bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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

ABSTRACTAimTo investigate factors associated with intention to have the COVID-19 vaccination following initiation of the UK national vaccination programme.Methods1,500 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.Results73.5% 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.ConclusionsMost 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

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

AbstractSARS-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

AbstractIn 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

ABSTRACTBottlenecks 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

AbstractMost 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

AbstractIn 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

SummaryThe 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

AbstractIntroductionWhite 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).MethodsImaging 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.ResultsMCI, 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.ConclusionsWMHs 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

ABSTRACTAmbient 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.