bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhamnolipids stabilize quorum sensing mediated cooperation in Pseudomonas aeruginosa
Authors: García-Contreras Rodolfo , Loarca Daniel , Pérez-González Caleb , Jiménez-Cortés J Guillermo , Gonzalez-Valdez Abigail , Soberón-Chávez Gloria
Published: May 2020

Pseudomonas aeruginosa is one of the main models to study social behaviors in bacteria since it synthesizes several exoproducts, including exoproteases and siderophores and release them to the environment. Exoproteases and siderophores are public goods that can be utilized by the individuals that produce them but also by non-producers, that are considered social cheaters. Molecularly exoprotease cheaters are mutants in regulatory genes such as lasR, and are commonly isolated from chronic infections and selected in the laboratory upon serial cultivation in media with protein as a sole carbon source. Despite that the production of exoproteases is exploitable, cooperators have also ways to restrict the growth and selection of social cheaters, for instance by producing toxic metabolites like pyocyanin. In this work, using bacterial competitions, serial cultivation and growth assays, we demonstrated that rhamnolipids which production is regulated by quorum sensing, selectively affect the growth of lasR mutants and are able to restrict social cheating, hence contributing to the maintenance of cooperation in Pseudomonas aeruginosa populations.
A machine-learning-based surrogate model of Mars’ thermal evolution
Authors: Agarwal S , Tosi N , Breuer D , Padovan S , Kessel P , Montavon G
Published: May 2020

Constraining initial conditions and parameters of mantle convection for a planet often requires running several hundred computationally expensive simulations in order to find those matching certain ‘observables’, such as crustal thickness, duration of volcanism, or radial contraction. A lower fidelity alternative is to use 1-D evolution models based on scaling laws that parametrize convective heat transfer. However, this approach is often limited in the amount of physics that scaling laws can accurately represent (e.g. temperature and pressure-dependent rheologies or mineralogical phase transitions can only be marginally simulated). We leverage neural networks to build a surrogate model that can predict the entire evolution (0–4.5 Gyr) of the 1-D temperature profile of a Mars-like planet for a wide range of values of five different parameters: reference viscosity, activation energy and activation volume of diffusion creep, enrichment factor of heat-producing elements in the crust and initial temperature of the mantle. The neural network we evaluate and present here has been trained from a subset of ∼10 000 evolution simulations of Mars ran on a 2-D quarter-cylindrical grid, from which we extracted laterally averaged 1-D temperature profiles. The temperature profiles predicted by this trained network match those of an unseen batch of 2-D simulations with an average accuracy of $99.7\, {\rm per~cent}$.
Network meta-analyses in reproductive medicine: challenges and opportunities
Authors: Wang Rui , Seidler Anna Lene , Askie Lisa , Norman Robert J , Bhattacharya Siladitya , van Wely Madelon , Mol Ben Willem
Published: May 2020

Network meta-analysis allows researchers to synthesise both direct and indirect evidence, thus enabling simultaneous comparisons of multiple treatments. A relatively recent addition to evidence synthesis in reproductive medicine, this approach has become increasingly popular. Yet, the underlying assumptions of network meta-analyses, which drive the validity of their findings, have been frequently ignored. In this article, we discuss the strengths and limitations of network meta-analyses. In addition, we present an overview of published network meta-analyses in reproductive medicine, summarize their challenges and provide insights into future research opportunities.
Time-harmonic elastic singularities and oscillating indentation of layered solids
Authors: Yu H Y , Lee Sanboh
Published: May 2020

A new approach is proposed for obtaining the dynamic elastic response of a multilayered elastic solid caused by axisymmetric, time-harmonic elastic singularities. The method for obtaining the elastodynamic Green’s functions of the point force, double forces and center of dilatation is presented. For this purpose, the boundary conditions in an infinite solid at the plane passing through the singularity are derived first by using Helmholtz potentials. Then the Green’s function solution for layered solids is obtained by solving a set of simultaneous linear algebraic equations using the boundary conditions for both the singularities and for the layer interfaces. The application of the point force solution for the oscillating normal indentation problem is also given. The solution of the forced normal oscillation is formulated by integrating the point force Green’s function over the contact area with unknown surface traction. The dual integral equations of the unknown surface traction are established by considering the boundary conditions on the contact surface of the multilayered solid, which can be converted into a Fredholm integral equation of the second kind and solved numerically.
An Energy Bound in the Affine Group
Authors: Petridis Giorgis , Roche-Newton Oliver , Rudnev Misha , Warren Audie
Published: May 2020

We prove a nontrivial energy bound for a finite set of affine transformations over a general field and discuss a number of implications. These include new bounds on growth in the affine group, a quantitative version of a theorem by Elekes about rich lines in grids. We also give a positive answer to a question of Yufei Zhao that for a plane point set $P$ for which no line contains a positive proportion of points from $P$, there may be at most one line, meeting the set of lines defined by $P$ in at most a constant multiple of $|P|$ points.
Enhanced Human Immunodeficiency Virus-1 Replication in CD4+ T Cells Derived From Individuals With Latent Mycobacterium tuberculosis Infection
Authors: He Xianbao , Eddy Jared J , Jacobson Karen R , Henderson Andrew J , Agosto Luis M
Published: May 2020

Background

Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection.

Methods

Plasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication.

Results

We observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells.

Conclusions

Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.
Quality and safety in the time of Coronavirus: design better, learn faster
Authors: Fitzsimons John
Published: May 2020

The COVID-19 pandemic has required health systems to change much faster than normal. Many staff have experienced training in quality improvement and patient safety methods which can be used to support the design of new systems and to accelerate learning about new and adapted practices. This article sets out the principles of quality improvement and patient safety science, applying them in a selection of approaches, methods and tools, which may be useful in crisis situations such as the current pandemic. The article also makes reference to several resources which may be of use to those keen to advance their knowledge.
The Diversity of Hornets in the Genus Vespa (Hymenoptera: Vespidae; Vespinae), Their Importance and Interceptions in the United States
Authors: Smith-Pardo Allan H , Carpenter James M , Kimsey Lynn
Published: May 2020

Hornets in the genus Vespa (Vespidae, Vespinae) are social wasps. They are primarily predators of other insects, and some species are known to attack and feed on honeybees (Apis mellifera L.), which makes them a serious threat to apiculture. Hornet species identification can be sometimes difficult because of the amount of intraspecific color and size variation. This has resulted in many species-level synonyms, scattered literature, and taxonomic keys only useful for local populations. We present a key to the world species, information on each species, as well as those intercepted at United States Ports of Entry during the last decade. Images of all the species and some of the subspecies previously described are also included.
Latent bias and the implementation of artificial intelligence in medicine
Authors: DeCamp Matthew , Lindvall Charlotta
Published: May 2020

Increasing recognition of biases in artificial intelligence (AI) algorithms has motivated the quest to build fair models, free of biases. However, building fair models may be only half the challenge. A seemingly fair model could involve, directly or indirectly, what we call “latent biases.” Just as latent errors are generally described as errors “waiting to happen” in complex systems, latent biases are biases waiting to happen. Here we describe 3 major challenges related to bias in AI algorithms and propose several ways of managing them. There is an urgent need to address latent biases before the widespread implementation of AI algorithms in clinical practice.
Effects of source and concentration of neutral detergent fiber from roughage in beef cattle diets: Comparison of methods to measure the effectiveness of fiber
Authors: Goulart Rodrigo S , Vieira Ricardo A M , Daniel Joao L P , Amaral Rafael C , Santos Vanessa P , Toledo Filho Sergio G , Cabezas-Garcia Edward H , Tedeschi Luis O , Nussio Luiz Gustavo
Published: May 2020

Methods have been developed to measure the effectiveness of many roughages, but few evaluations have been conducted with tropical feeds. The objectives of this research were to determine the effectiveness of roughage sources based on bioassay and laboratory methods and identify the biological attributes of the diets that correlate with these methods. Six ruminally cannulated Nellore steers (408 ± 12 kg of BW) were randomly assigned to a 6 × 6 Latin square design within six diets: negative control diet (NC) with aNDF as 10% from corn silage (CS); positive control diet (PC) with aNDF as 20% from CS; and four diets containing 10% aNDF from CS and 10% aNDF from each of the following sources: sugarcane (SC), sugarcane bagasse (SCB), soybean hulls (SH), or low oil cottonseed hulls (LOCH). Physical effectiveness factor (pef, related to the physical characteristics of aNDF) and effectiveness factor (ef, related to the ruminal pH) were determined based on a linear model approach that uses a bioassay method in which CS aNDF was assumed to be the standard fiber source. Laboratory methods to estimate pef of roughage sources were based on the proportion of DM of roughage retained on a 1.18-mm sieve pef(>1.18 mm) or retained on the 8.0-mm Penn State Particle Separator screen pef(>8.0 mm). The pef calculated by the bioassay method (total chewing time and ruminal mat resistance) for CS, SCB, and SC were higher values (P < 0.05) compared with SH and LOCH. The pef(rumen mat) of SC and SCB were higher (P < 0.05) than that of CS, SH, and LOCH. The pef(rumen mat) of LOCH was 61% higher than SH. The ef(rumen pH) of SC and LOCH was higher (P < 0.05) than CS and SH. The pef(chewing, min/d), pef(chewing, min/kg of DM), pef(rumen mat), and ef(rumen pH) positively correlated with rumination time, total chewing time, and ruminal mat resistance (values from transit time in seconds). No correlation was observed (P > 0.05) between pef(>8.0 mm) and rumination time, chewing time, and ruminal pH. The pef calculated using the bioassay method as well as pef (>8.0 mm) were negatively correlated with rumen pH (P > 0.05). The values of the effectiveness of fiber sources obtained in this research can be used as a guideline for nutritionists aiming to replace roughage sources from tropical regions in beef cattle finishing diets. Under our conditions, the pef using the bioassay method or laboratory methods were not adequate in predicting ruminal pH.
Machine tool architecture selection at the preliminary design stage: application to hard material machining
Authors: Lajili Montassar , Chanal Hélène , Bouzgarrou Belhassen Chedli
Published: May 2020

The preliminary design stage ensures to evaluate machine tool performances according to the simulation of reduced models. Performance criteria are defined regarding the attempted machining process requirements. In our case, we study the problem of machine tool design for hard metal cutting, where a high level of stiffness is required. In this context, this paper’s aim is to introduce a new methodology of machine tool architectures modeling, optimization, and selection with regards to their stiffness and dynamic performances at the preliminary design stage. However, this type of study requires a quantitative evaluation of performance indicators. Studied machine tool structures are modelled with simplified shape parts. The dimensions of these parts are defined as design variables. Afterward, for each considered architecture, parametric design optimization is performed to minimize its mass under the constraint of a minimal attempted stiffness all over the workspace. This approach allowed restricting the total number of machine tool architectures to be detailed further and analyzed more accurately. In a first time, the paper includes an illustration of the developed methodology through an example of machine tool architecture evaluation and optimization. In a second time, the method is used to compare different kinds of machine tool architectures regarding their ability to be light for an attempted stiffness.
Effects of the publication of Clinical Guidelines for the Management of Chemotherapy-Induced Peripheral Neuropathy on the Administration Preferences of Oncology Specialists: Japanese Association of Supportive Care in Cancer
Authors: Hirayama Yasuo , Yoshida Yoichiro , Mori Masanori , Tamura Kazuo
Published: May 2020

Objective

We conducted a questionnaire survey of oncology specialists to investigate the frequency of administration of different drugs for the management of chemotherapy-induced peripheral neuropathy in Japan in 2015. Our group published Clinical Guidelines for the Management of Chemotherapy-Induced Peripheral Neuropathy in 2017 (CIPN-GL2017). In these guidelines, we recommended duloxetine only. To verify the effect of the publication of the CIPN-GL2017, we conducted a questionnaire survey in 2019.

Methods

In 2015 and again in 2019, we investigated the use of vitamin B12, antiepileptic agents, duloxetine, antidepressants other than duloxetine, non-steroidal anti-inflammatory drugs, opioids and the Kampo compound (goshajinkigan) in a questionnaire employing a three-point scale wherein A implies routine or prophylactic administration, B implies occasional administration and C implies infrequent administration.

Results

We sent the questionnaires via email to 971 diplomates of the Subspecialty Board of Japanese Society of Medical Oncology in 2015 and 1239 diplomates in 2019. The administration ratio (A + B) of duloxetine for numbness and pain was 46.8 and 31.7%, respectively, in 2015 and 68.9% (P < 0.01) and 73.1% (P < 0.01) in 2019. In response to the question regarding awareness of the CIPN-GL2017, 53.2% of respondents to the 2019 questionnaire were aware of the CIPN-GL2017. Among the respondents with an awareness of the CIPN-GL2017, the prescription rate of duloxetine (78.3%) for pain was significantly higher than that among respondents without any awareness (67.4%).

Conclusions

It is possible that the publication of CIPN-GL2017 influenced administration preferences of oncology specialists.
Periventricular White Matter Alterations From Explosive Blast in a Large Animal Model: Mild Traumatic Brain Injury or “Subconcussive” Injury?
Authors: Kim Jung H , Goodrich James A , Situ Robert , Rapuano Amedeo , Hetherington Hoby , Du Fu , Parks Steve , Taylor Wesley , Westmoreland Ted , Ling Geoffrey , Bandak Faris A , de Lanerolle Nihal C
Published: May 2020

The neuropathology of mild traumatic brain injury in humans resulting from exposure to explosive blast is poorly understood as this condition is rarely fatal. A large animal model may better reflect the injury patterns in humans. We investigated the effect of explosive blasts on the constrained head minimizing the effects of whole head motion. Anesthetized Yucatan minipigs, with body and head restrained, were placed in a 3-walled test structure and exposed to 1, 2, or 3 explosive blast shock waves of the same intensity. Axonal injury was studied 3 weeks to 8 months postblast using β-amyloid precursor protein immunohistochemistry. Injury was confined to the periventricular white matter as early as 3–5 weeks after exposure to a single blast. The pattern was also present at 8 months postblast. Animals exposed to 2 and 3 blasts had more axonal injury than those exposed to a single blast. Although such increases in axonal injury may relate to the longer postblast survival time, it may also be due to the increased number of blast exposures. It is possible that the injury observed is due to a condition akin to mild traumatic brain injury or subconcussive injury in humans, and that periventricular injury may have neuropsychiatric implications.
Activation of CaMKII and GluR1 by the PSD-95-GluN2B Coupling-Dependent Phosphorylation of GluN2B in the Spinal Cord in a Rat Model of Type-2 Diabetic Neuropathic Pain
Authors: Zhu Ya-Bing , Jia Gai-Li , Wang Jun-Wu , Ye Xiu-Ying , Lu Jia-Hui , Chen Jia-Li , Zhang Mao-Biao , Xie Ci-Shan , Shen Yu-Jing , Tao Yuan-Xiang , Li Jun , Cao Hong
Published: May 2020

The mechanisms underlying type-2 diabetic neuropathic pain (DNP) are unclear. This study investigates the coupling of postsynaptic density-95 (PSD-95) to N-methyl-D-aspartate receptor subunit 2B (GluN2B), and the subsequent phosphorylation of GluN2B (Tyr1472-GluN2B) in the spinal cord in a rat model of type-2 DNP. Expression levels of PSD-95, Tyr1472-GluN2B, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and its phosphorylated counterpart (Thr286-CaMKII), and α-amino-3-hydroxy-5-methyl-4-soxazole propionic acid receptor subtype 1 (GluR1) and its phosphorylated counterpart (Ser831-GluR1) were significantly increased versus controls in the spinal cord of type-2 DNP rats whereas the expression of total spinal GluN2B did not change. The intrathecal injection of Ro25-6981 (a specific antagonist of GluN2B) or Tat-NR2B9c (a mimetic peptide disrupting the interaction between PSD-95 and GluN2B) induced an antihyperalgesic effect and blocked the increased expression of Tyr1472-GluN2B, CaMKII, GluR1, Thr286-CaMKII, and Ser831-GluR1 in the spinal cords; the increase in spinal cord PSD-95 was not affected. These findings indicate that the PSD-95-GluN2B interaction may increase phosphorylation of GluN2B, and subsequently induce the expression of phosphorylation of CaMKII and GluR1 in the spinal cord of type-2 DNP rats. Targeting the interaction of PSD-95 with GluN2B may provide a new therapeutic strategy for type-2 DNP.
Long-term outcomes of induction chemotherapy followed by chemoradiotherapy using volumetric-modulated arc therapy as an organ preservation approach in patients with stage IVA-B oropharyngeal or hypopharyngeal cancers
Authors: Kubo Katsumaro , Murakami Yuji , Kenjo Masahiro , Imano Nobuki , Takeuchi Yuki , Nishibuchi Ikuno , Kimura Tomoki , Kawahara Daisuke , Ueda Tsutomu , Takeno Sachio , Nagata Yasushi
Published: May 2020

The present study aimed to analyze treatment outcomes after induction chemotherapy followed by chemoradiotherapy (CRT) using volumetric-modulated arc therapy (VMAT) in patients with stage IVA-B oropharyngeal cancer (OPC) or hypopharyngeal cancer (HPC), with long-term observation, including examination of larynx preservation. A total of 60 patients with stage IVA-B OPC or HPC, who underwent induction TPF chemotherapy (a combination regimen consisting of docetaxel, cisplatin, and 5-fluorouracil) followed by CRT using VMAT were analyzed. Overall survival (OS), progression-free survival (PFS), laryngoesophageal dysfunction-free survival (LEDFS), and locoregional control (LRC) were calculated and compared. Univariate and multivariate analyses were performed to determine statistical differences in OS and LEDFS. The median follow-up period at the time of evaluation was 61 months. Twenty-six (43%) patients had OPC and 34 (57%) had HPC. The 5-year OS, PFS, LEDFS, and LRC rates were 57%, 52%, 52%, and 68%, respectively. Response to TPF therapy was the only significant predictive factor of OS and LEDFS in multivariate analyses. Regarding long-term toxicities, grade ≥ 2 late toxicities accounted for 15%. No patients experienced grade ≥ 3 xerostomia, and 5% of all patients developed grade 3 dysphagia. With long-term observation, the OS, PFS, and LEDFS rates were relatively good, and the incidence of late toxicities was low. TPF followed by CRT using VMAT was feasible and more effective in those who responded to induction chemotherapy.
Perianal basal cell carcinoma: a common cancer in an uncommon location
Authors: Hagen Edward R , Hite Nathan , Griffin John , Kratz Rodney
Published: May 2020

This is a case of a perianal basal cell carcinoma, a common skin cancer in an unusual location. Our patient is a 67-year-old male with a perianal lesion. He first noticed this painless lesion 5 years prior to presentation and was having fecal incontinence and weight loss. He had a fully encompassing ulcerated lesion involving the entirety of the anal margin. We performed a biopsy that returned on pathology as a basal cell carcinoma. Due to the size of the lesion and his current nutritional status, it was determined to be unresectable. We were able to provide him with a diverting colostomy to address his incontinence and this allowed the patient to recover enough to undergo treatment with radiation (total of 5400 cGy). To our knowledge, this is the largest perianal basal cell carcinoma reported in the literature and an example of combining palliative surgery and radiation as a treatment option.
Small bowel obstruction caused by 18FDG-negative ileocecal metastasis of lobular breast carcinoma
Authors: Meekel Jorn P , Coblijn Usha K , Flens Marcel J , Muller Sandra , Boer den Frank C
Published: May 2020

Breast carcinoma is the most frequently diagnosed cancer in women. In up to 30%, distant metastases will occur; however, ileocecal metastases are rare. Although there have been cases reported that demonstrate ileocecal metastases of breast carcinoma, PET/CT-negative cases have never been described. We present a patient with a small bowel obstruction, preoperatively complicated by pulmonary embolisms. The patient underwent placement of an inferior vena cava filter followed by hemicolectomy. Pathological examination revealed ileocecal lobular breast carcinoma metastases and adjacent peritoneal carcinomatosis, which had shown no intestinal 18FDG uptake 7 weeks prior to presentation. Subsequently, symptoms of metastases and the paraneoplastic syndrome progressed, and the patient was referred to the medical oncologist for palliative therapy. Although uncommon, physicians should be aware of potential presence of 18FDG-negative gastrointestinal metastases of breast cancer.
Why is C4 photosynthesis so rare in trees?
Authors: Young Sophie N R , Sack Lawren , Sporck-Koehler Margaret J , Lundgren Marjorie R
Published: May 2020

Since C4 photosynthesis was first discovered >50 years ago, researchers have sought to understand how this complex trait evolved from the ancestral C3 photosynthetic machinery on >60 occasions. Despite its repeated emergence across the plant kingdom, C4 photosynthesis is notably rare in trees, with true C4 trees only existing in Euphorbia. Here we consider aspects of the C4 trait that could limit but not preclude the evolution of a C4 tree, including reduced quantum yield, increased energetic demand, reduced adaptive plasticity, evolutionary constraints, and a new theory that the passive symplastic phloem loading mechanism observed in trees, combined with difficulties in maintaining sugar and water transport over a long pathlength, could make C4 photosynthesis largely incompatible with the tree lifeform. We conclude that the transition to a tree habit within C4 lineages as well as the emergence of C4 photosynthesis within pre-existing trees would both face a series of challenges that together explain the global rarity of C4 photosynthesis in trees. The C4 trees in Euphorbia are therefore exceptional in how they have circumvented every potential barrier to the rare C4 tree lifeform.
Functional analysis of two STAT1 gain-of-function mutations in two Iranian families with autosomal dominant chronic mucocutaneous candidiasis
Authors: Ostadi Vajiheh , Sherkat Roya , Migaud Melanie , Modaressadeghi Seyed-Mehran , Casanova Jean-Laurent , Puel Anne , Nekooie-Marnany Nioosha , Ganjalikhani-Hakemi Mazdak
Published: May 2020

Candidiasis is characterized by susceptibility to recurrent or persistent infections caused by Candida spp., typically Candida albicans, of cutaneous and mucosal surfaces. In this report, function and frequency of Th17 cells as well as genetics of patients susceptible to mucocutaneous candidiasis were studied. For patients, T-cell proliferation tests in response to Candida antigen, Th17 cell proportions, and STAT1 phosphorylation were evaluated through flow cytometry. Expression of IL17A, IL17F and IL22 genes were measured by real-time quantitative PCR. At the same time, whole exome sequencing was performed for all patients. We identified two heterozygous substitutions, one: c.821G > A (p. R274Q) was found in a multiplex family with three individuals affected, the second one: c.812A > C (p. Q271P) was found in a sporadic case. Both mutations are located in the coiled-coil domain (CCD) of STAT1. The frequency of Th17 cells, IL17A, IL17F, and IL22 gene expression in patients’ peripheral blood mononuclear cells (PBMCs), and T-cell proliferation to Candida antigens were significantly reduced in the patients as compared to healthy controls. An increased STAT1 phosphorylation was observed in patients’ PBMCs upon interferon (IFN)-γ stimulation as compared to healthy controls. We report two different but neighboring heterozygous mutations, located in exon 10 of the STAT1 gene, in four Iranian patients with CMC, one of whom also had hypothyroidism. These mutations were associated with impaired T cell proliferation to Candida antigen, low Th17 cell proportions, and increased STAT1 phosphorylation upon IFN-γ. We suggest that interfering with STAT1 phosphorylation might be a promising way for potential therapeutic measurements for such patients.
The relationship between mid-infrared and sub-millimetre variability of deeply embedded protostars
Authors: Contreras Peña Carlos , Johnstone Doug , Baek Giseon , Herczeg Gregory J , Mairs Steve , Scholz Aleks , Lee Jeong-Eun ,   The JCMT Transient Team
Published: May 2020

We study the relationship between the mid-infrared (mid-IR) and sub-millimetre (sub-mm) variability of deeply embedded protostars using the multi-epoch data from the Wide-field Infrared Survey Explorer (WISE/NEOWISE) and the ongoing James Clerk Maxwell Telescope (JCMT) Transient Survey. Our search for signs of stochastic (random) and/or secular (roughly monotonic in time) variability in a sample of 59 young stellar objects (YSOs) revealed that 35 are variable in at least one of the two surveys. This variability is dominated by secular changes. Of those objects with secular variability, 14 objects ($22{{\ \rm per\ cent}}$ of the sample) show correlated secular variability over mid-IR and sub-mm wavelengths. Variable accretion is the likely mechanism responsible for this type of variability. Fluxes of YSOs that vary in both wavelengths follow a relation of log10F4.6(t) = ηlog10F850(t) between the mid-IR and sub-mm, with η = 5.53 ± 0.29. This relationship arises from the fact that sub-mm fluxes respond to the dust temperature in the larger envelope whereas the mid-IR emissivity is more directly proportional to the accretion luminosity. The exact scaling relation, however, depends on the structure of the envelope, the importance of viscous heating in the disc, and dust opacity laws.
Young bilateral supernova remnants evolving into a turbulent interstellar magnetic field
Authors: Ávila-Aroche A , Velázquez P F , Camps-Fariña A , Toledo-Roy J C , Esquivel A
Published: May 2020

We employ 3D magnetohydrodynamic simulations to study the morphology and synchrotron emission of young supernova remnants evolving in a turbulent interstellar magnetic field, seeking to shed new light on to the polarization structure of the emission and on the debate concerning the quasi-parallel and quasi-perpendicular acceleration mechanisms. In the simulations, we consider a non-homogeneous interstellar medium magnetic field by introducing small random perturbations in the direction and intensity of the field. In order to analyse the dependence of the radio morphology on the degree of magnetic field perturbation and the observer’s point of view, we compute synthetic maps of the polarized intensity, position-angle, polarization fraction, and the polar-reference angle. By comparing the distribution of this angle to the polarization intensity, we show that it is possible to identify what type of acceleration mechanism is taking place at the main shock front.
Genomic Analysis of European Drosophila melanogaster Populations Reveals Longitudinal Structure, Continent-Wide Selection, and Previously Unknown DNA Viruses
Authors: Kapun Martin , Barrón Maite G , Staubach Fabian , Obbard Darren J , Wiberg R Axel W , Vieira Jorge , Goubert Clément , Rota-Stabelli Omar , Kankare Maaria , Bogaerts-Márquez María , Haudry Annabelle , Waidele Lena , Kozeretska Iryna , Pasyukova Elena G , Loeschcke Volker , Pascual Marta , Vieira Cristina P , Serga Svitlana , Montchamp-Moreau Catherine , Abbott Jessica , Gibert Patricia , Porcelli Damiano , Posnien Nico , Sánchez-Gracia Alejandro , Grath Sonja , Sucena Élio , Bergland Alan O , Guerreiro Maria Pilar Garcia , Onder Banu Sebnem , Argyridou Eliza , Guio Lain , Schou Mads Fristrup , Deplancke Bart , Vieira Cristina , Ritchie Michael G , Zwaan Bas J , Tauber Eran , Orengo Dorcas J , Puerma Eva , Aguadé Montserrat , Schmidt Paul , Parsch John , Betancourt Andrea J , Flatt Thomas , González Josefa
Published: May 2020

Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatiotemporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in European Drosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterize variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.
The Architecture of Metabolism Maximizes Biosynthetic Diversity in the Largest Class of Fungi
Authors: Gluck-Thaler Emile , Haridas Sajeet , Binder Manfred , Grigoriev Igor V , Crous Pedro W , Spatafora Joseph W , Bushley Kathryn , Slot Jason C
Published: May 2020

Ecological diversity in fungi is largely defined by metabolic traits, including the ability to produce secondary or “specialized” metabolites (SMs) that mediate interactions with other organisms. Fungal SM pathways are frequently encoded in biosynthetic gene clusters (BGCs), which facilitate the identification and characterization of metabolic pathways. Variation in BGC composition reflects the diversity of their SM products. Recent studies have documented surprising diversity of BGC repertoires among isolates of the same fungal species, yet little is known about how this population-level variation is inherited across macroevolutionary timescales. Here, we applied a novel linkage-based algorithm to reveal previously unexplored dimensions of diversity in BGC composition, distribution, and repertoire across 101 species of Dothideomycetes, which are considered the most phylogenetically diverse class of fungi and known to produce many SMs. We predicted both complementary and overlapping sets of clustered genes compared with existing methods and identified novel gene pairs that associate with known secondary metabolite genes. We found that variation among sets of BGCs in individual genomes is due to nonoverlapping BGC combinations and that several BGCs have biased ecological distributions, consistent with niche-specific selection. We observed that total BGC diversity scales linearly with increasing repertoire size, suggesting that secondary metabolites have little structural redundancy in individual fungi. We project that there is substantial unsampled BGC diversity across specific families of Dothideomycetes, which will provide a roadmap for future sampling efforts. Our approach and findings lend new insight into how BGC diversity is generated and maintained across an entire fungal taxonomic class.
RPS28B mRNA acts as a scaffold promoting cis-translational interaction of proteins driving P-body assembly
Authors: Fernandes Nikita , Buchan J Ross
Published: May 2020

P-bodies (PBs) are cytoplasmic mRNA-protein (mRNP) granules conserved throughout eukaryotes which are implicated in the repression, storage and degradation of mRNAs. PB assembly is driven by proteins with self-interacting and low-complexity domains. Non-translating mRNA also stimulates PB assembly, however no studies to date have explored whether particular mRNA transcripts are more critical than others in facilitating PB assembly. Previous work revealed that rps28bΔ (small ribosomal subunit-28B) mutants do not form PBs under normal growth conditions. Here, we demonstrate that the RPS28B 3′UTR is important for PB assembly, consistent with it harboring a binding site for the PB assembly protein Edc3. However, expression of the RPS28B 3′UTR alone is insufficient to drive PB assembly. Intriguingly, chimeric mRNA studies revealed that Rps28 protein, translated in cis from an mRNA bearing the RPS28B 3′UTR, physically interacts more strongly with Edc3 than Rps28 protein synthesized in trans. This Edc3-Rps28 interaction in turn facilitates PB assembly. Our work indicates that PB assembly may be nucleated by specific RNA ‘scaffolds’. Furthermore, this is the first description in yeast to our knowledge of a cis-translated protein interacting with another protein in the 3′UTR of the mRNA which encoded it, which in turn stimulates assembly of cellular structures.
Oviz-Bio: a web-based platform for interactive cancer genomics data visualization
Authors: Jia Wenlong , Li Hechen , Li Shiying , Chen Lingxi , Li Shuai Cheng
Published: May 2020

Genetics data visualization plays an important role in the sharing of knowledge from cancer genome research. Many types of visualization are widely used, most of which are static and require sufficient coding experience to create. Here, we present Oviz-Bio, a web-based platform that provides interactive and real-time visualizations of cancer genomics data. Researchers can interactively explore visual outputs and export high-quality diagrams. Oviz-Bio supports a diverse range of visualizations on common cancer mutation types, including annotation and signatures of small scale mutations, haplotype view and focal clusters of copy number variations, split-reads alignment and heatmap view of structural variations, transcript junction of fusion genes and genomic hotspot of oncovirus integrations. Furthermore, Oviz-Bio allows landscape view to investigate multi-layered data in samples cohort. All Oviz-Bio visual applications are freely available at https://bio.oviz.org/.
Analyzing pre-symptomatic tissue to gain insights into the molecular and mechanistic origins of late-onset degenerative trinucleotide repeat disease
Authors: Chu Yongjun , Hu Jiaxin , Liang Hanquan , Kanchwala Mohammed , Xing Chao , Beebe Walter , Bowman C Bradley , Gong Xin , Corey David R , Mootha V Vinod
Published: May 2020

How genetic defects trigger the molecular changes that cause late-onset disease is important for understanding disease progression and therapeutic development. Fuchs’ endothelial corneal dystrophy (FECD) is an RNA-mediated disease caused by a trinucleotide CTG expansion in an intron within the TCF4 gene. The mutant intronic CUG RNA is present at one–two copies per cell, posing a challenge to understand how a rare RNA can cause disease. Late-onset FECD is a uniquely advantageous model for studying how RNA triggers disease because: (i) Affected tissue is routinely removed during surgery; (ii) The expanded CTG mutation is one of the most prevalent disease-causing mutations, making it possible to obtain pre-symptomatic tissue from eye bank donors to probe how gene expression changes precede disease; and (iii) The affected tissue is a homogeneous single cell monolayer, facilitating accurate transcriptome analysis. Here, we use RNA sequencing (RNAseq) to compare tissue from individuals who are pre-symptomatic (Pre_S) to tissue from patients with late stage FECD (FECD_REP). The abundance of mutant repeat intronic RNA in Pre_S and FECD_REP tissue is elevated due to increased half-life in a corneal cells. In Pre_S tissue, changes in splicing and extracellular matrix gene expression foreshadow the changes observed in advanced disease and predict the activation of the fibrosis pathway and immune system seen in late-stage patients. The absolute magnitude of splicing changes is similar in pre-symptomatic and late stage tissue. Our data identify gene candidates for early drivers of disease and biomarkers that may represent diagnostic and therapeutic targets for FECD. We conclude that changes in alternative splicing and gene expression are observable decades prior to the diagnosis of late-onset trinucleotide repeat disease.
CVCDAP: an integrated platform for molecular and clinical analysis of cancer virtual cohorts
Authors: Guan Xiaoqing , Cai Meng , Du Yang , Yang Ence , Ji Jiafu , Wu Jianmin
Published: May 2020

Recent large-scale multi-omics studies resulted in quick accumulation of an overwhelming amount of cancer-related data, which provides an unprecedented resource to interrogate diverse questions. While certain existing web servers are valuable and widely used, analysis and visualization functions with regard to re-investigation of these data at cohort level are not adequately addressed. Here, we present CVCDAP, a web-based platform to deliver an interactive and customizable toolbox off the shelf for cohort-level analysis of TCGA and CPTAC public datasets, as well as user uploaded datasets. CVCDAP allows flexible selection of patients sharing common molecular and/or clinical characteristics across multiple studies as a virtual cohort, and provides dozens of built-in customizable tools for seamless genomic, transcriptomic, proteomic and clinical analysis of a single virtual cohort, as well as, to compare two virtual cohorts with relevance. The flexibility and analytic competence of CVCDAP empower experimental and clinical researchers to identify new molecular mechanisms and develop potential therapeutic approaches, by building and analyzing virtual cohorts for their subject of interests. We demonstrate that CVCDAP can conveniently reproduce published findings and reveal novel insights by two applications. The CVCDAP web server is freely available at https://omics.bjcancer.org/cvcdap/.
Low-Grade Infection and Implant Failure Following Spinal Instrumentation: A Prospective Comparative Study
Authors: Shiban Ehab , Joerger Ann-Kathrin , Janssen Insa , Issa Mohammed , Lange Nicole , Wagner Arthur , Feihl Susanne , Ringel Florian , Meyer Bernhard
Published: May 2020

BACKGROUND

Spinal instrumentation can be associated with complications, including implant loosening. Hitherto, implant loosening has mainly been attributed to mechanical overload.

OBJECTIVE

To examine the role of low-grade infections as the cause of implant failure in suspected aseptic implant loosening following spinal instrumentation.

METHODS

A prospective single center observational study was performed. All patients who had revision surgery following spinal instrumentation between August 2015 and February 2018 were screened. Patients with revision surgery due to screw loosening on the computed tomograhy scan constituted the study group. Patients in which the screws where not loosened but removal was performed for other reasons formed the comparison group. Intraoperative swabs were taken and sonication was performed with the explanted material. Results of microbiological cultivation were analyzed.

RESULTS

A total of 59 patients were included in the study group and 34 in the comparison group. In the study group in 42.4% of the cultures a bacterium was detected, while in the comparison group only in 17.6%. 84%, and 83.3% of these germs were detected by sonication in the study and comparison group, respectively. The rate of positive cultures was significantly higher in the study group compared to the comparison group (P = .001). The most frequent bacterium cultivated in both groups was Propionibacterium acnes, followed by Staphylococcus species.

CONCLUSION

For patients with screw loosening a high level of suspicion for a low-grade infection should be raised. Cultures should be performed from the sonication fluid of the explanted devices in all patients with symptomatic screw loosening.
Women With First-Hand Tobacco Smoke Exposure Have a Higher Likelihood of Having an Unruptured Intracranial Aneurysm Than Nonsmokers: A Nested Case-Control Study
Authors: Ogilvy Christopher S , Gomez-Paz Santiago , Kicielinski Kimberly P , Salem Mohamed M , Maragkos Georgios A , Lee Michelle , Vergara-Garcia David , Rojas Rafael , Moore Justin M , Thomas Ajith J
Published: May 2020

BACKGROUND

The prevalence of unruptured intracranial aneurysms (UIA) in females who smoke cigarettes and the association between smoking and hypertension with purely incidental UIAs have been unexplored.

OBJECTIVE

To obtain the prevalence of UIA among females and to assess the relationship between smoking and hypertension with a diagnosis of incidental UIAs.

METHODS

A nested case-control study from a cohort of female patients aged between 30 and 60 yr with a brain magnetic resonance angiography (MRA) between 2016 and 2018. Incidental UIAs were compared to patients with normal MRAs. Smoking was characterized as never or former/current smokers. A logistic regression was used to evaluate the association between smoking, hypertension, or both, with a diagnosis of incidental UIAs.

RESULTS

A total of 1977 patients had a brain MRA between 2016 and 2018. From 1572 nonsmoker patients, we encountered 30 with an UIA (prevalence: 1.9%). There were 405 patients with a positive smoking history, and 77 patients harbored an UIA (prevalence: 19%). Of 64 aneurysm patients and 130 random controls eligible for the case control, aneurysm patients were more likely to have a positive smoking history and hypertension compared with healthy controls (60% vs 18%, P ≤ .001; 44% vs 14%, P ≤ .001). A multivariable analysis demonstrated a significant association between a smoking history, hypertension, or both factors with an incidental UIA (odds ratio [OR] 5.8 CI 1.22-11.70; OR 3.8 CI 2.31-14.78; OR 12.6 CI 4.38-36.26; respectively).

CONCLUSION

Females who smoke cigarettes have a higher prevalence of UIAs than the general population. Smoking confers a higher risk for having a silent UIA, aggravated by hypertension. This population is an ideal target for potential screening.
Ependymoma, NOS and anaplastic ependymoma incidence and survival in the United States varies widely by patient and clinical characteristics, 2000-2016
Authors: Achey Rebecca L , Vo Sierra , Cioffi Gino , Gittleman Haley , Schroer Julia , Khanna Vishesh , Buerki Robin , Kruchko Carol , Barnholtz-Sloan Jill S
Published: May 2020

Background

Ependymoma is a rare CNS tumor arising from the ependymal lining of the ventricular system. General differences in incidence and survival have been noted but not examined on a comprehensive scale for all ages and by histology. Despite the rarity of ependymomas, morbidity/mortality associated with an ependymoma diagnosis justifies closer examination.

Methods

Incidence data were obtained from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, and survival data from Surveillance Epidemiology and End Results, from 2000 to 2016 for anaplastic ependymoma and ependymoma, not otherwise specified (NOS). Age-adjusted incidence rates (IRs) per 100 000 person-years were analyzed by age, sex, race, and location. Survival analysis was performed with Kaplan-Meier curves and multivariable Cox proportional hazards models.

Results

Incidence of anaplastic ependymoma was highest in ages 0 to 4 years. African American populations had lower incidence but had a 78% increased risk of death compared to white populations (hazard ratio [HR]: 1.78 [95% CI, 1.30-2.44]). Incidence was highest for anaplastic ependymoma in the supratentorial region. Adults (age 40+ years) had almost twice the risk of death compared to children (ages 0-14 years) (HR: 1.97 [95% CI, 1.45-2.66]). For ependymoma, NOS, subtotal resection had a risk of mortality 1.86 times greater than gross total resection ([HR: 1.86 [95% CI, 1.32-2.63]).

Conclusions

African American populations experienced higher mortality rates despite lower incidence compared to white populations. Extent of resection is an important prognostic factor for survival. This highlights need for further evaluation of treatment patterns and racial disparities in the care of patients with ependymoma subtypes.