bluuebunny/crossref_metadata_2025 huggingface dataset:
A new twist of rubredoxin function inM. tuberculosis
Authors: Sushko Tatsiana , Kavaleuski Anton , Grabovec Irina , Kavaleuskaya Anna , Vakhrameev Daniil , Bukhdruker Sergei , Marin Egor , Kuzikov Alexey , Masamrekh Rami , Sigolaeva Larisa V. , Shumyantseva Victoria , Tsumoto Kouhei , Borshchevskiy Valentin , Gilep Andrei , Strushkevich Natallia
Published: October 2020

Electron transfer mediated by metalloproteins drives many biological processes. Rubredoxins are ubiquitous iron-containing electron carriers that play important roles in bacterial adaptation to changing environmental conditions. InMycobacterium tuberculosis, oxidative and acidic stresses as well as iron starvation induce rubredoxin expression. However, their functions duringM. tuberculosisinfection is unknown. In the present work, we show that rubredoxin B (RubB) supports catalytic activity of mycobacterial cytochrome P450s, CYP124, CYP125, and CYP142, which are important for bacterial viability and pathogenicity. We solved the crystal structure of RubB and characterized the interaction between RubB and CYPs using site-directed mutagenesis. Mutations that neutralized single charge on the surface of RubB did not dramatically decrease activity of studied CYPs, and isothermal calorimetry (ITC) experiments indicated that interactions are transient and not highly specific. Our findings suggest that a switch from ferredoxins to rubredoxins support CYP activity inM. tuberculosis-infected macrophages. Our electrochemical experiments suggest potential applications of RubB in biotechnology.
A skyline birth-death process for inferring the population size from a reconstructed tree with occurrences
Authors: Andréoletti Jérémy , Zwaans Antoine , Warnock Rachel C. M. , Aguirre-Fernández Gabriel , Barido-Sottani Joëlle , Gupta Ankit , Stadler Tanja , Manceau Marc
Published: October 2020

Phylodynamic models generally aim at jointly inferring phylogenetic relationships, model parameters, and more recently, population size through time for clades of interest, based on molecular sequence data. In the fields of epidemiology and macroevolution these models can be used to estimate, respectively, the past number of infected individuals (prevalence) or the past number of species (paleodiversity) through time. Recent years have seen the development of “total-evidence” analyses, which combine molecular and morphological data from extant and past sampled individuals in a unified Bayesian inference framework. Even sampled individuals characterized only by their sampling time, i.e. lacking morphological and molecular data, which we calloccurrences, provide invaluable information to reconstruct past population sizes.

Here, we present new methodological developments around the Fossilized Birth-Death Process enabling us to (i) efficiently incorporate occurrence data while remaining computationally tractable and scalable; (ii) consider piecewise-constant birth, death and sampling rates; and (iii) reconstruct past population sizes, with or without knowledge of the underlying tree. We implement our method in the RevBayes software environment, enabling its use along with a large set of models of molecular and morphological evolution, and validate the inference workflow using simulations under a wide range of conditions.

We finally illustrate our new implementation using two empirical datasets stemming from the fields of epidemiology and macroevolution. In epidemiology, we apply our model to the Covid-19 outbreak on the Diamond Princess ship. We infer the total prevalence throughout the outbreak, by taking into account jointly the case count record (occurrences) along with viral sequences for a fraction of infected individuals. In macroevolution, we present an empirical case study of cetaceans. We infer the diversity trajectory using molecular and morphological data from extant taxa, morphological data from fossils, as well as numerous fossil occurrences. Our case studies highlight that the advances we present allow us to further bridge the gap between between epidemiology and pathogen genomics, as well as paleontology and molecular phylogenetics.
RL-118 and 11β-HSD1 target engagement through TAPS assay: behaviour and molecular analysis
Authors: Puigoriol-Illamola D. , Companys-Alemany J. , Homer N. , Leiva R. , Vázquez S. , Mole D. , Griñán-Ferré C. , Pallàs M.
Published: October 2020

1.

Taking into consideration the convergence of ageing, stress and neurodegenerative diseases, such as AD, there is impaired GC signalling. Therefore, the study of GC-mediated stress response to chronic moderate stressful situations, as account in daily life, becomes of huge interest to design pharmacological strategies to prevent neurodegeneration.

To address this issue, SAMP8 were exposed for 4 weeks to the CMS paradigm and treated with RL-118, an 11β-HSD1 inhibitor. In fact, several pieces of evidence link the inhibition of this enzyme with reduction of GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could restore the deleterious effects of CMS on cognition and behavioural abilities, but also on molecular mechanisms that compromise healthy ageing in SAMP8 mice.

On the one hand, we determined the target engagement between RL-118 and 11β-HSD1. Therefore all the beneficial effects previously described in SAMP8 treated with the drug can undoubtedly be attributed to the inhibition of this enzyme. Besides, herein we observed decreased DNA methylation, hydroxymethylation and histone phosphorylation induced by CMS but, on the contrary, increased after RL-118 treatment. In addition, CMS exposure produced ROS damage accumulation, and increments of pro-oxidant enzymes as well as pro-inflammatory mediators through NF-κB pathway and astrogliosis markers, likeGfap. Ofnote, those modifications were recovered by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signalling, autophagy was increased in SAMP8 treated with RL-118 mice. Also, we found amyloidogenic APP processing pathway favoured and decreased synaptic plasticity and neuronal remodelling markers in mice under CMS, but changed after RL-118 treatment. In consequence, detrimental effects on behaviour and cognitive performance were detected in CMS exposed mice, but restored after concomitant 11β-HSD1 inhibition by RL-118.

Overall, CMS is a feasible intervention to understand the influence of stress on epigenetic mechanisms underlying cognition and accelerating senescence. However and most important, 11β-HSD1 inhibition through RL-118 turned up to restore the majority of these detrimental effects caused by CMS, indicating that GC excess attenuation may become a potential therapeutic strategy for age-related cognitive decline and AD.
Blood gene expression-based prediction of lethality after respiratory infection by influenza A virus in mice
Authors: Milanez-Almeida Pedro , Martins Andrew J. , Torabi-Parizi Parizad , Franco Luis M. , Tsang John S. , Germain Ronald N.
Published: October 2020

Lethality after respiratory infection with influenza A virus (IAV) is associated with potent immune activation and lung tissue damage. In a well-controlled animal model of infection, we sought to determine if one could predict lethality using transcriptional information obtained from whole blood early after influenza virus exposure. We started with publicly available transcriptomic data from the lung, which is the primary site of the infection and pathology, to derive a multigene transcriptional signature of death reflective of innate inflammation associated with tissue damage. We refined this affected tissue signature with data from infected mouse and human blood to develop and validate a machine learning model that can robustly predict survival in mice after IAV challenge using data obtained from as little as 10 μl of blood from early time points post infection. Furthermore, in genetically identical, cohoused mice infected with the same viral bolus, the same model can predict the lethality of individual animals but, intriguingly, only within a specific time window that overlapped with the early effector phase of adaptive immunity. These findings raise the possibility of predicting disease outcome in respiratory virus infections with blood transcriptional data and pave the way for translating such approaches to humans.
The labor-managed firm, Jaroslav Vanek and me
Authors: Dow Gregory K.
Published: October 2020

Purpose

The purpose of this article is to summarize the relationship between the research of Jaroslav Vanek on labor-managed firms (LMFs) and the research of Gregory K. Dow on the same topic.

Design/methodology/approach

The article reviews the research of Jaroslav Vanek in the 1970s and explains how this influenced the publications of Gregory K. Dow extending from the 1980s to the present. A particular focus involves Dow's book “The Labor-Managed Firm: Theoretical Foundations” published by Cambridge University Press in 2018. The methodology is to present an intellectual history in narrative form. The scope of the paper is the economic theory of the LMF.

Findings

The article finds that Dow's interest in LMFs was stimulated by Vanek's publications from the early 1970s. However, Dow's publications in the 1980s were motivated to a large degree by efforts to overcome the limitations of Vanek's theory of the LMF, a goal that shaped much of Dow's later research in the field.

Originality/value

The paper illuminates the strong intellectual influence Jaroslav Vanek exerted on the economic theory of the LMF. Readers who want information about the influences on Dow's work may also find it useful.
Buckling behavior of laminated composite cylinders under external hydrostatic pressure
Authors: Li Zhun , Pan Guang , Shen KeChun
Published: October 2020

Purpose

The objective of this paper is to investigate numerically the buckling behavior of submersible composite cylinders.

Design/methodology/approach

By means of FEM and golden section method, the search of hoop winding layers, longitudinal winding layers and helical winding layers are studied to optimize the buckling pressure. Considering the mid-strengthening cylinder, the size and distribution of stiffeners are studied systematically.

Findings

The results show that laying the hoop winding layers in the two outer sidewalls and the longitudinal winding layers in the middle of the shell is helpful to increase the buckling pressure, and the optimal helical winding angle changes with slenderness ratio.

Originality/value

For mid-strengthening cylinder, the effect of helical winding angle of stiffener on buckling pressure becomes weak gradually with the increase of stiffener thickness. With the increasing of the spacing between stiffeners, the buckling pressure increases first and decreases later. What is more, the mid-strengthening cylinder is less sensitive to the initial geometric imperfections than unstiffened shells.
Awake Prone Positioning in COVID‐19 Hypoxemic Respiratory Failure: Exploratory Findings in a Single‐center Retrospective Cohort Study
Authors: Padrão Eduardo M. H. , Valente Fernando S. , Besen Bruno A. M. P. , Rahhal Hassan , Mesquita Paula S. , de Alencar Julio C. G. , da Costa Millena G. P. , Wanderley Annelise P. B. , Emerenciano Debora L. , Bortoleto Felipe M. , Fortes Julio C. L. , Marques Bruno , de Souza Stefany F. B. , Marchini Júlio F. M. , Neto Rodrigo A. B. , de Souza Heraldo P. ,   for the COVIDTEAM
Published: October 2020

Background

Awake prone positioning has been widely used in patients with COVID‐19 respiratory failure to avoid intubation despite limited evidence. Our objective was to evaluate if prone positioning is associated with a reduced intubation rate when compared to usual care.

Methods

This was a retrospective cohort study in the emergency department of a large quaternary hospital in Sao Paulo. We retrieved data from all admitted patients in need of oxygen supplementation (>3 L/min) and tachypnea (>24 ipm) from March 1 to April 30, 2020, excluding those who had any contraindication to the prone position or who had an immediate need for intubation. The primary endpoint was endotracheal intubation up to 15 days. Secondary outcomes included a 6‐point clinical outcome ordinal scale, mechanical ventilation–free days, admission to the intensive care unit, and need of hemodialysis and of vasoactive drugs, all assessed at or up to 15 days. We analyzed unadjusted and adjusted effect estimates with Cox proportional hazards models, logistic regression, quantile regression, and sensitivity analyses using propensity score models.

Results

Of 925 suspected COVID‐19 patients admitted off mechanical ventilation, 166 patients fulfilled inclusion and exclusion criteria: 57 were exposed to prone positioning and 109 to usual care. In the intervention group, 33 (58%) were intubated versus 53 (49%) in the control group. We observed no difference in intubation rates in the univariate analysis (hazard ratio = 1.21, 95% confidence interval [CI] = 0.78 to 1.88, p = 0.39) nor in the adjusted analysis (hazard ratio = 0.90, 95% CI = 0.55 to 1.49, p = 0.69). Results were robust to the sensitivity analyses. Secondary outcomes did not differ between groups.

Conclusions

Awake prone positioning was not associated with lower intubation rates. Caution is necessary before widespread adoption of this technique, pending results of clinical trials.
Caring for “Hassle‐Free Highs” in Amsterdam
Authors: Hardon Anita , Hymans Takeo David , van Schipstal Inge , Mishra Swasti , Berning Moritz , Murray Hayley , Kamps Daan , Mandler Tait
Published: October 2020

In this article we present some of our ethnographic findings from the city of Amsterdam, where health authorities and practitioners have implemented harm reduction strategies that build on and reinforce young drug users’ practices of self‐regulation and care. Amsterdam’s harm reduction policies build on the premises that harm is not a direct, always present consequence of recreational drug use and that harm reduction strategies will be more effective when they engage with the collective, material, and affective practices constantly evolving within drug‐using communities. This approach to caring for drug‐using youth is “unsettled” in two ways. In light of both, the city carefully tailors drug information campaigns to speak to the lived experiences of drug users. First, it concerns finding the right balance between warning drug users about negative effects and acknowledging that they are seeking and experiencing positive effects. Second, it concerns the ever‐changing market for recreational drugs. Ethnographic fieldwork in the ChemicalYouth project sought to better understand the lived experiences of young drug users and what they do to minimize risks. We identified five distinct and interlocking self‐regulation techniques that youth themselves employ and share with their peers in their quest for “hassle‐free highs.”
Challenging Care: Professionally Not Knowing What Good Care Is
Authors: McKearney Patrick
Published: October 2020

A dominant trope in the anthropology of care—of revealing a practice to be, despite our moral intuitions to the contrary, really a form of care—limits our understanding of the dynamic processes whereby care’s morality is established in practice. In the British care sector the ideal of care is clear: avoiding coercion and neglect. There are manifold rules designed to hold carers accountable to realizing it. But the rules do not reliably lead to the ideal. Rather, they leave undetermined an enormous amount for carers to fill in. In this setting, whether or not a worker's action becomes “caring” depends on far more than good intentions or following rules. The action's moral status rests, instead, on the contingencies of the relationship with the care recipient. We should refrain from entering into the evaluative work of rearranging the borders of good care in order to investigate how our informants themselves do this in the midst of care’s relational vicissitudes. Doing so enables us to attend to how debates about what constitutes good care are part of broader patterns by which moral responsibility is assigned and distributed within caring relationships.
A Postcolonial Critique of Community Energy: Searching for Community as Solidarity in India and Scotland
Authors: Kumar Ankit , Taylor Aiken Gerald
Published: October 2020

Community renewable energy (CRE) represents a growing empirical and academic turn towards community‐based sustainability and climate change interventions. This paper brings together postcolonial theory and CRE for the first time to outline fundamental tensions in the conceptualisation and application of the idea of community. The understanding of community within the CRE discourse is largely: (1) location‐based; and/or (2) a community of choice that is consciously opted into. Driven by postcolonial theory, this paper counterpoises both as a form of community as contract against an idea of community as solidarity. Its central thesis is that actually existing community, contrary to how the bulk of CRE literature commonly understands it, is a combination of bonds of solidarity and emergent purposes. The paper conceptualises community as fluid bonds of solidarity that align and realign differently around different purposes.
Discovery of potent α‐glucosidase inhibitors through structure‐based virtual screening of an in‐house azole collection
Authors: Sari Suat , Barut Burak , Özel Arzu , Saraç Selma
Published: October 2020

Diabetes mellitus, a chronic disorder characterized by hyperglycemia, is considered a pandemic of modern times. α‐Glucosidase inhibitors emerged as a promising class of antidiabetic drugs with better tolerability compared with its alternatives. Azoles, although widely preferred in drug design, have scarcely been investigated for their potential against α‐glucosidase. In this study, we evaluated α‐glucosidase inhibitory effects 20 azole derivatives selected out of an in‐house collection via structure‐based virtual screening (VS) with consensus scoring approach. Seven compounds were identified with better IC50 values than acarbose (IC50 = 68.18 ± 1.01 µM), a well‐known α‐glucosidase inhibitor drug, which meant 35% success for our VS methodology. Compound 52, 54, 56, 59, and 81 proved highly potent with IC50 values in the range of 40–60 µM. According to the enzyme kinetics study, four of them were competitive, 56 was non‐competitive inhibitor. Structure‐activity relationships, quantum mechanical, and docking analyses showed that azole rings at ionized state may be key to the potency observed for the active compounds and modifications to shift the balance between the neutral and ionized states further to the latter could yield more potent derivatives.
BCL2 enhances survival of porcine pluripotent stem cells through promoting FGFR2
Authors: Zhu Zhenshuo , Pan Qin , Zhao Wenxu , Wu Xiaolong , Yu Shuai , Shen Qiaoyan , Zhang Juqing , Yue Wei , Peng Sha , Li Na , Zhang Shiqiang , Lei Anmin , Hua Jinlian
Published: October 2020

Objectives

The establishment of porcine pluripotent stem cells (pPSCs) is still a critical topic. However, all pPSCs were failed to contribute to efficient chimeric pig and were extremely sensitive to changes of culture conditions. This study aimed to investigate the role of BCL2 in pPSCs and further explain the mechanism.

Materials and Methods

Porcine BCL2 gene was cloned and overexpressed in porcine induce pluripotent stem cells (piPSCs). Digital RNA‐seq was performed to explain the mechanism of anti‐apoptosis. Finally, the cells carrying BCL2 were injected into mouse early embryo to evaluate its chimeric ability.

Results

Here, we found that overexpression of porcine BCL2 gene significantly improved the survivability of piPSCs and the efficiency of embryonic chimerism, and did not wreck the pluripotency of piPSCs. Furthermore, the Digital RNA‐seq analysis revealed that BCL2, as a downstream gene of the PI3K signal pathway, enhanced the expression of PI3K signal pathway receptors, such as FGFR2, and further promoted oxidoreductases activity and lipid metabolism, thus maintaining the survival and pluripotency of piPSCs.

Conclusion

Our data not only suggested that porcine BCL2 gene could enhance the survivability and chimeric ability of pPSCs, but also explained the positive feedback mechanism in this process, providing strong support for the chimeric experiment of pPSCs.
FGF9 promotes mouse spermatogonial stem cell proliferation mediated by p38 MAPK signalling
Authors: Yang Fan , Whelan Eoin C. , Guan Xuebing , Deng Bingquan , Wang Shu , Sun Jiachen , Avarbock Mary R. , Wu Xin , Brinster Ralph L.
Published: October 2020

Objectives

Fibroblast growth factor 9 (FGF9) is expressed by somatic cells in the seminiferous tubules, yet little information exists about its role in regulating spermatogonial stem cells (SSCs).

Materials and Methods

Fgf9 overexpression lentivirus was injected into mouse testes, and PLZF immunostaining was performed to investigate the effect of FGF9 on spermatogonia in vivo. Effect of FGF9 on SSCs was detected by transplanting cultured germ cells into tubules of testes. RNA‐seq of bulk RNA and single cell was performed to explore FGF9 working mechanisms. SB203580 was used to disrupt p38 MAPK pathway. p38 MAPK protein expression was detected by Western blot and qPCR was performed to determine different gene expression. Small interfering RNA (siRNA) was used to knock down Etv5 gene expression in germ cells.

Results

Overexpression of Fgf9 in vivo resulted in arrested spermatogenesis and accumulation of undifferentiated spermatogonia. Exposure of germ cell cultures to FGF9 resulted in larger numbers of SSCs over time. Inhibition of p38 MAPK phosphorylation negated the SSC growth advantage provided by FGF9. Etv5 and Bcl6b gene expressions were enhanced by FGF9 treatment. Gene knockdown of Etv5 disrupted the growth effect of FGF9 in cultured SSCs along with downstream expression of Bcl6b.

Conclusions

Taken together, these data indicate that FGF9 is an important regulator of SSC proliferation, operating through p38 MAPK phosphorylation and upregulating Etv5 and Bcl6b in turn.
Invasive fungal disease of the central nervous system: Challenging diagnosis of a rare fungus by intraoperative squash cytology
Authors: Chaurasia Jai Kumar , Naik Bitan , Tandon Ashwani , Tadepalli Karuna , Khurana Ujjawal , Kapoor Neelkamal
Published: October 2020

This case report describes invasive fungal disease of CNS due to a rare hyalohyphomycotic fungus, diagnosed by intraoperative squash cytology and deals with diagnostic challenges involved in the differential diagnosis.
Left ventricle and mitral valve reverse remodeling in response to cardiac resynchronization therapy in nonischemic cardiomyopathy
Authors: Mihos Christos G. , Yucel Evin , Upadhyay Gaurav A. , Orencole Mary P. , Singh Jagmeet P. , Picard Michael H.
Published: October 2020

Background

Cardiac resynchronization therapy (CRT) improves left heart geometry and function in nonischemic cardiomyopathy (NICMP). We aimed to detail the effects of CRT on left ventricular (LV) and mitral valve (MV) remodeling using 2‐dimensional transthoracic echocardiography.

Methods

Forty‐five consecutive patients with NICMP who underwent CRT implantation between 2009 and 2012, and had pre‐CRT and follow‐up echocardiograms available, were included. Paired t test, linear and logistic regression, and Kaplan–Meier survival analyses were used for statistical assessment.

Results

The mean age and QRS duration were 60 years and 157 ms, respectively, and 13 (28.9%) were female. At a mean follow‐up of 3 years, there were 22 (48.9%) “CRT responders” (≥15% reduction in LV end‐systolic volume index [LVESVi]). Significant improvements were observed in LV ejection fraction (26.3% vs 34.3%) and LVESVi (87.7 vs 71.1 mL/m2), as well as mitral regurgitation vena contracta width, MV tenting height and area, and end‐systolic interpapillary muscle distance. Five‐year actuarial survival was 87.5%. Multivariate regression analyses revealed the pre‐CRT LVESVi (β = 0.52), and MV coaptation length (β = −0.34) and septolateral annular diameter (β = 0.25) as good correlates of follow‐up LVESVi. Variables associated with CRT response were pre‐CRT MV coaptation length (OR 1.75, 95% CI 1.0‐3.1) and posterior leaflet tethering angle (OR 1.07, 95% CI 1.0‐1.14), irrespective of baseline QRS morphology and duration (all P < .05).

Conclusions

Cardiac resynchronization therapy improves LV and MV geometry and function in half of patients with NICMP, which is paralleled by decreased mitral regurgitation severity. The extent of pre‐CRT LV remodeling and MV tethering are associated with CRT response.
Prognosis and risk factors associated with asymptomatic intracranial hemorrhage after endovascular treatment of large vessel occlusion stroke: a prospective multicenter cohort study
Authors: Constant Dit Beaufils P. , Preterre C. , De Gaalon S. , Labreuche J. , Mazighi M. , Di Maria F. , Sibon I. , Marnat G. , Gariel F. , Blanc R. , Gory B. , Consoli A. , Zhu F. , Richard S. , Fahed R. , Desal H. , Lapergue B. , Guillon B. , Bourcier R. ,   the Endovascular Treatment in Ischemic Stroke (ETIS) Research Investigators
Published: October 2020

Background and purpose

Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address its impact on 3‐month functional outcome and to identify risk factors for aICH after EVT.

Methods

Patients with AIS attributable to anterior circulation large vessel occlusion who underwent EVT were enrolled in a multicenter prospective registry. Based on imaging performed 22–36 h post‐EVT, we included patients with no intracranial hemorrhage (ICH) or aICH. Poor outcome defined as a 3‐month modified Rankin Scale (mRS) score 4–6 and overall 3‐month mRS score distribution were compared according to presence/absence of aICH, and aICH subtype using logistic regression. We assessed the risk factors of aICH using a multivariate logistic regression model.

Results

Of the 1526 patients included in the study, 653 (42.7%) had aICH. Patients with aICH had a higher rate of poor outcome: odds ratio (OR) 1.88 (95% confidence interval [CI] 1.44–2.44). Shift analysis of mRS score found a fully adjusted OR of 1.79 (95% CI 1.47–2.18). Hemorrhagic infarction (OR 1.63 [95% CI 1.22–2.18]) and parenchymal hematoma (OR 2.99 [95% CI 1.77–5.02]) were associated with higher risk of poor outcome. Male sex, diabetes, coronary artery disease, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, number of passes and onset to groin puncture time were independently associated with aICH.

Conclusions

Patients with aICH, irrespective of the radiological pattern, have a worse functional outcome at 3 months compared with those without ICH after EVT for AIS. The number of EVT passes and the time from onset to groin puncture are factors that could be modified to reduce deleterious ICH.
Judging in a Time of COVID
Authors: Warner Judge Randall H.
Published: October 2020

The pandemic of 2020 has turned much of the world upside down and courts have had to find new ways to meet obligations to the law and the people they serve. This is especially difficult in child welfare courts, where children’s needs cannot be delayed. This reflection piece addresses the challenges faced by all the dependency court participants in a COVID environment.
COVID‐19: An overview for dermatologists
Authors: Sanghvi Akanksha R.
Published: October 2020

Numerous unexplained pneumonia cases were reported to the World Health Organization (WHO) by Wuhan, China, in December 2020. Severe acute respiratory syndrome coronavirus−2 (SARS‐CoV‐2), a zoonotic pathogen, came into sight, spreading coronavirus disease 2019 (COVID‐19) all over the globe. Association of cutaneous signs and symptoms with COVID‐19 is being studied worldwide, principally, to determine if these dermatoses can help in early recognition of SARS‐CoV‐2 infection. These dermatological manifestations can range from erythematous rash, urticaria to livedo reticularis, and acrocyanosis in patients of all age groups. Correspondingly, dermatologists treating COVID‐19 patients, suffering from inflammatory dermatoses, with biologics or immunomodulators should exert caution and use specific protocols to adjust the doses of these medications. Prevention of person‐to‐person transmission of COVID‐19 is being promoted universally, with the use of personal protective equipment (PPE), hand washes, and hand sanitizers around the clock. However, an array of cutaneous adverse effects such as contact dermatitis, irritant contact dermatitis, friction blisters, contact urticaria, acne, and infections are associated with the use of PPE. Extra‐pulmonary manifestations of COVID‐19 are still emerging in the community, and physicians and researchers are working together globally to strengthen the clinical management of these patients. Cases of COVID‐19 continue to rise across the world, and an unprecedented approach has been taken to develop effective vaccines and therapeutic strategies against existing and forthcoming mutagenic strains of SARS‐CoV‐2.
Historical legacies and contemporary processes shape beta diversity in Neotropical montane streams
Authors: González‐Trujillo Juan David , Saito Victor S. , Petsch Danielle K. , Muñoz Isabel , Sabater Sergi
Published: October 2020

Aim

Contemporary dispersal constraints and environmental conditions are broadly recognized as significant drivers of beta diversity patterns. However, beta diversity patterns may also reflect the legacy of past climatic and geological events. In this study, we investigated the relative importance of historical and contemporary factors as drivers of taxonomic, functional and phylogenetic beta diversity in Neotropical stream communities.

Location

The Colombian Orinoco basin.

Taxon

Diatoms and insects.

Methods

We estimated taxonomic, phylogenetic and functional beta diversity using Baselga's (BAS) and Podani's (POD) frameworks. Following both frameworks, we further partitioned every biodiversity facet into turnover and nestedness or richness difference components. Then, we used generalized linear models (GLM) to relate each biodiversity facet with environmental, spatial and historical factors.

Results

We found that both historical and contemporary factors affected current patterns of beta diversity. Historical factors and water pH and temperature had the strongest effect on beta diversity patterns, particularly for taxonomic and phylogenetic facets. GLM models performed better for insects than for diatoms in all three facets. Within communities, our analysis also revealed a partial congruence between BAS‐ and POD‐based results.

Main conclusions

Due to their past geological history and contemporary environmental gradients, tropical montane streams are natural laboratories for disentangling the joint effects of ecological and biogeographical factors on biodiversity patterns. Our study reveals that present‐day distribution patterns cannot be fully explained without accounting for the effects of past geological and climatic events on mountain landscapes. In the Neotropics, montane geology sets the stage for speciation and landscape formation, with which ecological (e.g., dispersal limitation) and environmental factors interact to generate spatial variation in species turnover.
A Bayesian multilevel analysis of the longitudinal associations between relationship quality and suicidal ideation and attempts among youth with bipolar disorder
Authors: Sewall Craig J.R. , Girard Jeffrey M. , Merranko John , Hafeman Danella , Goldstein Benjamin I. , Strober Michael , Hower Heather , Weinstock Lauren M. , Yen Shirley , Ryan Neal D. , Keller Martin B. , Liao Fangzi , Diler Rasim S. , Kay Gill Mary , Axelson David , Birmaher Boris , Goldstein Tina R.
Published: October 2020

Background

Youth with bipolar disorder (BD) are at high risk for suicidal thoughts and behaviors and frequently experience interpersonal impairment, which is a risk factor for suicide. Yet, no study to date has examined the longitudinal associations between relationship quality in family/peer domains and suicidal thoughts and behaviors among youth with BD. Thus, we investigated how between‐person differences – reflecting the average relationship quality across time – and within‐person changes, reflecting recent fluctuations in relationship quality, act as distal and/or proximal risk factors for suicidal ideation (SI) and suicide attempts.

Methods

We used longitudinal data from the Course and Outcome of Bipolar Youth Study (N = 413). Relationship quality variables were decomposed into stable (i.e., average) and varying (i.e., recent) components and entered, along with major clinical covariates, into separate Bayesian multilevel models predicting SI and suicide attempt. We also examined how the relationship quality effects interacted with age and sex.

Results

Poorer average relationship quality with parents (β = −.33, 95% Bayesian highest density interval (HDI) [−0.54, −0.11]) or friends (β = −.33, 95% HDI [−0.55, −0.11]) was longitudinally associated with increased risk of SI but not suicide attempt. Worsening recent relationship quality with parents (β = −.10, 95% HDI [−0.19, −0.03]) and, to a lesser extent, friends (β = −.06, 95% HDI [−0.15, 0.03]) was longitudinally associated with increased risk of SI, but only worsening recent relationship quality with parents was also associated with increased risk of suicide attempt (β = −.15, 95% HDI [−0.31, 0.01]). The effects of certain relationship quality variables were moderated by gender but not age.

Conclusions

Among youth with BD, having poorer average relationship quality with peers and/or parents represents a distal risk factor for SI but not suicide attempts. Additionally, worsening recent relationship quality with parents may be a time‐sensitive indicator of increased risk for SI or suicide attempt.
Riluzole attenuates glutamatergic tone and cognitive decline in AβPP/PS1 mice
Authors: Hascup Kevin N. , Findley Caleigh A. , Britz Jesse , Esperant‐Hilaire Nahayo , Broderick Sarah O. , Delfino Kristin , Tischkau Shelley , Bartke Andrzej , Hascup Erin R.
Published: October 2020

We have previously demonstrated hippocampal hyperglutamatergic signaling occurs prior to plaque accumulation in AβPP/PS1 mice. Here, we evaluate 2‐Amino‐6‐(trifluoromethoxy) benzothiazole (riluzole) as an early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to substantial Beta amyloid (Aβ) plaque accumulation and cognitive decline. Male AβPP/PS1 mice, a model of progressive cerebral amyloidosis, were treated with riluzole from 2–6 months of age. Morris water maze, in vivo electrochemistry, and immunofluorescence were performed to assess cognition, glutamatergic neurotransmission, and pathology, respectively, at 12 months. Four months of prodromal riluzole treatment in AβPP/PS1 mice resulted in long‐lasting procognitive effects and attenuated glutamatergic tone that was observed six months after discontinuing riluzole treatment. Riluzole‐treated AβPP/PS1 mice had significant improvement in long‐term memory compared to vehicle‐treated AβPP/PS1 mice that was similar to normal aging C57BL/6J control mice. Furthermore, basal glutamate concentration and evoked‐glutamate release levels, which were elevated in vehicle‐treated AβPP/PS1 mice, were restored to levels observed in age‐matched C57BL/6J mice in AβPP/PS1 mice receiving prodromal riluzole treatment. Aβ plaque accumulation was not altered with riluzole treatment. This study supports that interventions targeting the glutamatergic system during the early stages of AD progression have long‐term effects on disease outcome, and importantly may prevent cognitive decline. Our observations provide preclinical support for targeting glutamate neurotransmission in patients at risk for developing AD.

image

Read the Editorial Highlight for this article on page 399.
Vibratory testing with the 64 Hz Rydel‐Seiffer tuning fork and its relation to the sural nerve action potential
Authors: Xirou Sophia , Kokotis Panagiotis , Zambelis Thomas , Anagnostou Evangelos
Published: October 2020

Despite its widespread use, little is known regarding the ability of the semi‐quantitative Rydel‐Seiffer tuning fork to designate peripheral nerve function. We sought to determine in a large sample of normal and abnormal nerves the relationship between vibration sense and compound sensory nerve action potential (SNAP) parameters recorded in a corresponding innervation area. Vibratory thresholds were determined on a scale of 0 to 8 with a 64 Hz Rydel‐Seiffer tuning fork placed on the lateral malleolus of 303 subjects. Sural nerve sensory neurography was employed to derive SNAP parameters, which were related to vibration sense by means of multiple linear regression. ROC curve analysis was performed to determine the classification efficacy of the tuning fork in distinguishing normal from abnormal sural nerve responses. SNAP amplitude was the most significant predictor in the whole subjects group and in the subgroup of subjects with normal SNAPs, whereas conduction velocity played a major role in subjects with abnormal SNAPs. Age was significantly associated with vibration perception, particularly in subjects with normal SNAPs. With an area under the curve of 0.730, vibration sense was a fair classifier for decreased SNAP amplitudes. The optimal vibratory cutoff was 4.2. Age is a major determinant of vibratory test results, highlighting the importance of aging of central and peripheral pathways in mediating vibration sense. Hence, neurophysiological testing cannot be omitted in the context of polyneuropathy work‐up, since even at the optimal cutoff threshold, vibratory examination still displays 40% false negative test results.
Cardiovascular risk factors and lifestyle behaviours in relation to longevity: a Mendelian randomization study
Authors: van Oort S. , Beulens J. W. J. , van Ballegooijen A. J. , Burgess S. , Larsson S. C.
Published: October 2020

Background

The American Heart Association introduced the Life's Simple 7 initiative to improve cardiovascular health by modifying cardiovascular risk factors and lifestyle behaviours. It is unclear whether these risk factors are causally associated with longevity.

Objectives

This study aimed to investigate causal associations of Life's Simple 7 modifiable risk factors, as well as sleep and education, with longevity using the two‐sample Mendelian randomization design.

Methods

Instrumental variables for the modifiable risk factors were obtained from large‐scale genome‐wide association studies. Data on longevity beyond the 90th survival percentile were extracted from a genome‐wide association meta‐analysis with 11,262 cases and 25,483 controls whose age at death or last contact was ≤ the 60th survival percentile.

Results

Risk factors associated with a lower odds of longevity included the following: genetic liability to type 2 diabetes (OR 0.88; 95% CI: 0.84;0.92), genetically predicted systolic and diastolic blood pressure (per 1‐mmHg increase: 0.96; 0.94;0.97 and 0.95; 0.93;0.97), body mass index (per 1‐SD increase: 0.80; 0.74;0.86), low‐density lipoprotein cholesterol (per 1‐SD increase: 0.75; 0.65;0.86) and smoking initiation (0.75; 0.66;0.85). Genetically increased high‐density lipoprotein cholesterol (per 1‐SD increase: 1.23; 1.08;1.41) and educational level (per 1‐SD increase: 1.64; 1.45;1.86) were associated with a higher odds of longevity. Fasting glucose and other lifestyle factors were not significantly associated with longevity.

Conclusion

Most of the Life's Simple 7 modifiable risk factors are causally related to longevity. Prevention strategies should focus on modifying these risk factors and reducing education inequalities to improve cardiovascular health and longevity.
Telomeric alterations in the default mode network during the progression of Alzheimer’s disease: Selective vulnerability of the precuneus
Authors: Mahady Laura J. , He Bin , Malek‐Ahmadi Michael , Mufson Elliott J.
Published: October 2020

Aims

Although telomere length (TL) and telomere maintenance proteins (shelterins) are markers of cellular senescence and peripheral blood biomarkers of Alzheimer's disease (AD), little information is available on telomeric alterations during the prodromal stage (MCI) of AD. We investigated TL in the default mode network (DMN), which underlies episodic memory deficits in AD, as well as shelterin protein and mRNA levels in the precuneus (PreC).

Methods

Telomere length was evaluated in DMN hubs and visual cortex using quantitative PCR (qPCR). In the PreC, western blotting and NanoString nCounter expression analyses evaluated shelterin protein and mRNA levels, respectively, in cases with an antemortem clinical diagnosis of no cognitive impairment (NCI), MCI and AD.

Results

TL was significantly reduced in the PreC in MCI and AD compared to NCI, but stable in frontal, inferior temporal, posterior cingulate and visual cortex. PreC TL correlated significantly with performance on cognitive tests. NCI cases with high vs low Braak scores displayed significantly shorter TL in posterior cingulate and frontal cortex, which correlated significantly with neuritic and diffuse amyloid‐β plaque counts. Shelterin protein levels (TIN2, TRF1, TRF2 and POT1) declined in MCI and AD compared to NCI. The PreC displayed stable expression of shelterins TERF1, TERF2, POT1, RAP1 and TPP1, while TINF2 mRNA significantly increased in AD compared to NCI.

Conclusions

These findings indicate a selective vulnerability to telomere attrition within different nodes of the DMN in prodromal AD and in aged NCI individuals with high Braak scores highlighting a putative role in the pathogenesis of AD.
It’s the Culture!—How systemic and societal constructs impact well‐being
Authors: Vinson Amy E. , Bachiller Patricia R.
Published: October 2020

Pediatric anesthesiologists practice within a culture, a system, and a society. In this article, we provide an overview of the influence these have on the well‐being or the unwellness of pediatric anesthesiologists. The scope of these issues is broad and far‐reaching; thus, our goal has been to highlight those areas which would be likely to have the largest impact on well‐being if addressed fully by society, institutions, and leaders in our field. We discuss the burnout‐promoting aspects of medical education and training. We survey occupational factors, such as the high‐stake pediatric anesthesia environment, occupational health hazards, time pressure, and the reduction in physician autonomy. We then describe societal barriers, such as the marginalization of certain populations, the US system of malpractice litigation, the stigma surrounding psychiatric care, and some of the issues related to physician reimbursement in the United States. We conclude that in order to move forward, improving physician wellness must be a focus of society, of the medical system as a whole, and of individual departments and leaders in pediatric anesthesia.
Development and validation of gene‐based markers for shrunken2‐Reference allele and their utilization in marker‐assisted sweet corn (Zea maysSachharata) breeding programme
Authors: Chhabra Rashmi , Hossain Firoz , Muthusamy Vignesh , Baveja Aanchal , Mehta Brijesh Kumar , Uttamrao Zunjare Rajkumar
Published: October 2020

The recessive shrunken2‐Reference (sh2‐Ref) allele is traditionally used in sweet corn cultivar development worldwide. However, non‐availability of suitable gene‐based marker(s) for sh2‐Ref has considerably delayed its utilization in molecular breeding. Here, 7,320 bp sequence of Sh2 gene among five wild‐ and six sh2‐Ref‐based inbreds was analysed by employing 13 overlapping primers. SNP583 (A in wild and G in mutant) and SNP755 (T in wild and C in mutant) in 5’UTR, and SNP5112 (C in wild and T in mutant) in intron‐12 clearly differentiated dominant (Sh2) and recessive (sh2‐Ref) allele. These SNPs were used to develop four gene‐based PCR markers. The newly developed markers were validated in six F2 populations segregating for sh2‐Ref allele, and 230 diverse inbreds of normal and sweet corn types. These markers were further used in genotyping of BC1F1 populations leading to successful selection of sh2‐Ref allele in the marker‐assisted breeding. Globally, this assumes great significance in molecular breeding of sweet corn.
Adiposity is associated with anovulation independent of serum free testosterone: A prospective cohort study
Authors: Bloom Michael S. , Perkins Neil J. , Sjaarda Lindsey A. , Mumford Sunni L. , Ye Aijun , Kim Keewan , Kuhr Daniel L. , Nobles Carrie J. , Connell Matthew T. , Schisterman Enrique F.
Published: October 2020

Background

Obesity, a body mass index (BMI) ≥30 kg/m2, is linked to infertility, potentially through a greater risk of anovulation due to elevated androgens. Yet, previous studies have not directly assessed the impact of adiposity, or body fat, on anovulation in the absence of clinical infertility.

Objective

To characterise the associations between adiposity and anovulation among women menstruating on a regular basis.

Methods

Women from the EAGeR trial (n = 1200), a randomised controlled trial of low‐dose aspirin and pregnancy loss among women trying to conceive, were used to estimate associations between adiposity and incident anovulation. Participants completed baseline questionnaires and anthropometry, and provided blood specimens. Women used fertility monitors for up to six consecutive menstrual cycles, with collection of daily first morning voids for hormone analysis in the first two menstrual cycles for prospective assessment of anovulation. Anovulation was assessed by urine pregnanediol glucuronide or luteinising hormone concentration or the fertility monitor. Weighted mixed‐effects log‐binomial regression was used to estimate associations between measures of adiposity and incident anovulation, adjusted for free (bioavailable) testosterone, anti‐Mullerian hormone (AMH), serum lipids, and demographic and life style factors.

Results

343 (28.3%) women experienced at least one anovulatory cycle. Anovulation risk was higher per kg/m2 greater BMI (relative risk [RR] 1.03, 95% confidence interval (CI) 1.01, 1.04), cm waist circumference (RR 1.01, 95% CI 1.00, 1.02), mm subscapular skinfold (RR 1.02, 95% CI 1.01, 1.03), and mm middle upper arm circumference (RR 1.04, 95% CI 1.01, 1.06) adjusted for serum free testosterone, AMH, lipids, and other factors.

Conclusions

Adiposity may be associated with anovulation through pathways other than testosterone among regularly menstruating women. This may account in part for reported associations between greater adiposity and infertility among women having menstrual cycles regularly. Understanding the association between adiposity and anovulation might lead to targeted interventions for preventing infertility.