bluuebunny/crossref_metadata_2025 huggingface dataset:
ME-VAE: Multi-Encoder Variational AutoEncoder for Controlling Multiple Transformational Features in Single Cell Image Analysis
Authors: Ternes Luke , Dane Mark , Gross Sean , Labrie Marilyne , Mills Gordon , Gray Joe , Heiser Laura , Chang Young Hwan
Published: April 2021

Image-based cell phenotyping relies on quantitative measurements as encoded representations of cells; however, defining suitable representations that capture complex imaging features is challenged by the lack of robust methods to segment cells, identify subcellular compartments, and extract relevant features. Variational autoencoder (VAE) approaches produce encouraging results by mapping an image to a representative descriptor, and outperform classical hand-crafted features for morphology, intensity, and texture at differentiating data. Although VAEs show promising results for capturing morphological and organizational features in tissue, single cell image analyses based on VAEs often fail to identify biologically informative features due to uninformative technical variation. Herein, we propose a multi-encoder VAE (ME-VAE) in single cell image analysis using transformed images as a self-supervised signal to extract transform-invariant biologically meaningful features, including emergent features not obvious from prior knowledge. We show that the proposed architecture improves analysis by making distinct cell populations more separable compared to traditional VAEs and intensity measurements by enhancing phenotypic differences between cells and by improving correlations to other analytic modalities.
Cerebrovascular responses to O2-CO2 exchange ratio under brief breath-hold challenge in patients with chronic mild traumatic brain injury
Authors: Chan Suk Tak , Ordway Cora , Calvanio Ronald J. , Buonanno Ferdinando S. , Rosen Bruce R. , Kwong Kenneth K.
Published: April 2021

Breath-by-breath O2-CO2exchange ratio (bER) is a respiratory gas exchange (RGE) metric, which is the ratio of the changes in the partial pressure of O2(ΔPO2) to CO2(ΔPCO2) between endinspiration and end-expiration, has been demonstrated to characterize the cerebrovascular responses to breath-hold challenge in healthy individuals. We aimed to explore if bER could characterize cerebrovascular responses in patients with chronic mild traumatic brain injury (mTBI) under breath-hold challenge. We also investigated the correlation between bER and the severity of post-concussion symptoms.

Blood-oxygenation-level-dependent (BOLD) images were acquired using functional magnetic resonance imaging (fMRI) on eleven patients with chronic mTBI and eleven controls without brain injury history when performing a breath-hold task. Time series of RGE metrics of ΔPO2, ΔPCO2, and bER were computed, and their cross-correlation with regional change in BOLD (ΔBOLD) was calculated. Symptom burden was assessed using the Rivermead Post Concussion Questionnaire (RPQ), and its correlation with RGE changes was also measured.

Compared with controls, a diffuse decrease in the correlation between regional ΔBOLD and bER was found in the brain of mTBI patients (pfdr<0.05). No significant difference was found between patients and controls for the correlation of regional ΔBOLD with ΔPO2and ΔPCO2. The averaged changes in bER (ρ=0.79, p=0.01) and ΔPO2(ρ=0.70, p=0.03) in breath-hold epochs decreased with increased symptom severity indicated by RPQ scores.

Our imaging and symptom severity findings suggest that bER can be used to characterize cerebrovascular responses to breath-hold in mTBI patients. RGE may contribute to the post-concussive symptom severity.
Multicomponent nature underlies the extraordinary mechanical properties of spider dragline silk
Authors: Kono Nobuaki , Nakamura Hiroyuki , Mori Masaru , Yoshida Yuki , Ohtoshi Rintaro , Malay Ali D , Pedrazzoli Moran Daniel A , Tomita Masaru , Numata Keiji , Arakawa Kazuharu
Published: April 2021

Dragline silk of golden orb-weaver spiders (Nephilinae) is noted for its unsurpassed toughness, combining extraordinary extensibility and tensile strength, suggesting industrial application as a sustainable biopolymer material. To pinpoint the molecular composition of dragline silk and the roles of its constituents in achieving its mechanical properties, we report a multiomics approach combining high-quality genome sequencing and assembly, silk gland transcriptomics, and dragline silk proteomics of four Nephilinae spiders. We observed the consistent presence of the MaSp3B spidroin unique to this subfamily, as well as several non-spidroin SpiCE proteins. Artificial synthesis and combination of these components in vitro showed that the multicomponent nature of dragline silk, including MaSp3B and SpiCE, along with MaSp1 and MaSp2, is essential to realize the mechanical properties of spider dragline silk.
Simultaneous hybrid genome sequencing of Vermamoeba vermiformis and its Dependentiae endosymbiont Vermiphilus pyriformis
Authors: Delafont Vincent , Gasqué Mégane , Héchard Yann
Published: April 2021

A hybrid sequencing approach, using short and long reads sequencing, was employed for characterizing the genomes of the free-living amoeba host Vermamoeba vermiformis, along with its Dependentiae endosymbiont Vermiphilus pyriformis. The amoeba host reconstructed nuclear genome is 39.5 Mb, and its full mitochondrial genome is 61.7 kb. The closed, circular genome of the Dependentiae endosymbiont Vermiphilus pyriformis, naturally infecting V. vermiformis is 1.1 Mb.
Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated primary human airway cells
Authors: Guo Wenrui , Porter Linsey M , Crozier Thomas WM , Coates Matthew , Jha Akhilesh , McKie Mikel , Nathan James A , Lehner Paul J , Greenwood Edward JD , McCaughan Frank
Published: April 2021

Background

There are limited effective prophylactic treatments for SARS-CoV-2 infection, and limited early treatment options. Viral cell entry requires spike protein binding to the ACE2 receptor and spike cleavage by TMPRSS2, a cell surface serine protease. Targeting of TMPRSS2 by either androgen blockade or direct inhibition is already in clinical trials in early SARS-CoV-2 infection.

Methods

The likely initial cells of SARS-CoV-2 entry are the ciliated cells of the upper airway. We therefore used differentiated primary human airway epithelial cells maintained at the air-liquid interface (ALI) to test the impact of targeting TMPRSS2 on the prevention of SARS-CoV-2 infection.

Results

We first modelled the systemic delivery of compounds. Enzalutamide, an oral androgen receptor antagonist, had no impact on SARS-Cov-2 infection. By contrast, camostat mesylate, an orally available serine protease inhibitor, blocked SARS-CoV-2 entry. However, camostat is rapidly metabolised in the circulationin vivo, and systemic bioavailability after oral dosing is low. We therefore modelled local airway administration by applying camostat to the apical surface of the differentiated ALI cultures. We demonstrated that a brief exposure to topical camostat is effective at restricting SARS-CoV-2 viral infection.

Conclusion

These experiments demonstrate a potential therapeutic role for topical camostat for pre- or post-exposure prophylaxis of SARS-CoV-2, which can now be evaluated in a clinical trial.
One more avenue for whale-watching contributions to science: the study of cetacean-cephalopod interactions
Authors: Suciu Stéphanie R.A. , Zereba Jasmine , Fiori Lorenzo , Azevedo José M.N.
Published: April 2021

Cephalopods are the primary source of food for several species of odontocetes. The unstable nature of this trophic resource is likely to affect the ecology of their cetacean predators, and this can be reflected on their conservation status but also on the tourist activities which target the observation of these animals. However, the study of the cetacean-cephalopod interaction is limited by the heavy logistics and expense of dedicated scientific campaigns. Fortunately, this gap can be filled by coupling modern molecular tools with indirect sampling methods. In this note we test if whale watching activities, which represent an intense observation effort worldwide, could be a source of material for studies of cetacean-cephalopod interactions. All contacted companies welcomed the invitation and received the sampling kit. Nine samples were collected, most of them in close association with sperm whales. All samples were determined as the seven-arm octopusHaliphron atlanticus(Octopoda, Alloposidae). We conclude that, although the Azores may have particularly favorable conditions for participatory science, similar programs can be replicated elsewhere
Recurrent fusions inPLAGL1define a distinct subset of pediatric-type supratentorial ependymoma
Authors: Sievers Philipp , Henneken Sophie C. , Blume Christina , Sill Martin , Schrimpf Daniel , Stichel Damian , Okonechnikov Konstantin , Reuss David E. , Benzel Julia , Maaß Kendra , Kool Marcel , Sturm Dominik , Kohlhof-Meinecke Patricia , Cruz Ofelia , Suñol Mariona , Lavarino Cinzia , Ruf Viktoria , Boldt Henning B. , Pagès Mélanie , Pouget Celso , Schweizer Leonille , Kranendonk Mariëtte E. G. , Akhtar Noreen , Schüller Ulrich , Mueller Wolf C. , Dohmen Hildegard , Acker Till , Harter Patrick N. , Mawrin Christian , Beschorner Rudi , Brandner Sebastian , Snuderl Matija , Abdullaev Zied , Aldape Kenneth , Gilbert Mark R. , Armstrong Terri S. , Ellison David W. , Capper David , Ichimura Koichi , Reifenberger Guido , Grundy Richard G. , Jabado Nada , Krskova Lenka , Zapotocky Michal , Vicha Ales , Varlet Pascale , Wesseling Pieter , Rutkowski Stefan , Korshunov Andrey , Wick Wolfgang , Pfister Stefan M. , Jones David T. W. , Deimling Andreas von , Pajtler Kristian W. , Sahm Felix
Published: April 2021

Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving thepleomorphic adenoma gene-like 1(PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion beingEWSR1:PLAGL1(n = 13). Five tumors showed aPLAGL1:FOXO1fusion and one aPLAGL1:EP300fusion. High transcript levels ofPLAGL1were noted in these tumors, with concurrent overexpression of the imprinted genesH19andIGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of largely ependymoma-like tumors. Immunohistochemically, tumors were GFAP-positive and OLIG2- and SOX10-negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. Consistent with other fusion-positive ependymal groups, all tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Analysis of time to progression or recurrence revealed survival times comparable to those of patients withZFTA:RELA-fused ependymoma. In summary, our findings suggest the existence of a novel group of supratentorial ependymomas that are characterized by recurrentPLAGL1fusions and enriched for pediatric patients.
Age-related pathological impairments in induced neurons derived from patients with idiopathic Parkinson’s disease
Authors: Drouin-Ouellet Janelle , Pircs Karolina , Legault Emilie M. , Birtele Marcella , Nilsson Fredrik , Shrigley Shelby , Pereira Maria , Storm Petter , Sharma Yogita , Vuono Romina , Stoker Thomas B. , Jakobsson Johan , Barker Roger A. , Parmar Malin
Published: April 2021

Understanding the pathophysiology of Parkinson’s disease has been hampered by the lack of models that recapitulate all the critical factors underlying its development. Here, we generated functional induced dopaminergic neurons (iDANs) that were directly reprogrammed from adult human dermal fibroblasts of patients with idiopathic Parkinson’s disease to investigate diseaserelevant pathology. We show that iDANs derived from Parkinson’s disease patients exhibit lower basal chaperone-mediated autophagy as compared to iDANs of healthy donors. Furthermore, stress-induced autophagy resulted in an accumulation of macroautophagic structures in induced neurons (iNs) derived from Parkinson’s disease patients, independently of the specific neuronal subtype but dependent on the age of the donor. Finally, we found that these impairments in patient-derived iNs lead to an accumulation of phosphorylated alpha-synuclein, a hallmark of Parkinson’s disease pathology. Taken together, our results demonstrate that direct neural reprogramming provides a patient-specific model to study aged neuronal features relevant to idiopathic Parkinson’s disease.
In vivoKRAS G12D/V degradation mediated by CANDDY using a modified proteasome inhibitor
Authors: Imanishi Satoshi , Huang Lijuan , Itakura Shoko , Ishizaka Masamichi , Iwasaki Yoichi , Yamaguchi Tomohiro , Miyamoto-Sato Etsuko
Published: April 2021

“Undruggable” proteins, such as RAS proteins, remain problematic despite efforts to discover inhibitors against them. KRAS mutants are prevalent in human cancers. Recently, the KRAS G12C inhibitor have been clinically approved, but inhibitors for KRAS G12D/V are still under development. Here, we described the development of a novel chemical knockdown strategy, termed CANDDY (Chemical knockdown with Affinity aNd Degradation DYnamics). This strategy involves a CANDDY tag modified from a proteasome inhibitor inducing direct proteasomal degradation. We constructed TUS-007 as a multispecific small molecule tethered from a KRAS interactor and CANDDY tag to target KRAS G12D/V. We confirmed that the degradation by TUS-007 was independent of target ubiquitination. This allows to solve a laborious design of matchmaker in the current ubiquitination-dependent proteolysis technology. And TUS-007 successfully suppressed tumors due to in vivo degradation of KRAS G12D/V. The CANDDY technology could represent a simple and rational strategy to degrade currently “undruggable” proteins.
Assembly-free rapid differential gene expression analysis in non-model organisms using DNA-protein alignment
Authors: Shrestha Anish M.S. , Guiao Joyce Emlyn B. , Santiago Kyle Christian R.
Published: April 2021

Background

RNA-seq is being increasingly adopted for gene expression studies in a panoply of non-model organisms, with applications spanning the fields of agriculture, aquaculture, ecology, and environment. For organisms that lack a well-annotated reference genome or transcriptome, a conventional RNA-seq data analysis workflow requires constructing a de-novo transcriptome assembly and annotating it against a high-confidence protein database. The assembly serves as a reference for read mapping, and the annotation is necessary for functional analysis of genes found to be differentially expressed. However, assembly is computationally expensive. It is also prone to errors that impact expression analysis, especially since sequencing depth is typically much lower for expression studies than for transcript discovery.

Results

We propose a shortcut, in which we obtain counts for differential expression analysis by directly aligning RNA-seq reads to the high-confidence proteome that would have been otherwise used for annotation. By avoiding assembly, we drastically cut down computational costs – the running time on a typical dataset improves from the order of tens of hours to under half an hour, and the memory requirement is reduced from the order of tens of Gbytes to tens of Mbytes. We show through experiments on simulated and real data that our pipeline not only reduces computational costs, but has higher sensitivity and precision than a typical assembly-based pipeline. A Snakemake implementation of our workflow is available at:https://bitbucket.org/project_samar/samar

Conclusions

The flip side of RNA-seq becoming accessible to even modestly resourced labs has been that the time, labor, and infrastructure cost of bioinformatics analysis has become a bottleneck. Assembly is one such resource-hungry process, and we show here that it can be avoided for quick and easy, yet more sensitive and precise, differential gene expression analysis in non-model organisms.
Amino acid residues involved in inhibition of host gene expression by influenza A/Brevig Mission/1/1918 PA-X
Authors: Chiem Kevin , Martinez-Sobrido Luis , Nogales Aitor , DeDiego Marta L.
Published: April 2021

Influenza A virus (IAV) PA-X protein is a virulence factor that selectively degrades host mRNAs leading to protein shutoff. This function modulates host inflammation, antiviral responses, cell apoptosis, and pathogenesis. In this work we describe a novel approach based on the use of bacteria and a plasmid encoding the PA-X gene under the control of the bacteriophage T7 promoter to identify amino acid residues important for A/Brevig Mission/1/1918 H1N1 PA-X’s shutoff activity. Using this system, we have identified PA-X mutants encoding single or double amino acid changes, which diminish its host shutoff activity, as well as its ability to counteract interferon responses upon viral infection. This novel bacteria-based approach could be used for the identification of viral proteins that inhibit host gene expression as well as the amino acid residues responsible for inhibition of host gene expression.
The effect of stress on memory for temporal context
Authors: Montijn Nicole D. , Gerritsen Lotte , Engelhard Iris. M.
Published: April 2021

Stress and emotional arousal interfere with encoding of temporal context memory for episodic events. However, it remains unclear how stress affects more fine-grained temporal memory, such as episodic events sequences and event times. Here, 86 healthy participants (M age = 22.5; 46% women, 54% men) were subjected to either a stress condition (socially evaluated cold pressor test) or a control condition, directly after or at a delay of 30 minutes they were presented the temporal structure of four virtual days. In these virtual days, time was scaled and participants could use clock cues to construe the passage of time within a day. We examined whether acute stress would interfere with encoding of episodic event sequences and temporal memory. Our results show that when learning took place directly after a stressor, virtual time estimates were more strongly biased towards a generalized timeline but temporal memory overall was not differentially affected between the stress and control groups. Exploratory analyses suggest that memory accuracy improved in men and deteriorated in women as a function of subjective stress levels following acute stress. In conclusion, acute stress amplified memory generalization but we found no stress related differences in memory accuracy across levels of temporal granularity,.
Hair regrowth in cicatricial alopecia: A literature review
Authors: Poliner Anna D. , Tosti Antonella
Published: April 2021

Cicatricial alopecias (CA) describes multiple subtypes of hair loss in which the hair follicle is destroyed by an unknown inflammatory mechanism. The main goal of treatment is to stop this inflammatory process and prevent further hair loss; however, there have been occasional reports of hair regrowth following treatment in some subtypes of CA. This review aims to highlight these reports. A total of 71 cases of hair regrowth were found documented in the literature. The treatments used varied widely both between and within each subtype of alopecia. This review highlights that regrowth is possible in at least a subset of patients with cicatricial alopecia; however, the mechanism by which this occurs has yet to be elucidated.
The Impact of Growth in Manufactured Imports from China on Employment in Australia*
Authors: Blanco Aaron , Borland Jeff , Coelli Michael , Maccarrone James
Published: April 2021

We examine how rapid growth in imports of manufactured goods from China affected employment in Australia from 1991 to 2006. Alternative sources of variation in Chinese import exposure (at industry level and between local labour markets) are used to identify the effect on employment. Growth in imports from China is estimated to have reduced manufacturing employment by around 53,200 to 78,900 workers, representing 5.3 to 7.5 per cent of that workforce in 1991. Largest impacts are found for manufacturing industries most exposed to import competition from China; and from 2001 to 2006 when import growth was strongest.
Empirical attrition modelling and discrimination: Balancing validity and group differences
Authors: Speer Andrew B.
Published: April 2021

Attrition models combine variables into statistical algorithms to understand and predict employee turnover. People analytics teams and external vendors use attrition models to offer insights and to develop organisational interventions. However, if attrition models or other data‐driven models inform employment decisions, model scores may then be subjected to civil rights laws and diversity concerns resulting from group differences in scores. This paper discusses adverse impact when building attrition models, outlining how researchers test for adverse impact in this context, strategies to reduce group differences and how attrition modelling and other human resources ‘big data’ predictions fit within larger validity frameworks. Procedures were applied to field data in an applied demonstration of an attrition model with disparate impact. Model revisions resulted in adverse impact reductions while simultaneously maintaining model validity. Collectively, this paper provides timely attention to important aspects of the people analytics, turnover and legal domains.
Hazardous and harmful alcohol use in the Northern Territory, Australia: the impact of alcohol policy on critical care admissions using an extended sampling period
Authors: Secombe Paul , Campbell Lewis , Brown Alex , Bailey Michael , Pilcher David
Published: April 2021

Aims

To describe the effect of alcohol policy on the incidence of intensive care unit (ICU) admissions associated with hazardous and harmful alcohol use in the Northern Territory (NT) of Australia

Design, setting and participants

Before and after analysis of admissions to NT ICUs between April 2018 and September 2019, extending on both a descriptive study describing hazardous and harmful alcohol use and single‐centre analyses of harm minimization policies. After exclusions, 2281 (83%) admissions were analysed, 20.3% of which were associated with hazardous and harmful alcohol use.

Measurements

Primary outcome was the incidence of admissions associated with hazardous and harmful alcohol use in the 5 months preceding (baseline period) the introduction of new alcohol policies [full‐time stationing of Police Auxiliary Liquor Inspectors (PALIs) and minimum unit price (MUP)] compared with 12 months (post‐intervention) following. Secondary outcomes included measures of resource use [length of stay (LoS), need for mechanical ventilation] and mortality, stratified by site.

Findings

Overall, there was a 4.5% [95% confidence interval (CI) = 0.8–8.2%] absolute risk reduction between the time‐periods (95% CI = 23.4 versus 18.9% for baseline and post‐intervention, respectively, P = 0.01), predominantly due to a reduction in admissions associated with acute misuse (2.3%, 95% CI = −0.2 to 4.9% risk reduction, P = 0.06). There were regional differences, with a more marked relative risk reduction observed in Central Australia compared with the city of Darwin (27.0 versus 16.7% relative risk reduction, respectively).

Conclusions

Introduction of new alcohol harm minimization policies in the Northern Territory of Australia appears to have reduced the number of intensive care unit admissions associated with hazardous and harmful alcohol use. Strength of effect varies by geographical region and chronicity of hazardous and harmful alcohol use.
Who, me? Optimism bias about US teenagers’ ability to quit vaping
Authors: Strombotne Kiersten , Sindelar Jody , Buckell John
Published: April 2021

Background and aims

The vaping rate among US teenagers has doubled in the last 2 years, which may be explained in part by teenagers’ optimism that they would have relatively little trouble in quitting. The aim of this study was to estimate the extent to which teenagers exhibited optimism bias, what characteristics are associated with optimism bias and which factors are related to respondents’ perceptions of how hard it would be for them to quit.

Design

A national, on‐line, cross‐sectional survey in 2018 using quota sampling.

Setting

United States.

Participants

Respondents were 1610 teenagers aged 14–18 years who had ever tried or heard of JUULs or e‐cigarettes generally.

Measurements

Optimism bias was defined as respondents’ perceptions of their own difficulty quitting vaping compared with that of an average US person of their own age. Linear regression was used to examine associations between respondents’ characteristics with both optimism bias and their own perceived difficulty quitting vaping.

Findings

More than 60% of teenagers were optimistically biased about their ability to quit vaping. Smoking (b = −0.69, P < 0.01) and JUULing (b = −0.62, P < 0.01) were negatively associated with optimism bias but reduced‐price school lunch eligibility (0.27, P = 0.02) and school satisfaction were positively associated (b = 0.05, P = 0.02). Smoking (b = 0.85, P < 0.01) was associated with an increased perception of the difficulty of quitting. That association was negative for black respondents (b = −0.81, P = 0.01) and those eligible for reduced‐priced lunches (b = −0.48, P = 0.01), and positive for Hispanic respondents (b = 0.47, P = 0.04).

Conclusions

On average, US teenagers appear to show optimism bias about their ability to quit vaping, which decreases with smoking and vaping and increases with eligibility for reduced‐price school lunches.
Gynaecological and IVF procedures billed through the Medicare Benefits Schedule (MBS) during the COVID‐19 pandemic
Authors: Alonso Anais , Deans Rebecca , Nesbitt‐Hawes Erin , Yazdani Anusch , McCormack Lalla , Koh Yi Ying , Abbott Jason
Published: April 2021

Background

In response to the COVID‐19 pandemic in Australia, restrictions to elective surgeries were implemented nationwide.

Aims

To investigate the response to these restrictions in elective gynaecological and In vitro fertilisation (IVF) procedures during the first wave of the COVID‐19 pandemic.

Materials and Methods

We analysed the Medicare Item Reports for the number of elective gynaecological (labioplasty, vulvoplasty; prolapse and continence; operative hysteroscopy; hysterectomy; fertility) and IVF procedures claimed in Australia between January–June 2020 and compared these to January–June 2019.

Results

The number of included gynaecological and IVF procedures performed in January–June 2020 decreased by −13.71% and −12.56%, respectively, compared to January–June 2019. The greatest reductions were in May 2020 (gynaecology −43.71%; IVF −51.63% compared to May 2019), while April 2020 reported decreases of −37.69% and −31.42% in gynaecological and IVF procedures, respectively. In April 2020, 1963 IVF cycle initiations (−45.20% compared to April 2019), 2453 oocyte retrievals (−26.99%) and 3136 embryo transfers (−22.95%) were billed. The procedures with greatest paired monthly decrease were prolapse and continence surgeries in April (676 procedures; −51.85%) and May 2020 (704 procedures; −60.05%), and oocyte retrievals in May 2020 (1637 procedures; −56.70%).

Conclusions

While we observed a decrease in procedural volumes, elective gynaecological and IVF procedures continued in considerable numbers during the restricted timeframes. In the event of future overwhelming biological threat, careful consideration must be given to more effective measures of limiting access for non‐emergency procedures to conserve essential resources and reduce risk to both the public and healthcare staff.
Effect of deglucuronidation on the results of the Basel phenotyping cocktail
Authors: Bachmann Fabio , Duthaler Urs , Krähenbühl Stephan
Published: April 2021

We investigated the effect of deglucuronidation on the plasma concentration of the constituents of the Basel phenotyping cocktail and on the interpretation of the phenotyping results under basal conditions and after cytochrome P450 (CYP) induction with metamizole. The cocktail containing caffeine (CYP1A2), efavirenz (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), metoprolol (CYP2D6) and midazolam (CYP3A4) was administered to 12 healthy subjects before (basal) and after treatment with metamizole for 1 week. In the basal state, deglucuronidation caused an increase in the plasma concentrations and area under the curve (AUC) of metoprolol, 8′‐hydroxyefavirenz, 4′‐hydroxyflurbiprofen and 1′‐hydroxymidazolam. This effect could be visualized in Bland–Altman plots, where the values for 8′‐hydroxyefavirenz, 4′‐hydroxyflurbiprofen and 1′‐hydroxymidazolam were mostly above the +20% threshold. As a result, the metabolic ratio (MR), calculated as AUCparent drug/AUCmetabolite, decreased with deglucuronidation for CYP2B6, CYP2C9 and CYP3A4 and increased for CYP2D6. Treatment with metamizole, a constitutive androstane receptor‐dependent inducer of CYP2B6, CYP2C9, CYP2C19 and CYP3A4, accentuated the effect of deglucuronidation on AUC and MR. The correlation of MRs calculated as the plasma concentration ratio parent drug/metabolite with the MR calculated as the AUC ratio showed that 1 sample obtained between 2 and 6 hours after cocktail ingestion and analysed with and without deglucuronidation is sufficient to obtain reliable phenotyping results. Importantly, CYP2C9 and 3A4 induction would have been missed without deglucuronidation of the plasma samples. In conclusion, deglucuronidation of the plasma samples improves the stability of the phenotyping results of the Basel phenotyping cocktail and is necessary to reliably detect CYP induction.
Periodontal (formerly type VIII) Ehlers–Danlos syndrome: Description of 13 novel cases and expansion of the clinical phenotype
Authors: El Chehadeh Salima , Legrand Anne , Stoetzel Corinne , Geoffroy Véronique , Billon Clarisse , Adham Salma , Jeunemaître Xavier , Jaussaud Roland , Muller Jean , Schaefer Elise , Benistan Karelle , Gaertner Sébastien , Bloch‐Zupan Agnès , Courval Aymeric , Manière Marie‐Cécile , Petit Catherine , Bursztejn Anne‐Claire , Bal Laurence , Reyre Anthony , Chammas Agathe , Busa Tiffany , Dollfus Hélène , Lipsker Dan
Published: April 2021

Periodontal Ehlers–Danlos syndrome (pEDS) is a rare condition caused by pathogenic variants in the C1R and C1S genes, encoding subunits C1r and C1s of the first component of the classical complement pathway. It is characterized by early‐onset periodontitis with premature tooth loss, pretibial hyperpigmentation and skin fragility. Rare arterial complications have been reported, but venous insufficiency is rarely described. Here we report 13 novel patients carrying heterozygous pathogenic variants in C1R and C1S including three novel C1S variants (c.962G > C, c.961 T > G and c.961 T > A). In addition to the pEDS phenotype, three patients and one relative displayed widespread venous insufficiency leading to persistent varicose leg ulcers. One patient suffered an intracranial aneurysm with familial vascular complications including thoracic and abdominal aortic aneurysm and dissection and intracranial aneurysm rupture. This work confirms that vascular complications can occur, although they are not frequent, which leads us to propose to carry out a first complete non‐invasive vascular evaluation at the time of the diagnosis in pEDS patients. However, larger case series are needed to improve our understanding of the link between complement pathway activation and connective tissue alterations observed in these patients, and to better assess the frequency, type and consequences of the vascular complications.
Growth in Criticism?
Authors: De Mey Peter
Published: April 2021

Reports of global ecumenical conversations are regularly published by the World Council of Churches in a collection of volumes titled Growth in Agreement. The assumption is that the dialogues are not just repeating the same arguments they made half a century ago, but that relations between member churches have grown qualitatively as a result of this process. This paper asks whether Orthodox critique of Roman Catholic ecclesiology reflects signs of growth or continues “traditional” stereotypical thinking about other churches and religions. The paper first examines Orthodox reactions to Lumen Gentium during and immediately after the Second Vatican Council, then compares them with Orthodox reactions to the council’s 50th anniversary. The paper concludes by asking whether Pope Francis’ endeavour to reform the Catholic Church in the direction of greater synodality is partly the result of the expectations of our sister churches’ representatives over the past 50 years.
What Have Lutherans Learned from Orthodox?
Authors: Kärkkäinen Veli‐Matti
Published: April 2021

The purpose of this article is to consider the influence of Eastern Orthodox theology and spirituality, particularly soteriology, upon the Lutheran doctrine of salvation. It focuses on the emergence of a new interpretation of Martin Luther’s view of justification as union and Christ’s “real” presence in the believer through the Holy Spirit. This account materially reflects key intuitions of the Eastern Orthodox vision of deification (divinization, theosis) and was developed in Helsinki, Finland, under the tutelage of Tuomo Mannermaa and his school. Even though this new interpretation continues to be contested and debated, particularly in German Luther scholarship, it has also exercised wide influence on international theological discussion. The latter part of the article, more constructive in nature, seeks to link the Helsinki School insights to some other current Lutheran contributions as well as relevant viewpoints from the wider Christian West.
EQUILIBRIUM COUNTERFACTUALS
Authors: Chemla Gilles , Hennessy Christopher
Published: April 2021

We incorporate structural modelers into the economy they model. Using traditional moment matching, they treat policy changes as zero probability (or exogenous) “counterfactuals.” Bias occurs since real‐world agents understand policy changes are positive probability events guided by modelers. Downward, upward, or sign bias occurs. Bias is illustrated by calibrating the Leland model to the 2017 tax cut. The traditional identifying assumption, constant moment partial derivative sign, is incorrect with policy optimization. The correct assumption is constant moment total derivative sign accounting for estimation‐policy feedback. Model agent expectations can be updated iteratively until policy advice converges to agent expectations, with bias vanishing.
Surgical treatment of non‐small‐cell lung cancer in octogenarians: a single‐centre retrospective study
Authors: Chen Charlotte , Kolbe John , Christmas Tim
Published: April 2021

Lung resection in patients aged ≥80 years is considered high risk and contributes to the low rates of resection in this population. This review of 79 octogenarians who underwent curative surgery for non‐small‐cell lung cancer demonstrated no intraoperative mortality, 30‐day mortality of 1.3% and 12‐month mortality of 10%. In this selected cohort of octogenarians, surgery resulted in acceptable short‐ to medium‐term outcomes.
COVID‐19: The future of nursing will determine the fate of our health services
Authors: Catton Howard
Published: April 2021

Preparing the world to manage future pandemics must take priority. It is clear that we were not prepared for the COVID‐19 pandemic which continues to cause great suffering around the world. Nurses and other health professionals everywhere must be involved in health policy planning and implementation of public health measures to combat this and future pandemics. Such preparation needs community policy involvement at grassroots levels and needs to be collaboratively instigated at international levels. The death so far of over 2000 nurses is unacceptable in this pandemic, and we need to better protect and sustain the workforce. The International Council of Nurses has been instrumental in data gathering of nurses' experiences during COVID‐19. Key points from analysis of this data have been included in Second Progress Report of the World Health Organization's Independent Panel for Pandemic Preparedness and Response. This paper summarises the key messages from this report, as well as the nursing shortage. The International Council of Nurses resounds the call for massive investment in nursing education, leadership and jobs, as well as protection for our nurses on the frontlines of the pandemic.
Clinician mental health, nursing shortages and the COVID‐19 pandemic: Crises within crises
Authors: Turale Sue , Nantsupawat Apiradee
Published: April 2021

Around the world, nurses are working under enormous pressure providing care to sick and dying patients during the pandemic. Many are faced with increased stress, and other negative effects on their mental health. They are also faced with the possibility of infection and death from COVID‐19. Before the pandemic there was a global shortage of nurses, but this is likely to be exacerbated by the increased demands of caring during COVID‐19 as well as the usual care of non‐COVID patients. One serious concern is that the pandemic and multitudinous effects on the nursing profession will exacerbate nursing attrition and their poor mental health into the future. Another serious concern is whether the profession will be able to attract sufficient numbers of nurses to care for populations into the future. Governments and health policymakers everywhere need to invest in nursing and health care and pay attention to the needs of health systems to ensure a healthy population. It is argued that without this, economies will not recover and prosper, and health systems will not be able to provide quality care.
Analyzing the Influence of Occupational Licensing Duration and Grandfathering on Wage Determination
Authors: Han Suyoun , Kleiner Morris M.
Published: April 2021

The length of time from the implementation of an occupational licensing statute (i.e., licensing duration) may matter in influencing labor‐market outcomes as entry requirements evolve. In addition, states enact grandfather clauses that allow existing workers to continue employment following these regulations, while ratcheting up requirements to increase entry costs for new entrants. We analyze the labor‐market influence of the duration of occupational licensing statutes for fifteen state universally licensed occupations over a 75‐year period. We find a positive nonlinear wage effect for licensing duration. Further, we find that occupational licensing raises the wages of grandfathered workers by almost 5 percent. The licensed occupations, however, exhibit heterogeneity in outcomes. Duration of occupational licensing influences wage determination when measured over longer time periods.
Hybrid alginate–copper sulfate textile coating for coronavirus inactivation
Authors: Bataglioli Rogério A. , Rocha Neto João B. M. , Calais Guilherme B. , Lopes Laise M. , Tsukamoto Junko , de Moraes Ana P. , Arns Clarice W. , Beppu Marisa M.
Published: April 2021

The sanitary crisis caused by the SARS‐CoV‐2 has increased the demand for bioactive materials to mitigate coronavirus spread. The use of masks has been reported as an essential strategy to prevent coronavirus transmission, but they can become contaminated rapidly after use. Metals species containing compounds, especially those from the copper group, present properties that can be explored to suppress viral activity. Natural polymers, like alginate, can improve biocompatibility and adjust metal ion availability on hybrid coatings. This study assesses iron, copper, silver, and gold salts and their combination with biopolymers to design surfaces with virucidal properties. Viral inactivation assays with MHV‐3 coronavirus strain and cytotoxicity tests with L929 cells were conducted to the hybrid coatings on polypropylene masks. These coatings were characterized by scanning electron microscopy with energy dispersive spectroscopy, Fourier‐transform infrared spectroscopy with attenuated total reflectance device, and atomic absorption spectroscopy techniques. Multilayer coatings of alginate–copper sulfate presented 99.99% viral inactivation in a timely release of copper ions.
Use of plants by Myzus persicae in agroecosystems: Potential applications in conservation biological control
Authors: Zumoffen Leticia , Carla Ghiglione , Signorini Marcelo , Salvo Adriana
Published: April 2021

Myzus persicae (Sulzer) is a highly polyphagous aphid species that attacks several economically important crop plants. Here, trophic webs involving M. persicae, its host plants and its parasitoids were described and quantified in wheat, oat and alfalfa agroecosystems from central Argentina, with special emphasis on the sub‐habitats where interactions occur: crops and adjacent field margins. Three fields cultivated with each crop species and their margins were sampled during three years; aphid abundance and mummification percentage were compared among crop plants and the diverse natural vegetation in the borders. Interactions were described using a quantitative food web approach, and abundance and mummification percentage e data were analysed using a generalized linear model. Four plant species present in the borders (Capsella bursa‐pastori, Rapistrum sp., Melilotus sp. and Trifolium repens) hosted M. persicae and its parasitoids. The alfalfa agroecosystem produced a significantly higher number of aphids than oat and wheat; however, in all cases, crops and borders sustained similar aphid abundance. A total of six Aphidiinae species attacked M. persicae, with no significant differences in the richness of parasitoid species between the borders and the crops, but with significant differences in parasitoid abundance, being higher in the crops. Mummification percentage were higher in crops than in the borders, with Lysiphlebus testaceipes, Aphidius colemani and A. ervi being the most abundant species. Almost 70% of M. persicae individuals were collected from fields borders, which highlights the importance of including these sites in studies of trophic interactions in crop fields.
Osmotic dehydration under low agitation laminar flow condition: Effect on dielectric properties of broccoli stalk slices at 2.45 GHz
Authors: Md Salim Nora Salina , Garièpy Yvan , Raghavan Vijaya
Published: April 2021

The variation in dielectric constant, ε′ and the loss factor, ε″ of broccoli stalk slices after osmotic dehydration process conducted under continuous solution circulation with low agitation laminar flow condition was studied using open‐ended coaxial probe technique at 2.45 GHz. The results showed that both ε′ and ε″ were significantly influenced by all the osmotic dehydration operating variables. The relationship of osmotic dehydration operating variables on the dielectric properties of the broccoli stalk slices could be established by second‐order polynomial model, with the coefficient of determination higher than .9. Compared to fresh sample, the ε′ decreases and ε″ increases when broccoli stalk is subjected to the osmotic dehydration pretreatment under its optimum conditions of mass transfer exchange process. Higher dissipation factor with shorter penetration depth was obtained after osmotic pretreatment, which could facilitate absorption of energy during microwave drying of broccoli stalk slices.

Practical Applications

Dielectric properties are key factors to understand the interaction of microwaves with food materials. In recent years, there has been an increasing interest in osmotic dehydration used as pretreatment prior to microwave drying to achieve faster drying time and improves the final product quality. As osmotic dehydration process will cause a change in the dielectric properties of the food material and its ability to absorb microwaves energy, this work investigated the effects of osmotic dehydration on the dielectric properties of broccoli stalk slices at 2.45 GHz. The osmo‐pretreated sample improved the dielectric properties which result in rapid heating and therefore lead to fast drying process. The information provided in this study is helpful in the development of dried broccoli stalk slices using microwave drying.
Microglial synaptic pruning on axon initial segment spines of dentate granule cells: Sexually dimorphic effects of early‐life stress and consequences for adult fear response
Authors: Zetter Mario A. , Hernández Vito S. , Roque Angélica , Hernández‐Pérez Oscar R. , Gómora María J. , Ruiz‐Velasco Silvia , Eiden Lee E. , Zhang Limei
Published: April 2021

Axon initial segments (AIS) of dentate granule cells in the hippocampus exhibit prominent spines (AISS) during early development that are associated with microglial contacts. In the present study, we investigated whether developmental changes in AISS could be modified by early‐life stress (ELS), specifically neonatal maternal separation (MS), through stress hormones and microglial activation and examined the potential behavioural consequences. We examined AISS at postnatal day (PND)5, 15 and 50, using Golgi‐Cox staining and anatomical analysis. Neurone‐microglial interaction was assessed using antibodies against ankyrin‐G, PSD‐95 and Iba1, for AIS, AISS and microglia visualisation, respectively, in normally reared and neonatal maternally separated male and female rats. We observed a higher density of AISS in ELS rats at both PND15 and PND50 compared to controls. Effects were more pronounced in females than males. AIS‐associated microglia in ELS rats showed a hyper‐ramified morphology and less co‐localisation with PSD‐95 compared to controls at PND15. ELS‐associated alteration in microglial morphology and synaptic pruning was mimicked by treatment of acute hippocampal slices of normally reared rats with vasopressin. ELS rats exhibited increased freezing behaviour during auditory fear memory testing, which was more pronounced in female subjects and corresponded with increased Fos expression in dorsal and ventral dentate granule cells. Thus, microglial synaptic pruning in dentate AIS of hippocampus is influenced by ELS, with demonstrable sex bias regarding its anatomical characteristics and subsequent fear‐induced defensive behaviours.