bluuebunny/crossref_metadata_2025 huggingface dataset:
Error analysis of an L2-type method on graded meshes for a fractional-order parabolic problem
Authors: Kopteva Natalia
Published: April 2020

An initial-boundary value problem with a Caputo time derivative of fractional order

α
∈
(
0
,
1
)

\alpha \in (0,1)

is considered, solutions of which typically exhibit a singular behaviour at an initial time. An L2-type discrete fractional-derivative operator of order

3
−
α

3-\alpha

is considered on nonuniform temporal meshes. Sufficient conditions for the inverse-monotonicity of this operator are established, which yields sharp pointwise-in-time error bounds on quasi-graded temporal meshes with arbitrary degree of grading. In particular, those results imply that milder (compared to the optimal) grading yields optimal convergence rates in positive time. Semi-discretizations in time and full discretizations are addressed. The theoretical findings are illustrated by numerical experiments.
Euler characteristics of Brill-Noether varieties
Authors: Chan Melody , Pflueger Nathan
Published: April 2020

We prove an enumerative formula for the algebraic Euler characteristic of Brill-Noether varieties, parametrizing degree

d
d

and rank

r
r

linear series on a general genus

g
g

curve, with ramification profiles specified at up to two general points. Up to sign, this Euler characteristic is the number of standard set-valued tableaux of a certain skew shape with

g
g

labels. We use a flat degeneration via the Eisenbud-Harris theory of limit linear series, relying on moduli-theoretic advances of Osserman and Murray-Osserman; the count of set-valued tableaux is an explicit enumeration of strata of this degeneration.
Histological Description and Histopathology in Polypedilum sp. (Diptera: Chironomidae): A Potential Biomarker for the Impact of Mining on Tributaries
Authors: Grueso-Gilaberth Rosa N , Jaramillo-Timarán Keiner S , Ospina-Pérez Erika M , Richardi Vinicius S , Ossa-López Paula A , Rivera-Páez Fredy A
Published: April 2020

The Neotropical region has a wide aquatic biodiversity, which is affected by anthropogenic activities. Mining has caused a negative impact on these ecosystems, directly affecting benthic communities. Aquatic macroinvertebrates are effective bioindicators of water quality, especially Chironomidae larvae, since these show high species richness, abundance, and sensitivity to human activities. The genus Polypedilum is among the most representative of the family Chironomidae. Research on these species is focused on their abundance and dominance in water bodies. In addition, several studies have addressed alterations in the external morphology of some Chironomidae due to mining pollution (heavy metals). However, little is known about the effects of mining on the internal morphology of these species. This study provides the first histological description of different systems and organs of Polypedilum sp. larvae. Furthermore, we report histopathological alterations in larvae collected from two tributaries affected by mining, namely Toldafría and La Elvira streams located in the municipalities of Villamaría and Manizales (Caldas – Colombia). Our findings show target organs of mining pollution in a species of Polypedilum, which represent potential early-warning histopathological biomarkers with relevant implications for water quality monitoring.
Invited Commentary: Opportunities That Come With Studying the Co-Occurrence of Multiple Outcomes
Authors: Haneuse Sebastien , Schrag Deborah , Nevo Daniel
Published: April 2020

In almost all clinical settings, patients are at risk for multiple potential events and, in consultation with health-care providers, must weigh the potential benefits and harms across these events when making decisions. As researchers seek to build an evidence base to inform these decisions, they must contend with a choice as to how they will handle the different events. One approach, arguably the standard approach in the literature, is to consider the events individually by conducting analyses and publishing results for each one at a time. Doing so, however, fails to acknowledge or exploit the inherent multivariate nature of the data, represents a lost opportunity, and results in an evidence base that is not aligned with how clinical decision-making is actually performed. The article by Prentice et al. (Am J Epidemiol. 2020;189(9):972–981) in this issue of the Journal moves beyond this standard by illustrating recently developed methods that directly take advantage of information on the co-occurrence of multiple events. Moreover, their article highlights the role of modern methods in deriving additional information and insight from studies of multiple clinical outcomes by making full use of multivariate data, with the goal being to complement, not replace, existing methods.
Standardizing Discrete-Time Hazard Ratios With a Disease Risk Score
Authors: Richardson David B , Keil Alexander P , Edwards Jessie K , Kinlaw Alan C , Cole Stephen R
Published: April 2020

The disease risk score (DRS) is a summary score that is a function of a potentially large set of covariates. The DRS can be used to control for confounding by the covariates that went into estimation of the DRS and obtain a standardized estimate of an exposure’s effect on disease. However, to date, literature on the DRS has not addressed analyses that focus on estimation of survival or hazard functions, which are common in epidemiologic analyses of cohort data. Here, we propose a method for standardization of hazard ratios using the DRS in longitudinal analyses of the association between a binary exposure and an outcome. This approach to handling a potentially large set of covariates through a model-based approach to standardization may provide a useful tool for cohort analyses of hazard ratios and may be particularly well-suited to settings where an exposure propensity score is difficult to model. Simulations are used in this paper to illustrate the approach, and an empirical example is provided.
Icotinib Attenuates Monocrotaline-Induced Pulmonary Hypertension by Preventing Pulmonary Arterial Smooth Muscle Cell Dysfunction
Authors: Peng Li-Yao , Yu Min , Yang Ming-Xia , Liu Ping , Zhou Hong , Huang Wen , Kong Hui , Xie Wei-Ping
Published: April 2020

Background

Aberrant activation of epidermal growth factor receptor (EGFR) signaling pathway is associated with the pathogenesis of pulmonary hypertension (PH). However, the effect of icotinib, a first generation of EGFR tyrosine kinase inhibitor (EGFR-TKI), on PH remains to be elucidated.

Methods

PH rat model was established by a single intraperitoneal injection of monocrotaline (MCT, 60 mg/kg). Icotinib (15, 30, and 60 mg/kg/day) was administered by oral gavage from the day of MCT injection. After 4 weeks, hemodynamic parameters and histological changes of the pulmonary arterial vessels were assessed, and the phenotypic switching of pulmonary arterial smooth muscle cells (PASMCs) was determined in vivo. Moreover, the effects of icotinib (10 µM) on epidermal growth factor (EGF, 50 ng/ml)-stimulated proliferation, migration, and phenotypic switching of human PASMCs were explored in vitro.

Results

Icotinib significantly reduced the right ventricular systolic pressure and right ventricle hypertrophy index in rats with MCT-induced PH. Moreover, icotinib improved MCT-induced pulmonary vascular remodeling. The expression of contractile marker (smooth muscle 22 alpha (SM22α)) and synthetic markers (osteopontin (OPN) and vimentin) in pulmonary artery was restored by icotinib treatment. In vitro, icotinib suppressed EGF-induced PASMCs proliferation and migration. Meanwhile, icotinib inhibited EGF-induced downregulation of α-smooth muscle actin and SM22α and upregulation of OPN and Collagen I in PASMCs, suggesting that icotinib could inhibit EGF-induced phenotypic switching of PASMCs. Mechanistically, these effects of icotinib were associated with the inhibition of EGFR-Akt/ERK signaling pathway.

Conclusions

Icotinib can attenuate MCT-induced pulmonary vascular remodeling and improve PH. This effect of icotinib might be attributed to preventing PASMC dysfunction by inhibiting EGFR-Akt/ERK signaling pathway.
Hyperalgesia after a Drinking Episode in Young Adult Binge Drinkers: A Cross-Sectional Study
Authors: You Dokyoung S , Hahn Hunter A , Welsh Thomas H , Meagher Mary W
Published: April 2020

Aims

Rodent studies propose potential mechanisms linking excessive drinking and pain hypersensitivity (hyperalgesia), such that stress hormones (i.e. epinephrine and cortisol) mediate induction and maintenance of alcohol withdrawal-induced hyperalgesia. The first aim of this study was to examine whether hyperalgesia would occur within 48 h after a drinking episode in healthy young adult binge drinkers. The second was to examine whether stress hormones and negative effect would be associated with binge drinking or alcohol withdrawal-associated hyperalgesia.

Methods

A cross-sectional experiment was conducted in five groups with naturally occurring drinking (mean age = 19.6, range 18–29 years): abstainers (n = 43, 54% female), moderate drinkers with (n = 50, 50% female) or without recent drinking (i.e. within 48 h, n = 23, 26% female) and binge drinkers with (n = 36, 58% female) or without recent drinking (n = 25, 44% female). All types of drinkers endorsed drinking about 2–3 times a month and 2–3 years of drinking history.

Results

Muscle pressure pain thresholds were significantly lower in the binge group with recent drinking compared to other groups, but cutaneous mechanical and heat pain thresholds were not significantly different across the five groups. Basal epinephrine levels were significantly higher in binge groups regardless of recent drinking, but cortisol and negative effect were not significantly different across the five groups.

Conclusions

This is the first study to show that alcohol withdrawal-associated muscle hyperalgesia may occur in healthy episodic binge drinkers with only 2–3 years of drinking history, and epinephrine may play a role in binge drinking-associated hyperalgesia.
Complications of Cosmetic Surgery Tourism: Case Series and Cost Analysis
Authors: Venditto Chelsea , Gallagher Margaret , Hettinger Patrick , Havlik Robert , Zarb Rakel , Argenta Anne , Doren Erin , Sanger James , Klement Kristen , Dzwierzynski William , LoGiudice John , Jensen John
Published: April 2020

Background

Cosmetic surgery tourism is increasing exponentially. Patients seek cosmetic procedures within the United States and abroad, lured by lower cost procedures, shorter waiting lists, and affordable airfare and hotel accommodations. Unfortunately, operations are often performed by non–board-certified plastic surgeons, sometimes not even by plastic surgeons. Preoperative counseling, frequently limited to a video-chat with an office secretary, provides inadequate discussion regarding potential complications. Postoperative care is careless and rarely involves the operating surgeon. Complications are frequent, with management falling into the hands of plastic surgeons unfamiliar with the patient’s care. Furthermore, the physician, rather than the patient or hospital, faces the largest cost burden.

Objectives

The authors sought to explore their institution’s experience treating complications of cosmetic tourism and investigate associated costs.

Methods

The retrospective review of 16 patients treated for complications related to cosmetic surgery tourism plus cost analysis revealed a substantial discrepancy between money saved by undergoing surgery abroad and massive costs accrued to treat surgical complications.

Results

The most common complication was infection, often requiring surgery or IV antibiotics on discharge. Mean cost per patient was $26,657.19, ranging from $392 (single outpatient visit) to $154,700.79 (prolonged admission and surgery). Overall, the hospital retained 63% of billed charges, while physicians retained only 9%. The greatest amount paid by any single patient was $2635.00 by a patient with private insurance.

Conclusions

Cosmetic tourism has severe medical repercussions for patients and complications that burden hospitals, physicians, and the US medical system. Physicians treating the complications suffer the greatest financial loss.

Level of Evidence: 4
Sequoya: multiobjective multiple sequence alignment in Python
Authors: Benítez-Hidalgo Antonio , Nebro Antonio J , Aldana-Montes José F
Published: April 2020

Motivation

Multiple sequence alignment (MSA) consists of finding the optimal alignment of three or more biological sequences to identify highly conserved regions that may be the result of similarities and relationships between the sequences. MSA is an optimization problem with NP-hard complexity (non-deterministic polynomial-time hardness), because the time needed to find optimal alignments raises exponentially along with the number of sequences and their length. Furthermore, the problem becomes multiobjective when more than one score is considered to assess the quality of an alignment, such as maximizing the percentage of totally conserved columns and minimizing the number of gaps. Our motivation is to provide a Python tool for solving MSA problems using evolutionary algorithms, a nonexact stochastic optimization approach that has proven to be effective to solve multiobjective problems.

Results

The software tool we have developed, called Sequoya, is written in the Python programming language, which offers a broad set of libraries for data analysis, visualization and parallelism. Thus, Sequoya offers a graphical tool to visualize the progress of the optimization in real time, the ability to guide the search toward a preferred region in run-time, parallel support to distribute the computation among nodes in a distributed computing system, and a graphical component to assist in the analysis of the solutions found at the end of the optimization.

Availability and implementation

Sequoya can be freely obtained from the Python Package Index (pip) or, alternatively, it can be downloaded from Github at https://github.com/benhid/Sequoya.

Supplementary information

Supplementary data are available at Bioinformatics online.
LeafCutterMD: an algorithm for outlier splicing detection in rare diseases
Authors: Jenkinson Garrett , Li Yang I , Basu Shubham , Cousin Margot A , Oliver Gavin R , Klee Eric W
Published: April 2020

Motivation

Next-generation sequencing is rapidly improving diagnostic rates in rare Mendelian diseases, but even with whole genome or whole exome sequencing, the majority of cases remain unsolved. Increasingly, RNA sequencing is being used to solve many cases that evade diagnosis through sequencing alone. Specifically, the detection of aberrant splicing in many rare disease patients suggests that identifying RNA splicing outliers is particularly useful for determining causal Mendelian disease genes. However, there is as yet a paucity of statistical methodologies to detect splicing outliers.

Results

We developed LeafCutterMD, a new statistical framework that significantly improves the previously published LeafCutter in the context of detecting outlier splicing events. Through simulations and analysis of real patient data, we demonstrate that LeafCutterMD has better power than the state-of-the-art methodology while controlling false-positive rates. When applied to a cohort of disease-affected probands from the Mayo Clinic Center for Individualized Medicine, LeafCutterMD recovered all aberrantly spliced genes that had previously been identified by manual curation efforts.

Availability and implementation

The source code for this method is available under the opensource Apache 2.0 license in the latest release of the LeafCutter software package available online at http://davidaknowles.github.io/leafcutter.

Supplementary information

Supplementary data are available at Bioinformatics online.
Testing hypotheses about the microbiome using the linear decomposition model (LDM)
Authors: Hu Yi-Juan , Satten Glen A
Published: April 2020

Motivation

Methods for analyzing microbiome data generally fall into one of two groups: tests of the global hypothesis of any microbiome effect, which do not provide any information on the contribution of individual operational taxonomic units (OTUs); and tests for individual OTUs, which do not typically provide a global test of microbiome effect. Without a unified approach, the findings of a global test may be hard to resolve with the findings at the individual OTU level. Further, many tests of individual OTU effects do not preserve the false discovery rate (FDR).

Results

We introduce the linear decomposition model (LDM), that provides a single analysis path that includes global tests of any effect of the microbiome, tests of the effects of individual OTUs while accounting for multiple testing by controlling the FDR, and a connection to distance-based ordination. The LDM accommodates both continuous and discrete variables (e.g. clinical outcomes, environmental factors) as well as interaction terms to be tested either singly or in combination, allows for adjustment of confounding covariates, and uses permutation-based P-values that can control for sample correlation. The LDM can also be applied to transformed data, and an ‘omnibus’ test can easily combine results from analyses conducted on different transformation scales. We also provide a new implementation of PERMANOVA based on our approach. For global testing, our simulations indicate the LDM provided correct type I error and can have comparable power to existing distance-based methods. For testing individual OTUs, our simulations indicate the LDM controlled the FDR well. In contrast, DESeq2 often had inflated FDR; MetagenomeSeq generally had the lowest sensitivity. The flexibility of the LDM for a variety of microbiome studies is illustrated by the analysis of data from two microbiome studies. We also show that our implementation of PERMANOVA can outperform existing implementations.

Availability and implementation

The R package LDM is available on GitHub at https://github.com/yijuanhu/LDM in formats appropriate for Macintosh or Windows.

Contact

yijuan.hu@emory.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Learning context-aware structural representations to predict antigen and antibody binding interfaces
Authors: Pittala Srivamshi , Bailey-Kellogg Chris
Published: April 2020

Motivation

Understanding how antibodies specifically interact with their antigens can enable better drug and vaccine design, as well as provide insights into natural immunity. Experimental structural characterization can detail the ‘ground truth’ of antibody–antigen interactions, but computational methods are required to efficiently scale to large-scale studies. To increase prediction accuracy as well as to provide a means to gain new biological insights into these interactions, we have developed a unified deep learning-based framework to predict binding interfaces on both antibodies and antigens.

Results

Our framework leverages three key aspects of antibody–antigen interactions to learn predictive structural representations: (i) since interfaces are formed from multiple residues in spatial proximity, we employ graph convolutions to aggregate properties across local regions in a protein; (ii) since interactions are specific between antibody–antigen pairs, we employ an attention layer to explicitly encode the context of the partner; (iii) since more data are available for general protein–protein interactions, we employ transfer learning to leverage this data as a prior for the specific case of antibody–antigen interactions. We show that this single framework achieves state-of-the-art performance at predicting binding interfaces on both antibodies and antigens, and that each of its three aspects drives additional improvement in the performance. We further show that the attention layer not only improves performance, but also provides a biologically interpretable perspective into the mode of interaction.

Availability and implementation

The source code is freely available on github at https://github.com/vamships/PECAN.git.
Incidence of Pelvic Inflammatory Disease Associated With Mycoplasma genitalium Infection: Evidence Synthesis of Cohort Study Data
Authors: Lewis Joanna , Horner Paddy J , White Peter J
Published: April 2020

We synthesized evidence from the POPI sexual-health cohort study and estimated that 4.9% (95% credible interval, .4–14.1%) of Mycoplasma genitalium infections in women progress to pelvic inflammatory disease versus 14.4% (5.9–24.6%) of chlamydial infections. For validation, we predicted PID rates in 4 age groups that agree well with surveillance data.
English medium instruction: teachers’ challenges and coping strategies
Authors: Pun Jack K H , Thomas Nathan
Published: April 2020

English medium instruction (EMI) is a growing phenomenon in many countries. Some researchers have investigated the difficulties and strategies students use to cope with EMI. However, the pedagogical challenges faced and strategies used by other key participants, teachers, have been surprisingly under-researched. This study utilizes questionnaire and interview data to identify the challenges and coping strategies used by secondary school EMI science teachers in Hong Kong. A number of challenges and strategies were reported. The authors argue that many of these challenges can be overcome with principles and strategies from ELT, as the ‘English’ in EMI is often the main issue. The most prevalent strategy reported is the use of L1. Two perspectives on L1 usage in EMI contexts are discussed. Two emergent realities are presented as possible solutions: the idealized reality and the immediate reality. Implications for teachers and suggestions for future research are provided.
Priorities for improving chemicals management in the WHO European Region—stakeholders’ views
Authors: Vincenten Joanne A , Zastenskaya Irina , Schröder-Bäck Peter , Jarosinska Dorota Iwona
Published: April 2020

Background

Prevention of the impact of chemicals on human health and the environment is an increasing focus of public health polices and policy makers. The World Health Organization European Centre for Environment and Health wanted to know what were stakeholders’ priorities for improving chemicals management and prevention.

Methods

Semi-structured interviews were undertaken with 18 diverse stakeholders to answer this question. The interview questionnaire was developed using current WHO chemical meeting reports, the Evidence Implementation Model for Public Health Systems and categories of the theory of diffusion. Stakeholder views were attained on three main questions within the questionnaire. (i) What priority actions should be undertaken to minimize the negative impact of chemicals? (ii) Who needs to be more involved and what roles should they have? (iii) How can science and knowledge on chemicals and health be translated into policies more effectively and what are the greatest barriers to overcome?

Results

Cross cutting issues, such as legislation strengthening and enforcement, further collection of information, capacity building, education and awareness raising were considered priorities. The responders had the same vision on roles and responsibilities of different stakeholders. The greatest barrier to adoption, implementation and enforcement of evidence-based policies reported was leadership and political commitment to chemical safety.

Conclusions

Priorities raised differed depending on knowledge, professional background and type of stakeholder. Factors influencing priority identification at the national level include international and global context, availability of information, knowledge of the current situation and evidence-based good practice, and risks and priorities identified through national assessments.
Isolation and characterization of the novel oil-degrading strain Kosakonia cowanii IUMR B67 and expression of the degradation enzyme
Authors: Ren Jianjun , Wang Zhenzhu , Niu Dongze , Huhetaoli  , Huang Xu , Fan Bo , Li Chunyu
Published: April 2020

Oils in food waste can pollute the environment and negatively affect human health. Biodegradation is a promising method for disposing of waste edible oils. In this study, an oil-degrading bacterium was isolated from kitchen waste for efficient degradation of edible oils. Its growth and oil degradation characteristics were investigated in basic salt medium with edible oils as the sole carbon and energy source; the triacylglycerol lipase gene (EC 3.1.1.3) was cloned and expressed in Escherichia coli. A novel oil-degrading bacterium assigned as IUMR B67 was successfully isolated. Morphological and molecular analyses revealed that strain IUMR B67 belongs to Kosakonia cowanii. After 144 h of incubation, the oil degradation rate at 37°C was 95.80%. Optimal conditions for IUMR B67 were recorded at 37°C and 0.1% NaCl with 0.1% ammonium sulfate supplementation. The lipase gene of strain IUMR B67 was determined to be 912 base pairs, and the lipase activity of the expressed protein was 3.02 U/mL, which was significantly higher than the control (P < 0.05). Overall, Kosakonia cowanii IUMR B67 is a novel edible oil-degrading strain that can hydrolyze oil via its lipase activity, which may be useful in the disposal of oils and oily food waste.
The Epithelial adhesin 1 tandem repeat region mediates protein display through multiple mechanisms
Authors: Raposo Colin J , McElroy Kyle A , Fuchs Stephen M
Published: April 2020

The pathogenic yeast Candida glabrata is reliant on a suite of cell surface adhesins that play a variety of roles necessary for transmission, establishment and proliferation during infection. One particular adhesin, Epithelial Adhesin 1 [Epa1p], is responsible for binding to host tissue, a process which is essential for fungal propagation. Epa1p structure consists of three domains: an N-terminal intercellular binding domain responsible for epithelial cell binding, a C-terminal GPI anchor for cell wall linkage and a serine/threonine-rich linker domain connecting these terminal domains. The linker domain contains a 40-amino acid tandem repeat region, which we have found to be variable in repeat copy number between isolates from clinical sources. We hypothesized that natural variation in Epa1p repeat copy may modulate protein function. To test this, we recombinantly expressed Epa1p with various repeat copy numbers in S. cerevisiae to determine how differences in repeat copy number affect Epa1p expression, surface display and binding to human epithelial cells. Our data suggest that repeat copy number variation has pleiotropic effects, influencing gene expression, protein surface display and shedding from the cell surface of the Epa1p adhesin. This study serves to demonstrate repeat copy number variation can modulate protein function through a number of mechanisms in order to contribute to pathogenicity of C. glabrata.
ALS-associated genes in SCA2 mouse spinal cord transcriptomes
Authors: Scoles Daniel R , Dansithong Warunee , Pflieger Lance T , Paul Sharan , Gandelman Mandi , Figueroa Karla P , Rigo Frank , Bennett C Frank , Pulst Stefan M
Published: April 2020

The spinocerebellar ataxia type 2 (SCA2) gene ATXN2 has a prominent role in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS). In addition to cerebellar ataxia, motor neuron disease is often seen in SCA2, and ATXN2 CAG repeat expansions in the long normal range increase ALS risk. Also, lowering ATXN2 expression in TDP-43 ALS mice prolongs their survival. Here we investigated the ATXN2 relationship with motor neuron dysfunction in vivo by comparing spinal cord (SC) transcriptomes reported from TDP-43 and SOD1 ALS mice and ALS patients with those from SCA2 mice. SC transcriptomes were determined using an SCA2 bacterial artificial chromosome mouse model expressing polyglutamine expanded ATXN2. SCA2 cerebellar transcriptomes were also determined, and we also investigated the modification of gene expression following treatment of SCA2 mice with an antisense oligonucleotide (ASO) lowering ATXN2 expression. Differentially expressed genes (DEGs) defined three interconnected pathways (innate immunity, fatty acid biosynthesis and cholesterol biosynthesis) in separate modules identified by weighted gene co-expression network analysis. Other key pathways included the complement system and lysosome/phagosome pathways. Of all DEGs in SC, 12.6% were also dysregulated in the cerebellum. Treatment of mice with an ATXN2 ASO also modified innate immunity, the complement system and lysosome/phagosome pathways. This study provides new insights into the underlying molecular basis of SCA2 SC phenotypes and demonstrates annotated pathways shared with TDP-43 and SOD1 ALS mice and ALS patients. It also emphasizes the importance of ATXN2 in motor neuron degeneration and confirms ATXN2 as a therapeutic target.
Loss of function mutations in CCDC32 cause a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies
Authors: Harel Tamar , Griffin John N , Arbogast Thomas , Monroe Tanner O , Palombo Flavia , Martinelli Marcella , Seri Marco , Pippucci Tommaso , Elpeleg Orly , Katsanis Nicholas
Published: April 2020

Despite the wide use of genomics to investigate the molecular basis of rare congenital malformations, a significant fraction of patients remains bereft of diagnosis. As part of our continuous effort to recruit and perform genomic and functional studies on such cohorts, we investigated the genetic and mechanistic cause of disease in two independent consanguineous families affected by overlapping craniofacial, cardiac, laterality and neurodevelopmental anomalies. Using whole exome sequencing, we identified homozygous frameshift CCDC32 variants in three affected individuals. Functional analysis in a zebrafish model revealed that ccdc32 depletion recapitulates the human phenotypes. Because some of the patient phenotypes overlap defects common to ciliopathies, we asked if loss of CCDC32 might contribute to the dysfunction of this organelle. Consistent with this hypothesis, we show that ccdc32 is required for normal cilia formation in zebrafish embryos and mammalian cell culture, arguing that ciliary defects are at least partially involved in the pathomechanism of this disorder.
Surgical repair of a giant pulmonary artery aneurysm that caused severe left bronchial obstruction
Authors: Nagato Hisao , Nishiwaki Noboru , Kaneda Kozo , Tamura Nobushige
Published: April 2020

A 63-year-old woman on oral steroids for systemic lupus erythematosus presented with a giant pulmonary artery aneurysm severely compressing the left main bronchus and lung. Her presenting symptom was severe respiratory distress. Surgical graft replacement of the main and branch pulmonary arteries was performed, and her respiratory function improved dramatically. Bronchial obstruction was resolved immediately after the procedure.
How hospitals in mainland China responded to the outbreak of COVID-19 using information technology–enabled services: An analysis of hospital news webpages
Authors: Yan Aihua , Zou Yi , Mirchandani Dinesh A
Published: April 2020

Objective

Many countries have implemented quarantine rules during the global outbreak of coronavirus disease 2019 (COVID-19). Understanding how hospitals can continue providing services in an effective manner under these circumstances is thus important. In this study, we investigate how information technology (IT) helped hospitals in mainland China better respond to the outbreak of the pandemic.

Materials and Methods

We conducted a content analysis of pages published on the websites of the top 50 hospitals in mainland China between January 22 and February 21, 2020. In total, we analyzed 368 pages that the hospitals published during the initial days of the COVID-19 pandemic. The purpose was to identify common themes related to the utilization of IT by these hospitals in response to the pandemic’s outbreak.

Results

We identified 5 focal themes across the webpages published by the hospitals during our study period, including (1) popular medical science education, (2) digitalized hospital processes, (3) knowledge management for medical professionals, (4) telemedicine, and (5) new IT initiatives for healthcare services. Our analysis revealed that Chinese hospitals spent greater effort in promoting popular medical science education in the initial stages of our study period and more on telemedicine in the latter stages.

Discussion

We propose a configurational approach for hospitals to design response strategies to pandemic outbreaks based on their available resources.

Conclusions

Our study provides rich insights for hospitals to better utilize their IT resources and some recommendations for policymaker to better support hospitals in the future.
Biology, Ecology, and Management of Eastern Grape Leafhopper (Hemiptera: Cicadellidae), a Key Pest of Vineyards in North America
Authors: Jarrell Kevin R , Rebek Eric J , Wayadande Astri C , Giles Kristopher L
Published: April 2020

Eastern grape leafhopper, Erythroneura comes (Say), is a key pest of grapes (Vitales: Vitaceae) in the central and northeastern United States and eastern Canada. This native insect uses its piercing-sucking mouthparts to puncture the mesophyll cells of leaves and suck out the contents, thereby reducing the quality and quantity of fruit. Eastern grape leafhopper has been reported as a vineyard pest for nearly 200 yr and is one of several Erythroneura spp. that feed on grapes in North America. Overwintered adults become active in early spring and may feed on grasses, weeds, and other plants before feeding on grapevines. Although eastern grape leafhopper has an extensive host range, it is only known to oviposit on wild and cultivated grapes. This multivoltine species can outbreak periodically, which has generated much research into improved monitoring and integrated pest management strategies employed throughout its native range. In this review, we describe the biology, life history, population dynamics, and phenology of eastern grape leafhopper and provide a historical account of monitoring and management strategies for this important vineyard pest.
Mon-735: a new low-mass pre-main-sequence eclipsing binary in NGC 2264
Authors: Gillen Edward , Hillenbrand Lynne A , Stauffer John , Aigrain Suzanne , Rebull Luisa , Cody Ann Marie
Published: April 2020

We present Mon-735, a detached double-lined eclipsing binary (EB) member of the ∼3 Myr old NGC 2264 star-forming region, detected by Spitzer. We simultaneously model the Spitzer light curves, follow-up Keck/HIRES radial velocities, and the system’s spectral energy distribution to determine self-consistent masses, radii, and effective temperatures for both stars. We find that Mon-735 comprises two pre-main-sequence M dwarfs with component masses of M = 0.2918 ± 0.0099 and 0.2661 ± 0.0095 M⊙, radii of R = 0.762 ± 0.022 and 0.748 ± 0.023 R⊙, and effective temperatures of Teff = 3260 ± 73 and 3213 ± 73 K. The two stars travel on circular orbits around their common centre of mass in P = 1.9751388 ± 0.0000050 d. We compare our results for Mon-735, along with another EB in NGC 2264 (CoRoT 223992193), to the predictions of five stellar evolution models. These suggest that the lower mass EB system Mon-735 is older than CoRoT 223992193 in the mass–radius diagram (MRD) and, to a lesser extent, in the Hertzsprung–Russell diagram (HRD). The MRD ages of Mon-735 and CoRoT 223992193 are ∼7–9 and 4–6 Myr, respectively, with the two components in each EB system possessing consistent ages.
Stellar coronal mass ejections – II. Constraints from spectroscopic observations
Authors: Odert P , Leitzinger M , Guenther E W , Heinzel P
Published: April 2020

Detections of stellar coronal mass ejections (CMEs) are still rare. Observations of strong Balmer line asymmetries during flare events have been interpreted as being caused by CMEs. Here, we aim to estimate the maximum possible Balmer line fluxes expected from CMEs to infer their detectability in spectroscopic observations. Moreover, we use these results together with a model of intrinsic CME rates to infer the potentially observable CME rates for stars of different spectral types under various observing conditions, as well as the minimum required observing time to detect stellar CMEs in Balmer lines. We find that generally CME detection is favoured for mid- to late-type M dwarfs, as they require the lowest signal-to-noise ratio for CME detection, and the fraction of observable-to-intrinsic CMEs is largest. They may require, however, longer observing times than stars of earlier spectral types at the same activity level, as their predicted intrinsic CME rates are lower. CME detections are generally favoured for stars close to the saturation regime, because they are expected to have the highest intrinsic rates; the predicted minimum observing time to detect CMEs on just moderately active stars is already >100 h. By comparison with spectroscopic data sets including detections as well as non-detections of CMEs, we find that our modelled maximum observable CME rates are generally consistent with these observations on adopting parameters within the ranges determined by observations of solar and stellar prominences.
Chandra observations of the planetary nebula IC 4593
Authors: Toalá J A , Guerrero M A , Bianchi L , Chu Y-H , De Marco O
Published: April 2020

The Advanced CCD Imaging Spectrometer (ACIS-S) camera on board the Chandra X-ray Observatory has been used to discover a hot bubble in the planetary nebula (PN) IC 4593, the most distant PN detected by Chandra so far. The data are used to study the distribution of the X-ray-emitting gas in IC 4593 and to estimate its physical properties. The hot bubble has a radius of ∼2 arcsec and is found to be confined inside the optically bright innermost cavity of IC 4593. The X-ray emission is mostly consistent with that of an optically thin plasma with temperature kT ≈ 0.15 keV (or TX ≈ 1.7 × 106 K), electron density ne ≈ 15 cm−3, and intrinsic X-ray luminosity in the 0.3–1.5 keV energy range LX = 3.4 × 1030 erg s−1. A careful analysis of the distribution of hard (E >0.8 keV) photons in IC 4593 suggests the presence of X-ray emission from a point source likely associated with its central star (CSPN). If this was the case, its estimated X-ray luminosity would be LX, CSPN = 7 × 1029 erg s−1, fulfilling the log(LX, CSPN/Lbol) ≈ −7 relation for self-shocking winds in hot stars. The X-ray detection of the CSPN helps explain the presence of high-ionization species detected in the ultraviolet spectra as predicted by stellar atmosphere models.
The 2019 super-Eddington outburst of RX J0209.6−7427: detection of pulsations and constraints on the magnetic field strength
Authors: Vasilopoulos G , Ray P S , Gendreau K C , Jenke P A , Jaisawal G K , Wilson-Hodge C A , Strohmayer T E , Altamirano D , Iwakiri W B , Wolff M T , Guillot S , Malacaria C , Stevens A L
Published: April 2020

In 2019 November, MAXI detected an X-ray outburst from the known Be X-ray binary system RX J0209.6−7427 located in the outer wing of the Small Magellanic Cloud. We followed the outburst of the system with NICER, which led to the discovery of X-ray pulsations with a period of 9.3 s. We analysed simultaneous X-ray data obtained with NuSTAR and NICER, allowing us to characterize the spectrum and provide an accurate estimate of its bolometric luminosity. During the outburst, the maximum broad-band X-ray luminosity of the system reached (1–2) × 1039 erg s−1, thus exceeding by about one order of magnitude the Eddington limit for a typical 1.4 M⊙ mass neutron star (NS). Monitoring observations with Fermi/GBM and NICER allowed us to study the spin evolution of the NS and compare it with standard accretion torque models. We found that the NS magnetic field should be of the order of 3 × 1012 G. We conclude that RX J0209.6−7427 exhibited one of the brightest outbursts observed from a Be X-ray binary pulsar in the Magellanic Clouds, reaching similar luminosity level to the 2016 outburst of SMC X-3. Despite the super-Eddington luminosity of RX J0209.6−7427, the NS appears to have only a moderate magnetic field strength.
Intra-abdominal hypertension in early post-kidney transplantation period is associated with impaired graft function
Authors: Dupont Vincent , Debrumetz Alexandre , Leguillou Adrien , Morland David , Wynckel Alain , Colosio Charlotte , Mokri Laetitia , Schvartz Betoul , Vuiblet Vincent , Larre Stephane , Barbe Coralie , Rieu Philippe
Published: April 2020

Background

Moderate hyperhydration is often achieved in the early post-kidney transplantation period. Whether this strategy could lead to the development of intra-abdominal hypertension (IAH) has never been assessed so far. We aimed to study the incidence of IAH after kidney transplantation and its association with graft function recovery.

Methods

We conducted a prospective monocentric study among patients undergoing kidney transplantation at the University Hospital of Reims between May 2017 and April 2019. Intravesical pressure (IVP) was monitored every 8 h from Day 0 to 3.

Results

A total of 107 patients were enrolled. Among 55 patients included in the analysis, 74.5% developed IAH. Body mass index >25 kg/m2 was associated with IAH development {odds ratio [OR] 10.4 [95% confidence interval (CI) 2.0–52.9]; P = 0.005}. A previous history of peritoneal dialysis was protective [OR 0.06 (95% CI 0.01–0.3); P = 0.001]. IAH Grades III and IV occurred in 30.9% of patients and correlated with higher Day 3 creatininaemia (419.6 ± 258.5 versus 232.5 ± 189.4 μmol/L; P = 0.02), higher delayed graft function incidence (41.2 versus 7.9%; P = 0.04), lower Kirchner index measured using scintigraphy (0.47 ± 0.09 versus 0.64 ± 0.09; P = 0.0005) and decreased Day 30 estimated glomerular filtration rate (35.8 ± 18.8 versus 52.5 ± 21.3, P = 0.05). IAH patients had higher fluid balance (P = 0.02). Evolution of IVP correlated with weight gain (P < 0.01) and central venous pressure (P < 0.001).

Conclusions

IAH is frequent after kidney transplantation and IAH Grades III and IV are independently associated with impaired graft function. These results question current haemodynamic objectives and raise for the first time interest in intra-abdominal pressure monitoring in these patients.

Clinical Trial Notation

ClinicalTrials.gov identifier: NCT03478176
Value of [18F]-FDG positron emission tomography in patients with recurrent glioblastoma receiving bevacizumab
Authors: Graham Maya S , Krebs Simone , Bale Tejus , Domfe Kwaku , Lobaugh Stephanie M , Zhang Zhigang , Dunphy Mark P , Kaley Thomas , Young Robert J
Published: April 2020

Background

Treatment of recurrent glioblastoma (GBM) with bevacizumab can induce MRI changes that confound the determination of progression. We sought to determine the value of [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in GBM patients receiving bevacizumab at the time of suspected progression and, thereby, its utility as a potential prognostic adjunct in progressive disease.

Methods

This retrospective study included patients who underwent brain FDG PET within 4 weeks of receiving bevacizumab for recurrent GBM with suspected progression. Volumes-of-interest were placed over the reference lesion with measurement of maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), metabolic tumor volume, total lesion glycolysis (TLG), and tumor-to-normal contralateral white matter ratios (TNR-WM). Tumors were additionally categorized as non-avid or avid based on qualitative FDG uptake. Associations between baseline variables and overall survival (OS) were examined using univariable and multivariable Cox proportional hazards regression, with P < .05 considered significant.

Results

Thirty-one patients were analyzed. Qualitative FDG uptake was significantly associated with OS (P = .03), with a median OS of 9.0 months in non-avid patients versus 4.5 months in avid patients. SUVmax, SUVpeak, TNR-WM, and TLG were significantly associated with OS (P < .001, TLG: P = .009). FDG avidity and SUVmax remained significantly associated with OS (P = .046 and .048, respectively) in the multivariable analysis including age, KPS, and MGMT status. Dichotomizing patients using an SUVmax cutoff of 15.3 was associated with OS (adjusted P = .048).

Conclusion

FDG PET is a promising imaging tool to further stratify prognosis in recurrent GBM patients on antiangiogenic therapy.
Pregnant Smokers Receiving Opioid Agonist Therapy Have an Elevated Nicotine Metabolite Ratio: A Replication Study
Authors: Kranzler Henry R , Washio Yukiko , Zindel Leah R , Lynch Kevin G , Hand Dennis , Tyndale Rachel F , Oncken Cheryl , Schnoll Robert
Published: April 2020

Introduction

Pregnant women exposed chronically to opioids smoked more cigarettes per day (CPD) and had a higher nicotine metabolite ratio (NMR), 3-hydroxycotinine/cotinine, a biomarker of nicotine metabolism and clearance, than those not receiving opioids. We examined CPD and NMR in a group of pregnant smokers, a quarter of whom were receiving opioid agonist therapy (OAT).

Aims and Methods

Pregnant smokers recruited to participate in a placebo-controlled trial of bupropion for smoking cessation provided a blood sample for measurement of NMR.

Results

Half (52.4%) of the 124 women with NMR data were African American. OAT-treated women (n = 34, 27.4%; 27 receiving methadone and 7 buprenorphine) were more likely to be white (79% vs. 30%, p < .001) and to have a lower mean PHQ-9 total score (2.91 [SD = 2.83] vs. 4.83 [SD = 3.82], p = .007). OAT-treated women reported smoking more CPD (9.50 [SD = 5.26] vs. 7.20 [SD = 3.65], p = .005) and had higher NMR (0.78 [SD = 0.36] vs. 0.56 [SD = 0.25], p = .001) than the non-OAT-treated group. In a linear regression analysis adjusting for race, depression severity, and CPD, NMR was greater in the OAT group (p = .025), among whom the daily methadone-equivalent dosage correlated with NMR (Spearman’s ρ = 0.49, p = .003).

Conclusions

Consistent with the findings of Oncken et al. (2019), we found that OAT smokers smoked more and had higher NMR than non-OAT smokers. As higher NMR is associated with a reduced likelihood of smoking cessation, the effects on NMR of both pregnancy and OAT could contribute to a lower smoking cessation rate in pregnant smokers receiving chronic opioid therapy.

Implications

We replicated the finding that the NMR is significantly greater among pregnant smokers receiving OAT than those not receiving this treatment for opioid use disorder. Furthermore, we found that the dosage of the OAT was significantly associated with the NMR level. These findings may contribute to a poorer response to smoking cessation treatment in pregnant women treated with OAT, particularly those receiving high-dose therapy, and raise the question of whether novel approaches are needed to treat smoking in this subgroup of pregnant smokers.
The Time for Universal Masking of the Public for Coronavirus Disease 2019 Is Now
Authors: Gandhi Monica , Havlir Diane
Published: April 2020

In this perspective, we recommend universal masking of the US public during coronavirus disease 2019 due to the high contagiousness of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), viral shedding of viable SARS-CoV-2 from asymptomatic individuals, and the likely contribution of masking to core distancing public health strategies for curbing transmission.