bluuebunny/crossref_metadata_2025 huggingface dataset:
Worldwide strains of the nematophagous fungusPochonia chlamydosporiaare endophytic in banana roots and promote plant growth
Authors: Mingot-Ureta Cristina , Lopez-Moya Federico , Lopez-Llorca Luis Vicente
Published: June 2020

The biocontrol fungus,Pochonia chlamydosporia, colonizes endophytically banana roots. Root hairs and root surface were found colonize by the fungus using a stable GFP transformant. Hyphal penetration of root cells was also observed. Spores ofP. chlamydosporia123, significantly increase root and leaf length and weight in banana plantlets(Musa acuminatacv. ‘Dwarf Cavendish’) in growth chamber experiments 30 days post-inoculation (dpi). In greenhouse 8L pot experiments,P. chlamydosporia123 spore inoculation significantly increases leaf and root length and leaf weight in banana plants (75 dpi). Spore inoculation ofP. chlamydosporiastrains from worldwide origin (Pc21 Italy, Pc123 Spain, Pc399 China, and Pccat Cuba), significantly increases root, corm and leaf length and weight in banana plantlets. Pc21 was the best colonizer of banana roots. Consequently, this strain significantly increases most banana root and leaf length. Root colonization byP. chlamydosporiawas also detected using cultural techniques and qPCR.
On phage adsorption to bacterial chains
Authors: Eriksen R. S. , Mitarai N. , Sneppen K.
Published: June 2020

Bacteria often arrange themselves in various spatial configurations which changes how they interact with their surroundings. In this paper, we investigatein silicohow the structure of the bacterial arrangements influences the adsorption of bacteriophages. We quantify how the adsorption rate scales with the number of bacteria in the arrangement, and show that the adsorption rates for microcolonies (increasing with exponent ∼1/3) and bacterial chains (increasing with exponent ∼0.5 − 0.8) are substantially lower than for well-mixed bacteria (increasing with exponent 1). We further show that, after infection, the spatially clustered arrangements reduce the effective burst size by more than 50 % and cause substantial superinfections in a very short time interval after phage lysis.

SIGNIFICANCE

When bacteria forms clusters they substantially change their exposure to invading phages and other external agents from the well-mixed scenario. Despite this fact, much research has focused on and is focusing on using well-mixed bacteria. Understanding the kinetics of the spatial structures is paramount to developing robust analyses and theories of experimental results. We carefully investigate how the clusters lower the adsorption rate of external phages and how the clustering modifies the hit probabilities for the bacteria.
Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations
Authors: Rath Soumya Lipsa , Kumar Kishant
Published: June 2020

Statistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-30 °C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 °C and attains a completely closed conformation at 50 °C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics.

Graphical Abstract

Highlights

Statistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same.

Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2.

Results show that the Spike’s S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain.

The N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30° C.

The Receptor Binding Motif adopts a closed conformation at 40°C and completely closes at higher temperatures making it unsuitable of binding to human receptors
α-Synuclein facilitates dopamine release during burst firing of substantia nigra neuronsin vivo
Authors: Somayaji Mahalakshmi , Cataldi Stefano , Edwards Robert H. , Mosharov Eugene V. , Sulzer David
Published: June 2020

α-Synuclein is expressed at high levels at presynaptic terminals, but defining its role on neurotransmission under physiologically-relevant conditions has proven elusive. We report that α-synuclein is responsible for a rapid facilitation of dopamine release during action potential burstsin vivo. This occurs in tandem with a far slower stimulus-dependent depression, appears to be independent of the presence of β- and γ-synucleins or effects on presynaptic calcium and is consistent with a role for synucleins in the enhancement of synaptic vesicle fusion and turnover. The results indicate that the presynaptic effects of α-synuclein are dependent on specific patterns of neuronal activity.
The long-distance flight behavior ofDrosophilasuggests a general model for wind-assisted dispersal in insects
Authors: Leitch Katherine , Ponce Francesca , van Breugel Floris , Dickinson Michael H.
Published: June 2020

Despite the ecological importance of long-distance dispersal in insects, its underlying mechanistic basis is poorly understood. One critical question is how insects interact with the wind to increase their travel distance as they disperse. To gain insight into dispersal using a species amenable to further investigation using genetic tools, we conducted release-and-recapture experiments in the Mojave Desert using the fruit fly,Drosophila melanogaster. We deployed chemically-baited traps in a 1 km-radius ring around the release site, equipped with machine vision systems that captured the arrival times of flies as they landed. In each experiment, we released between 30,000 and 200,000 flies. By repeating the experiments under a variety of conditions, we were able to quantify the influence of wind on flies’ dispersal behavior. Our results confirm that even tiny fruit flies could disperse ∼15 km in a single flight in still air, and might travel many times that distance in a moderate wind. The dispersal behavior of the flies is well explained by a model in which animals maintain a fixed body orientation relative to celestial cues, actively regulate groundspeed along their body axis, and allow the wind to advect them sideways. The model accounts for the observation that flies actively fan out in all directions in still air, but are increasingly advected downwind as winds intensify. In contrast, our field data do not support a Lévy flight model of dispersal, despite the fact that our experimental conditions almost perfectly match the core assumptions of that theory.

Significance Statement

Flying insects play a vital role in terrestrial ecosystems, and their decline over the past few decades has been implicated in a collapse of many species that depend upon them for food. By dispersing over large distances, insects transport biomass from one region to another and thus their flight behavior influences ecology on a global scale. Our experiments provide key insight into the dispersal behavior of insects, and suggest that these animals employ a single algorithm that is functionally robust in both still air and under windy conditions. Our results will make it easier to study the ecologically important phenomenon of long-distance dispersal in a genetic model organism, facilitating the identification of cellular and genetic mechanisms.
COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data
Authors: Rakha Allah , Rasheed Haroon , Batool Zunaira , Akram Javed , Adnan Atif , Du Jiang
Published: June 2020

COVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available athttp://covid-19.dnageography.com.
The architecture of co-morbidity networks of physical and mental health conditions in military veterans
Authors: Alexander-Bloch Aaron F , Raznahan Armin , Shinohara Russell T , Mathias Samuel R , Bathulapalli Harini , Bhalla Ish P , Goulet Joseph , Satterthwaite Theodore , Bassett Danielle S. , Glahn David C , Brandt Cynthia A.
Published: June 2020

Co-morbidity between medical and psychiatric conditions is commonly considered between individual pairs of conditions. However, an important alternative is to consider all conditions as part of a co-morbidity network, which encompasses all interactions between patients and a healthcare system. Analysis of co-morbidity networks could detect and quantify general tendencies not observed by smaller-scale studies. Here, we investigate the co-morbidity network derived from longitudinal healthcare records from approximately 1-million U.S. military veterans, a population disproportionately impacted by psychiatric morbidity and psychological trauma. Network analyses revealed marked and heterogenous patterns of co-morbidity, including a multi-scale community structure composed of groups of commonly co-morbid conditions. Psychiatric conditions including posttraumatic stress disorder were strong predictors of future medical morbidity. Neurological conditions and conditions associated with chronic pain were particularly highly co-morbid with psychiatric conditions. Across conditions, the degree of co-morbidity was positively associated with mortality. Co-morbidity was modified by biological sex and could be used to predict future diagnostic status, with out-of-sample prediction accuracy of 90-92%. Understanding complex patterns of disease co-morbidity has the potential to lead to improved designs of systems of care and the development of targeted interventions that consider the broader context of mental and physical health.
Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach
Authors: Li Mengyuan , Zhang Zhilan , Cao Wenxiu , Liu Yijing , Du Beibei , Chen Canping , Liu Qian , Uddin Md. Nazim , Jiang Shanmei , Chen Cai , Zhang Yue , Wang Xiaosheng
Published: June 2020

The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.
On the interplay between mobility and hospitalization capacity during the COVID-19 pandemic: The SEIRHUD model
Authors: Veloz Tomás , Maldonado Pedro , Ropert Samuel , Ravello César , Mora Soraya , Barrios Alejandra , Villaseca Tomás , Valdenegro César , Perez-Acle Tomás
Published: June 2020

Measures to reduce the impact of the COVID-19 pandemic require a mix of logistic, political and social capacity. Depending on the country, different approaches to increase hospitalization capacity or to properly apply lock-downs are observed. In order to better understand the impact of these measures we have developed a compartmental model which, on the one hand allows to calibrate the reduction of movement of people within and among different areas, and on the other hand it incorporates a hospitalization dynamics that differentiates the available kinds of treatment that infected people can receive. By bounding the hospitalization capacity, we are able to study in detail the interplay between mobility and hospitalization capacity.
The interplay between information flux and temporal dynamics in infraslow frequencies
Authors: Golesorkhi Mehrshad , Tumati Shankar , Gomez-Pilar Javier , Stamatakis Emmanuel. A. , Northoff Georg.
Published: June 2020

Unlike the brain’s faster frequencies, the exact role of its more powerful infraslow frequencies (ISF, 0.01 – 0.1Hz) in information processing remains poorly understood. Do and how ISF process information? We investigate information processing and related temporal dynamics of ISF in resting and task state fMRI. To quantify information, we apply the Lempel-Ziv complexity (LZC), a measure of signal compression indexing information. The LZC is combined with direct measurement of the dynamics of ISF themselves, namely their power spectral density by median frequency (MF). We demonstrate the following: (I) topographical differences in resting state between higher- and lower-order networks, showing statistically lower LZC in the former; (II) task-related changes in LZC; (III) modulation of LZC associated with MF changes, with low and high MF resting-state values correlated with different degrees of LZC change. In sum, we provide evidence that ISF carry and process information as mediated through their temporal dynamics.
Phase-separation of EML4-ALK variant 3 is dependent upon an active ALK conformation
Authors: Sampson Josephina , Richards Mark W. , Choi Jene , Fry Andrew M. , Bayliss Richard
Published: June 2020

Oncogenic fusions involving tyrosine kinases are common drivers of non-small cell lung cancer (NSCLC). There are at least 15 different variants of the EML4-ALK fusion, all of which have a similar portion of ALK that includes the kinase domain, but different portions of EML4. Targeted treatment with ALK tyrosine kinase inhibitors (TKIs) has proven effective but patient outcomes are variable. Here, we focus on one common variant, EML4-ALK V3, which drives an aggressive form of the disease. EML4-ALK V3 protein forms cytoplasmic liquid droplets that contain the signalling proteins GRB2 and SOS1. The TKIs ceritinib and lorlatinib dissolve these droplets and the EML4-ALK V3 protein re-localises to microtubules, an effect recapitulated by an inactivating mutation in the ALK catalytic site. Mutations that promote a constitutively active ALK stabilise the liquid droplets even in the presence of TKIs, indicating that droplets do not depend on kinase activityper se. Uniquely, the TKI alectinib promotes droplet formation of both the wild-type and catalytically inactive EML4-ALK V3 mutant, but not in a mutant that disrupts a hallmark of the kinase activity, the Lys-Glu salt-bridge. We propose that EML4-ALK V3 liquid droplet formation occurs through transient dimerization of the ALK kinase domain in its active conformation in the context of stable EML4-ALK trimers. Our results provide insights into the relationship between ALK activity, conformational state and the sub-cellular localisation of EML4-ALK V3 protein, and reveal the different effects of structurally divergent ALK TKIs on these properties.
An integrative study of five biological clocks in somatic and mental health
Authors: Jansen Rick , Verhoeven Josine , Han Laura KM , Aberg Karolina A , van den Oord Edwin CGJ , Milaneschi Yuri , Penninx Brenda WJH
Published: June 2020

Biological clocks have been developed at different molecular levels and were found to be more advanced in the presence of somatic illnesses and mental disorders. However, it is unclear whether different biological clocks reflect similar aging processes and determinants. In ~3000 subjects, we examined whether 5 biological clocks (telomere length, epigenetic, transcriptomic, proteomic and metabolomic clocks) were interrelated and associated to somatic and mental health determinants. Correlations between biological clocks were small (allr<0.2), indicating little overlap. The most consistent associations with the advanced biological clocks were found for male sex, higher BMI, metabolic syndrome, smoking and depression. As compared to the individual clocks, a composite index of all five clocks showed most pronounced associations with health determinants. The large effect sizes of the composite index and the low correlation between biological clocks, indicate that one’s biological age is best reflected by combining aging measures from multiple cellular levels.
2-amino-1,3-benzothiazole-6-carboxamide Preferentially Binds the Tandem Mismatch Motif r(UY:GA)
Authors: Chang Andrew T. , Chen Lu , Song Luo , Zhang Shuxing , Nikonowicz Edward P.
Published: June 2020

RNA helices are often punctuated with non-Watson-Crick features that can be the target of chemical compounds, but progress towards identifying small molecules specific for non-canonical elements has been slow. We have used a tandem UU:GA mismatch motif (5’-UG-3’:5’-AU-3’) embedded within the helix of an RNA hairpin as a model to identify compounds that bind the motif specifically. The three-dimensional structure of the RNA hairpin and its interaction with a small molecule compound identified through a virtual screen are presented. The G-A of the mismatch forms a sheared pair upon which the U-U base pair stacks. The hydrogen bond configuration of the U-U pair involves the O2 of the U adjacent to the G and the O4 of the U adjacent to the A. The G-A and U-U pairs are flanked by A-U and G-C base pairs, respectively, and the mismatch exhibits greater stability than when the motif is within the context of other flanking base pairs or when the 5’-3’ orientation of the G-A and U-U is swapped. Residual dipolar coupling constants were used to generate an ensemble of structures against which a virtual screen of 64,480 small molecules was performed to identify candidate compounds that the motif specifically binds. The tandem mismatch was found to be specific for one compound, 2-amino-1,3-benzothiazole-6-carboxamide, which binds with moderate affinity but extends the motif to include the flanking A-U and G-C base pairs. The finding that affinity for the UU:GA mismatch is flanking sequence dependent emphasizes the importance of motif context and potentially increases the number of small non-canonical features within RNA that can be specifically targeted by small molecules.
Critical role of WNK1 in MYC-dependent early thymocyte development
Authors: Köchl Robert , Vanes Lesley , Sopena Miriam Llorian , Chakravarty Probir , Hartweger Harald , Fountain Kathryn , White Andrea , Cowan Jennifer , Anderson Graham , Tybulewicz Victor L. J.
Published: June 2020

WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+T cells.Wnk1is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the β-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development.
A study on the appropriate use of topdown approach for stepping up economic activities in districts of different States/Union Territories in India
Authors: Chakraborty Arindom , Das Kalyan
Published: June 2020

At the beginning of phase 4.0 of lockdown, every State /Union Territories(UT) needs to take appropriate mitigation efforts (lockdown and testing) that may change red zones to orange and even to green zones by May 31, 2020. On the contrary, negligence in following the guidelines (for interventions) strictly, may be alarming and may change green zone status to even the worst red zone status. This has been established through a Statistical model based study here. From the present investigation, the Government can decide the right measures to take up so as to reduce the transmission of the virus and to open partial economic activities in different districts of a state. The whole idea can also be extended to containment zones in a district with sufficient data at hand.
Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study
Authors: Morales Daniel R. , Conover Mitchell M. , You Seng Chan , Pratt Nicole , Kostka Kristin , Duarte-Salles Talita , Fernández-Bertolín Sergio , Aragón Maria , DuVall Scott L. , Lynch Kristine , Falconer Thomas , van Bochove Kees , Sung Cynthia , Matheny Michael E. , Lambert Christophe G. , Nyberg Fredrik , Alshammari Thamir M. , Williams Andrew E. , Park Rae Woong , Weaver James , Sena Anthony G. , Schuemie Martijn J. , Rijnbeek Peter R. , Williams Ross D. , Lane Jennifer C.E. , Prats-Uribe Albert , Zhang Lin , Areia Carlos , Krumholz Harlan M. , Prieto-Alhambra Daniel , Ryan Patrick B. , Hripcsak George , Suchard Marc A.
Published: June 2020

Introduction

Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results.

Methods

Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) users to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments.

Results

Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 - 1.14), nor any difference for mono/combination use (1.01; 0.90 - 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 - 1.05) and marginally significant for mono/combination users (0.88; 0.79 - 0.99). We observed, however, no significant difference between drug-classes for COVID-19 hospitalization or pneumonia risk across all comparisons.

Conclusion

There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.
Even one metre seems generous. A reanalysis of data in: Chu et al. (2020) Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19.
Authors: Lonergan Mike
Published: June 2020

Re-examination of the large dataset collected and meta-analysed by Dr Chu and his colleagues contradicts their conclusions about the effects of separation distance on infection risk. Their conclusion was based on misunderstandings of the datasets. Each of these estimated risk relative to that incurred when touching infected individuals. Allowing for this suggests that the main advantage of social distancing, a perhaps 78% (95% CI 24, 92) reduction in risk of infection, occurs at distances below 1m. The data imply an 11% chance of further distances reducing the risk, with any effects likely to be small. However the limitations of the dataset do limit the strength of these conclusions.
Optimizing the COVID-19 Intervention Policy in Scotland and the Case for Testing and Tracing
Authors: Grothey Andreas , Mckinnon Ken
Published: June 2020

Abstract

Unlike other European countries the UK has abandoned widespread testing and tracing of known SARS-CoV-2 carriers in mid-March. The reason given was that the pandemic was out of control and with wide community based spread it would not be possible to contain it by tracing any longer. Like other countries the UK has since relied on a lockdown as the main measure to contain the virus (or more precisely the reproduction numberℛ) at significant economic and social cost. It is clear that this level of lockdown cannot be sustained until a vaccine is available, yet it is not clear what an exit strategy would look like that avoids the danger of a second (or subsequent waves).

In this paper we argue that, when used within a portfolio of intervention strategies, widespread testing and tracing leads to significant cost savings compared to using lockdown measures alone. While the effect is most pronounced if a large proportion of the infectious population can be identified and their contacts traced, under reasonable assumptions there are still significant savings even if the fraction of infectious people found by tracing is small.

We also present a policy optimization model that finds, for given assumptions on the disease parameters, the best intervention strategy to contain the virus by varying the degree of tracing and lockdown measure (and vaccination once that option is available) over time. We run the model on data fitted to the published COVID-19 outbreak figures for Scotland. The model suggests an intervention strategy that keeps the number of COVID-19 deaths low using a combination of tracing and lockdown. This strategy would only require lockdown measures equivalent to a reduction ofℛto about 1.8–2.0 if lockdown was used alone, at acceptable economic cost, while the model finds no such strategy without tracing enabled.
Risk Factors for Developing Diabetic Foot Ulcer with Nephropathy, Diabetic Kidney Disease and Renal Failure Statistical Analysis of 10,680 Patients’ Cohort
Authors: Aziz Kamran Mahmood Ahmed
Published: June 2020

It has been cited in the research that patients with diabetic kidney disease (DKD) and foot ulcer have poor prognosis; and foot ulceration is associated with kidney dysfunction. However, no study have found association of diabetic foot ulcer (DFU) with diabetic kidney dysfunction and their co-existing risk factors including blood pressure, serum creatinine, microalbumin, spot urine protein, HbA1c and associations of nephropathy and DKD with low ankle brachial index (ABI). We monitored, collected and analyzed the data for 10,680 patients for a duration of more than 13 years. 12% of patients demonstrated DFU. Nephropathy was observed in 39% of patients; 43% was hypertensive while 15% demonstrated DKD or CKD. Levels of HbA1c, creatinine,, systolic and diastolic blood pressures, microalbuminuria, spot urine protein, and spot urine protein to creatinine ratio were higher among the groups with foot ulcers (p-value < 0.0001 for all). Average ABI was observed to be lower among the groups demonstrating nephropathy and DKD with significant p-values (p=0.025 and 0.022 respectively). Pearson’s χ2and logistic regression with odds ratio were also analyzed for DFU with HTN, nephropathy and DKD. DFU was significantly associated with HTN (odds ratio 2.2 ; 95% CI 1.66 to 2.9; p < 0.0001), nephropathy (odds ratio 4.77 ;95% CI 3.53 to 6.5; p < 0.0001) and DKD (odds ratio 4.77 and 6.83; 95% CI 4.6 to 10.2; p < 0.0001). ROC was used to find out cutoff values, sensitivity and specificity. HbA1c of 7.8% was 60% sensitive and 52% specific for the development of DFU (AUC = 0.58; 95% CI 0.521 to 0.624; p < 0.0006). Creatinine of 1.2 mg/dl was 75% sensitive and 48% specific for DFU (AUC = 0.58; 95% CI 0.640 to 0.715; p < 0.0001). Spot urine protein excretion from nephrons of 35 mg/dl was 88% sensitive and 90% specific for the development of DFU (AUC = 0.585; 95% CI 0.555 to 0.616; p < 0.0001). Our data has demonstrated the first time such associations and confirmed that nephropathy or renal failure are risk factors for the development of DFU. HbA1c should be optimal and near to the targets to improve wound healing. Our study has prompted diabetologists for regular and routine assessment of the feet and early screening of diabetic patients for neuropathy, nephropathy, hypertension, dyslipidemia and other diabetic complications as well.
Patterns and Predictors of Weight Loss with Exenatide Treatment in Overweight and Obese Women
Authors: Dushay Jody , Flier Eleftheria Maratos , Gerzsten Robert E , Rodgers Megan , Heineman Brent , Migdal Alexandra , Kasid Natasha , Ghorbani Tahereh , Toschi Elena , Tripaldi Juliet , Nath Anjali , Chen Zsu Zsu , Phan Minh , Ngo Long
Published: June 2020

In the medical management of obesity, treating physicians observe significant heterogeneity in responses to pharmacotherapy. Indeed one of the most important clinical questions in obesity medicine is whether we can predict how an individual will respond to a particular pharmacotherapeutic agent. The present study examines patterns and predictors of weight loss among overweight and obese women who demonstrated early robust response to twice daily exenatide treatment.

182 women were assigned using single-blind randomization to either treatment with twice daily exenatide injections or to matched placebo injections with dietary counseling. Women who demonstrated > 5% weight loss after 12 weeks of treatment were deemed high responders and remained on study treatment for up to 52 weeks; women who lost < 5% body weight at 12 weeks were deemed low responders and stopped study treatment. We additionally characterized individuals who lost > 10% of body weight as super responders. Our primary outcome was change in body weight; secondary outcomes included changes in metabolic parameters including lipids, waist circumference, resting energy expenditure, and response to a meal tolerance test. We also performed an exploratory metabolomic analysis.

Consistent with published literature, we observed individual heterogeneity in the weight loss response to exenatide and diet/placebo. Although there was no significant difference between treatment groups in the percentage of participants who achieved > 5% weight loss (56% of exenatide group and 76% of diet/placebo group), or those who achieved > 10% weight loss (43% of exenatide group and 55% of diet/placebo group), in both cases there was a trend toward a higher response rate in the group that received placebo with dietary counseling. In addition to achieving similar average weight loss, both treatment groups also demonstrated similar maximum weight loss. The range of maximum weight loss was greater in the diet/placebo group and there was more weight regain among individuals in the exenatide group compared to the diet/placebo group. In our exploratory metabolomic analysis, we observed lower baseline circulating cysteine concentrations in the exenatide responder group and we also found a trend toward higher baseline levels of serotonin, aminoisobutyric acid, anandamide, and sarcosine in the exenatide super responder group. We did not identify any metabolic predictors of weight loss in either the exenatide or the diet/placebo treatment group.
Early epidemic spread, percolation and Covid-19
Authors: Oliveira Gonçalo
Published: June 2020

Human to human transmissible infectious diseases spread in a population using human interactions as its transmission vector. The early stages of such an outbreak can be modeled by a graph whose edges encode these interactions between individuals, the vertices. This article attempts to account for the case when each individual entails in different kinds of interactions which have therefore different probabilities of transmitting the disease. The majority of these results can be also stated in the language of percolation theory.

The main contributions of the article are: (1) Extend to this setting some results which were previously known in the case when each individual has only one kind of interactions. (2) Find an explicit formula for the basic reproduction numberR0which depends only on the probabilities of transmitting the disease along the different edges and the first two moments of the degree distributions of the associated graphs. (3) Motivated by the recent Covid-19 pandemic, we use the framework developed to compute theR0of a model disease spreading in populations whose trees and degree distributions are adjusted to several different countries. In this setting, we shall also compute the probability that the outbreak will not lead to an epidemic. In all cases we find such probability to be very low if no interventions are put in place.
Neonatal respiratory failure due to novel compound heterozygous mutations in the ABCA3 lipid transporter
Authors: Oltvai Zoltán N. , Smith Eric A. , Wiens Katie , Nogee Lawrence M. , Luquette Mark , Nelson Andrew C. , Wikenheiser-Brokamp Kathryn A.
Published: June 2020

The ATP-binding cassette transporter member A3 (ABCA3) is a lipid transporter with a critical function in pulmonary surfactant biogenesis. Biallelic loss-of-function mutations in ABCA3 result in severe surfactant deficiency leading to neonatal respiratory failure with death in the first year of life. Herein, we describe a newborn with severe respiratory distress at birth progressing to respiratory failure requiring transplant. This patient was found to have a maternally inherited frameshift loss-of-function ABCA3 mutation and a paternally inherited synonymous variant in ABCA3 predicted to create a cryptic splice site. Additional studies showed reduced ABCA3 expression in hyperplastic alveolar epithelial type II cells and lamellar body alterations characteristic of ABCA3 deficiency, leading to a diagnosis of autosomal recessive ABCA3-related pulmonary surfactant dysfunction. This case highlights the need for an integrated, comprehensive approach for the diagnosis of inherited diseases when in silico modeling is utilized in the interpretation of key novel genetic mutations.
Early-onset cerebellar ataxia in a patient with CMT2A2
Authors: Madrid Ricardo , Guariglia Sara R. , Haworth Andrea , Korosh William , Gavin Maureen , Lyon Gholson J.
Published: June 2020

A 9-yr 8-mo-old right-handed female presented with a history of gait difficulties, which first became apparent at age 9 mo of age, along with slurred speech and hand tremors while holding a tray. Her past medical history was significant for global developmental delay, and she was attending fourth grade special education classes. On examination, she had an ataxic gait, dysarthria, absent deep tendon reflexes, and flexor plantar responses. There were no signs of optic atrophy or hearing loss. Nerve conduction studies were consistent with an axonal neuropathy. A fascicular sural nerve biopsy showed a marked decrease of myelinated fibers larger than 6 µm in diameter as compared with an age-matched control. By electron microscopy, clusters of degenerating axonal mitochondria in both myelinated and unmyelinated fibers were frequently found. Whole-exome sequencing revealed a heterozygous c.314C > T (p.Thr105Met) missense variant in MFN2 in the patient but not in her mother. The father was unavailable for testing. The phenotypes with MFN2 variants can be quite variable, including intellectual disability, optic atrophy, auditory impairment, spinal atrophy with or without hydromyelia, and hydrocephalus. We report here that early onset ataxia with intellectual disability can also be associated with MFN2-related Charcot–Marie–Tooth, Type 2A2A diagnosis, the most common type of autosomal dominant axonal neuropathy.
EDDIDAT: a graphical user interface for the analysis of energy-dispersive diffraction data
Authors: Apel Daniel , Genzel Martin , Meixner Matthias , Boin Mirko , Klaus Manuela , Genzel Christoph
Published: June 2020

EDDIDAT is a MATLAB-based graphical user interface for the convenient and versatile analysis of energy-dispersive diffraction data obtained at laboratory and synchrotron sources. The main focus of EDDIDAT up to now has been on the analysis of residual stresses, but it can also be used to prepare measurement data for subsequent phase analysis or analysis of preferred orientation. The program provides access to the depth-resolved analysis of residual stresses at different levels of approximation. Furthermore, the graphic representation of the results also serves for the consideration of microstructural and texture-related properties. The included material database allows for the quick analysis of the most common materials and is easily extendable. The plots and results produced with EDDIDAT can be exported to graphics and text files. EDDIDAT is designed to analyze diffraction data from various energy-dispersive X-ray sources. Hence it is possible to add new sources and implement the device-specific properties into EDDIDAT. The program is freely available to academic users.
Crystallography of γ′-Fe4N formation in single-crystalline α-Fe whiskers
Authors: Schumann Helge , Richter Gunther , Leineweber Andreas
Published: June 2020

Gaseous nitriding of steel and iron can significantly improve their properties, for example corrosion resistance, fatigue endurance and tribological properties. In order to obtain a better understanding of the early stages of formation of the initial cubic primitive γ′-Fe4N, the mechanism and crystallography of the α–γ′ phase transformation was investigated under simplified conditions. Single-crystal α-Fe whiskers were nitrided at 823 K and a nitriding potential of 0.7 atm−1/2for 20 min. The resulting microstructure and phases, as well as the crystallographic orientation of crystallites belonging to a particular phase, were characterized by scanning electron microscopy coupled with electron backscatter diffraction. The habit planes were investigated by single- and two-surface trace analysis. The α-Fe whiskers partly transform into γ′-Fe4N, where γ′ grows mainly in a plate-like morphology. An orientation relationship close to the rational Pitsch orientation relationship and {0.0780.4320.898}αand {0.3910.3670.844}γ′as habit planes were predicted by the phenomenological theory of martensite crystallography (PTMC), adopting a {101}α〈101〉αshear system for lattice invariant strain, which corresponds to a {111}γ′〈112〉γ′shear system in γ′. The encountered orientation relationship and the habit planes exhibit excellent agreement with predictions from the PTMC, although the transformation definitely requires diffusion. The γ′ plates mainly exhibit one single internally untwinned variant. The formation of additional variants due to strain accommodation, as well as the formation of a complex microstructure, was suppressed to a considerable extent by the fewer mechanical constraints imposed on the transforming regions within the iron whiskers as compared to the situation at the surface of bulk samples.
Dynamical X-ray diffraction imaging of voids in dislocation-free high-purity germanium single crystals
Authors: Gradwohl Kevin-P. , Danilewsky Andreas N. , Roder Melissa , Schmidbauer Martin , Janicskó-Csáthy József , Gybin Alexander , Abrosimov Nikolay , Sumathi R. Radhakrishnan
Published: June 2020

White-beam X-ray topography has been performed to provide direct evidence of micro-voids in dislocation-free high-purity germanium single crystals. The voids are visible because of a dynamical diffraction contrast. It is shown that voids occur only in dislocation-free parts of the crystal and do not show up in regions with homogeneous and moderate dislocation density. It is further suggested that the voids originate from clustering of vacancies during the growth process. A general method is proposed to verify the presence of voids for any crystalline material of high structural perfection.
Dynamic stall of an airfoil with different mounting angle of gurney flap
Authors: Masdari Mehran , Mousavi Milad , Tahani Mojtaba
Published: June 2020

Purpose

One of the best methods to improve wind turbine aerodynamic performance is modification of the blade’s airfoil. The purpose of this paper is to investigate the effects of gurney flap geometry and its oscillation parameters on the pitching NACA0012 airfoil.

Design/methodology/approach

This numerical solution has been carried out for different cases of gurney flap mounting angles, heights, reduced frequencies and oscillation amplitudes, then the results were compared to each other. The finite volume method was used for the discretization of the governing equations, and the PISO algorithm was used to solve the equations. Also, the “SST” was adopted as the turbulence model in the simulation.

Findings

In this paper, the different parameters of gurney flap were investigated. The results showed that the best range of gurney flap height are between 1 and 3.2% of chord and the best ratio of lifting to drag coefficient is achieved in gurney flap with an angle of 90° relative to the chord direction. The dynamic stall angle of the airfoil with gurney flap decreases were compared to without gurney flap. Earlier LEV formation can be one of the main reasons for decreasing the dynamic stall angle of the airfoil with gurney flap. Increasing the reduced frequency and oscillation amplitude causes rising of maximum lift coefficient and consequently lift curve slope. Moreover, gurney flap with mounting angle has a lower hinge moment than the gurney flap without mounting angle but with the same vertical axis length. So, there is more complexity in structural design concerning the gurney flap without mounting angle.

Practical implications

Improving aerodynamic efficiency of airfoils is vital for obtaining more output power in VAWTs. Gurney flaps are one of the best mechanisms to increase the aerodynamic performance of the airfoil and increases the efficiency of VAWTs.

Originality/value

Investigating the hinge moment on the connection point of the airfoil, gurney flap and try to compare the gurney flap with and without angle.
Lifelong activism and women’s entrepreneurship: how a social movement organization improves conditions for self-employed women in India
Authors: Colovic Ana , Mehrotra Sonia
Published: June 2020

Purpose

The purpose of this paper is to investigate how a local trade union improves living conditions for women entrepreneurs in India and how its activities have evolved over time.

Design/methodology/approach

The authors conducted a longitudinal case study of the self-employed women’s association (SEWA) in India. Founded in 1972, this organization fosters and supports women’s entrepreneurship. The approach of this study combines qualitative face-to-face interviews and secondary data analysis.

Findings

The findings highlight the fact that SEWA, which combines the features of a trade union and a social movement, improves women’s conditions in several different ways. The study shows that the organization’s main role has evolved from creating a community to expanding it and finally to becoming an agent of societal change.

Originality/value

The study contributes to the literature by analyzing how locally grown organizations fight social exclusion and improve the conditions of deprived groups in emerging economies.