4+ T cells was found in lymphoid tissues. CMV− and Mycobacterium tuberculosis-specific CD4+ T cells were predominantly CCR5+.

Conclusion:

These results reveal for the first time the prodigious heterogeneity of function and trafficking of CCR5+ CD4+ T cells in blood and in lymphoid tissue, with significant implications for rational approaches to prophylaxis for HIV-1 infection and for purging of the HIV-1 reservoir in those participants already infected.
Productive HIV infection in astrocytes can be established via a nonclassical mechanism
Authors: Li Guan-Han , Maric Dragan , Major Eugene O. , Nath Avindra
Published: February 2020

Objective:

Astrocytes are proposed to be a critical reservoir of HIV in the brain. However, HIV infection of astrocytes is inefficient in vitro except for cell-to-cell transmission from HIV-infected cells. Here, we explore mechanisms by which cell-free HIV bypasses entry and postentry barriers leading to a productive infection.

Methods:

HIV infection of astrocytes was investigated by a variety of techniques including transfection of CD4-expressing plasmid, treatment with lysosomotropic agents or using a transwell culture system loaded with HIV-infected lymphocytes. Infection was monitored by HIV-1 p24 in culture supernatants and integrated proviral DNA was quantified by Alu-PCR.

Results:

Persistent HIV infection could be established in astrocytes by transfection of proviral DNA, transduction with VSV-G-pseudotyped viruses, transient expression of CD4 followed by HIV infection, or simultaneous treatment with lysosomotropic chloroquine or Tat-HA2 peptide with HIV infection. In absence of these treatments, HIV entered via endocytosis as seen by electronmicroscopy and underwent lysosomal degradation without proviral integration, indicating endocytosis is a dead end for HIV in astrocytes. Nevertheless, productive infection was observed when astrocytes were in close proximity but physically separated from HIV-infected lymphocytes in the transwell cultures. This occurred with X4 or dual tropic R5X4 viruses and was blocked by an antibody or antagonist to CXCR4.

Conclusion:

A CD4-independent, CXCR4-dependent mechanism of viral entry is proposed, by which immature HIV particles from infected lymphocytes might directly bind to CXCR4 on astrocytes and trigger virus--cell fusion during or after the process of viral maturation. This mechanism may contribute to the formation of brain HIV reservoirs.
Evaluating new evidence in the early dynamics of the novel coronavirus COVID-19 outbreak in Wuhan, China with real time domestic traffic and potential asymptomatic transmissions
Authors: Zhou Can
Published: February 2020

The novel coronavirus (COVID-19), first detected in Wuhan, China in December 2019, has spread to 28 countries/regions with over 43,000 confirmed cases. Much about this outbreak is still unknown. At this early stage of the epidemic, it is important to investigate alternative sources of information to understand its dynamics and spread. With updated real time domestic traffic, this study aims to integrate recent evidence of international evacuees extracted from Wuhan between Jan. 29 and Feb. 2, 2020 to infer the dynamics of the COVD-19 outbreak in Wuhan. In addition, a modified SEIR model was used to evaluate the empirical support for the presence of asymptomatic transmissions. Based on the data examined, this study found little evidence for the presence of asymptomatic transmissions. However, it is still too early to rule out its presence conclusively due to sample size and other limitations. The updated basic reproductive number was found to be 2.12 on average with a 95% credible interval of [2.04, 2.18]. It is smaller than previous estimates probably because the new estimate factors in the social and non-pharmaceutical mitigation implemented in Wuhan through the evacuee dataset. Detailed predictions of infected individuals exported both domestically and internationally were produced. The estimated case confirmation rate has been low but has increased steadily to 23.37% on average. The findings of this study depend on the validity of the underlying assumptions, and continuing work is needed, especially in monitoring the current infection status of Wuhan residents.
Study on SARS-COV-2 transmission and the effects of control measures in China
Authors: Zhang Bo , Zhou Hongwei , Zhou Fang
Published: February 2020

Objective

To reconstruct the transmission trajectory of SARS-COV-2 and analyze the effects of control measures in China.

Methods

Python 3.7.1 was used to write a SEIR class to model the epidemic procedure and a back propagation class to estimate the initial true infected number. The epidemic area in China was divided into three parts, Wuhan city, Hubei province (except Wuhan) and China (except Hubei) based on the different transmission pattern. A limitation factor for the medical resource was imposed to model the infected but not quarantined. Credible data source from Baidu Qianxi were used to assess the number of infected cases migrated from Wuhan to other areas.

Results

Basic reproduction number, R0, was 3.6 in the very early stage. The true infected number was 4508 in our model in Wuhan before January 22, 2020. By January 22 2020, it was estimated that 1764 infected cases migrated from Wuhan to other cities in Hubei province. Effective reproductive number, R, gradually decreased from 3.6 (Wuhan, stage 1), 3.4 (Hubei except Wuhan, stage 1) and 3.3 (China except Hubei, stage 1) to 0.67 (Wuhan, stage 4), 0.83 (Hubei except Wuhan, stage 2) and 0.63 (China except Hubei, stage 2), respectively. Especially after January 23, 2020 when Wuhan City was closed, the infected number showed a turning point in Wuhan. By early April, there would be 42073, 21342 and 13384 infected cases in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively, and there would be 2179, 633 and 107 death in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively.

Conclusion

A series of control measures in China have effectively prevented the spread of COVID-19, and the epidemic will end in early April.
Autonomic arousal tracks outcome salience not valence in monkeys making social decisions
Authors: Basile Benjamin M. , Joiner Jessica A. , Monte Olga Dal , Fagan Nicholas A. , Karaskiewicz Chloe L. , Lucas Daniel R. , Chang Steve W. C. , Murray Elisabeth A.
Published: February 2020

The evolutionary and neural underpinnings of human prosociality are still largely unknown. A growing body of evidence suggests that some species find the sight of another individual receiving a reward reinforcing, often called vicarious reinforcement. One hypothesis is that vicarious reward is reinforcing because it is arousing like a primary reward. We evaluated this hypothesis by measuring the autonomic pupil response of eight monkeys across two laboratories in two different versions of a vicarious reinforcement paradigm. Monkeys were cued as to whether an upcoming reward would be delivered to them, another monkey, or nobody and could accept or decline the offer. As expected, all monkeys in both laboratories showed a marked preference for juice to the self, together with a reliable prosocial preference for juice to a social partner compared to juice to nobody. However, contrary to the autonomic arousal hypothesis, we found that pupils were widest in anticipation of juice to the self, moderately-sized in anticipation of juice to nobody, and narrowest in anticipation of juice to a social partner. This effect was seen across both laboratories and regardless of specific task parameters. The seemingly paradoxical pupil effect can be explained by a model in which pupil size tracks outcome salience, prosocial tendencies track outcome valence, and the relation between salience and valence is U-shaped.
RASA1-driven cellular export of collagen IV is required for the development of lymphovenous and venous valves in mice
Authors: Chen Di , Geng Xin , Lapinski Philip E. , Davis Michael J. , Srinivasan R. Sathish , King Philip D.
Published: February 2020

RASA1, a negative regulator of the Ras-mitogen-activated protein kinase (MAPK) signaling pathway, is essential for the development and maintenance of lymphatic vessel (LV) valves. However, whether RASA1 is required for the development and maintenance of lymphovenous valves (LVV) and venous valves (VV) is unknown. In this study we show that induced endothelial cell (EC)-specific disruption ofRasa1in mid-gestation mouse embryos did not affect initial specification of LVV or central VV but did affect their continued development. Similarly, switch to expression of a catalytically inactive form of RASA1 resulted in impaired LVV and VV development. Blocked development of LVV in RASA1-deficient embryos was associated with accumulation of the basement membrane protein, collagen IV, in LVV-forming EC and could be partially or completely rescued by MAPK inhibitors and drugs that promote collagen IV folding. Disruption ofRasa1in adult mice resulted in venous hypertension and impaired VV function that was associated with loss of EC from VV leaflets. In conclusion, RASA1 functions as a negative regulator of Ras signaling in EC that is necessary for EC export of collagen IV, thus permitting the development of LVV and the development and maintenance of VV.
Consilience in the Peripheral Sensory Adaptation Response
Authors: Wong Willy
Published: February 2020

Measurements of the peripheral sensory adaptation response were compared to a simple mathematical relationship involving the spontaneous, peak and steady-state activities. This relationship is based on the geometric mean and is found to be obeyed to good approximation in peripheral sensory units showing a sustained response to prolonged stimulation. From an extensive review of past studies, the geometric mean relationship is shown to be independent of modality and is satisfied in a wide range of animal species. The consilience of evidence, from nearly one hundred years of experiments beginning with the work of Edgar Adrian, suggests that this is a fundamental result of neurophysiology.
Association between 2019-nCoV transmission and N95 respirator use
Authors: Wang Xinghuan , Pan Zhenyu , Cheng Zhenshun
Published: February 2020

2019-nCoV had caused pneumonia outbreak in Wuhan. Existing evidence have confirmed the human-to-human transmission of 2019-nCoV. We retrospectively collected infection data from 2 January to 22 January at six departments from Zhongnan Hospital of Wuhan University. In our study, we found N95 respirators, disinfection and hand washing can help to reduce the risk of 2019-nCoV infection in medical staffs. Our results call for re-emphasizing strict occupational protection code in battling this novel contagious disease. The risk of 2019-nCoV infection was higher in the open area than in the quarantined area. N95 may be more effective for 2019-nCoV infections.
The PP2A/4/6 subfamily of phosphoprotein phosphatases regulates DAF-16 during aging and confers resistance to environmental stress in postreproductive adultC. elegans
Authors: Rivard Rebecca S. , Morris Julia M. , Youngman Matthew J.
Published: February 2020

Insulin and insulin-like growth factors are longevity determinants that negatively regulate Forkhead box class O (FoxO) transcription factors. InC. elegansmutations that constitutively activate DAF-16, the ortholog of mammalian FoxO3a, extend lifespan by two-fold. While environmental insults induce DAF-16 activity in younger animals, it also becomes activated in an age-dependent manner in the absence of stress, modulating gene expression well into late adulthood. The mechanism by which DAF-16 activity is regulated during aging has not been defined. Since phosphorylation of DAF-16 generally leads to its inhibition, we asked whether phosphatases might be necessary for its increased transcriptional activity in adultC. elegans. We focused on the PP2A/4/6 subfamily of phosphoprotein phosphatases, members of which had been implicated to regulate DAF-16 under low insulin signaling conditions but had not been investigated during aging in wildtype animals. Using reverse genetics, we functionally characterized allC. elegansorthologs of human catalytic, regulatory, and scaffolding subunits of PP2A/4/6 holoenzymes in postreproductive adults. We found that PP2A complex constituents PAA-1 and PPTR-1 regulate DAF-16 during aging and that they cooperate with the catalytic subunit LET-92 to protect adult animals from ultraviolet radiation. PP4 complex members PPH-4.1/4.2, SMK-1, and PPFR-2 also appear to regulate DAF-16 in an age-dependent manner, and they contribute to innate immunity. Interestingly, SUR-6 but no other subunit of the PP2A complex was necessary for the survival of pathogen-infected animals, suggesting that a heterotypic PP4 complex functions during aging. Finally, we found that PP6 complex constituents PPH-6 and SAPS-1 contribute to host defense during aging, apparently without affecting DAF-16 transcriptional activity. Our studies indicate that a set of PP2A/4/6 complexes protect adultC. elegansfrom environmental stress, thus preserving healthspan. Therefore, along with their functions in cell division and development, the PP2A/4/6 phosphatases also appear to play critical roles later in life.
An anatomical substrate of credit assignment in reinforcement learning
Authors: Kornfeld J , Januszewski M , Schubert P , Jain V , Denk W , Fee MS
Published: February 2020

Learning turns experience into better decisions. A key problem in learning is credit assignment—knowing how to change parameters, such as synaptic weights deep within a neural network, in order to improve behavioral performance. Artificial intelligence owes its recent bloom largely to the error-backpropagation algorithm1, which estimates the contribution of every synapse to output errors and allows rapid weight adjustment. Biological systems, however, lack an obvious mechanism to backpropagate errors. Here we show, by combining high-throughput volume electron microscopy2and automated connectomic analysis3–5, that the synaptic architecture of songbird basal ganglia supports local credit assignment using a variant of the node perturbation algorithm proposed in a model of songbird reinforcement learning6, 7. We find that key predictions of the model hold true: first, cortical axons that encode exploratory motor variability terminate predominantly on dendritic shafts of striatal spiny neurons, while cortical axons that encode song timing terminate almost exclusively on spines. Second, synapse pairs that share a presynaptic cortical timing axon and a postsynaptic spiny dendrite are substantially more similar in size than expected, indicating Hebbian plasticity8, 9. Combined with numerical simulations, these findings provide strong evidence for a biologically plausible credit assignment mechanism6.
Semantic segmentation of microscopic neuroanatomical data by combining topological priors with encoder-decoder deep networks
Authors: Banerjee Samik , Magee Lucas , Wang Dingkang , Li Xu , Huo Bingxing , Jayakumar Jaik-ishan , Matho Katie , Lin Adam , Ram Keerthi , Sivaprakasam Mohanasankar , Huang Josh , Wang Yusu , Mitra Partha P.
Published: February 2020

Understanding of neuronal circuitry at cellular resolution within the brain has relied on tract tracing methods which involve careful observation and interpretation by experienced neuroscientists. With recent developments in imaging and digitization, this approach is no longer feasible with the large scale (terabyte to petabyte range) images. Machine learning based techniques, using deep networks, provide an efficient alternative to the problem. However, these methods rely on very large volumes of annotated images for training and have error rates that are too high for scientific data analysis, and thus requires a significant volume of human-in-the-loop proofreading. Here we introduce a hybrid architecture combining prior structure in the form of topological data analysis methods, based on discrete Morse theory, with the best-in-class deep-net architectures for the neuronal connectivity analysis. We show significant performance gains using our hybrid architecture on detection of topological structure (e.g. connectivity of neuronal processes and local intensity maxima on axons corresponding to synaptic swellings) with precision/recall close to 90% compared with human observers. We have adapted our architecture to a high performance pipeline capable of semantic segmentation of light microscopic whole-brain image data into a hierarchy of neuronal compartments. We expect that the hybrid architecture incorporating discrete Morse techniques into deep nets will generalize to other data domains.
Magnetometer-based autonomous orbit determination via a measurement differencing extended Kalman filter during geomagnetic storms
Authors: Cui Feng , Gao Dong , Zheng Jianhua
Published: February 2020

Purpose

The main reason for the low accuracy of magnetometer-based autonomous orbit determination is the coarse accuracy of the geomagnetic field model. Furthermore, the geomagnetic field model error increases obviously during geomagnetic storms, which can still further reduce the navigation accuracy. The purpose of this paper is to improve the accuracy of magnetometer-based autonomous orbit determination during geomagnetic storms.

Design/methodology/approach

In this paper, magnetometer-based autonomous orbit determination via a measurement differencing extended Kalman filter (MDEKF) is studied. The MDEKF algorithm can effectively remove the time-correlated portion of the measurement error and thus can evidently improve the accuracy of magnetometer-based autonomous orbit determination during geomagnetic storms. Real flight data from Swarm A are used to evaluate the performance of the MDEKF algorithm presented in this study. A performance comparison between the MDEKF algorithm and an extended Kalman filter (EKF) algorithm is investigated for different geomagnetic storms and sampling intervals.

Findings

The simulation results show that the MDEKF algorithm is superior to the EKF algorithm in terms of estimation accuracy and stability with a short sampling interval during geomagnetic storms. In addition, as the size of the geomagnetic storm increases, the advantages of the MDEKF algorithm over the EKF algorithm become more obvious.

Originality/value

The algorithm in this paper can improve the real-time accuracy of magnetometer-based autonomous orbit determination during geomagnetic storms with a low computational burden and is very suitable for low-orbit micro- and nano-satellites.
Perceived social media marketing activities and consumer-based brand equity
Authors: Koay Kian Yeik , Ong Derek Lai Teik , Khoo Kim Leng , Yeoh Hui Jing
Published: February 2020

Purpose

The purpose of this research is to investigate the influence of perceived social media marketing activities on consumer-based brand equity, mainly predicated on the S-O-R model. Furthermore, brand experience is tested as a mediator of the relationship between perceived social media marketing activities and consumer-based brand equity, whereas co-creation behaviour is also examined as a moderator on the relationship between perceived social media marketing activities and brand experience.

Design/methodology/approach

A structured survey questionnaire was developed and distributed to social media users from a large private university in Malaysia. A total of 253 valid responses were obtained. Hypotheses were tested employing partial least squares structural equation modelling (PLS-SEM).

Findings

The results indicated that perceived social media marketing activities have a significant positive influence on consumer-based brand equity. In addition, brand experience mediates the relationship between perceived social media marketing activities and consumer-based brand equity. Surprisingly, co-creation behaviour was found to have no moderating effect on the relationship between perceived social media marketing activities and brand experience. Furthermore, using the PROCESS macro, we found that the indirect effect of perceived social media marketing activities on consumer-based brand equity through brand experience is not moderated by co-creation behaviour.

Originality/value

This research further extended the current knowledge by demonstrating that the influence of perceived social media marketing activities on consumer-based brand equity is mediated by brand experience. Also, this research utilised the strength of PLS–SEM in dealing with higher-order constructs, allowing us to develop and test a parsimonious model that is useful for practitioners.