bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding multiple reaction pathways of ligand unbinding
Authors: Rydzewski Jakub , Valsson Omar
Published: June 2019

Searching for reaction pathways describing rare events in large systems presents a long-standing challenge in chemistry and physics. Incorrectly computed reaction pathways result in the degeneracy of microscopic configurations and inability to sample hidden energy barriers. To this aim, we present a general enhanced sampling method to find multiple diverse reaction pathways of ligand unbinding through nonconvex optimization of a loss function describing ligand-protein interactions. The method successfully overcomes large energy barriers using an adaptive bias potential and constructs possible reaction pathways along transient tunnels without the initial guesses of intermediate or final states, requiring crystallographic information only. We examine the method on the T4 lysozyme L99A mutant which is often used as a model system to study ligand binding to proteins, provide a previously unknown reaction pathway, and show that by using the bias potential and the tunnel widths, it is possible to capture heterogeneity of the unbinding mechanisms between the found transient protein tunnels.
原始閩北區方言裡的*ə
Authors: Akitani Hiroyuki
Published: June 2019

抽象

本文在Jerry Norman (1969)和孫順(2016)的基礎上，在原始閩北區方言的韻母系統裡構擬了*ə組韻母(*ə、*iə、*əu、*əŋ、*iəŋ)。
Iso-α-acids and matured hop bitter acids in beer improve obesity-induced cognitive impairment
Authors: Ayabe Tatsuhiro , Ohya Rena , Ano Yasuhisa
Published: June 2019

Dementia and cognitive decline have become public health issues worldwide and life-style-related diseases and obesity have recently been reported as key risk factors. We have recently demonstrated that short-term administration of iso-α-acids (IAAs), hop-derived bitter components of beer, improves spatial and object recognition memory. However, the short-term effects of IAAs on obesity-induced cognitive impairment remain to be investigated. Furthermore, although matured hop bitter acids (MHBAs) are also derived from hops, their effect on obesity-induced cognitive decline remains unknown. In the present study, the short-term administration of IAAs improved memory deficits in high-fat diet (HFD)-fed mice, as assessed in the novel object recognition test (NORT). Dietary MHBAs supplementation administered to HFD-fed mice prevented obesity and improved memory deficits in the NORT. Moreover, the short-term administration of MHBAs improved episodic and spatial reference memory in obese mice. These hop-derived bitter acids may contribute toward improving obesity-induced cognitive impairments.

Abbreviations: IAAs: iso-α-acids; MHBAs: matured hop bitter acids; HFD: high fat diet; NORT: novel object recognition test; NOLT: novel object location test
E-protein–regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex
Authors: Kadakia Tejas , Tai Xuguang , Kruhlak Michael , Wisniewski Jan , Hwang Il-Young , Roy Sumedha , Guinter Terry I. , Alag Amala , Kehrl John H. , Zhuang Yuan , Singer Alfred
Published: June 2019

Preselection thymocytes are normally retained in the thymic cortex, but the mechanisms responsible remain incompletely understood. We now report that deletion of genes encoding the E-protein transcription factors E2A and HEB disorders chemokine receptor expression on developing thymocytes to allow escape of preselection TCR−CD8+ thymocytes into the periphery. We document that CXCR4 expression normally anchors preselection thymocytes to the thymic cortex via interaction with its ligand CXCL12 on cortical thymic epithelial cells, and that disruption of CXCR4–CXCL12 engagements release preselection thymocytes from the thymic cortex. We further document that CXCR4 expression must be extinguished by TCR-mediated positive selection signals to allow migration of TCR-signaled thymocytes out of the thymic cortex into the medulla. Thus, E-protein transcription factors regulate the ordered expression pattern of chemokine receptors on developing thymocytes, and the interaction of the chemokine receptor CXCR4 with its ligand adheres TCR-unsignaled preselection thymocytes to the thymic cortex.
KLRG1 and NKp46 discriminate subpopulations of human CD117+CRTH2− ILCs biased toward ILC2 or ILC3
Authors: Nagasawa Maho , Heesters Balthasar A. , Kradolfer Chantal M.A. , Krabbendam Lisette , Martinez-Gonzalez Itziar , de Bruijn Marjolein J.W. , Golebski Korneliusz , Hendriks Rudi W. , Stadhouders Ralph , Spits Hergen , Bal Suzanne M.
Published: June 2019

Recently, human ILCs that express CD117 and CD127 but lack CRTH2 and NKp44 have been shown to contain precursors of ILC1, ILC2, and ILC3. However, these ILCs have not been extensively characterized. We performed an unbiased hierarchical stochastic neighbor embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCs, which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, and the third expressed KLRG1, but not NKp46 or CD56. Analysis of their cytokine production profiles and transcriptome revealed that NKp46+ ILCs predominantly develop into ILC3s; some of them can differentiate into ILC1/NK-like cells, but they are unable to develop into ILC2s. In contrast, KLRG1+ ILCs predominantly differentiate into ILC2s. Single-cell cultures demonstrate that KLRG1+ ILCs can also differentiate into other ILC subsets depending on the signals they receive. Epigenetic profiling of KLRG1+ ILCs is consistent with the broad differentiation potential of these cells.
An Analysis of Beverage Size Restrictions
Authors: Bourquard Brian A , Wu Steven Y
Published: June 2019

Due to high levels of obesity, various government interventions have been proposed to curb the consumption of sugar‐sweetened beverages (SSBs). The New York City “soda ban,” which proposed to limit the size of SSBs is among the most well‐known and controversial. While public debates about beverage‐size‐restrictions tend to focus on how consumers are impacted, we use a nonlinear pricing model to show that, for all but extremely tight restrictions, consumer welfare would be unaffected by an enforceable restriction. However, sellers’ profit would decline. While consumption is predicted to decline overall, the magnitude of the decline will vary by consumer segment.
A Factorial Survey Investigating the Effect of Disclosing Parental Intellectual Disability on Risk Assessments by Children’s Social Workers in Child Safeguarding Scenarios
Authors: Retzer Ameeta , Kaye Jane , Gray Ron
Published: June 2019

Literature suggests that, as parents, people with intellectual disabilities experience disproportionately high rates of child removal compared to other groups. A factorial survey of 191 children’s social workers investigated the effect of disclosing parental intellectual disability (ID) upon risk assessments in a range of hypothetical child safeguarding scenarios. The case scenarios depicted a range of child safeguarding situations and parents’ ID status was randomly included as an additional item of information. The data were fitted into a generalised ordinal logistic regression model. Findings indicate that when presented with scenarios considered to be less risky, the parental ID disclosure contributed significantly to a higher risk assessment score. However, when presented with scenarios that were considered more risky, the additional parental ID disclosure did not significantly contribute to a higher score. These findings indicate that the risk associated with parental ID is not fixed but relative to the situation in which it is encountered. The research concludes that in cases of low risk, the effect of parental ID is identified as a support need, whereas the lesser contribution of the disclosure to assessments of higher risk cases may indicate that parental ID is overlooked.
Class inequality and capital accumulation in Brazil, 1992–2013
Authors: Loureiro Pedro Mendes
Published: June 2019

This article explores the patterns of class inequality and capital accumulation in Brazil, showing the drivers and limits of the decline in inequality that occurred during the Workers’ Party governments. It proposes that minimum wage hikes and greater social security changed the demand pattern and kick-started a cumulative causation process. Growth and redistribution thus reinforced each other for a period, and then spelled their own limits. As growth accelerated in the 2000s, a Gini decomposition indicates that class inequality decreased, but confined to changes between workers—capitalist income and social stratification were preserved. This also endogenously led to a regressive structural change, as low-productivity, labour-intensive services grew and international trade patterns worsened. This created a medium-term dependence on commodity prices for balance-of-trade solvency, and heightened cost-push inflation, which could not be overcome under the limited policy framework in place. The constrained basis for reducing inequality and the regressive structural change underscore that developmental strategies requires broad, multi-dimensional inequality-reducing measures and an encompassing catching-up project.
AAV9-mediated delivery of miR-23a reduces disease severity in Smn2B/−SMA model mice
Authors: Kaifer Kevin A , Villalón Eric , O'Brien Benjamin S , Sison Samantha L , Smith Caley E , Simon Madeline E , Marquez Jose , O'Day Siri , Hopkins Abigail E , Neff Rachel , Rindt Hansjörg , Ebert Allison D , Lorson Christian L
Published: June 2019

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in survival motor neuron 1 (SMN1). The molecular mechanisms underlying motor neuron degeneration in SMA remain elusive, as global cellular dysfunction obscures the identification and characterization of disease-relevant pathways and potential therapeutic targets. Recent reports have implicated microRNA (miRNA) dysregulation as a potential contributor to the pathological mechanism in SMA. To characterize miRNAs that are differentially regulated in SMA, we profiled miRNA levels in SMA induced pluripotent stem cell (iPSC)-derived motor neurons. From this array, miR-23a downregulation was identified selectively in SMA motor neurons, consistent with previous reports where miR-23a functioned in neuroprotective and muscle atrophy-antagonizing roles. Reintroduction of miR-23a expression in SMA patient iPSC-derived motor neurons protected against degeneration, suggesting a potential miR-23a-specific disease-modifying effect. To assess this activity in vivo, miR-23a was expressed using a self-complementary adeno-associated virus serotype 9 (scAAV9) viral vector in the Smn2B/− SMA mouse model. scAAV9-miR-23a significantly reduced the pathology in SMA mice, including increased motor neuron size, reduced neuromuscular junction pathology, increased muscle fiber area, and extended survival. These experiments demonstrate that miR-23a is a novel protective modifier of SMA, warranting further characterization of miRNA dysfunction in SMA.
Maintenance Pharmacological Treatment of Juvenile Bipolar Disorder: Review and Meta-Analyses
Authors: Yee Caitlin S , Hawken Emily R , Baldessarini Ross J , Vázquez Gustavo H
Published: June 2019

Background

Guidelines for maintenance treatment of juvenile bipolar disorder rely heavily on evidence from adult studies and relatively brief trials in juveniles, leaving uncertainties about optimal long-term treatment. We aimed to systematically review long-term treatment trials for juvenile bipolar disorder.

Methods

We analyzed data recovered by a systematic literature search using the PRISMA guidelines statement, through 2018, for peer-reviewed reports on pharmacological treatments for juvenile bipolar disorder lasting ≥24 weeks.

Results

Of 13 reports with 16 trials of 9 treatments (18.8% were randomized and controlled), with 1773 subjects (94.4% BD-I; ages 6.9–15.1 years), lasting 11.7 (6–22) months. Pooled clinical response rates were 66.8% (CI: 64.4–69.1) with drugs vs 60.6% (53.0–66.7) in 3 placebo-control arms. Random-effects meta-analysis of 4 controlled trials yielded pooled odds ratio (OR) = 2.88 ([0.87–9.60], P = .08) for clinical response, and OR = 7.14 ([1.12–45.6], P = .04) for nonrecurrence. Apparent efficacy ranked: combined agents >anticonvulsants ≥lithium ≥antipsychotics. Factors favoring response ranked: more attention deficit/hyperactivity disorder, polytherapy, randomized controlled trial design, nonrecurrence vs response. Adverse events (incidence, 5.50%–28.5%) notably included cognitive dulling, weight-gain, and gastrointestinal symptoms; early dropout rates averaged 49.8%.

Conclusions

Pharmacological treatments, including anticonvulsants, lithium, and second-generation antipsychotics, may reduce long-term morbidity in juvenile bipolar disorder. However, study number, quality, and effect magnitude were limited, leaving the status of scientific support for maintenance treatment for juvenile bipolar disorder inconclusive.
Next Generation Sequencing and Bioinformatics Methodologies for Infectious Disease Research and Public Health: Approaches, Applications, and Considerations for Development of Laboratory Capacity
Authors: Maljkovic Berry Irina , Melendrez Melanie C , Bishop-Lilly Kimberly A , Rutvisuttinunt Wiriya , Pollett Simon , Talundzic Eldin , Morton Lindsay , Jarman Richard G
Published: June 2019

Next generation sequencing (NGS) combined with bioinformatics has successfully been used in a vast array of analyses for infectious disease research of public health relevance. For instance, NGS and bioinformatics approaches have been used to identify outbreak origins, track transmissions, investigate epidemic dynamics, determine etiological agents of a disease, and discover novel human pathogens. However, implementation of high-quality NGS and bioinformatics in research and public health laboratories can be challenging. These challenges mainly include the choice of the sequencing platform and the sequencing approach, the choice of bioinformatics methodologies, access to the appropriate computation and information technology infrastructure, and recruiting and retaining personnel with the specialized skills and experience in this field. In this review, we summarize the most common NGS and bioinformatics workflows in the context of infectious disease genomic surveillance and pathogen discovery, and highlight the main challenges and considerations for setting up an NGS and bioinformatics-focused infectious disease research public health laboratory. We describe the most commonly used sequencing platforms and review their strengths and weaknesses. We review sequencing approaches that have been used for various pathogens and study questions, as well as the most common difficulties associated with these approaches that should be considered when implementing in a public health or research setting. In addition, we provide a review of some common bioinformatics tools and procedures used for pathogen discovery and genome assembly, along with the most common challenges and solutions. Finally, we summarize the bioinformatics of advanced viral, bacterial, and parasite pathogen characterization, including types of study questions that can be answered when utilizing NGS and bioinformatics.
An apparent paradox: resistance mutations in HIV-1 DNA predict improved virological responses to antiretroviral therapy
Authors: Geretti Anna Maria , Abdullahi Adam , Mafotsing Fopoussi Olga , Bonnett Laura , Fokom Defo Victoire , Moudourou Sylvie , Fokam Joseph , Kouanfack Charles , Torimiro Judith
Published: June 2019

Background

In sub-Saharan Africa, detecting resistance-associated mutations (RAMs) at failure of first-line ART with two NRTIs plus an NNRTI predicts improved virological responses to second-line therapy with two NRTIs plus a ritonavir-boosted PI (PI/r). This indicates residual NRTI activity in the presence of RAMs, although additional factors may contribute to the effect.

Objectives

The aim of this study was to investigate the influence of pre-existing RAMs on the outcomes of maintenance monotherapy with ritonavir-boosted darunavir within a randomized trial in Cameroon.

Methods

RAMs were detected in HIV-1 DNA using PBMCs collected at initiation of darunavir/ritonavir monotherapy. Adherence was assessed by pill count and visual analogue scale (VAS). Predictors of virological failure (confirmed or last available viral load >400 copies/mL) were explored by logistic regression analysis. Trial name = MANET (NCT02155101).

Results

After NNRTI-based therapy, participants (n = 81) had received PI/r-based therapy for a median of 3.2 years and had a confirmed viral load <60 copies/mL and a median CD4 count of 466 cells/mm3. NRTI and NNRTI RAMs were detected in 39/60 (65.0%) and 41/60 (68.3%) HIV-1 DNA sequences, respectively. Over 48 weeks of monotherapy, 16/81 (19.8%) patients experienced virological failure. After adjusting for age, HIV-1 DNA load, adherence by VAS and RAM status, virological failure was less likely with higher VAS-measured adherence (adjusted OR 0.04, 95% CI 0.01–0.37; P = 0.004) and detectable HIV-1 DNA RAMs (adjusted OR 0.15, 95% CI 0.03–0.82; P = 0.028).

Conclusions

Pre-existing NRTI and NNRTI RAMs are associated with improved virological responses to NRTI-sparing ART in sub-Saharan Africa, indicating a predictive effect that is independent of residual NRTI activity.
Characterization of Tn6349, a novel mosaic transposon carrying poxtA, cfr and other resistance determinants, inserted in the chromosome of an ST5-MRSA-II strain of clinical origin
Authors: D’Andrea Marco Maria , Antonelli Alberto , Brenciani Andrea , Di Pilato Vincenzo , Morroni Gianluca , Pollini Simona , Fioriti Simona , Giovanetti Eleonora , Rossolini Gian Maria
Published: June 2019

Objectives

To characterize the genetic element carrying the poxtA oxazolidinone resistance gene found in the poxtA index strain Staphylococcus aureus AOUC-0915 isolated from a cystic fibrosis patient.

Methods

The genetic context of poxtA was investigated by bioinformatics analysis of WGS data of strain AOUC-0915, followed by PCR and confirmatory Sanger sequencing for repetitive regions. Conjugation and electrotransformation experiments were carried out to assess horizontal transferability using S. aureus and Enterococcus faecalis recipients. Production of phage particles was evaluated by PCR using DNA preparations obtained after phage induction. Excision of the transposon carrying poxtA was evaluated by inverse PCR experiments for detection of circular intermediates.

Results

poxtA was found to be associated with a 48 kb composite transposon of original structure, named Tn6349, inserted into a φN315-like prophage. The transposon was bounded by two IS1216 insertion sequences, carried several resistance genes [erm(B), cfr, poxtA and fexB] and exhibited a mosaic structure made by a derivative of plasmid pE35048-oc (previously described in an Enterococcus faecium clinical isolate) and Tn6657, a novel composite transposon carrying the poxtA and fexB genes. Excision ability of Tn6349 as a circular intermediate was demonstrated. Transferability of Tn6349 or modules thereof to S. aureus or E. faecalis by either conjugation or electrotransformation was not detected. Induction of the φN315-like prophage carrying Tn6349 was not observed.

Conclusions

This study describes the structure of Tn6349, a novel composite transposon carrying several resistance determinants to anti-ribosomal drugs, including cfr and poxtA, from an oxazolidinone-resistant MRSA strain. Analysis of Tn6349 revealed a modular structure that could favour the mobilization of its resistance determinants.
Establishing a baseline for a national paediatric antimicrobial stewardship programme
Authors: Gibbons C L , Malcolm W , Sneddon J , Doherty C , Cairns S , Milne A , Llano M , Reilly J S
Published: June 2019

Background

The majority of antimicrobial stewardship programmes focus on prescribing in adult populations; however, there is a recognized need for targeted paediatric antimicrobial stewardship to improve the quality and safety of prescribing amongst this patient group.

Objectives

To describe the current epidemiology of antimicrobial prescribing in paediatric inpatient populations in Scotland to establish a baseline of evidence and identify priority areas for quality improvement to support a national paediatric antimicrobial stewardship programme.

Methods

A total of 559 paediatric inpatients were surveyed during the Scottish national point prevalence survey of healthcare-associated infections and antimicrobial prescribing, 2016. The prevalence of antimicrobial prescribing was calculated and characteristics of antimicrobial prescribing were described as proportions and compared between specialist hospitals and paediatric wards in acute hospitals.

Results

Prevalence of antimicrobial use in paediatric inpatients was 35.4% (95% CI = 31.6%–39.4%). Treatment of community- and hospital-acquired infections accounted for 47.1% and 20.7% of antimicrobial use, respectively, with clinical sepsis being the most common diagnosis and gentamicin the most frequently prescribed antimicrobial for the treatment of infection. The reason for prescribing was documented in the notes for 86.5% of all prescriptions and, of those assessed for compliance against local policy, 92.9% were considered compliant.

Conclusions

Data from national prevalence surveys are advantageous when developing antimicrobial stewardship programmes. Results have highlighted differences in the prescribing landscape between paediatric inpatient populations in specialist hospitals and acute hospitals, and have informed priorities for the national antimicrobial stewardship programme, which reinforces the need for a targeted paediatric antimicrobial stewardship programme.
Genetic and biochemical characterization of FRI-3, a novel variant of the Ambler class A carbapenemase FRI-1
Authors: Schauer Jennifer , Gatermann Sören G , Marschal Matthias , Pfennigwerth Niels
Published: June 2019

Objectives

To characterize a new variant of the FRI class A carbapenemase isolated from an MDR clinical Enterobacter cloacae isolate.

Methods

A carbapenem-resistant E. cloacae was isolated from a rectal swab from a patient in an ICU in Southern Germany. Various phenotypic tests confirmed production of a putative class A carbapenemase. The new bla gene variant, blaFRI-3, and its genetic environment were characterized by WGS. Biochemical characterization was performed by heterologous expression in Escherichia coli TOP10 and by purification of the enzyme with subsequent determination of its kinetic parameters.

Results

PCR and sequencing carried out for different class A carbapenemase genes confirmed the presence of a novel variant of blaFRI-1. The novel variant was named FRI-3 and exhibited 91%, 96% and 92% amino acid identity to FRI-1, FRI-2 and FRI-4, respectively. E. coli TOP10 expressing blaFRI-3 showed increased resistance to almost all β-lactams. Comparing the catalytic behaviour of FRI-3 and FRI-1, it was shown that FRI-3 had the same substrate spectrum, but basically hydrolysed β-lactams less efficiently than FRI-1. WGS data revealed that blaFRI-3 was located on a 111 kb plasmid.

Conclusions

The biochemical characterization of FRI-3 illustrates that even a few differences in the amino acid sequence can lead to altered catalytic activities of β-lactamases belonging to the same family.
Polyclonal gut colonization with extended-spectrum cephalosporin- and/or colistin-resistant Enterobacteriaceae: a normal status for hotel employees on the island of Zanzibar, Tanzania
Authors: Büdel Thomas , Kuenzli Esther , Clément Mathieu , Bernasconi Odette J , Fehr Jan , Mohammed Ali Haji , Hassan Nadir Khatib , Zinsstag Jakob , Hatz Christoph , Endimiani Andrea
Published: June 2019

Objectives

For low-income countries, data regarding the intestinal colonization with extended-spectrum cephalosporin-resistant (ESC-R) and colistin-resistant (CST-R) Enterobacteriaceae in the community are still scarce. Here, we investigated this phenomenon by analysing hotel employees in Zanzibar.

Methods

During June to July 2018, rectal swabs from 59 volunteers were screened implementing selective enrichments and agar plates. Species identification was achieved using MALDI-TOF MS. Strains were characterized using microdilution panels (MICs), microarray, PCRs for mcr-1/-8, repetitive extragenic palindromic-PCR (rep-PCR) and WGS.

Results

Colonization prevalence with ESC-R-, CST-R- and mcr-1-positive Enterobacteriaceae were 91.5%, 66.1% and 18.6%, respectively (average: 2.2 strains per volunteer). Overall, 55 ESC-R Escherichia coli (3 also CST-R), 33 ESC-R Klebsiella pneumoniae (1 also CST-R), 17 CST-R E. coli and 21 CST-R K. pneumoniae were collected. The following main resistance genes were found: ESC-R E. coli (blaCTX-M-15-like, 51.0%), ESC-R K. pneumoniae (blaCTX-M-9-like, 42.9%), CST-R E. coli (mcr-1, 55%) and CST-R K. pneumoniae (D150G substitution in PhoQ). ESBL-producing E. coli mainly belonged to ST361, ST636 and ST131, whereas all those that were mcr-1 positive belonged to ST46 that carried mcr-1 in a 33 kb IncX4 plasmid. ESBL-producing K. pneumoniae mainly belonged to ST17, ST1741 and ST101, whereas CST-R strains belonged to ST11.

Conclusions

We recorded remarkably high colonization prevalence with ESC-R and/or CST-R Enterobacteriaceae in hotel staff. Further research in the local environment, livestock and food chain is warranted to understand this phenomenon. Moreover, as Zanzibar is a frequent holiday destination, attention should be paid to the risk of international travellers becoming colonized and thereby importing life-threatening pathogens into their low-prevalence countries.
Adverse drug event and medication extraction in electronic health records via a cascading architecture with different sequence labeling models and word embeddings
Authors: Dai Hong-Jie , Su Chu-Hsien , Wu Chi-Shin
Published: June 2019

Objective

An adverse drug event (ADE) refers to an injury resulting from medical intervention related to a drug including harm caused by drugs or from the usage of drugs. Extracting ADEs from clinical records can help physicians associate adverse events to targeted drugs.

Materials and Methods

We proposed a cascading architecture to recognize medical concepts including ADEs, drug names, and entities related to drugs. The architecture includes a preprocessing method and an ensemble of conditional random fields (CRFs) and neural network–based models to respectively address the challenges of surrogate string and overlapping annotation boundaries observed in the employed ADEs and medication extraction (ADME) corpus. The effectiveness of applying different pretrained and postprocessed word embeddings for the ADME task was also studied.

Results

The empirical results showed that both CRFs and neural network–based models provide promising solution for the ADME task. The neural network–based models particularly outperformed CRFs in concept types involving narrative descriptions. Our best run achieved an overall micro F-score of 0.919 on the employed corpus. Our results also suggested that the Global Vectors for word representation embedding in general domain provides a very strong baseline, which can be further improved by applying the principal component analysis to generate more isotropic vectors.

Conclusions

We have demonstrated that the proposed cascading architecture can handle the problem of overlapped annotations and further improve the overall recall and F-scores because the architecture enables the developed models to exploit more context information and forms an ensemble for creating a stronger recognizer.
The identify of Cancer (Arges) parallelus De Haan, 1833 (Decapoda: Brachyura: Pilumnidae), a fossil crab described from Japan during the 19th century
Authors: Karasawa Hiroaki , Kato Hisayoshi
Published: June 2019

The revised diagnosis and description are given for Cancer (Arges) parallelusDe Haan, 1833, a fossil crab first described from Japan during the 19th century. The neotype of this species from the Holocene (about 9,000–5,000 ybp) Nanyo Formation of Ise Bay, central Japan, is herein designated. The monotypic genus ArgesDe Haan, 1833 belongs to the pilumnid subfamily Rhizopinae Stimpson, 1858 and has close affinities with TyphlocarcinusStimpson, 1858, a genus of Rhizopinae.
Delayed Diagnosis of Leprosy in a Micronesian Soldier – Case Report
Authors: Bossalini John P , Bandino Justin P , Miletta Nathanial R
Published: June 2019

Lepromatous leprosy represents a cutaneous infection by the bacterium Mycobacterium leprae. Once considered a common, fatal disease, leprosy has become increasingly rare with modern, inexpensive antibiotics. Most healthcare workers will never encounter a case of leprosy due to the low prevalence of the disease. However, military physicians, through deployments and contact with foreign-born servicemembers, are one of the first lines of defense against this disease. With an unknown method of transmission and an insidiously slow replication, it can take years for the disease to fully manifest. There are multiple cutaneous manifestations associated with the infection that can mimic other infectious etiologies, stalling appropriate diagnosis and treatment. To determine which treatment course is recommended requires evaluation of disease dissemination and the level of host immune response. As the incidence of reported leprosy cases continues to decline, disease education on diagnosis and treatment is imperative to enhance early detection and intervention. Understanding the populations at risk for leprosy and its insidious presentation will aid the practitioner in minimizing disease burden for both U.S. servicemembers and our foreign partners.
Phase and amplitude asymmetry in the quasi-biennial oscillation of solar Hα flare activity
Authors: Deng L H , Zhang X J , Li G Y , Deng H , Wang F
Published: June 2019

Quasi-biennial oscillation (QBO) of solar magnetic activities is intrinsic to dynamo mechanism, but still far from fully understood. In this work, the phase and amplitude asymmetry of solar QBO of Hα flare activity in the northern and southern hemispheres is studied by the ensemble empirical mode decomposition, the cross-correlation analysis, and the wavelet transform technique. The following results are found: (1) solar QBO of Hα flare index in the two hemispheres has a complicated phase relationship, but does not show any systematic regularity; and (2) the solar cycle mode of solar Hα flare index in the northern hemisphere generally leads that in the southern one by nine months for the time interval from 1966 to 2014. The possible origin of these results is discussed.
Study of the reflection spectrum of the bright atoll source GX 3 + 1 with NuSTAR
Authors: Mondal Aditya S , Dewangan G C , Raychaudhuri B
Published: June 2019

We report on the NuSTAR observation of the atoll type neutron star (NS) low-mass X-ray binary GX 3 + 1 performed on 2017 October 17. The source was found in a soft X-ray spectral state with 3–70 keV luminosity of LX ∼ 3 × 1037 erg s−1 (${\sim } 16{{\ \rm per\ cent}}$ of the Eddington luminosity), assuming a distance of 6 kpc. A positive correlation between intensity and hardness ratio suggests that the source was in the banana branch during this observation. The broad-band 3–70 keV NuSTAR spectral data can be described by a two-component continuum model consisting of a disc blackbody (kTdisc ∼ 1.8 keV) and a single temperature blackbody model (kTbb ∼ 2.7 keV). The spectrum shows a clear and robust indication of relativistic reflection from the inner disc which is modelled with a self-consistent relativistic reflection model. The accretion disc is viewed at an inclination of i ≃ 22°–26° and extended close to the NS, down to $R_\text{in}=(1.2\!-\!1.8) R_\text{ISCO}\:(\simeq 6.1\!-\!9.1\, R_{\mathrm{ g}}\: \text{or}\: 14\!-\!20.5$ km) which allows an upper limit on the NS radius (≤13.5 km). Based on the measured flux and the mass accretion rate, the maximum radial extension for the boundary layer is estimated to be ∼6.3 Rg from the NS surface. However, if the disc is not truncated by the boundary layer but by the magnetosphere, an estimated upper limit on the polar magnetic field would be of B ≤ 6 × 108 G.
Early-type galaxies in low-density environments: NGC 6876 explored through its globular cluster system
Authors: Ennis Ana I , Bassino Lilia P , Caso Juan P , De Bórtoli Bruno J
Published: June 2019

We present the results of a photometric study of the early-type galaxy NGC 6876 and the surrounding globular cluster (GC) system. The host galaxy is a massive elliptical, the brightest of this type in the Pavo Group. According to its intrinsic brightness (Mv ∼ −22.7), it is expected to belong to a galaxy cluster instead of a poor group. Observational material consists of g′, r′, i′ images obtained with the Gemini/GMOS camera. The selected GC candidates present a clear bimodal colour distribution at different galactocentric radii, with mean colours and dispersions for the metal-poor (‘blue’) and metal-rich (‘red’) typical of old GCs. The red subpopulation dominates close to the galaxy centre, in addition to the radial projected distribution showing that they are more concentrated towards the galaxy centre. The azimuthal projected distribution shows an overdensity in the red subpopulation in the direction of a trail observed in X-ray that could be evidence of interactions with its spiral neighbour NGC 6872. The turnover of the luminosity function gives an estimated distance modulus (m − M) ≈ 33.5 and the total population amounts to 9400 GCs, i.e. a quite populous system. The halo mass obtained using the number ratio (i.e. the number of GCs with respect to the baryonic and dark mass) gives a total of ∼1013, meaning it is a very massive galaxy, given the environment.
PRIME: PSF Reconstruction and Identification for Multiple-source characterization Enhancement – application to Keck NIRC2 imager
Authors: Beltramo-Martin O , Correia C M , Ragland S , Jolissaint L , Neichel B , Fusco T , Wizinowich P L
Published: June 2019

In order to enhance the scientific exploitation of adaptive optics (AO)-assisted observations, we investigate a novel hybrid concept to improve the parametric estimation of point spread function (PSF) called PSF Reconstruction and Identification for Multiple-source characterization Enhancement (PRIME). PRIME uses both focal and pupil-plane measurements to estimate jointly the model parameters related to the atmosphere [$C_n^2(h)$, seeing] and the AO system (e.g. optical gains and residual low-order errors). Photometry and astrometry are provided as by-products. The parametric model in use is flexible enough to be scaled with field location and wavelength, making it a proper choice for optimized on-axis and off-axis data-reduction across the spectrum. Here, we present the methodology and validate PRIME on engineering and binary Keck II telescope NIRC2 images. We also present applications of PSF model parameters retrieval using PRIME: (i) calibrate the PSF model for observations void of stars on the acquired images, i.e. optimize the PSF reconstruction process, (ii) update the AO error breakdown mutually constrained by the telemetry and the images in order to speculate on the origin of the missing error terms and evaluate their magnitude, and (iii) measure photometry and astrometry with an application to the triple system Gl569 images.
Effects of the albedo and disc on the zero velocity curves and linear stability of equilibrium points in the generalized restricted three-body problem
Authors: Yousuf Saleem , Kishor Ram
Published: June 2019

The important aspects of a dynamical system are its stability and the factors that affect its stability. In this paper, we present an analysis of the effects of the albedo and the disc on the zero velocity curves, the existence of equilibrium points and their linear stability in a generalized restricted three-body problem (RTBP). The proposed problem consists of the motion of an infinitesimal mass under the gravitational field of a radiating-oblate primary, an oblate secondary and a disc that is rotating about the common centre of mass of the system. Significant effects of the albedo and the disc are observed on the zero velocity curves, on the positions of equilibrium points and on the stability region. A linear stability analysis of collinear equilibrium points L1, 2, 3 is performed with respect to the mass parameter μ and albedo parameter QA of the secondary, separately. It is found that L1, 2, 3 are unstable in both cases. However, the non-collinear equilibrium points L4, 5 are stable in a finite range of mass ratio μ. After analysing the individual as well as combined effects of the radiation pressure force of the primary, the albedo force of the secondary, the oblateness of both the primary and secondary and the disc, it is found that these perturbations play a significant role in the design of the trajectories in the vicinity of equilibrium points and in the analysis of their stability property. In the future, the results obtained will improve existing results and will help in the analysis of different space missions. These results are limited to the regular symmetric disc and radiation pressure, which can be extended later.
Spectroscopy with the Engineering Development Array: cold H+ at 63 MHz towards the Galactic Centre
Authors: Oonk J B R , Alexander E L , Broderick J W , Sokolowski M , Wayth R
Published: June 2019

The Engineering Development Array (EDA) is a single test station for Square Kilometre Array (SKA) precursor technology. We have used the EDA to detect low-frequency radio recombination lines (RRLs) from the Galactic Centre region. Low-frequency RRLs are an area of interest for future low-frequency SKA work as these lines provide important information on the physical properties of the cold neutral medium. In this project, we investigate the EDA, its bandpass, and the radio frequency interference environment for low-frequency spectroscopy. We present line spectra from 30 to 325 MHz for the Galactic Centre region. The decrease in sensitivity for the EDA at the low end of the receiver prevents carbon and hydrogen RRLs to be detected below 40 and 60 MHz, respectively. RFI strongly affects frequencies in the range 276–292, 234–270, 131–138, 95–102, and below 33 MHz. Cnα RRLs were detected in absorption for quantum levels n = 378–550 (39–121 MHz) and in emission for n = 272–306 (228–325 MHz). Cnβ lines were detected in absorption for n = 387–696 (39–225 MHz). Hnα RRLs were detected in emission for n = 272–480 (59–325 MHz). Hnβ lines were detected for n = 387–453 (141–225 MHz). The stacked Hnα detection at 63 MHz is the lowest frequency detection made for hydrogen RRLs and shows that a cold (partially) ionized medium exists along the line of sight to the Galactic Centre region. The size and velocity of this cold H+ gas indicates that it is likely associated with the nearby Riegel–Crutcher cloud.
Association of Overlapping Neurosurgery With Patient Outcomes at a Large Academic Medical Center
Authors: Agarwal Prateek , Ramayya Ashwin G , Osiemo Benjamin , Goodrich Stephen , Glauser Gregory , McClintock Scott D , Chen H Isaac , Schuster James M , Grady M Sean , Malhotra Neil R
Published: June 2019

BACKGROUND

Limited data exist on the safety of overlapping surgery, a practice that has recently received widespread attention.

OBJECTIVE

To examine the association of overlapping neurosurgery with patient outcomes.

METHODS

A total of 3038 routinely scheduled, elective neurosurgical procedures were retrospectively reviewed at a single, multihospital academic medical center. Procedures were categorized into any overlap or no overlap and further subcategorized into beginning overlap (first 50% of procedure only), end overlap (last 50% of procedure only), and middle overlap (overlap at the midpoint).

RESULTS

A total of 1030 (33.9%) procedures had any overlap, whereas 278 (9.2%) had beginning overlap, 190 (6.3%) had end overlap, and 476 (15.7%) had middle overlap. Compared with no overlap patients, patients with any overlap had lower American Society of Anesthesiologists scores (P = .0018), less prior surgery (P < .0001), and less prior neurosurgery (P < .0001), though they tended to be older (P < .0001) and more likely in-patients (P = .0038). Any-overlap patients had decreased overall mortality (2.8% vs 4.5%; P = .025), 30- to 90-d readmission rate (3.1% vs 5.5%; P = .0034), 30- to 90-d reoperation rate (1.0% vs 2.0%; P = .03), 30- to 90-d emergency room (ER) visit rate (2.1% vs 3.7%; P = .018), and future surgery on index admission (2.8% vs 7.3%; P < .0001). Multiple regression analysis validated noninferior outcomes for overlapping surgery, except for the association of increased future surgery on index admission with middle overlap (odds ratio 3.99; 95% confidence interval [1.91, 8.33]).

CONCLUSION

Overlapping neurosurgery is associated with noninferior patient outcomes that may be driven by surgeon selection of healthier patients, regardless of specific overlap timing.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Incidence of Shunt-Dependent Hydrocephalus in Infants With Myelomeningocele After Prenatal Versus Postnatal Repair
Authors: Tamber Mandeep S , Flannery Ann Marie , McClung-Smith Catherine , Assassi Nadege , Bauer David F , Beier Alexandra D , Blount Jeffrey P , Durham Susan R , Klimo Jr Paul , Nikas Dimitrios C , Rehring Patricia , Tyagi Rachana , Mazzola Catherine A
Published: June 2019

BACKGROUND

Myelomeningocele (MM) is a condition that is responsible for considerable morbidity in the pediatric population. A significant proportion of the morbidity related to MM is attributable to hydrocephalus and the surgical management thereof. Postnatal repair remains the most common form of treatment; however, increased rates of prenatal diagnosis, advances in fetal surgery, and a hypothesis that neural injury continues in utero until the MM defect is repaired have led to the development and evaluation of prenatal surgery as a means to improve outcomes in afflicted infants.

OBJECTIVE

The objective of this guideline is to systematically evaluate the literature to determine whether there is a difference in the proportion of patients who develop shunt-dependent hydrocephalus in infants who underwent prenatal MM repair compared to infants who had postnatal repair.

METHODS

The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Full-text articles were then reviewed, and when appropriate, included as evidence.

RESULTS

A total of 87 abstracts were identified and reviewed by 3 independent reviewers. Thirty-nine full-text articles were selected for analysis. Three studies met selection criteria and were included in the evidence table.

CONCLUSION

Class I evidence from 1 study and class III evidence from 2 studies suggest that, in comparison to postnatal repair, prenatal surgery for MM reduces the risk of developing shunt-dependent hydrocephalus. Therefore, prenatal repair of MM is recommended for those fetuses who meet specific criteria for prenatal surgery to reduce the risk of developing shunt-dependent hydrocephalus (level I). Differences between prenatal and postnatal repair with respect to the requirement for permanent cerebrospinal fluid diversion should be considered alongside other relevant maternal and fetal factors when deciding upon a preferred method of MM closure.

 The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-2.
Routine Immediate Eye Examination at the Point of Care for Diagnosis of AIDS-Related Cytomegalovirus Retinitis Among Patients With a CD4 Count <100 in Myanmar
Authors: Ei Win Le Shwe Sin , Pyar Soe Kyi , Hilbig Adelene , Murray Jillian , Heiden David
Published: June 2019

A retrospective review of diagnosis of cytomegalovirus retinitis (CMVR) before and after introduction of routine immediate eye examination among AIDS patients in Myanmar with an absolute CD4 T-cell count <100 cells/μL demonstrated an increased detection of CMVR from 1.1% (14/1233) to 10.7% (65/608), an improvement of ~10-fold. Diagnosis of CMVR was achieved a mean of 2 days after clinic enrollment.
Phenotypes Conferred by Wheat Multiple Pathogen Resistance Locus, Sr2, Include Cell Death in Response to Biotic and Abiotic Stresses
Authors: Tabe Linda , Samuel Sharon , Dunn Matthew , White Rosemary , Mago Rohit , Estavillo Gonzalo , Spielmeyer Wolfgang
Published: June 2019

The wheat Sr2 locus confers partial resistance to four biotrophic pathogens: wheat stem rust (Puccinia graminis f. sp. tritici), leaf rust (P. triticina), stripe rust (P. striiformis f. sp. tritici), and powdery mildew (Blumeria graminis f. sp. tritici). In addition, Sr2 is linked with a brown coloration of ears and stems, termed pseudo-black chaff (PBC). PBC, initially believed to be elicited by stem rust infection, was subsequently recognized to occur in the absence of pathogen infection. The current study demonstrates that the resistance response to stem rust is associated with the death of photosynthetic cells around rust infection sites in the inoculated leaf sheath. Similarly, Sr2-dependent resistance to powdery mildew was associated with the death of leaf mesophyll cells around mildew infection sites. We demonstrate that PBC occurring in the absence of pathogen inoculation also corresponds with death and the collapse of photosynthetic cells in the affected parts of stems and ears. In addition, Sr2-dependent necrosis was inducible in leaves by application of petroleum jelly or by heat treatments. Thus, Sr2 was found to be associated with cell death, which could be triggered by either biotic or abiotic stresses. Our results suggest a role for the Sr2 locus in controlling cell death in response to stress.
Structured Cognitive Training Yields Best Results in Healthy Older Adults, and Their ApoE4 State and Baseline Cognitive Level Predict Training Benefits
Authors: Roheger Mandy , Kessler Josef , Kalbe Elke
Published: June 2019

Background:

Cognitive training has been shown to improve cognitive functions in healthy older adults. However, little is known about which specific variables are responsible for the improvement.

Objective:

Our aim was to evaluate whether healthy older adults benefit more from a structured cognitive training program than an unstructured brain jogging program and to identify possible predictors for training success, including apolipoprotein E4 (apoE4).

Methods:

In a randomized controlled trial, participants completed either a 6-week structured cognitive training program (n=35) or a 6-week unstructured brain jogging program (n=35). A control group received no training and was not part of the randomization procedure (n=35). Overall, 105 participants were included in the training data analyses, focusing on verbal memory, attention, and executive functions. Data from an additional 45 previously trained, healthy older adults were used for the predictor analysis.

Results:

A significant Time×Training interaction in favor of the structured cognitive training program was found in verbal memory. Low baseline performance on neuropsychological tests was a significant predictor for benefits in verbal memory, attention, and executive functions. A subgroup analysis (n=35) revealed that only noncarriers of the apoE4 allele showed significant gains in long-term verbal memory and attention.

Conclusions:

Our results support the greater effectiveness of structured cognitive training on verbal memory compared with brain jogging and no training. The success of this type of training program may be predicted by sociodemographic, cognitive, and genetic variables.