bluuebunny/crossref_metadata_2025 huggingface dataset:
Parasitism of Adult Pentatomidae by Tachinidae in Soybean in the North Central Region of the United States
Authors: Anderson Pheylan A , Pezzini Daniela T , Bueno Nádia M , DiFonzo Christina D , Finke Deborah L , Hunt Thomas E , Knodel Janet J , Krupke Christian H , McCornack Brian P , Philips Christopher R , Varenhorst Adam J , Wright Robert J , Koch Robert L
Published: April 2020

Stink bugs (Hemiptera: Pentatomidae) are agricultural pests of increasing significance in the North Central Region of the United States, posing a threat to major crops such as soybean. Biological control can reduce the need for insecticides to manage these pests, but the parasitism of stink bugs by Tachinidae (Diptera) is poorly characterized in this region. The objective of this study was to evaluate the rate of parasitism of stink bugs by tachinids over 2 yr from nine states across the North Central Region. Parasitism was assessed by quantifying tachinid eggs on the integument of stink bug adults. Parasitism rates (i.e., percent of adult stink bugs with tachinid eggs) were compared across stink bug species, states, stink bug sex, and years. The mean percent parasitism of stink bugs by tachinids was about 6% across the region and did not differ among stink bug species. Mean percent parasitism was significantly higher in Missouri than in northern and western states. In addition, male stink bugs had significantly higher mean percent parasitism than females. Stink bug species commonly found in soybean in the region showed some parasitism and are therefore potentially vulnerable to oviposition by these parasitoids. This is the first study to characterize the level of parasitism of stink bugs by tachinids across the North Central Region.
Governing through imaginaries: on the place and role of constructions of Japan within UK policy discourse regarding science, technology, and innovation
Authors: Pickersgill Martyn
Published: April 2020

This article employs the notion of ‘sociotechnical imaginaries’ from the discipline of science and technology studies in order to consider the role that constructions of Japan play within UK policy discourse on science, technology, and innovation. The analysis is parsed in relation to the three dominant constructions that emerged from within the discourse under study: Japan as collaborator, as comparator, and as competitor. The mentioning of Japan within policy texts seems often aimed at evoking an imaginary of an economically successful and technoscientifically inventive nation, geared up for investment and innovation. Japan was present in the texts analyzed as a country that was simultaneously the same and other to the UK: similar enough for meaningful comparisons to be made, while sufficiently different to motivate the UK to ‘do better’ and to galvanize symbolic and material resource to become ‘more like’ Japan. Thus, a sociotechnical imaginary emerged that was at once familiar to and yet also distinct from that of the UK. Sociotechnical imaginaries of other/Other nations can govern through enabling and shaping political and policy conversations, which can ultimately inflect and indeed help to determine different forms of legal and regulatory tools, processes, and discourses.
Multifocal abdominal endometriosis, a case report
Authors: Porter Julia , Eisdorfer Jacob , Yi Crystal , Nguyen Cecilia
Published: April 2020

Multifocal endometriosis found outside of the pelvis is very rare. We present here a case of endometriosis found in the pelvis, appendix and umbilicus. A 52-year-old female had a previous umbilical hernia repair, and years later started to develop a recurrent umbilical mass. After a full work-up, it was decided the patient have a diagnostic laparoscopy with wide local excision of umbilical mass to rule out any underlying malignancy. Findings during the procedure included an umbilical mass, dilated appendix and ovoid mass abutting the appendix. Pathology of the umbilical mass was found to be consistent with endometriosis. Umbilical and pelvic endometriosis is a rare condition. Options for diagnosis prior to surgical interventions are limited in endometriosis. In this case, ruling out underlying malignancy took priority, and the mass was removed and she will have less chance of recurrence.
Epigenetics: possible applications in climate-smart crop breeding
Authors: Varotto Serena , Tani Eleni , Abraham Eleni , Krugman Tamar , Kapazoglou Aliki , Melzer Rainer , Radanović Aleksandra , Miladinović Dragana
Published: April 2020

To better adapt transiently or lastingly to stimuli from the surrounding environment, the chromatin states in plant cells vary to allow the cells to fine-tune their transcriptional profiles. Modifications of chromatin states involve a wide range of post-transcriptional histone modifications, histone variants, DNA methylation, and activity of non-coding RNAs, which can epigenetically determine specific transcriptional outputs. Recent advances in the area of ‘-omics’ of major crops have facilitated identification of epigenetic marks and their effect on plant response to environmental stresses. As most epigenetic mechanisms are known from studies in model plants, we summarize in this review recent epigenetic studies that may be important for improvement of crop adaptation and resilience to environmental changes, ultimately leading to the generation of stable climate-smart crops. This has paved the way for exploitation of epigenetic variation in crop breeding.
KNAT7 regulates xylan biosynthesis in Arabidopsis seed-coat mucilage
Authors: Wang Yiping , Xu Yan , Pei Shengqiang , Lu Mingmin , Kong Yingzhen , Zhou Gongke , Hu Ruibo
Published: April 2020

As a major hemicellulose component of plant cell walls, xylans play a determining role in maintaining the wall structure. However, the mechanisms of transcriptional regulation of xylan biosynthesis remain largely unknown. Arabidopsis seed mucilage represents an ideal system for studying polysaccharide biosynthesis and modifications of plant cell walls. Here, we identify KNOTTED ARABIDOPSIS THALIANA 7 (KNAT7) as a positive transcriptional regulator of xylan biosynthesis in seed mucilage. The xylan content was significantly reduced in the mucilage of the knat7-3 mutant and this was accompanied by significantly reduced expression of the xylan biosynthesis-related genes IRREGULAR XYLEM 14 (IRX14) and MUCILAGE MODIFIED 5/MUCILAGE-RELATED 21 (MUM5/MUCI21). Electrophoretic mobility shift assays, yeast one-hybrid assays, and chromatin immunoprecipitation with quantitative PCR verified the direct binding of KNAT7 to the KNOTTED1 (KN1) binding site [KBS,TGACAG(G/C)T] in the promoters of IRX7, IRX14, and MUM5/MUCI21 in vitro, in vivo, and in planta. Furthermore, KNAT7 directly activated the expression of IRX14 and MUM5/MUCI21 in transactivation assays in mesophyll protoplasts, and overexpression of IRX14 or MUM5/MUCI21 in knat7-3 partially rescued the defects in mucilage adherence. Taken together, our results indicate that KNAT7 positively regulates xylan biosynthesis in seed-coat mucilage via direct activation of the expression of IRX14 and MUM5/MUCI21.
Collimated outflows from long-lived binary neutron star merger remnants
Authors: Ciolfi Riccardo
Published: April 2020

The connection between short gamma-ray bursts (SGRBs) and binary neutron star (BNS) mergers was recently confirmed by the association of GRB 170817A with the merger event GW170817. However, no conclusive indications were obtained on whether the merger remnant that powered the SGRB jet was an accreting black hole (BH) or a long-lived massive neutron star (NS). Here, we explore the latter case via BNS merger simulations covering up to 250 ms after merger. We report, for the first time in a full merger simulation, the formation of a magnetically driven collimated outflow along the spin axis of the NS remnant. For the system at hand, the properties of such an outflow are found largely incompatible with an SGRB jet. With due consideration of the limitations and caveats of our present investigation, our results favour a BH origin for GRB 170817A and SGRBs in general. Even though this conclusion needs to be confirmed by exploring a larger variety of physical conditions, we briefly discuss possible consequences of all SGRB jets being powered by accreting BHs.
IKBKE activity enhances AR levels in advanced prostate cancer via modulation of the Hippo pathway
Authors: Bainbridge Alex , Walker Scott , Smith Joseph , Patterson Kathryn , Dutt Aparna , Ng Yi Min , Thomas Huw D , Wilson Laura , McCullough Benjamin , Jones Dominic , Maan Arussa , Banks Peter , McCracken Stuart R , Gaughan Luke , Robson Craig N , Coffey Kelly
Published: April 2020

Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this is accomplished include AR amplification and expression of AR splice variants, demonstrating that AR remains a key therapeutic target in advanced disease. For the first time we show that IKBKE drives AR signalling in advanced PC. Significant inhibition of AR regulated gene expression was observed upon siRNA-mediated IKBKE depletion or pharmacological inhibition due to inhibited AR gene expression in multiple cell line models including a LNCaP derivative cell line resistant to the anti-androgen, enzalutamide (LNCaP-EnzR). Phenotypically, this resulted in significant inhibition of proliferation, migration and colony forming ability suggesting that targeting IKBKE could circumvent resistance to AR targeting therapies. Indeed, pharmacological inhibition in the CWR22Rv1 xenograft mouse model reduced tumour size and enhanced survival. Critically, this was validated in patient-derived explants where enzymatic inactivation of IKBKE reduced cell proliferation and AR expression. Mechanistically, we provide evidence that IKBKE regulates AR levels via Hippo pathway inhibition to reduce c-MYC levels at cis-regulatory elements within the AR gene. Thus, IKBKE is a therapeutic target in advanced PC suggesting repurposing of clinically tested IKBKE inhibitors could be beneficial to castrate resistant PC patients.
A Scoping Review of Registered Clinical Studies on Mild Traumatic Brain Injury and Concussion (2000 to 2019)
Authors: Furlan Julio C , Radan Michael M , Tator Charles H
Published: April 2020

BACKGROUND

While many patients with mild traumatic brain injury (mTBI) or concussion recover completely, prolonged postconcussion symptoms remain a challenge for patients and an opportunity for clinical research. This has led to numerous research initiatives over the last 2 decades.

OBJECTIVE

To review the characteristics of clinical studies on management of mTBI/concussion; and to examine their definitions of mTBI/concussion.

METHODS

This scoping review included all clinical studies on diagnosis and management of patients with mTBI/concussion registered at www.clinicaltrials.gov from 2000 to June/2019. The terms “mild TBI/concussion” were used for the primary search. Definitions of mTBI/concussion were obtained from the protocols. When a definition was missing in the website, the study's investigators were contacted for clarification.

RESULTS

There were 225 interventional and 95 observational studies. Most of the studies are focused on treatment (54.7%) or diagnosis (37.5%), while 3.4% examined preventive measures, 2.8% evaluated prognostic instruments, and 1.6% developed registries. Most of the studies in this American database were single-center initiatives led by American and Canadian institutions. The definitions of mTBI/concussion differed widely among 109 studies.

CONCLUSION

The results of this review suggest that most of the clinical studies are focused on diagnosis and non-pharmacological therapies for patients with mTBI/concussion. The large number of differing definitions of mTBI/concussion among the studies creates significant limitations when comparing studies. The requirements for registering research protocols on mTBI/concussion should include the necessity to state the definition being used. There is a need for consensus on a uniform definition of concussion.
Parvovirus B19 activates in vitro normal human dermal fibroblasts: a possible implication in skin fibrosis and systemic sclerosis
Authors: Arvia Rosaria , Margheri Francesca , Stincarelli Maria A , Laurenzana Anna , Fibbi Gabriella , Gallinella Giorgio , Ferri Clodoveo , Del Rosso Mario , Zakrzewska Krystyna
Published: April 2020

Objective

Fibrosis is the most characteristic pathological hallmark of SSc, a connective tissue disease characterized by vascular and immunological abnormalities, inflammation and enhanced extracellular matrix production, leading to progressive fibrosis of skin and internal organs. We previously demonstrated that parvovirus B19 (B19V) can infect normal human dermal fibroblasts (NHDFs) and that B19V persists in SSc fibroblasts. In this study, we investigated whether parvovirus B19V is able to activate in vitro NHDFs and to induce in these cells some phenotypic features similar to that observed in the SSc fibroblasts.

Methods

We preliminarily analysed the time course of B19V infection in cultured NHDFs, then we investigated the ability of B19V to induce cell migration, invasive phenotype and mRNA expression of some profibrotic and/or proinflammatory genes.

Results

We confirmed our previous findings that B19V infects NHDFs, but the infection is not productive. After incubation with B19V, NHDFs showed a significant increase of both migration and invasiveness, along with mRNA expression of different profibrotic genes (α-SMA, EDN-1, IL-6, TGF-β1 receptors 1 and 2, Col1α2), some genes associated with inflammasome platform (AIM2, IFI16, IL-1β, CASP-1) and genes for metalloprotease (MMP 2, 9 and 12).

Conclusion

These data suggest that B19V can activate dermal fibroblasts and may have a role in the pathogenesis of fibrosis. B19V-induced fibroblast migration and invasiveness could be due to the B19V-associated MMP9 overexpression and activation. Moreover, the up-regulation of MMP12, typical of SSc, could link the B19V infection of fibroblasts to the anti-angiogenic process.
The genetics of rheumatoid arthritis
Authors: Dedmon Laura E
Published: April 2020

RA is a chronic systemic inflammatory disease that primarily affects the small joints of the hands and feet, and results in a mean reduction in life expectancy of 3–10 years. RA is a multigene disorder with a substantial genetic component and a heritability estimate of 60%. Large-scale Genome-Wide Association Studies (GWAS) and meta-analyses have revealed common disease-associated variants in the population that may contribute cumulatively to RA pathogenesis. This review identifies the most significant genetic variants associated with RA susceptibility to date, with particular focus on the contribution of the HLA class II genes across different ethnic groups. Also discussed are the potential applications of pharmacogenomics to RA management by identifying polymorphisms associated with variation in treatment response or toxicity. The use of genetic variants to guide treatment strategy has the potential to not only reduce National Health Service costs, but also drastically improve patient experience and quality of life.
Complex Ecological Phenotypes on Phylogenetic Trees: A Markov Process Model for Comparative Analysis of Multivariate Count Data
Authors: Grundler Michael , Rabosky Daniel L
Published: April 2020

The evolutionary dynamics of complex ecological traits—including multistate representations of diet, habitat, and behavior—remain poorly understood. Reconstructing the tempo, mode, and historical sequence of transitions involving such traits poses many challenges for comparative biologists, owing to their multidimensional nature. Continuous-time Markov chains are commonly used to model ecological niche evolution on phylogenetic trees but are limited by the assumption that taxa are monomorphic and that states are univariate categorical variables. A necessary first step in the analysis of many complex traits is therefore to categorize species into a predetermined number of univariate ecological states, but this procedure can lead to distortion and loss of information. This approach also confounds interpretation of state assignments with effects of sampling variation because it does not directly incorporate empirical observations for individual species into the statistical inference model. In this study, we develop a Dirichlet-multinomial framework to model resource use evolution on phylogenetic trees. Our approach is expressly designed to model ecological traits that are multidimensional and to account for uncertainty in state assignments of terminal taxa arising from effects of sampling variation. The method uses multivariate count data across a set of discrete resource categories sampled for individual species to simultaneously infer the number of ecological states, the proportional utilization of different resources by different states, and the phylogenetic distribution of ecological states among living species and their ancestors. The method is general and may be applied to any data expressible as a set of observational counts from different categories. [Comparative methods; Dirichlet multinomial; ecological niche evolution; macroevolution; Markov model.]
Look closely and listen carefully: unexpected cicada diversity in northern Sardinia, with the description of a new species (Cicadidae: Tibicina)
Authors: Hertach Thomas
Published: April 2020

Integrative taxonomy combines different data sources as a way to detect separately evolving metapopulation lineages or species. This method is applied to cicada populations found in northern Sardinia, based on acoustic, morphological and ecological data. Thereby, the genus Tibicina turned out to be more diverse than previously expected. Besides the anticipated Tibicina corsica corsica and T. nigronervosa, both scientifically described from the neighbouring island of Corsica, two poorly or previously unknown species have been discovered. Tibicina longisyllaba sp. nov. is here described as new. Tibicina corsica s.l. forms a small species complex where syllable periods of the song – the movement cycle of the acoustic organs – are specific without overlaps. Some coloration and hair cover characters, as well as the shape of the song apparatus, are not diagnostic on their own, but highly significant between species. Species occur sympatrically, parapatrically or allopatrically and prefer specific habitats from grassland to closed forests. All four Tibicina taxa are endemic to parts of Sardinia or to the Corso-Sardinian archipelago. The new findings are important for biodiversity conservation and public awareness. The loud, strident calling songs dominate the summer sounds of the islands. The group could form a showcase with respect to biogeography, phylogeny, speciation and sound production.
The Importance of Being Earnest
Authors: El-Dalati Sami , Cronin Daniel
Published: April 2020

Attempting to effect change in modern medicine, particularly as trainees or junior faculty, is often an overwhelming undertaking. While early-career physicians are in close contact with patients, they often lack the credibility or access to resources that are necessary to implement new ideas at large institutions. Although there may be scientific evidence to support new models of care, existing cultural patterns of practice can foster resistance to these interventions.

The authors describe their own experience as residents reforming the management of endocarditis patients at an academic medical center, emphasizing the important role that residents can play in changing medical practice. Starting with a devastating patient case, the authors share their story of creating a multidisciplinary endocarditis team while navigating the many obstacles, some unseen, that can derail innovative ideas. Ultimately, through a combination of new perspectives, data-driven analysis, determination, and—most importantly—hope, the authors were able to dramatically improve outcomes for patients. Moving forward, their experience can serve as a model for young physicians and inspire them to effect change in their own institutions.
Motivations for and Challenges in the Development of Global Medical Curricula: A Scoping Review
Authors: Giuliani Meredith , Martimianakis Maria Athina (Tina) , Broadhurst Michaela , Papadakos Janet , Fazelzad Rouhi , Driessen Erik W. , Frambach Janneke
Published: April 2020

Purpose

The aim of this scoping review is to understand the motivations for the creation of global medical curricula, summarize methods that have been used to create these curricula, and understand the perceived premises for the creation of these curricula.

Method

In 2018, the authors used a comprehensive search strategy to identify papers on existing efforts to create global medical curricula published from 1998 to March 29, 2018, in the following databases: MEDLINE; MEDLINE Epub Ahead of Print, In-Process, and Other Non-Indexed Citations; Embase; Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; PsycINFO; CINAHL; ERIC; Scopus; African Index Medicus; and LILACS. There were no language restrictions. Two independent researchers applied the inclusion and exclusion criteria. Demographic data were abstracted from publications and summarized. The stated purposes, methods used for the development, stated motivations, and reported challenges of curricula were coded.

Results

Of the 18,684 publications initially identified, 137 met inclusion criteria. The most common stated purposes for creating curricula were to define speciality-specific standards (50, 30%), to harmonize training standards (38, 23%), and to improve the quality or safety of training (31, 19%). The most common challenges were intercountry variation (including differences in health care systems, the operationalization of medical training, and sociocultural differences; 27, 20%), curricular implementation (20, 15%), and the need for a multistakeholder approach (6, 4%). Most curricula were developed by a social group (e.g., committee; 30, 45%) or Delphi or modified Delphi process (22, 33%).

Conclusions

The challenges of intercountry variation, the need for a multistakeholder approach, and curricular implementation need to be considered if concerns about curricular relevance are to be addressed. These challenges undoubtedly impact the uptake of global medical curricula and can only be addressed by explicit efforts to make curricula applicable to the realities of diverse health care settings.
Impact of Tobacco Smoking on Outcomes After Posterior Decompression Surgery in Patients With Cervical Spondylotic Myelopathy
Authors: Nagoshi Narihito , Kono Hitoshi , Tsuji Osahiko , Aoyama Ryoma , Fujiyoshi Kanehiro , Shiono Yuta , Ishikawa Masayuki , Daimon Kenshi , Hosogane Naobumi , Takeuchi Ayano , Okada Eijiro , Fujita Nobuyuki , Yagi Mitsuru , Nakamura Masaya , Matsumoto Morio , Watanabe Kota , Ishii Ken , Yamane Junichi
Published: April 2020

Study Design:

This was a case-control study.

Objective:

The objective of this study was to clarify the surgical outcomes after cervical posterior decompression in patients who smoked.

Summary of Background Data:

Smoking is associated with poor outcomes in the field of spinal surgery. However, the impact of tobacco smoking on the outcomes after posterior decompression surgery has not been fully evaluated in patients with cervical spondylotic myelopathy.

Materials and Methods:

In this retrospective multicenter study, 587 patients with cervical spondylotic myelopathy were enrolled at 17 institutions in Japan. Patients underwent cervical laminoplasty or laminectomy and were followed up for at least 1 year after surgery. Outcome measures were: preoperative smoking status, perioperative complications, the Japanese Orthopedic Association scale, and the Visual Analog Scale for neck pain. After adjusting for age and sex by exact matching, smoking and nonsmoking groups were compared using an unpaired t test for continuous variables or a χ2 test for categorical variables.

Results:

There were 182 (31%) current smokers and 405 (69%) nonsmokers including previous smokers. After matching, 158 patients were extracted from each group. Demographic data and surgical information were almost the same between the groups. Regarding postoperative complications, there was no significant difference in the rate of surgical site infection, cerebrospinal fluid leakage, hematoma, segmental motor paralysis, or neurological deficit. However, smokers showed a significantly higher risk for delirium (3.8% vs. 0.0%, P=0.039). Smokers and nonsmokers showed comparable changes in functional recovery according to Japanese Orthopedic Association scores (3.2±2.1 vs. 3.0±2.1, P=0.425) and in neck pain reduction using the Visual Analog Scale (−1.7±3.1 vs. −1.4±2.8, P=0.417) at the final follow-up.

Conclusions:

Smokers exhibited functional restoration and neck pain reduction after cervical posterior decompression. Attention is required, however, for the postoperative complication of delirium, which could be caused by the acute cessation of tobacco smoking after admission.

Level of Evidence:

Level III.
Joint Society of Critical Care Medicine-Extracorporeal Life Support Organization Task Force Position Paper on the Role of the Intensivist in the Initiation and Management of Extracorporeal Membrane Oxygenation
Authors: DellaVolpe Jeffrey , Barbaro Ryan P. , Cannon Jeremy W. , Fan Eddy , Greene Wendy R. , Gunnerson Kyle J. , Napolitano Lena M. , Ovil Ace , Pamplin Jeremy C. , Schmidt Matthieu , Sorce Lauren R. , Brodie Daniel
Published: April 2020

Objectives:

To define the role of the intensivist in the initiation and management of patients on extracorporeal membrane oxygenation.

Design:

Retrospective review of the literature and expert consensus.

Setting:

Series of in-person meetings, conference calls, and emails from January 2018 to March 2019.

Subjects:

A multidisciplinary, expert Task Force was appointed and assembled by the Society of Critical Care Medicine and the Extracorporeal Life Support Organization. Experts were identified by their respective societies based on reputation, experience, and contribution to the field.

Interventions:

A MEDLINE search was performed and all members of the Task Force reviewed relevant references, summarizing high-quality evidence when available. Consensus was obtained using a modified Delphi process, with agreement determined by voting using the RAND/UCLA scale, with score ranging from 1 to 9.

Measurements and Main Results:

The Task Force developed 18 strong and five weak recommendations in five topic areas of extracorporeal membrane oxygenation initiation and management. These recommendations were organized into five areas related to the care of patients on extracorporeal membrane oxygenation: patient selection, management, mitigation of complications, coordination of multidisciplinary care, and communication with surrogate decision-makers. A common theme of the recommendations is extracorporeal membrane oxygenation is best performed by a multidisciplinary team, which intensivists are positioned to engage and lead.

Conclusions:

The role of the intensivist in the care of patients on extracorporeal membrane oxygenation continues to evolve and grow, especially when knowledge and familiarity of the issues surrounding extracorporeal membrane oxygenation selection, cannulation, and management are applied.
QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF INACTIVE MACULAR NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION
Authors: Serra Rita , Coscas Florence , Pinna Antonio , Cabral Diogo , Coscas Gabriel , Souied Eric H.
Published: April 2020

Purpose:

To compare quantitative optical coherence tomography angiography parameters between treatment-naïve quiescent macular neovascularizations (MNVs) and previously treated nonexudative Type 1 MNVs, in patients with age-related macular degeneration.

Methods:

The eyes included in the study were analyzed by fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. According to their medical history and multimodal imaging evaluation, Type 1 MNVs were divided into 2 groups: 1) treatment-naïve quiescent MNVs; 2) previously treated nonexudative Type 1 MNVs. Quantitative optical coherence tomography angiography parameters, including perfusion density (PD), fractal dimension (FD), and lacunarity (LAC) were calculated. Receiver operating characteristic curves, showing the ability of PD, FD, and LAC to discriminate between the two MNV groups, were built.

Results:

Twenty-two eyes with treatment-naïve quiescent MNVs and 20 eyes with MNVs previously treated nonexudative Type 1 MNVs were analyzed. Mean FD and LAC were statistically different between the two study groups (P < 0.05). Lacunarity showed the best discrimination ability, followed by FD and PD (area under curve = 0.83, 0.78, 0.62, respectively).

Conclusion:

Results suggest that FD and LAC may be useful optical coherence tomography angiography biomarkers to objectively discriminate inactive MNVs with different prognosis, such as treatment-naïve quiescent MNVs and previously treated nonexudative Type 1 MNVs, in age-related macular degeneration patients.
Computational fluid dynamic study of multiple sequential coronary artery bypass anastomoses in a native coronary stenosis model
Authors: Matsuura Kaoru , Jin Wei Wei , Liu Hao , Matsumiya Goro
Published: April 2020

Background

The objective of this study was to evaluate the hemodynamic characteristics of multiple sequential coronary artery bypass grafting using a computational fluid dynamics study.

Methods

First anastomosis was configured into parallel and diamond anastomoses, and the second anastomosis was set as end-side anastomosis. The anastomosis incision lengths were fixed at 2 mm. Various combinations of the degree of first and second stenoses were studied. The diameter of both the native and graft vessels was set at 2 mm. The inlet boundary condition was set by a sample of the transient time flow measurement, which was measured intraoperatively.

Results

Both swirl and stagnation were observed at the outlets of the stenosis and the anastomosis sites. When the severity of the second stenosis was larger than that of the first, the flow at the outlet of the second stenosis was more unstable. Higher wall shear stress and larger oscillatory shear index regions were observed when the severe stenosis was bypassed by the first anastomosis, especially with diamond anastomoses. Less energy loss and higher energy efficiency were present when the vessel with more severe stenosis was bypassed as the second anastomosis. Energy loss was lower and energy efficiency was higher with parallel anastomosis than diamond anastomosis when the severity of the two stenoses was the same.

Conclusions

It is ideal to bypass the less severe stenosis vessel first with a parallel anastomosis method when employing multiple sequential bypass grafting. This improves hemodynamic stability and energy efficiency, according to a computational fluid dynamics model.
Invasive Stratified Mucinous Carcinoma (iSMC) of the Cervix Often Presents With High-risk Features That Are Determinants of Poor Outcome
Authors: Stolnicu Simona , Boros Monica , Segura Sheila , Horn Lars-Christian , Parra-Herran Carlos , Oliva Esther , Abu-Rustum Nadeem , Soslow Robert A. , Park Kay J.
Published: April 2020

Invasive stratified mucinous carcinoma (iSMC) has been suggested to represent an aggressive subtype of endocervical adenocarcinoma. We sought to investigate the outcomes of iSMC and determine which clinical and pathologic parameters may influence the prognosis. Slides from 52 cases of iSMC were collected and classified as follows: pure iSMC (>90% of the entire tumor) and iSMC mixed with other human papillomavirus–associated adenocarcinoma components (miSMC) (>10%, but <90% of the entire tumor). Clinical and pathologic parameters were evaluated and compared with overall survival (OS) and recurrence-free survival (RFS). One third of patients with iSMC presented with lymph node metastases (LNM) and 25% developed local recurrences, whereas 4 (7.7%) developed distant recurrences. 29 cases (55.8%) were pure iSMC, whereas 23 cases (44.23%) were miSMC. OS was 74.7% in pure iSMC versus 85.2% in miSMC (P=0.287). RFS was 56.5% in pure iSMC and 72.9% in miSMC (P=0.185). At 5 years, OS in stage I was 88.9% versus stage II to IV 30% (P=0.004), whereas RFS in stage I was 73.9% versus stage II to IV 38.1% (P=0.02). OS was influenced by International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.013), tumor size (P=0.02), LNM (P=0.015), and local recurrence (P=0.022), whereas RFS was influenced by FIGO stage (P=0.031), tumor size (P=0.001), local recurrence (P=0.009), LNM (P=0.008), and type of surgical treatment (P=0.044). iSMC is an aggressive cervical tumor biologically different from other human papillomavirus–associated adenocarcinomas due to the propensity for LNM, local/distant recurrence. FIGO stage, tumor size, LNM, and presence of local/pelvic recurrences are determinants of outcome in iSMCs.
Deep Learning AI Applications in the Imaging of Glioma
Authors: Zlochower Avraham , Chow Daniel S. , Chang Peter , Khatri Deepak , Boockvar John A. , Filippi Christopher G.
Published: April 2020

This manuscript will review emerging applications of artificial intelligence, specifically deep learning, and its application to glioblastoma multiforme (GBM), the most common primary malignant brain tumor. Current deep learning approaches, commonly convolutional neural networks (CNNs), that take input data from MR images to grade gliomas (high grade from low grade) and predict overall survival will be shown. There will be more in-depth review of recent articles that have applied different CNNs to predict the genetics of glioma on pre-operative MR images, specifically 1p19q codeletion, MGMT promoter, and IDH mutations, which are important criteria for the diagnosis, treatment management, and prognostication of patients with GBM. Finally, there will be a brief mention of current challenges with DL techniques and their application to image analysis in GBM.
Diffusely Increased Myocardial Extracellular Volume With or Without Focal Late Gadolinium Enhancement
Authors: Lundin Magnus , Sörensson Peder , Maret Eva , Jenner Jonas , Abdula Goran , Nickander Jannike , Themudo Raquel , Caidahl Kenneth , Kellman Peter , Sigfridsson Andreas , Ugander Martin
Published: April 2020

Purpose:

Myocardial extracellular volume fraction (ECV) using cardiovascular magnetic resonance (CMR) can identify diffuse lesions not detected by late gadolinium enhancement (LGE). We aimed to determine the prevalence of increased ECV and its relation to other CMR findings.

Materials and Methods:

Consecutive patients (n=609, age median [interquartile range] 53 [39 to 66] y, 62% male) underwent CMR at 1.5 T. Focal lesions on LGE images were noted. ECV in regions without focal LGE findings defined diffuse changes. Pronounced increases in left ventricular (LV) end-diastolic volume index and LV mass index, and pronounced decreases in LV ejection fraction were defined as >3 SD from the sex-specific mean in healthy volunteers.

Results:

Of 609 patients without amyloidosis or hypertrophic cardiomyopathy, 8% had diffusely increased ECV and 5% of all patients had diffusely increased ECV without any focal LGE findings. Multivariate analysis showed that a pronounced increase in the LV end-diastolic volume index was associated with increased ECV (P=0.001), but not LGE (P=0.52). A pronounced decrease in LV ejection fraction was associated with the presence of LGE (P<0.001), but not with increased ECV (P=0.41).

Conclusions:

Eight percent of patients in this clinical cohort with known or suspected heart disease had diffusely increased ECV and 60% of these lacked focal LGE findings. LV size is independently associated with increased ECV, whereas systolic dysfunction is independently associated with LGE. This image-based clinical study demonstrates that ECV-CMR provides additional information negligibly related to the results of LGE imaging, and thereby increases the diagnostic yield of CMR.
Gexplora– user interface that highlights and explores the density of genomic elements along a chromosomal sequence
Authors: Nussbaumer Thomas , Debnath Olivia , Heidari Parviz
Published: April 2020

The density of genomic elements such as genes or transposable elements along its consecutive sequence can provide an overview of a genomic sequence while in the detailed analysis of candidate genes it may depict enriched chromosomal hotspots harbouring genes that explain a certain trait. The herein presented python-based graphical user interfaceGexploraallows to obtain more information about a genome by considering sequence-intrinsic information from external databases such as Ensembl, OMA and STRING database using REST API calls to retrieve sequence-intrinsic information, protein-protein datasets and orthologous groups. Gexplora is available underhttps://github.com/nthomasCUBE/Gexplora.
A Connectome and Analysis of the AdultDrosophilaCentral Brain
Authors: Scheffer Louis K. , Xu C. Shan , Januszewski Michal , Lu Zhiyuan , Takemura Shin-ya , Hayworth Kenneth J. , Huang Gary B. , Shinomiya Kazunori , Maitin-Shepard Jeremy , Berg Stuart , Clements Jody , Hubbard Philip , Katz William , Umayam Lowell , Zhao Ting , Ackerman David , Blakely Tim , Bogovic John , Dolafi Tom , Kainmueller Dagmar , Kawase Takashi , Khairy Khaled A. , Leavitt Laramie , Li Peter H. , Lindsey Larry , Neubarth Nicole , Olbris Donald J. , Otsuna Hideo , Trautman Eric T. , Ito Masayoshi , Goldammer Jens , Wolff Tanya , Svirskas Robert , Schlegel Philipp , Neace Erika R. , Knecht Christopher J. , Alvarado Chelsea X. , Bailey Dennis A. , Ballinger Samantha , Borycz Jolanta A , Canino Brandon S. , Cheatham Natasha , Cook Michael , Dreher Marisa , Duclos Octave , Eubanks Bryon , Fairbanks Kelli , Finley Samantha , Forknall Nora , Francis Audrey , Hopkins Gary Patrick , Joyce Emily M. , Kim SungJin , Kirk Nicole A. , Kovalyak Julie , Lauchie Shirley A. , Lohff Alanna , Maldonado Charli , Manley Emily A. , McLin Sari , Mooney Caroline , Ndama Miatta , Ogundeyi Omotara , Okeoma Nneoma , Ordish Christopher , Padilla Nicholas , Patrick Christopher , Paterson Tyler , Phillips Elliott E. , Phillips Emily M. , Rampally Neha , Ribeiro Caitlin , Robertson Madelaine K , Rymer Jon Thomson , Ryan Sean M. , Sammons Megan , Scott Anne K. , Scott Ashley L. , Shinomiya Aya , Smith Claire , Smith Kelsey , Smith Natalie L. , Sobeski Margaret A. , Suleiman Alia , Swift Jackie , Takemura Satoko , Talebi Iris , Tarnogorska Dorota , Tenshaw Emily , Tokhi Temour , Walsh John J. , Yang Tansy , Horne Jane Anne , Li Feng , Parekh Ruchi , Rivlin Patricia K. , Jayaraman Vivek , Ito Kei , Saalfeld Stephan , George Reed , Meinertzhagen Ian A. , Rubin Gerald M. , Hess Harald F. , Jain Viren , Plaza Stephen M.
Published: April 2020

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly’s brain.
Bitbow: a digital format of Brainbow enables highly efficient neuronal lineage tracing and morphology reconstruction in single brains
Authors: Li Ye , Walker Logan A , Zhao Yimeng , Edwards Erica M , Michki Nigel S , Cheng Hon Pong Jimmy , Ghazzi Marya , Chen Tiffany Y , Chen Maggie , Roossien Douglas H , Cai Dawen
Published: April 2020

Identifying the cellular origins and mapping the dendritic and axonal arbors of neurons have been century old quests to understand the heterogeneity among these brain cells. Classical chemical and genetic methods take advantage of light microscopy and sparse labeling to unambiguously, albeit inefficiently, trace a few neuronal lineages or reconstruct their morphologies in each sampled brain. To improve the analysis throughput, we designed Bitbow, a digital format of Brainbow which exponentially expands the color palette to provide tens of thousands of spectrally resolved unique labels. We generated transgenic BitbowDrosophilalines, established statistical tools, and streamlined sample preparation, image processing and data analysis pipelines to allow conveniently mapping neural lineages, studying neuronal morphology and revealing neural network patterns with an unprecedented speed, scale and resolution.
Subthreshold Voltage Analysis Demonstrates Neuronal Cell-Surface Sialic Acids Modulate Excitability and Network Integration
Authors: Kulkarni Rishikesh U. , Wang Catherine L. , Bertozzi Carolyn R.
Published: April 2020

All neurons are covered in a thick layer of carbohydrates called glycans. Glycans are modified during neurological processes and are thought to play a role in neuronal communication. We develop a voltage imaging platform for analyzing functional connectivity changes using simultaneous voltage recordings in small populations of neurons. We validate this platform using a culture model of development as well as with several pharmacological interventions. Using this platform, we show that ablation of SNA-binding glycans results in loss of functional connectivity in mouse hippocampal neurons, while ablation of MAL II binding glycans minimally perturbs functional connectivity. Altogether, our data reveal that subpopulations of glycans play different roles in maintenance of electrophysiology and provide a platform for modeling changes in functional connectivity with simultaneous voltage recordings.
Chlamydomonas reinhardtiiTubulin-Gene Disruptants for Efficient Isolation of Strains Bearing Novel Tubulin Mutations
Authors: Kato-Minoura Takako , Ogiwara Yutaro , Yamano Takashi , Fukuzawa Hideya , Kamiya Ritsu
Published: April 2020

The single-cell green algaChlamydomonas reinhardtiipossesses two α-tubulin genes (tua1andtua2) and two β-tubulin genes (tub1andtub2), with the two genes in each pair encoding identical amino acid sequences. Here, we used anaphVIIIgene cassette insertional library to establish eight disruptants with defectivetua2, tub1, ortub2expression. None of the disruptants exhibited apparent defects in cell growth, flagellar length, or flagellar regeneration after amputation. Because few tubulin mutants ofC. reinhardtiihave been reported to date, we then used our disruptants, together with atua1disruptant obtained from theChlamydomonasLibrary Project (CLiP), to isolate novel tubulin-mutants resistant to the anti-tubulin agents propyzamide and oryzalin. As a result of several trials, we obtained 8 strains bearing 7 different α-tubulin mutations and 24 strains bearing 12 different β-tubulin mutations. Some of these mutations are known to confer drug resistance in human cancer cells. Thus, single-tubulin-gene disruptants are an efficient means of isolating novelC. reinhardtiitubulin mutants.

IMPORTANCE

Chlamydomonas reinhardtiiis a useful organism for the study of tubulin function; however, only five kinds of tubulin mutations have been reported to date. This scarcity is partly due toC. reinhardtiipossessing two tubulin genes each for α- and β-tubulin. Here, we obtained several strains in which one of the α- or β-tubulin genes was disrupted, and then used those disruptants to isolate 32 strains bearing 19 mostly novel tubulin mutations that conferred differing degrees of resistance to two anti-tubulin compounds. The majority of the tubulin mutations were located outside of the drug-binding sites in the three-dimensional tubulin structure, suggesting that structural changes underlie the drug resistance conferred by these mutations. Thus, single-tubulin-gene disruptants are an efficient means of generating tubulin mutants for the study of the structure–function relationship of tubulin and for the development of novel therapies based on anti-tubulin agents.
Protein Interactomes Identify Distinct Pathways forStreptococcus mutansYidC1 and YidC2 Membrane Protein Insertases
Authors: Vasquez Patricia Lara , Mishra Surabhi , Kuppuswamy Senthil K. , Crowley Paula J. , Brady L. Jeannine
Published: April 2020

Virulence properties of cariogenicStreptococcus mutansdepend on integral membrane proteins. Bacterial protein trafficking involves the co-translational signal recognition particle (SRP) pathway components Ffh and FtsY, the SecY translocon, and membrane-localized YidC chaperone/insertases. UnlikeEscherichia coli, S. mutanssurvives loss of the SRP pathway. In addition,S. mutanshas twoyidCparalogs. TheΔyidC2phenotype largely parallels that ofΔffhandΔftsYwhile theΔyidC1phenotype is less severe. This study defined YidC1 and YidC2 interactomes to identify their respective functions alone and in concert with the SRP, ribosome, and/or Sec translocon. A chemical cross-linking approach was employed, whereby whole cell lysates were treated with formaldehyde followed by Western blotting using anti-Ffh, FtsY, YidC1 or YidC2 antibodies and mass spectrometry (MS) analysis of gel-shifted bands. Cross-linked lysates from WT andΔyidC2strains were also reacted with anti-YidC2 antibodies coupled to magnetic Dynabeads™, with co-captured proteins identified by MS. Additionally, C-terminal tails of YidC1 and YidC2 were engineered as glutathione-S-transferase fusion proteins and subjected to 2D Difference Gel Electrophoresis and MS analysis after being reacted with non-cross-linked lysates. Results indicate that YidC2 works in concert with the SRP-pathway, while YidC1 works in concert with the SecY translocon independently of the SRP. In addition, YidC1 and/or YidC2 can act alone in the insertion of a limited number of small integral membrane proteins. The YidC2-SRP and YidC1/SecY pathways appear to function as part of an integrated machinery that couples translation and transport with cell division, as well as transcription and DNA replication.

Importance

Streptococcus mutansis a prevalent oral pathogen and causative agent of tooth decay. Many proteins that enable this bacterium to thrive in its environmental niche, and cause disease, are embedded in its cytoplasmic membrane. The machinery that transports proteins into bacterial membranes differs between Gram-negative and Gram-positive organisms. One important difference is the presence of multiple YidC paralogs in Gram-positive bacteria. Characterization of a protein’s interactome can help define its physiological role. Herein, we characterized the interactomes ofS. mutansYidC1 and YidC2. Results indicate that YidC1 and YidC2 have individualized functions in separate membrane insertion pathways, and suggest putative substrates of the respective pathways. Furthermore,S. mutansmembrane transport proteins appear as part of a larger network of proteins involved in replication, transcription, translation, and cell division/cell shape. This information contributes to our understanding of protein transport in Gram-positive bacteria in general, and informs our understanding ofS. mutanspathogenesis.