bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing Posttraumatic Stress Disorder in Primary Care
Authors: Joneydi Rayan , Lack Kelly A. , Olsho Lauren E.W. , Corry Nida H. , Spera Christopher
Published: April 2021

Background:

Posttraumatic stress disorder (PTSD) is an undertreated psychological condition prevalent among service members and veterans. Members of the military community often raise mental health concerns in primary care settings. However, many primary care physicians (PCPs) lack training in PTSD within the military community and may be underprepared to discuss PTSD or trauma with patients.

Objectives:

We assessed PCPs’ knowledge of evidence-based PTSD screening and treatment practices, confidence in their abilities to provide clinical care around PTSD, and frequency of asking new patients about their military history. We also examined PCP characteristics related to these measures.

Research Design:

We surveyed a national sample of 7426 PCPs to assess their PTSD knowledge, confidence, and military history screening practices. Data were analyzed using weighted multivariable regressions.

Results:

Forty-three percent of PCPs reported they very often or always screened for military history and, on average, PCPs answered 41% of the PTSD knowledge items correctly. PCPs who rated their PTSD knowledge higher were more confident and more frequently screened for military history, but did not have higher knowledge scores compared with PCPs with lower self-assessed knowledge. Several PCP characteristics, such as sex, years of practice, and practice setting, predicted PTSD measures.

Conclusions:

PCPs have gaps in their knowledge and screening practices related to PTSD. The absence of a meaningful correlation of knowledge scores with PCP self-assessed knowledge or confidence suggests PCPs may not accurately rate their own knowledge. Targeted, evidence-based training on effective practices may promote PTSD clinical knowledge.
Corneal Biomechanical Changes Caused by Acute Elevation of IOP in Eyes with and without Glaucoma
Authors: Katiyar Suchitra , Tong Jennifer , Pensyl Denise , Sullivan-Mee Michael
Published: April 2021

SIGNIFICANCE

Although corneal biomechanical parameters are well linked with glaucoma, their clinical utility has not yet been fully elucidated. This study was designed to provide unique evidence about the dynamic nature of corneal biomechanical parameters and their potential prognostic ability for glaucoma.

PURPOSE

This study aimed to evaluate the effect of acute intraocular pressure (IOP) elevation on corneal hysteresis (CH) and corneal resistance factor (CRF) and the associations of these biomechanical parameters with glaucomatous disease.

METHODS

Subjects participating in a prospective, longitudinal glaucoma research study had CH and CRF measured before and during ophthalmodynamometry during visits in the years 2011 to 2012. All participants were diagnosed with primary open-angle glaucoma, ocular hypertension, glaucoma suspect, or normal eyes and had a minimum of 3 years of study participation with at least five reliable visual field (VF) tests. Changes in CH, CRF, and IOP induced by ophthalmodynamometry were compared between diagnostic groups and evaluated for relationships with existing and future glaucomatous VF loss.

RESULTS

In 248 eyes of 248 subjects followed up for 7.7 ± 2.3 years, ophthalmodynamometry induced a mean IOP increase from 15.1 to 29.9 mmHg, causing a mean 34 ± 28% increase in CRF and 21 ± 25% decrease in CH. Magnitude of CH change did not differ between diagnostic groups or between eyes that did (n = 20) and did not (n = 95) develop new VF loss during the study period, nor was it related to rate of future VF progression.

CONCLUSIONS

Ophthalmodynamometry-induced IOP elevation resulted in significant acute changes in CH and CRF in this study; this suggests accounting for IOP may be important in clinical interpretation of these parameters. However, because the degree of CH change was not related to glaucoma or its progression, acute changes in CH and CRF do not seem to have a prognostic value for glaucoma.
Topical Review: Assessment of Binocular Sensory Processes in Low Vision
Authors: Tong Janelle , Huang Jessie , Khou Vincent , Martin Jodi , Kalloniatis Michael , Ly Angelica
Published: April 2021

SIGNIFICANCE

This article summarizes the evidence for a higher prevalence of binocular vision dysfunctions in individuals with vision impairment. Assessment for and identification of binocular vision dysfunctions can detect individuals experiencing difficulties in activities including reading, object placement tasks, and mobility.

Comprehensive vision assessment in low vision populations is necessary to identify the extent of remaining vision and to enable directed rehabilitation efforts. In patients with vision impairment, little attention is typically paid to assessments of binocular vision, including ocular vergence, stereopsis, and binocular summation characteristics. In addition, binocular measurements of threshold automated visual fields are not routinely performed in clinical practice, leading to an incomplete understanding of individuals' binocular visual field and may affect rehabilitation outcomes.

First, this review summarizes the prevalence of dysfunctions in ocular vergence, stereopsis, and binocular summation characteristics across a variety of ocular pathologies causing vision impairment. Second, this review examines the links between clinical measurements of binocular visual functions and outcome measures including quality of life and performance in functional tasks. There is an increased prevalence of dysfunctions in ocular alignment, stereopsis, and binocular summation across low vision cohorts compared with those with normal vision. The identification of binocular vision dysfunctions during routine low vision assessments is especially important in patients experiencing difficulties in activities of daily living, including but not limited to reading, object placement tasks, and mobility. However, further research is required to determine whether addressing the identified deficits in binocular vision in low vision rehabilitative efforts directly impacts patient outcomes.
Contrast Sensitivity on 1/f Noise Is More Greatly Impacted by Older Age for the Fovea Than Parafovea
Authors: Srinivasan Rekha , Turpin Andrew , McKendrick Allison M.
Published: April 2021

SIGNIFICANCE

Contrast sensitivity changes across the visual field with age and is often measured clinically with various forms of perimetry on plain backgrounds. In daily life, the visual scene is more complicated, and therefore, the standard clinical measures of contrast sensitivity may not predict a patient's visual experience in more natural environments.

PURPOSE

This study aims to determine whether contrast thresholds in older adults are different from younger adults when measured on a 1/f noise background (a nonuniform background whose spatial frequency content is similar to those present in the natural vision environments).

METHODS

Twenty younger (age range, 20 to 35 years) and 20 older adults (age range, 61 to 79 years) with normal ocular health were recruited. Contrast thresholds were measured for a Gabor patch of 6 cycles per degree (sine wave grating masked by a Gaussian envelope of standard deviation 0.17°) presented on 1/f noise background (root-mean-square contrast, 0.05 and 0.20) that subtended 15° diameter of the central visual field. The stimulus was presented at four eccentricities (0°, 2°, 4°, and 6°) along the 45° meridian in the noise background, and nine contrast levels were tested at each eccentricity. The proportion of correct responses for detecting the target at each eccentricity was obtained, and psychometric functions were fit to estimate the contrast threshold.

RESULTS

Older adults demonstrate increased contrast thresholds compared with younger adults. There was an eccentricity-dependent interaction with age, with the difference between groups being highest in the fovea compared with other eccentricities. Performance was similar for the two noise backgrounds tested.

CONCLUSIONS

Our results revealed a strong eccentricity dependence in performance between older and younger adults, highlighting age-related differences in the contrast detection mechanisms between fovea and parafovea for stimuli presented on nonuniform backgrounds.
Infantile Rhabdomyosarcomas With VGLL2 Rearrangement Are Not Always an Indolent Disease
Authors: Cyrta Joanna , Gauthier Arnaud , Karanian Marie , Vieira Andre F. , Cardoen Liesbeth , Jehanno Nina , Bouvet Mégane , Bouvier Corinne , Komuta Mina , Le Loarer François , Orbach Daniel , Rome Angélique , Minard-Colin Véronique , Brichard Bénédicte , Pluchart Claire , Thebaud Estelle , Renard Marleen , Pannier Stéphanie , Brisse Hervé , Petit Philippe , Benoist Camille , Schleiermacher Gudrun , Geoerger Birgit , Vincent-Salomon Anne , Fréneaux Paul , Pierron Gaëlle
Published: April 2021

VGLL2-rearranged rhabdomyosarcomas (RMS) are rare low-grade tumors with only favorable outcomes reported to date. We describe 4 patients with VGLL2-rearranged RMS confirmed by molecular studies, who experienced local progression and distant metastases, including 2 with fatal outcomes. Tumors were diagnosed at birth (n=3) or at 12 months of age (n=1), and were all localized at initial diagnosis, but unresectable and therefore managed with chemotherapy and surveillance. Metastatic progression occurred from 1 to 8 years from diagnosis (median, 3.5 y). Three patients experienced multimetastatic spread and one showed an isolated adrenal metastasis. At initial diagnosis, 3 tumors displaying bland morphology were misdiagnosed as fibromatosis or infantile fibrosarcoma and initially managed as such, while 1 was a high-grade sarcoma. At relapse, 3 tumors showed high-grade morphology, while 1 retained a low-grade phenotype. Low-grade primary tumors showed only very focal positivity for desmin, myogenin, and/or MyoD1, while high-grade tumors were heterogenously or diffusely positive. Whole-exome sequencing, performed on primary and relapse samples for 3 patients, showed increased genomic instability and additional genomic alterations (eg, TP53, CDKN2A/B, FGFR4) at relapse, but no recurrent events. RNA sequencing confirmed that high-grade tumors retained VGLL2 fusion transcripts and transcriptomic profiles consistent with VGLL2-rearranged RMS. High-grade samples showed a high expression of genes encoding cell cycle proteins, desmin, and some developmental factors. These 4 cases with distinct medical history imply the importance of complete surgical resection, and suggest that RMS-type chemotherapy should be considered in unresectable cases, given the risk of high-grade transformation. They also emphasize the importance of correct initial diagnosis.
18F-FDG PET/CT in the Hyperparathyroidism–Jaw-Tumor Syndrome
Authors: Nazerani Hooshmand Tina , Pernthaler Birgit , Szurian Kinga , Pau Mauro , Aigner Reingard Maria
Published: April 2021

Hyperparathyroidism–jaw-tumor syndrome (HPT-JTS) is a rare autosomal dominant disorder. A typical manifestation of HPT-JTS is the association of jaw-ossifying fibroma with primary hyperparathyroidism. Due to its rarity and diversity in its manifestations, it is a challenging diagnosis. A 33-year-old woman was referred due to painful swelling of the right maxilla suggestive of malignancy. The clinical presentations were not conclusive until she underwent F18-fluorodeoxyglucose positron emission tomography/computed tomography (F18-FDG PET/CT). F18-FDG PET/CT proved to be a useful tool to assist the clinicians in visualizing the “bigger picture” and, therefore all manifestation as pieces of “one puzzle.”
Peptide Receptor Radionuclide Therapy in Patients With Neurofibromatosis Type 2
Authors: Kertels Olivia , Breun Maria , Hänscheid Heribert , Kircher Malte , Hartrampf Philipp E. , Schirbel Andreas , Monoranu Camelia-Maria , Ernestus Ralf-Ingo , Buck Andreas K. , Löhr Mario , Matthies Cordula , Lapa Constantin
Published: April 2021

Purpose

Neurofibromatosis type 2 (NF2) is a genetic disorder that is associated with multiple tumors of the nervous system, and approximately one half of patients present with meningiomas. For patients with multifocal disease, somatostatin receptor–targeted peptide receptor radionuclide therapy (PRRT) might be a suitable systemic treatment option.

Patients and Methods

Between March 2015 and August 2017, 11 NF2 patients (7 females and 4 males; mean age, 39 ± 12 years) with multifocal, progressive meningiomas underwent a median of 4 cycles of PRRT (range, 2–6 cycles). Acute and chronic adverse events were recorded according to National Institutes of Health’s Common Toxicity Criteria (CTC) version 5.0. Follow-up MRIs (every 3 to 6 months), using the Response Assessment in Neuro-Oncology response criteria for meningiomas, were used to assess treatment responses.

Results

Peptide receptor radionuclide therapy was well tolerated in all patients without any relevant acute adverse effects. Transient hematologic toxicity (CTC grade 3) was observed in 2 subjects. Somatostatin receptor–directed radiopeptide therapy resulted in radiological disease stabilization in 6 of 11 patients. Median progression-free survival was 12 months (range, 1–55 months), and overall survival was 37 months (range, 5–61 months).

Conclusions

Based on our retrospective pilot data, PRRT is feasible and well-tolerated in NF2 patients. It might offer a suitable treatment option in subjects with multiple, recurrent, or treatment-refractory meningiomas.
Lymphoscintigraphic Findings as Indicators of Lymphaticovenous Anastomosis Outcome in Patients With Extremity Lymphedema
Authors: Kim Hye Ok , Woo Kyong-Je , Kim Bom Sahn , Kang Seo Young , Moon Byung Seok , Yoon Hai-Jeon
Published: April 2021

Purpose

This study was performed to evaluate the usefulness of lymphoscintigraphy in predicting the surgical outcomes of lymphaticovenous anastomosis (LVA) in a patient with extremity lymphedema.

Patients and Methods

We retrospectively evaluated 133 patients with extremity lymphedema who underwent lymphoscintigraphy followed by LVA surgery from February 2018 to March 2020. Lymphoscintigraphic findings were evaluated on the following parameters: the extent of dermal backflow (small/large), lymphatic flow patterns (trunk flow pattern/proximal-restricted pattern/distal-restricted pattern), visualization of lymph nodes, and collateral lymphatic vessels. The mean circumferential difference change before and after surgery, circumferential reduction (CR) rate (%), was used as the clinical outcome variables.

Results

A decrease in circumference was observed in 93 (69.9%) of 133 patients after LVA. The extent of dermal backflow and lymphatic flow patterns was significantly correlated with improved clinical outcomes after LVA. The large extent of the dermal backflow group showed a more significant CR rate than the small extent (19.27% vs 1.24%, P = 0.005). The TP group showed the most significantly decreased CR rate to 21.46%, and the proximal-restricted pattern and distal-restricted pattern groups were −2.49% and −5.33%, respectively (P < 0.001). Multivariate analysis revealed that dermal backflow and lymphatic flow patterns were independent predictors of therapeutic outcome (P < 0.001).

Conclusions

Our study demonstrates that pretreatment lymphoscintigraphy may help predict the therapeutic effect of LVA in patients with extremity lymphedema. Furthermore, dermal backflow and lymphatic flow patterns are independent predictors of CR rate after LVA surgery for extremity lymphedema.
Molecular characterization of group A rotavirus strains detected in alpacas (Vicugna pacos) from Peru
Authors: Badaracco Alejandra , Cordero Aida , Vega Celina , Bok Marina , Zeller Mark , Heylen Elisabeth , Fernández Gonzalo , Díez-Baños Pablo , Morrondo Patrocinio , Guevara Héctor , Matthijnssens Jelle , Parreno Viviana
Published: April 2021

The alpaca is a very important social and economic resource for the production of fibre and meat for Andean communities. Peru is the main producer of alpacas. Group A rotavirus (RVA) has been sporadically detected in alpacas. In this study, a total of 1423 faecal samples from alpacas from different locations of the Puno department in Peru were collected and analysed by an antigen-capture ELISA in order to detect RVA. Four per cent of the samples were RVA-positive (57/1423). The genotype constellation of three selected alpaca RVA strains were G3/8 P[1/14]-I2-R2/5-C2/3-M2/3-A17-N2/3-T6-E3-H3. Two of the analysed strains presented a bovine-like genotype constellation, whereas the third strain presented six segments belonging to the AU-1-like genogroup (G3, M3, C3, N3, T3 and E3), suggesting reassorting events. Monitoring of the sanitary health of juvenile alpacas is essential to reduce the rates of neonatal mortality and for the development of preventive health strategies.
Discriminating arboviral species
Authors: Li Yiyuan , O’Donnell Angela C. , Ochman Howard
Published: April 2021

Mosquito-borne arboviruses, including a diverse array of alphaviruses and flaviviruses, lead to hundreds of millions of human infections each year. Current methods for species-level classification of arboviruses adhere to guidelines prescribed by the International Committee on Taxonomy of Viruses (ICTV), and generally apply a polyphasic approach that might include information about viral vectors, hosts, geographical distribution, antigenicity, levels of DNA similarity, disease association and/or ecological characteristics. However, there is substantial variation in the criteria used to define viral species, which can lead to the establishment of artificial boundaries between species and inconsistencies when inferring their relatedness, variation and evolutionary history. In this study, we apply a single, uniform principle – that underlying the Biological Species Concept (BSC) – to define biological species of arboviruses based on recombination between genomes. Given that few recombination events have been documented in arboviruses, we investigate the incidence of recombination within and among major arboviral groups using an approach based on the ratio of homoplastic sites (recombinant alleles) to non-homoplastic sites (vertically transmitted alleles). This approach supports many ICTV-designations but also recognizes several cases in which a named species comprises multiple biological species. These findings demonstrate that this metric may be applied to all lifeforms, including viruses, and lead to more consistent and accurate delineation of viral species.
The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection
Authors: Henss Lisa , Auste Arne , Schürmann Christoph , Schmidt Christin , von Rhein Christine , Mühlebach Michael D. , Schnierle Barbara S.
Published: April 2021

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and more than a million deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. No treatment exists. Epigallocatechin-3-gallate (EGCG), the major component of green tea, has several beneficial properties, including antiviral activities. Therefore, we examined whether EGCG has antiviral activity against SARS-CoV-2. EGCG blocked not only the entry of SARS-CoV-2, but also MERS- and SARS-CoV pseudotyped lentiviral vectors and inhibited virus infections in vitro. Mechanistically, inhibition of the SARS-CoV-2 spike–receptor interaction was observed. Thus, EGCG might be suitable for use as a lead structure to develop more effective anti-COVID-19 drugs.
An antipathogenic compound that targets the OxyR peroxide sensor in Pseudomonas aeruginosa
Authors: Oh Hyo-Young , Jalde Shivakumar S. , Chung In-Young , Yoo Yeon-Ji , Jang Hye-Jeong , Choi Hyun-Kyung , Cho You-Hee
Published: April 2021

Introduction. Antipathogenic or antivirulence strategy is to target a virulence pathway that is dispensable for growth, in the hope to mitigate the selection for drug resistance.

Hypothesis/Gap Statment. Peroxide stress responses are one of the conserved virulence pathways in bacterial pathogens and thus good targets for antipathogenic strategy.

Aim. This study aims to identify a new chemical compound that targets OxyR, the peroxide sensor required for the full virulence of the opportunistic human pathogen,

Pseudomonas aeruginosa

.

Methodology. Computer-based virtual screening under consideration of the ‘eNTRy’ rules and molecular docking were conducted on the reduced form of the OxyR regulatory domain (RD). Selected hits were validated by their ability to phenocopy the oxyR null mutant and modulate the redox cycle of OxyR.

Results. We first isolated three robust chemical hits that inhibit OxyR without affecting prototrophic growth or viability. One (compound 1) of those affected the redox cycle of OxyR in response to H2O2 treatment, in a way to impair its function. Compound 1 displayed selective antibacterial efficacy against

P. aeruginosa

in Drosophila infection model, without antibacterial activity against

Staphylococcus aureus

.

Conclusion. These results suggest that compound 1 could be an antipathogenic hit inhibiting the

P. aeruginosa

OxyR. More importantly, our study provides an insight into the computer-based discovery of new-paradigm selective antibacterials to treat Gram-negative bacterial infections presumably with few concerns of drug resistance.
COVID-19 vaccination acceptability in the UK at the start of the vaccination programme: a nationally representative cross-sectional survey (CoVAccS – wave 2)
Authors: Sherman Susan M. , Sim Julius , Cutts Megan , Dasch Hannah , Amlôt Richard , Rubin G James , Sevdalis Nick , Smith Louise E.
Published: April 2021

Aim

To investigate factors associated with intention to have the COVID-19 vaccination following initiation of the UK national vaccination programme.

Methods

1,500 adults completed an online cross-sectional survey (13th–15thJanuary 2021). Linear regression analyses were used to investigate associations between intention to be vaccinated for COVID-19 and sociodemographic factors, previous influenza vaccination, attitudes and beliefs about COVID-19, attitudes and beliefs about COVID-19 vaccination and vaccination in general. Participants’ main reasons for likely vaccination uptake/decline were also solicited.

Results

73.5% of participants (95% CI 71.2%, 75.7%) reported being likely to be vaccinated against COVID-19, 17.3% were unsure (95% CI 15.4%, 19.3%), and 9.3% (95% CI 7.9%, 10.8%) reported being unlikely to be vaccinated. The full regression model explained 69.8% of the variance in intention. Intention was associated with having been/intending to be vaccinated for influenza last winter/this winter, and with stronger beliefs about social acceptability of a COVID-19 vaccine; the need for vaccination; adequacy of information about the vaccine; and weaker beliefs that the vaccine is unsafe. Beliefs that only those at serious risk of illness should be vaccinated and that the vaccines are just a means for manufacturers to make money were negatively associated with vaccination intention.

Conclusions

Most participants reported being likely to get the COVID-19 vaccination. COVID-19 vaccination attitudes and beliefs are a crucial factor underpinning vaccine intention. Continued engagement with the public with a focus on the importance and safety of vaccination is recommended.
Examining changes in sleep duration associated with the onset of the COVID-19 pandemic: Who is sleeping and who is not?
Authors: Batool-Anwar Salma , Robbins Rebecca , Ali Shahmir H. , Capasso Ariadna , Foreman Joshua , Jones Abbey M. , Tozan Yesim , DiClemente Ralph J. , Quan Stuart F.
Published: April 2021

Introduction

The COVID-19 pandemic has resulted in social isolation and reports of insomnia. However, reports of changes in sleep duration and associated factors are few.

Methods

Data were from an online survey of adults recruited via social media that included a question asking whether the respondent slept less or more after the onset of the pandemic. Analyses determined the association between changes in sleep duration and self reported sociodemographic and occupational information; beliefs about COVID-19; changes in sleep patterns; and responses pertaining to loneliness, anxiety, and depression.

Results

There were 5,175 respondents; 53.9% had a change in sleep duration. 17.1% slept less and 36.7% slept more. Sleeping more was related to greater education, being single/divorced/separated, unemployed or a student. Being retired, divorced/separated or a homemaker, and living in the Mountain or Central time zones were associated with less sleep. Beliefs that COVID-19 would result in personal adverse consequences was associated with both more and less sleep. However, the strongest associations with both more and less sleep were seen with depression, anxiety, and loneliness with adjusted odds ratios ranging from 1.92 (95% CI1.67-2.21) for sleeping more and loneliness to 5.29 (95% CI4.1-6.7) for sleeping less and anxiety.

Conclusions

Changes in sleep duration since the start of the COVID-19 pandemic were highly prevalent among social media users and were associated with several sociodemographic factors and beliefs that COVID-19 would have adverse personal impacts. However, the strongest associations occurred with worse mental health suggesting that improvements may occur with better sleep.
TMPRSS2 and RNA-dependent RNA polymerase are effective targets of therapeutic intervention for treatment of COVID-19 caused by SARS-CoV-2 variants (B.1.1.7 and B.1.351)
Authors: Lee Jihye , Lee JinAh , Kim Hyeon Ju , Ko Meehyun , Jee Youngmee , Kim Seungtaek
Published: April 2021

SARS-CoV-2 is a causative agent of COVID-19 pandemic and the development of therapeutic interventions is urgently needed. So far, monoclonal antibodies and drug repositioning are the main methods for drug development and this effort was partially successful. Since the beginning of COVID-19 pandemic, the emergence of SARS-CoV-2 variants has been reported in many parts of the world and the main concern is whether the current vaccines and therapeutics are still effective against these variant viruses. The viral entry and viral RNA-dependent RNA polymerase (RdRp) are the main targets of current drug development, thus the inhibitory effects of TMPRSS2 and RdRp inhibitors were compared among the early SARS-CoV-2 isolate (lineage A) and the two recent variants (lineage B.1.1.7 and lineage B.1.351) identified in the UK and South Africa, respectively. Our in vitro analysis of viral replication showed that the drugs targeting TMPRSS2 and RdRp are equally effective against the two variants of concern.
Parametric Deconvolution for Cancer Cells Viscoelasticity Measurements from Quantitative Phase Images
Authors: Vicar Tomas , Gumulec Jaromir , Kolar Radim , Chmelik Jiri , Navratil Jiri , Chmelikova Larisa , Cmiel Vratislav , Provaznik Ivo , Masarik Michal
Published: April 2021

In this contribution, we focused on optimising a dynamic flow-based shear stress system to achieve a reliable platform for cell shear modulus (stiffness) and viscosity assessment using quantitative phase imaging. The estimation of cell viscoelastic properties is influenced by distortion of the shear stress waveform, which is caused by the properties of the flow system components (i.e., syringe, flow chamber and tubing). We observed that these components have a significant influence on the measured cell viscoelastic characteristics. To suppress this effect, we applied a correction method utilizing parametric deconvolution of the flow system’s optimized impulse response. Achieved results were compared with the direct fitting of the Kelvin-Voigt viscoelastic model and the basic steady-state model. The results showed that our novel parametric deconvolution approach is more robust and provides a more reliable estimation of viscosity with respect to changes in the syringe’s compliance compared to Kelvin-Voigt model.
Comparative analysis of Pure Hubs and Pure Bottlenecks in Human Protein-protein Interaction Networks
Authors: Nithya Chandramohan , Kiran Manjari , Nagarajaram Hampapathalu Adimurthy
Published: April 2021

Bottlenecks and hubs form a set of topologically important nodes in a network. In this communication, we have made a detailed investigation on hubs and bottlenecks in human protein-protein interaction networks. We find that, three distinct groups exist which we refer to as: a) pure hubs (PHs, nodes having high degree but low betweenness values), b) mix proteins (MXs, nodes having both high degree and high betweenness values) and c) pure bottlenecks (PBs, nodes having high betweenness values but low degree values). Our investigations have revealed that pure hubs, as compared with MXs and PBs, (i) are more disordered, (ii) have higher potential to bind to multiple partners, (iii) are enriched with essential proteins as well as enriched with a higher number of splice variants. The MX proteins, as compared with PHs and PBs, (i) show slower evolutionary patterns, (ii) are involved in multiple pathways, (iii) enriched with the products of genes associated with various diseases and (iv) are more often targeted by bacteria, viruses, protozoa, and fungi pathogens. PBs, as compared with the PHs and MXs, (i) are associated with cancer genes and (ii) are the targets or the nearest neighbors of the targets of most of the approved drugs. Furthermore, our study revealed that these three categories of proteins are involved in distinct functional roles; PHs are involved in housekeeping processes such as transcription and replication; MXs proteins are involved in core signaling pathways whereas PBs are involved in signal transduction processes. Our work, therefore, has identified the distinct characteristics features associated with pure hubs, mix proteins and pure bottlenecks and thus helps in prioritizing proteins based on their degree and betweenness centrality values.
Predicting population genetic change in an experimental stochastic environment
Authors: Rescan Marie , Grulois Daphné , Ortega Aboud Enrique , de Villemereuil Pierre , Chevin Luis-Miguel
Published: April 2021

Most natural environments exhibit a substantial component of random variation. Such environmental noise is expected to cause random fluctuations in natural selection, affecting the predictability of evolution. But despite a long-standing theoretical interest for understanding the population genetic consequences of stochastic environments, there has been a dearth of empirical validation and estimation of the underlying parameters of this theory. Indeed, tracking the genetics of a large number of replicate lines under a controlled level of environmental stochasticity is particularly challenging. Here, we tackled this problem by resorting to an automated experimental evolution approach. We used a liquid-handling robot to expose over a hundred lines of the micro-algaDunaliella salinato randomly fluctuating salinity over a continuous range, with controlled mean, variance, and autocorrelation. We then tracked the frequency of one of two competing strains through amplicon sequencing of a nuclear and choloroplastic barcode sequences. We show that the magnitude of environmental fluctuations (variance), but also their predictability (autocorrelation), have large impacts on the average selection coefficient. Furthermore, the stochastic variance in population genetic change is substantially higher in a fluctuating environment. Reaction norms of selection coefficients and growth rates of single strains against the environment captured the mean response accurately, but failed to explain the high variance induced by environmental stochasticity. Overall, our results provide exceptional insights on the prospects for understanding and predicting genetic evolution in randomly fluctuating environments.
Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to 2 years in sheep: Spatiotemporal insights augmented by Raman microspectroscopy
Authors: De Kort B.J. , Marzi J. , Brauchle E. , Lichauco A.M. , Bauer H.S. , Serrero A. , Dekker S. , Cox M.A.J. , Schoen F.J. , Schenke-Layland K. , Bouten C.V.C. , Smits A.I.P.M.
Published: April 2021

In situheart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf available scaffolds are used to induce endogenous heart valve restoration. Such scaffolds are designed to recruit endogenous cellsin vivo, which subsequently resorb polymer and produce and remodel new valvular tissuein situ. Recently, preclinical studies using electrospun supramolecular elastomeric valvular grafts have shown that this approach enablesin situregeneration of pulmonary valves with long-term functionalityin vivo. However, the evolution and mechanisms of inflammation, polymer absorption and tissue regeneration are largely unknown, and adverse valve remodeling and intra- and inter-valvular variability have been reported. Therefore, the goal of the present study was to gain a mechanistic understanding of thein vivoregenerative processes by combining routine histology and immunohistochemistry, using a comprehensive sheep-specific antibody panel, with Raman microspectroscopy for the spatiotemporal analysis ofin situtissue-engineered pulmonary valves with follow-up to 24 months from a previous preclinical study in sheep. The analyses revealed a strong spatial heterogeneity in the influx of inflammatory cells, graft resorption, and foreign body giant cells. Collagen maturation occurred predominantly between 6 and 12 months after implantation, which was accompanied by a progressive switch to a more quiescent phenotype of infiltrating cells with properties of valvular interstitial cells. Variability among specimens in the extent of tissue remodeling was observed for follow-up times after 6 months. Taken together, these findings advance the understanding of key events and mechanisms in material-drivenin situheart valve tissue engineering.
Altered O-glycosylation Level of SARS-CoV-2 Spike Protein by Host O-glycosyltransferase Strengthens Its Trimeric Structure
Authors: Xu Zhijue , Ku Xin , Tian Jiaqi , Zhang Han , Hou Jingli , Zhang Can , Shi Jingjing , Li Yang , Kaji Hiroyuki , Tao Sheng-Ce , Kuno Atsushi , Yan Wei , Da Lin-Tai , Zhang Yan
Published: April 2021

The trimeric spike protein (S) mediates host-cell entry and membrane fusion of SARS-CoV-2. S protein is highly glycosylated, whereas its O-glycosylation is still poorly understood. Herein, we site-specifically examine the O-glycosylation of S protein through a mass spectrometric approach with HCD-triggered-ETD model. We identify 15 high-confidence O-glycosites and at least 10 distinct O-glycan structures on S protein. Peptide microarray assays prove that human ppGalNAc-T6 actively participates in O-glycosylation of S protein. Importantly, the upregulation of ppGalNAc-T6 expression can profoundly enhance the O-glycosylation level by generating new O-glycosites and increasing both O-glycan heterogeneity and intensities. Further molecular dynamics simulations reveal that the O-glycosylation on the protomer-interface regions, which are mainly modified by ppGalNAc-T6, can potentially stabilize the trimeric S protein structure. Our work provides deep molecular insights of how viral infection harnesses the host O-glycosyltransferases to dynamically regulate the O-glycosylation level of the viral envelope protein responsible for membrane fusion.
White Matter Hyperintensities, Grey Matter Atrophy, and Cognitive Decline in Neurodegenerative Diseases
Authors: Dadar Mahsa , Manera Ana Laura , Collins D. Louis
Published: April 2021

Introduction

White matter hyperintensities (WMHs) as seen on T2w and FLAIR scans represent small-vessel disease related changes in the brain. WMHs are associated with cognitive decline in the normal aging population in general and more specifically in patients with neurodegenerative diseases. In this study, we assessed the different spatial patterns and relationships between WMHs and grey matter (GM) atrophy in normal aging, individuals with mild cognitive impairment (MCI), Alzheimer’s dementia (AD), fronto-temporal dementia (FTD), andde novoParkinson’s disease (PD).

Methods

Imaging and clinical data were obtained from 3 large multi-center databases: The Alzheimer’s Disease Neuroimaging Initiative (ADNI), the frontotemporal lobar degeneration neuroimaging initiative (NIFD), and the Parkinson’s Progression Markers Initiative (PPMI). WMHs and GM atrophy maps were measured in normal controls (N= 571), MCI (N= 577), AD (N= 222), FTD (N= 144), and PD (N= 363). WMHs were segmented using T1w and T2w/PD or FLAIR images and mapped onto 45 white matter tracts using the Yeh WM atlas. GM volume was estimated from the Jacobian determinant of the nonlinear deformation field required to map the subject’s MRI to a standard template. The CerebrA atlas was used to obtain volume estimates in 84 GM regions. Mixed effects models were used to compare WMH in different WM tracts and volume of multiple GM structures between patients and controls, assess the relationship between regional WMHs and GM loss for each disease, and investigate their impact on cognition.

Results

MCI, AD, and FTD patients had significantly higher WMH loads than the matched controls. There was no significant difference in WMHs between PD and controls. For each cohort, significant interactions between WMH load and GM atrophy were found for several regions and tracts, reflecting additional contribution of WMH burden to GM atrophy. While these associations were more relevant for insular and parieto-occipital regions in MCI and AD cohorts, WMH burden in FTD subjects had greater impact on frontal and basal ganglia atrophy. Finally, we found additional contribution of WMH burden to cognitive deficits in AD and FTD subjects compared with matched controls, whereas their impact on cognitive performance in MCI and PD were not significantly different from controls.

Conclusions

WMHs occur more extensively in MCI, AD, and FTD patients than age-matched normal controls. WMH burden on WM tracts also correlates with regional GM atrophy in regions anatomically and functionally related to those tracts, suggesting a potential involvement of WMHs in the neurodegenerative process.
Accounting for point count ambient noise increases population size estimates
Authors: Anderson Emily K. , Kerby-Miller Pete F. , Pupko Julia M. , Sharp Nathaniel R. , Tolan Kevin S. , Hill Jason M.
Published: April 2021

Ambient noise is an integral component of natural environments, but it also creates challenges for avian monitoring programs. Ambient noise can mask bird vocalizations from observers during point counts, which may lead to systematic undercounting of birds in noisy environments. Here, we estimate detection probability and population size in models that either account for or omit the influence of ambient noise. We used data for four bird species, from 2228 point counts that were conducted during the 2019 Mountain Birdwatch field season. Community scientists assessed ambient noise using a simple scale. Despite relatively quiet conditions at sampling locations (x= 2.48), our information theoretical approach favored N-mixture models that incorporated ambient noise into the detection function for all four species. At the noisiest sampling locations, our models predicted detection probabilities that were as low as 10% for some species. Accounting for ambient noise resulted in a modest, mean increase of ≤3.29% in the total population size for each species. Following our approach, other researchers can easily incorporate ambient noise assessments into their field protocols and analyses, with minimal costs or added complexity, to increase the comparability of studies conducted within different acoustic environments.
A rarefaction-without-resampling extension of PERMANOVA for testing presence-absence associations in the microbiome
Authors: Hu Yi-Juan , Satten Glen A.
Published: April 2021

Background

PERMANOVA [1] is currently the most commonly used method for testing community-level hypotheses about microbiome associations with covariates of interest. PERMANOVA can test for associations that result from changes in which taxa are present or absent by using the Jaccard or unweighted UniFrac distance. However, such presence-absence analyses face a unique challenge: confounding by library size (total sample read count), which occurs when library size is associated with covariates in the analysis. It is known thatrarefaction(subsampling to a common library size) controls this bias, but at the potential costs of information loss and the introduction of a stochastic component into the analysis.

Methods

Here we develop a non-stochastic approach to PERMANOVA presence-absence analyses that aggregates information overallpotential rarefaction replicates without actual resampling, when the Jaccard or unweighted UniFrac distance is used. We compare this new approach to three possible ways of aggregating PERMANOVA over multiple rarefactions obtained from resampling: averaging the distance matrix, averaging the (element-wise) squared distance matrix, and averaging theF-statistic.

Results

Our simulations indicate that our non-stochastic approach is robust to confounding by library size and outperforms each of the stochastic resampling approaches. We also show that, when overdispersion is low, averaging the (element-wise) squared distance outperforms averaging the unsquared distance, currently implemented in the R packagevegan. We illustrate our methods using an analysis of data on inflammatory bowel disease (IBD) in which samples from case participants have systematically smaller library sizes than samples from control participants.
Functional evaluation of the P681H mutation on the proteolytic activation the SARS-CoV-2 variant B.1.1.7 (Alpha) spike
Authors: Lubinski Bailey , Fernandes Maureen H. V. , Frazier Laura , Tang Tiffany , Daniel Susan , Diel Diego G. , Jaimes Javier A. , Whittaker Gary R.
Published: April 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing the COVID-19 pandemic. SARS-CoV-2 B.1.1.7 (Alpha), a WHO variant of concern (VOC) first identified in the UK in late 2020, contains several mutations including P681H in the spike S1/S2 cleavage site, which is predicted to increase cleavage by furin, potentially impacting the viral cell entry. Here, we studied the role of the P681H mutation in B.1.1.7 cell entry. We performed assays using fluorogenic peptides mimicking the Wuhan-Hu-1 and B.1.1.7 S1/S2 sequence and observed no significant difference in furin cleavage. Functional assays using pseudoparticles harboring SARS-CoV-2 spikes and cell-to-cell fusion assays demonstrated no differences between Wuhan-Hu-1, B.1.1.7 or a P681H point mutant. Likewise, we observed no differences in viral growth between USA-WA1/2020 and a B.1.1.7 isolate in cell culture. Our findings suggest that while the B.1.1.7 P681H mutation may slightly increase S1/S2 cleavage this does not significantly impact viral entry or cell-cell spread.

Highlights

SARS-CoV-2 B.1.1.7 VOC has a P681H mutation in the spike that is predicted to enhance viral infection

P681H does not significantly impact furin cleavage, viral entry or cell-cell spread

Other mutations in the SARS-CoV-2 B.1.1.7 VOC may account for increased infection rates

Graphical abstract
Transcript- and annotation-guided genome assembly of the European starling
Authors: Stuart Katarina C. , Edwards Richard J. , Cheng Yuanyuan , Warren Wesley C. , Burt David W. , Sherwin William B. , Hofmeister Natalie R. , Werner Scott J. , Ball Gregory F. , Bateson Melissa , Brandley Matthew C. , Buchanan Katherine L. , Cassey Phillip , Clayton David F. , De Meyer Tim , Meddle Simone L. , Rollins Lee A.
Published: April 2021

The European starling,Sturnus vulgaris, is an ecologically significant, globally invasive avian species that is also suffering from a major decline in its native range. Here, we present the genome assembly and long-read transcriptome of an Australian-sourced European starling (S. vulgarisvAU), and a second North American genome (S. vulgarisvNA), as complementary reference genomes for population genetic and evolutionary characterisation.S. vulgarisvAU combined 10x Genomics linked-reads, low-coverage Nanopore sequencing, and PacBio Iso-Seq full-length transcript scaffolding to generate a 1050 Mb assembly on 1,628 scaffolds (72.5 Mb scaffold N50). Species-specific transcript mapping and gene annotation revealed high structural and functional completeness (94.6% BUSCO completeness). Further scaffolding against the high-quality zebra finch (Taeniopygia guttata) genome assigned 98.6% of the assembly to 32 putative nuclear chromosome scaffolds. Rapid, recent advances in sequencing technologies and bioinformatics software have highlighted the need for evidence-based assessment of assembly decisions on a case-by-case basis. UsingS. vulgarisvAU, we demonstrate how the multifunctional use of PacBio Iso-Seq transcript data and complementary homology-based annotation of sequential assembly steps (assessed using a new tool, SAAGA) can be used to assess, inform, and validate assembly workflow decisions. We also highlight some counter-intuitive behaviour in traditional BUSCO metrics, and present Buscomp, a complementary tool for assembly comparison designed to be robust to differences in assembly size and base-calling quality. Finally, we present a second starling assembly,S. vulgarisvNA, to facilitate comparative analysis and global genomic research on this ecologically important species.
BDNF Val66Met polymorphism as putative genetic substrate of music-induced plasticity in auditory prediction
Authors: Bruzzone S.E.P. , Bonetti L. , Paunio T. , Kantojärvi K. , Kliuchko M. , Vuust P. , Brattico E.
Published: April 2021

Predictive processing of sounds depends on the constant updating of priors based on exposure to posteriors, which through repeated exposure mediates learning. The result of such corrections to the model is seen in musicians, whose lifelong training results in measurable plasticity of audio-motor brain anatomy and functionality. It has been suggested that the plasticity of auditory predictive processes depends on the interaction between the environment and the individual’s genetic substrate. However, empirical evidence to this is still missing. BDNF is a critical genetic factor affecting learning and plasticity, and its widely studied functional variant Val66Met single-nucleotide polymorphism offers a unique opportunity to investigate neuroplastic functional changes occurring upon a years-long training. We hypothesised that BDNF gene variations would be driving neuroplasticity of the auditory cortex in musically trained human participants. To this goal, musicians and non-musicians were recruited and divided in Val/Val and Met carriers and their brain activity measured with magnetoencephalography (MEG) while they listened to a regular auditory sequence containing different types of prediction errors. The auditory cortex responses to prediction errors was enhanced in Val/Val carriers who underwent intensive musical training, compared to Met and non-musicians. Our results point at a role of gene-regulated neurotrophic factors in the neural adaptations of auditory processing after long-term training.