bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the unusually large spatial extent of the TeV nebula HESS J1825−137: implication from the energy-dependent morphology
Authors: Liu Ruo-Yu , Yan Huirong 
Published: March 2020

ABSTRACT
Deep observation of the High Energy Stereoscopic System (HESS) on the most extended pulsar wind nebula HESS J1825−137 reveals an enhanced energy-dependent morphology, providing useful information on the particle transport mechanism in the nebula. We find that the energy-dependent morphology is consistent with a diffusion-dominated transport of electrons/positrons. It provides an alternative possible interpretation for the unusually large spatial extent (i.e. ${\gtrsim} 100$ pc) of the nebula, which could then be attributed to the diffusion of escaping electrons/positrons from a compact plerion. The influence of various model parameters on the energy-dependent extent of the nebula is studied in the diffusion-dominated scenario. We also show that the energy-dependent morphology of the nebula may also be used to study the spin-down history of the pulsar.
The ancient main-sequence solar proxy HIP 102152 unveils the activity and rotational fate of our Sun
Authors: Lorenzo-Oliveira Diego , Meléndez Jorge , Ponte Geisa , Yana Galarza Jhon 
Published: March 2020

ABSTRACT
We present a detailed analysis of the possible future Sun’s rotational evolution scenario based on the 8-Gyr-old solar twin HIP 102152. Using HARPS high-cadence observations (and TESS light curves), we analysed the modulation of a variety of activity proxies (Ca ii , H i Balmer, and Na i lines), finding a strong rotational signal of 35.7 ± 1.4 d (log Bfactor ∼ 70, in the case of Ca ii K line). This value matches with the theoretical expectations regarding the smooth rotational evolution of the Sun towards the end of the main sequence, validating the use of gyrochronology after solar age.
The initial maturation status of marmoset testicular tissues has an impact on germ cell maintenance and somatic cell response in tissue fragment culture
Authors: Heckmann L , Langenstroth-Röwer D , Wistuba J , Portela J M D , van Pelt A M M , Redmann K , Stukenborg J B , Schlatt S , Neuhaus N 
Published: March 2020

AbstractSuccessful in vitro spermatogenesis was reported using immature mouse testicular tissues in a fragment culture approach, raising hopes that this method could also be applied for fertility preservation in humans. Although maintaining immature human testicular tissue fragments in culture is feasible for an extended period, it remains unknown whether germ cell survival and the somatic cell response depend on the differentiation status of tissue. Employing the marmoset monkey (Callithrix jacchus), we aimed to assess whether the maturation status of prepubertal and peri-/pubertal testicular tissues influence the outcome of testis fragment culture. Testicular tissue fragments from 4- and 8-month-old (n = 3, each) marmosets were cultured and evaluated after 0, 7, 14, 28 and 42 days. Immunohistochemistry was performed for identification and quantification of germ cells (melanoma-associated antigen 4) and Sertoli cell maturation status (anti-Müllerian hormone: AMH). During testis fragment culture, spermatogonial numbers were significantly reduced (P &lt; 0.05) in the 4- but not 8-month-old monkeys, at Day 0 versus Day 42 of culture. Moreover, while Sertoli cells from 4-month-old monkeys maintained an immature phenotype (i.e. AMH expression) during culture, AMH expression was regained in two of the 8-month-old monkeys. Interestingly, progression of differentiation to later meiotic stage was solely observed in one 8-month-old marmoset, which was at an intermediate state regarding germ cell content, with gonocytes as well as spermatocytes present, as well as Sertoli cell maturation status. Although species-specific differences might influence the outcome of testis fragment experiments in vitro, our study demonstrated that the developmental status of the testicular tissues needs to be considered as it seems to be decisive for germ cell maintenance, somatic cell response and possibly the differentiation potential.
A phase II study of continuous oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1–associated pediatric low-grade glioma: a Neurofibromatosis Clinical Trials Consortium study
Authors: Ullrich Nicole J , Prabhu Sanjay P , Reddy Alyssa T , Fisher Michael J , Packer Roger , Goldman Stewart , Robison Nathan J , Gutmann David H , Viskochil David H , Allen Jeffrey C , Korf Bruce , Cantor Alan , Cutter Gary , Thomas Coretta , Perentesis John P , Mizuno Tomoyuki , Vinks Alexander A , Manley Peter E , Chi Susan N , Kieran Mark W 
Published: March 2020

Abstract

Background
Activation of the mammalian target of rapamycin (mTOR) pathway is observed in neurofibromatosis type 1 (NF1) associated low-grade gliomas (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not been studied in this population. We evaluate the efficacy of the orally administered mTOR inhibitor everolimus for radiographically progressive NF1-associated pediatric LGGs.

Methods
Children with radiologic-progressive, NF1-associated LGG and prior treatment with a carboplatin-containing chemotherapy were prospectively enrolled on this phase II clinical trial to receive daily everolimus. Whole blood was analyzed for everolimus and markers of phosphatidylinositol-3 kinase (PI3K)/mTOR pathway inhibition. Serial MRIs were obtained during treatment. The primary endpoint was progression-free survival at 48 weeks.

Results
Twenty-three participants (median age, 9.4 y; range, 3.2–21.6 y) were enrolled. All participants were initially evaluable for response; 1 patient was removed from study after development of a malignant peripheral nerve sheath tumor. Fifteen of 22 participants (68%) demonstrated a response, defined as either shrinkage (1 complete response, 2 partial response) or arrest of tumor growth (12 stable disease). Of these, 10/15 remained free of progression (median follow-up, 33 mo). All remaining 22 participants were alive at completion of therapy. Treatment was well tolerated; no patient discontinued therapy due to toxicity. Pharmacokinetic parameters and pre-dose concentrations showed substantial between-subject variability. PI3K/mTOR pathway inhibition markers demonstrating blood mononuclear cell mTOR pathway inactivation was achieved in most participants.

Conclusion
Individuals with recurrent/progressive NF1-associated LGG demonstrate significant disease stability/shrinkage during treatment with oral everolimus with a well-tolerated toxicity profile. Everolimus is well suited for future consideration as upfront or combination therapy in this patient population.
Role of CX3CR1 signaling in malignant transformation of gliomas
Authors: Lee Sungho , Latha Khatri , Manyam Ganiraju , Yang Yuhui , Rao Arvind , Rao Ganesh 
Published: March 2020

Abstract

Background
Chemokine signaling may contribute to progression of low-grade gliomas (LGGs) by altering tumor behavior or impacting the tumor microenvironment. In this study, we investigated the role of CX3C chemokine receptor 1 (CX3CR1) signaling in malignant transformation of LGGs.

Methods
Ninety patients with LGGs were genotyped for the presence of common CX3CR1 V249I polymorphism and examined for genotype-dependent alterations in survival, gene expression, and tumor microenvironment. A genetically engineered mouse model was leveraged to model endogenous intracranial gliomas with targeted expression of CX3C ligand 1 (CX3CL1) and CX3CR1, individually or in combination.

Results
LGG patients who were heterozygous (V/I; n = 43) or homozygous (I/I; n = 2) for the CX3CR1 V249I polymorphism had significantly improved median overall (14.8 vs 9.8 y, P &lt; 0.05) and progression-free survival (8.6 vs 6.5 y, P &lt; 0.05) compared with those with the wild type genotype (V/V; n = 45). Tumors from the V/I + I/I group exhibited significantly decreased levels of CCL2 and MMP9 transcripts, correlating with reduced intratumoral M2 macrophage infiltration and microvessel density. In an immunocompetent mouse model of LGGs, coexpression of CX3CL1 and CX3CR1 promoted a more malignant tumor phenotype characterized by increased microglia/macrophage infiltration and microvessel density, resulting in shorter survival.

Conclusions
CX3CR1 V249I polymorphism is associated with improved overall and progression-free survival in LGGs. CX3CR1 signaling enhances accumulation of tumor associated microglia/macrophages and angiogenesis during malignant transformation.
Examining the Effect of Geographic Region of Residence on Childhood Malnutrition in Uganda
Authors: Amegbor Prince M , Yankey Ortis , Sabel Clive E 
Published: March 2020

Abstract

Objectives
In our study, we examine how geographic region of residence may predict childhood malnutrition, expressed as stunting, wasting and underweight, among children under the age of 5 years in Uganda.

Methods
Using data from the 2016 Uganda Demographic and Health Survey, we performed an incremental multivariate multilevel mixed-effect modelling to examine the effect of a child, parental and household factors on the association between region of residence and each indicator of childhood malnutrition.

Results
Approximately 28%, 3% and 9% of children under age 5 suffered from stunting, wasting and underweight, respectively. The bivariate result shows that the proportion of children suffering from stunting and underweight was relatively lower in the Kampala region compared with the other regions. With the exception of the Northern region (6.44%), wasting was higher (4.12%) among children in the Kampala region. Children in the other regions were more likely to experience stunting and underweight. When controlling for child, parent and household factors, children in the other regions were less likely to suffer from underweight and stunting, compared with those in Kampala region. Children in the other regions, except the Northern region, were less likely to be wasted compared with those in Kampala region.

Conclusion
Our finding suggests that child, parental and household characteristics have effects on the association between region of residence and childhood malnutrition. Addressing individual and household socioeconomic disparities may be vital in tackling regional differences in childhood malnutrition.
Olanzapine for the Prevention of Postdischarge Nausea and Vomiting after Ambulatory Surgery
Authors: Hyman Jaime B. , Park Chang , Lin Hung-Mo , Cole Beatriz , Rosen Leigh , Fenske Suzanne S. , Barr Grzesh Rachel L. , Blank Stephanie V. , Polsky Sylvie B. , Hartnett Matthew , Taub Peter J. , Palvia Vijay , DeMaria Samuel , Ascher-Walsh Charles 
Published: March 2020

Abstract

Background
Postdischarge nausea and vomiting after ambulatory surgery is a common problem that is not adequately addressed in current practice. This prospective, randomized, double-blind, parallel-group, placebo-controlled study was designed to test the hypothesis that oral olanzapine is superior to placebo at preventing postdischarge nausea and vomiting.

Methods
In a single-center, double-blind, randomized, placebo-controlled trial, the authors compared a single preoperative dose of olanzapine 10 mg to placebo, in adult female patients 50 years old or less, undergoing ambulatory gynecologic or plastic surgery with general anesthesia. All patients received standard antiemetic prophylaxis with dexamethasone and ondansetron. The primary composite outcome was nausea and/or vomiting in the 24 h after discharge. Secondary outcomes included severe nausea, vomiting, and side effects.

Results
A total of 140 patients were randomized and evaluable. The primary outcome occurred in 26 of 69 patients (38%) in the placebo group and in 10 of 71 patients (14%) in the olanzapine group (relative risk, 0.37; 95% CI, 0.20 to 0.72; P = 0.003). Severe nausea occurred in 14 patients (20%) in the placebo group and 4 patients (6%) in the olanzapine group (relative risk, 0.28; 95% CI, 0.10 to 0.80). Vomiting occurred in eight patients (12%) in the placebo group and two patients (3%) in the olanzapine group (relative risk, 0.24; 95% CI, 0.05 to 1.10). The median score for sedation (scale 0 to 10, with 10 being highest) in the 24 h after discharge was 4 (interquartile range, 2 to 7) in the placebo group and 6 (interquartile range, 3 to 8) in the olanzapine group (P = 0.023).

Conclusions
When combined with ondansetron and dexamethasone, the addition of olanzapine relative to placebo decreased the risk of nausea and/or vomiting in the 24 h after discharge from ambulatory surgery by about 60% with a slight increase in reported sedation.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Direct-acting antivirals and viral RNA targeting for hepatitis B cure
Authors: French Janine , Locarnini Stephen , Zoulim Fabien 
Published: March 2020

Purpose of review
The current aim in the HBV landscape is to develop therapeutic strategies to achieve a functional cure of infection, characterized by a sustained loss of HBsAg off-treatment. Current treatment options, that is, nucleos(t)ide analogues and IFN are effective at viral suppression but very poor at achieving HBsAg loss. This article is designed to summarize the HBV life cycle in order to review the current treatment strategies and compounds targeting different points of the virus life cycle, which are either in preclinical or clinical phases.

Recent findings
Recently our developed understanding of the HBV life cycle has enabled the development of multiple novel treatment options, all aiming for functional cure.

Summary
It is likely that combinations of novel treatments will be needed to achieve a functional cure, including those that target the virus itself as well as those that target the immune system.
From Bimodal Hearing to Sequential Bilateral Cochlear Implantation in Children—A Within-Subject Comparison
Authors: Deep Nicholas L. , Green Janet E. , Chen Sophia , Shapiro William H. , McMenomey Sean O. , Thomas Roland J. , Waltzman Susan B. 
Published: March 2020

Objective:
To evaluate the performance changes after sequential bilateral cochlear implantation in a pediatric population of bimodal cochlear implant (CI) users. To evaluate the factors which influence the parental and recipient decision to discontinue hearing aid use and seek a second implant.

Study Design:
Retrospective case review, within-subject comparison.

Setting:
Tertiary referral center.

Patients:
Thirty-one pediatric (<18 yr) bimodal CI users who underwent sequential bilateral CI.

Interventions:
Sequential bilateral CI.

Main Outcome Measures:
Parental and/or recipient's reasons for discontinuing their hearing aid and pursuing a second implant, device usage from datalogs, speech understanding in the bimodal and bilateral CI condition.

Results:
Parents/patients were motivated to pursue sequential bilateral CI based on their positive performance with CI1, the expectation of further improvement with a second CI, and the prospect of having a second independently functional ear. In the bimodal condition, mean word recognition score (WRS), sentence recognition in quiet (SIQ), and sentence recognition in noise (SIN) scores were 87.4, 97.3, and 92.9% respectively. At 1-year post-sequential bilateral CI, the mean WRS, SIQ, and SIN score were 92.7, 98.7, and 97.7%, respectively. The improvement in bilateral CI speech scores compared with bimodal scores was statistically significant for WRS (p = 0.015). A ceiling effect limited the ability to detect further meaningful differences on speech perception testing.

Conclusions:
The bilateral CI condition demonstrates equivalent or slightly superior performance compared with the bimodal condition. Several non-speech benefits were elicited from parents as reasons for pursuing a second implant. Close monitoring of the residual acoustic hearing, inquiring about the perceived benefits provided by the HA, and early counseling regarding the potential for sequential bilateral CI are important aspects in determining if and when a second implant is indicated.
Exploring the Relationship Between Schizotypal Traits and Dispositional Mindfulness From a Network Perspective
Authors: Bronchain Jonathan , Chabrol Henri 
Published: March 2020

Abstract
Schizotypy has been associated with impairment in social cognition (e.g., emotional processing, social perception, Theory of Mind). To our knowledge, no study has investigated these processes in terms of dispositional mindfulness. This study aimed to use network theory to explore the relationship between dispositional mindfulness dimensions and schizotypal traits. Participants were 1572 college students who completed the Five Facet Mindfulness Questionnaire-Short Form (FFMQ-SF) and the Schizotypal Personality Questionnaire-Brief (SPQ-B). We first estimated a Gaussian Graphical Model including the FFMQ-SF and the SPQ-B dimensions. We then computed centrality indices and predictability, and we finally conducted a bootstrapping procedure to assess the accuracy of edge weights and the stability of the centrality indices. Describing was strongly and negatively related to interpersonal schizotypy. Acting with awareness and nonjudgment shared negative edges with interpersonal schizotypy. These results provide potential keys to understand alexithymia, decreased sense of self-agency, and emotion regulation in schizotypy.
Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract
Authors: Smith Joan C. , Sausville Erin L. , Girish Vishruth , Yuan Monet Lou , John Kristen M. , Sheltzer Jason M. 
Published: March 2020

AbstractThe factors mediating fatal SARS-CoV-2 infections are poorly understood. Here, we show that cigarette smoke causes a dose-dependent upregulation of Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV-2 receptor, in rodent and human lungs. Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of secretory cells in the respiratory tract. Chronic smoke exposure triggers the expansion of this cell population and a concomitant increase in ACE2 expression. In contrast, quitting smoking decreases the abundance of these secretory cells and reduces ACE2 levels. Finally, we demonstrate that ACE2 expression is responsive to inflammatory signaling and can be upregulated by viral infections or interferon treatment. Taken together, these results may partially explain why smokers are particularly susceptible to severe SARS-CoV-2 infections. Furthermore, our work identifies ACE2 as an interferon-stimulated gene in lung cells, suggesting that SARS-CoV-2 infections could create positive-feedback loops that increase ACE2 levels and facilitate viral dissemination.
Crystal structure of the SARS-CoV-2 non-structural protein 9, Nsp9
Authors: Littler D. R. , Gully B. S. , Colson R. N. , Rossjohn J 
Published: March 2020

AbstractMany of the proteins produced by SARS-CoV-2 have related counterparts across the Severe Acute Respiratory Syndrome (SARS-CoV) family. One such protein is non-structural protein 9 (Nsp9), which is thought to mediate both viral replication and virulence. Current understanding suggests that Nsp9 is involved in viral genomic RNA reproduction. Nsp9 is thought to bind RNA via a fold that is unique to this class of betacoronoaviruses although the molecular basis for this remains ill-defined. We sought to better characterise the SARS-CoV-2 Nsp9 protein and subsequently solved its X-ray crystal structure, in an apo-form and, unexpectedly, in a peptide-bound form with a sequence originating from a rhinoviral 3C protease sequence (LEVL). The structure of the SARS-CoV-2 Nsp9 revealed the high level of structural conservation within the Nsp9 family. The exogenous peptide binding site is close to the dimer interface and impacted on the relative juxtaposition of the monomers within the homodimer. Together we have established a protocol for the production of SARS-CoV-2 Nsp9, determined its structure and identified a peptide-binding site that may warrant further study from the perspective of understanding Nsp9 function.
The first three months of the COVID-19 epidemic: Epidemiological evidence for two separate strains of SARS-CoV-2 viruses spreading and implications for prevention strategies
Authors: Wittkowski Knut M. 
Published: March 2020

AbstractAbout one month after the COVID-19 epidemic peaked in Mainland China and SARS-CoV-2 migrated to Europe and then the U.S., the epidemiological data begin to provide important insights into the risks associated with the disease and the effectiveness of intervention strategies such as travel restrictions and lockdowns (“social distancing”). Respiratory diseases, including the 2003 SARS epidemic, remain only about two months in any given population, although peak incidence and lethality can vary. The epidemiological data suggest that at least two strains of the 2020 SARS-CoV-2 virus have evolved during its migration from Mainland China to Europe. South Korea, Iran, Italy, and Italy’s neighbors were hit by the more dangerous “SKII” variant. While the epidemic in continental Asia is about to end, and in Europe about to level off, the more recent epidemic in the younger US population is still increasing, albeit not exponentially anymore. The peak level will likely depend on which of the strains has entered the U.S. first. The same models that help us to understand the epidemic also help us to choose prevention strategies. Containment of high-risk people, like the elderly, and reducing disease severity, either by vaccination or by early treatment of complications, is the best strategy against a respiratory virus disease. Lockdowns can be effective during the month following the peak incidence in infections, when the exponential increase of cases ends. Earlier containment of low-risk people merely prolongs the time the virus needs to circulate until the incidence is high enough to initiate “herd immunity”. Later containment is not helpful, unless to prevent a rebound if containment started too early.About the AuthorDr. Wittkowski received his PhD in computer science from the University of Stuttgart and his ScD (Habilitation) in Medical Biometry from the Eberhard-Karls-University Tübingen, both Germany. He worked for 15 years with Klaus Dietz, a leading epidemiologist who coined the term “reproduction number”, on the Epidemiology of HIV before heading for 20 years the Department of Biostatistics, Epidemiology, and Research Design at The Rockefeller University, New York. Dr. Wittkowski is currently the CEO of ASDERA LLC, a company discovering novel interventions against complex (incl. coronavirus) diseases from data of genome-wide association studies.