bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutralization breadth of SARS CoV-2 viral variants following primary series and booster SARS CoV-2 vaccines in patients with cancer
Authors: Naranbhai Vivek , Denis Kerri J St. , Lam Evan C , Ofoman Onosereme , Beltran Wilfredo-Garcia , Berrios Cristhian , Bhan Atul K. , Gainor Justin F. , Balazs Alejandro B. , Iafrate A. John 
Published: November 2021

SummaryPatients with cancer are more likely to have impaired immune responses to SARS CoV-2 vaccines. We studied the breadth of responses against SARS CoV-2 variants followingly primary vaccination in 178 patients with a variety of tumor types, and after booster doses in a subset. Neutralization of alpha, beta, gamma and delta SARS-CoV-2 variants was impaired relative to wildtype (Wuhan), regardless of vaccine type. Regardless of viral variant, mRNA1273 was the most immunogenic, followed by BNT162b2 and then Ad26.COV2.S. Neutralization of more variants (breadth) was associated with higher magnitude of wildtype neutralization, and increase with time since vaccination; increased age associated with lower breadth. Anti-spike binding antibody concentrations were a good surrogate for breadth (PPV=90% at >1000U/ml). Booster SARS-CoV-2 vaccines conferred enhanced breadth. These data suggest that achieving a high antibody titer is desirable to achieve broad neutralization; a single booster dose with current vaccines increases breadth of responses against variants.
Purchasing high-cost medical equipment in hospitals: A systematic review
Authors: Hinrichs-Krapels Saba , Ditewig Bor , Boulding Harriet , Chalkidou Anastasia , Erskine Jamie , Shokraneh Farhad 
Published: November 2021

ABSTRACTObjectivesTo systematically review academic literature for empirical studies on any processes, procedures, methods or approaches to purchasing high-cost medical equipment within hospitals in high-income countries.DesignSystematic reviewMethodsOn 13 August 2020, we searched the following from inception: Cost-Effectiveness Analysis Registry, EconLit and ProQuest Dissertations & Theses A&I via ProQuest, Embase, MEDLINE, and MEDLINE in Process via Ovid SP, Google and Google Scholar, Health Management and Policy Database via Ovid SP, IEEE Xplore Digital Library, International HTA Database, NHS EED via CRD Web, Science Citation Index-Expanded, Conference Proceedings Citation Index-Science, and Emerging Sources Citation Index via Web of Science, Scopus, and Zetoc conference search. Studies were included if they described the approach to purchasing (also known as procurement or acquisition) of high-cost medical devices and/or equipment conducting within hospitals in high-income countries between 2000-2020. Studies were screened, data extracted, and summarised.ResultsOf 9437 records, 24 were included, based in 12 different countries and covering equipment types ranging from surgical robots to MRI scanners and orthopaedic implants. Study types included descriptions of processes taking place within or across hospitals (n=14), out of which three reported cost savings; empirical studies in which hospital records or participant data were analysed (n=8), and evaluations or pilots of proposed purchasing processes (n=2). Studies mainly highlight the importance of multidisciplinary involvement (especially clinical engineers and clinicians) in purchasing decision-making to balance technical, financial, safety and clinical aspects of device selection, and the potential of increasing evidence-based decisions using approaches ranging from hospital-based health technology assessments, ergonomics, to conducting user ‘trials’ of the device in use before purchase.ConclusionsWe highlight the lack of rigorous empirical work on this topic, calling for more intervention based and empirical work to advance the evidence base in this domain to advance knowledge, policy and practice.Strengths and limitations of this study-First systematic review of empirical work conducted in hospitals on purchasing of high-cost medical devices-Broad search covering a range of disciplines and study types-Limited to high-cost equipment which is challenging to differentiate across studies and has no standardised ‘value’ globally
Denoised VEGFR2 expression relates to sunitinib efficacy in advanced Clear Cell Renal Cell Carcinoma
Authors: Verlingue Loïc , Morel Daphné , Schaeffer Mickaël , Tanguy Laurent , Schmidt Jordane , Bernhard Jean-Christophe , Loubaton Bertrand , Bagnard Dominique 
Published: November 2021

ABSTRACTShort summaryPersonalized biomarkers can facilitate decision making upon multiple therapeutic options in ccRCC. VEGFR2 expression denoised with 37 normal and tumor gene-expressions relates to sunitinib effect whereas raw VEGFR2 expression doesn’t relate to sunitinib effect.BackgroundSeveral studies suggested that molecular analysis of patients with advanced clear cell renal cell carcinoma (ccRCC) could indicate whether a patient is susceptible of benefiting from sunitinib in first-line systemic treatment compared to immunotherapies. However, data remain conflicting and no predictive biomarker is validated so far to decipher if sunitinib could still represent a good therapeutic option in first line setting and beyond.MethodsPREDMED® denoised the tumor RNA expression of 37 genes including KDR (encoding VEGFR2) estimated by RT-qPCR, by normalizing it on the expression of normal kidney tissue and cell types. We investigated the performance of PREDMED® VEGFR2-scoring to predict the clinical effect of sunitinib for patients affected by ccRCC.ResultsAmong the 34 ccRCC patients’ samples retrospectively retrieved from the UroCCR project (NCT03293563), high VEGFR2 scores were associated with objective clinical responses under sunitinib treatment and low scores with stable disease or progression with a sensitivity of 86%, a specificity of 67% and an AUC of 72.5% (95%CI[50.1–94.9]; p=0.04). VEGFR2 scores were significantly and positively related to progression-free survival (HR = 0.465; 95%CI[0.221–0.978]; p=0.0311) and overall survival (HR = 0.400; 95%CI[0.192–0.834]; p=0.0134) under sunitinib treatment. In our cohort, raw VEGFR2 expression (before PREDMED® processing) was not related to the above mentioned outcomes.ConclusionWe describe a gene-expression based algorithm that is accurately related to the effect of sunitinib for patients with ccRCC. We further plan a validation of PREDMED® for combinatorial strategies involving antiangiogenics and immune-checkpoint blockers.
Globally elevated excitation-inhibition ratio in children with autism spectrum disorder and below-average intelligence
Authors: Manyukhina Viktoriya O. , Prokofyev Andrey O. , Galuta Ilia A. , Goiaeva Dzerassa E. , Obukhova Tatiana S. , Schneiderman Justin F. , Altukhov Dmitry I. , Stroganova Tatiana A. , Orekhova Elena V. 
Published: November 2021

AbstractBACKGROUNDAn altered balance of neuronal excitation and inhibition (E-I balance) might be implicated in the co-occurrence of autism and intellectual disability, but this hypothesis has never been tested. E-I balance changes can be estimated from the spectral slope of the aperiodic 1/f neural activity. Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with and without intellectual disability.METHODSMEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6-15 years with a broad range of IQs, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the LCMV beamformer approach. We then extracted the 1/f slope by fitting a linear function in to the log-log-scale power spectra in the high-frequency range.RESULTSThe grand averaged 1/f slope was steeper in the eyes closed than in the eyes open condition, but had high rank-order stability between them. In line with the previous research, the slope flattened with age. Children with ASD and below-average (<85) IQ had flatter slopes than either TD or ASD children with average IQ. These group differences could not be explained by differences in signal-to-noise ratio or periodic (alpha and beta) activity.CONCLUSIONSThe atypically flattened spectral slope of aperiodic activity in children with ASD and below-average IQ suggests a shift of the global E-I balance toward hyper-excitation. The spectral slope can provide an accessible non-invasive biomarker of the E-I ratio for translational research and making objective judgments about treatment effectiveness.
Children’s Species Literacy as Estimated and Desired by Biodiversity Communicators: a Mismatch with the Actual Level
Authors: Hooykaas Michiel J. D. , Aten Cathelijn , Hemelaar Elisabeth M. , Albers Casper J. , Schilthuizen Menno , Smeets Ionica 
Published: November 2021

AbstractWhile biodiversity decline continues and laypeople’s knowledge about species is limited, especially in children, high-quality communication is needed to raise awareness. For this, communicators should be aware of current knowledge levels in their target groups. We compared biodiversity communicators' estimates of the average species literacy level in primary school children with the actual level. Moreover, we explored the importance that communicators placed on species literacy and the level that they desired. Estimations of children’s average knowledge level varied widely and differed from the actual level. In particular, communicators overestimated the species literacy level. Although most biodiversity communicators agreed that knowledge about species is important, their view differed as to why species literacy would be important. Moreover, communicators differed with respect to the relative importance attached to different knowledge components. Professionals may thus benefit from a detailed framework of species literacy that illustrates different aspects and values. Most importantly, our findings suggest that to bridge the gap between actual and desired knowledge levels in children effectively, biodiversity communicators first need to become more aware of current perceptions in young audiences.
Semantic relation priming is not constituent-specific: Evidence from ERP
Authors: Jia Xiaofei , Zhou Changle 
Published: November 2021

AbstractIt is humankind’s unique wisdom to compose a limited number of words together through specific rules to convey endless information. Researchers have found that this composition process also plays a vital role in the comprehension of compounds. The specific manifestation is relation priming; that is, the previously used relation will promote subsequent word processing using the same relation. This priming phenomenon is bound to morpheme repetition (modifier or head). This study combines a self-paced priming paradigm with electrophysiological technology to explore whether relation priming will occur without sharing morphemes and its time course. We found that relation priming can occur independently of morpheme-repetition, which shows an independent representation of relation information. And it has been activated at a very early stage (about 200ms). As the word processing progresses, this activation gradually strengthens, indicating that the relation’s role is slowly increasing in the process of compound word recognition. It may first be used as a kind of context information to help determine the constituent morphemes’ meaning. After the meaning access of the constituent morphemes, they begin to play a role in the semantic composition process. This study uses electrophysiological technology to precisely describe the representation of relation and its time course for the first time. Which gives us a deeper understanding of the relation priming process, and at the same time, shed light on the meaning construction process of compounds.
Reduced platelet forces underlie impaired hemostasis in mouse models of MYH9-related disease
Authors: Baumann Juliane , Sachs Laura , Oliver Otto , Schoen Ingmar , Nestler Peter , Zaninetti Carlo , Kenny Martin , Kranz Ruth , von Eysmondt Hendrik , Rodriguez Johanna , Schäffer Tilman E. , Nagy Zoltan , Greinacher Andreas , Palankar Raghavendra , Bender Markus 
Published: November 2021

AbstractMYH9-related disease patients with mutations in the contractile protein non-muscle myosin heavy chain IIA display, among others, macrothrombocytopenia and a mild to moderate bleeding tendency. In this study, we used three mouse lines, each with one point mutation in the Myh9 gene at positions 702, 1424, or 1841, to investigate mechanisms underlying the increased bleeding risk. Agonist-induced activation of Myh9 mutant platelets was comparable to controls. However, myosin light chain phosphorylation after activation was reduced in mutant platelets, which displayed altered biophysical characteristics and generated lower adhesion, interaction, and traction forces. Treatment with tranexamic acid restored clot retraction and reduced bleeding. We verified our findings from the mutant mice with platelets from patients with the respective mutation. These data suggest that reduced platelet forces lead to an increased bleeding tendency in MYH9-related disease patients, and treatment with tranexamic acid can improve the hemostatic function.TeaserImpaired hemostasis in Myh9 mutant mice due to reduced platelet forces can be improved by tranexamic acid.
SARS-CoV-2 ORF8 encoded protein contains a histone mimic, disrupts chromatin regulation, and enhances replication
Authors: Kee John , Thudium Samuel , Renner David , Glastad Karl , Palozola Katherine , Zhang Zhen , Li Yize , Cesare Joseph , Lan Yemin , Truitt Rachel , Cardenas-Diaz Fabian L. , Kotton Darrell N. , Alysandratos Konstantinos D. , Zhang Xianwen , Xie Xuping , Shi Pei-Yong , Yang Wenli , Morrisey Edward , Garcia Benjamin A. , Berger Shelley L. , Weiss Susan R. , Korb Erica 
Published: November 2021

AbstractSARS-CoV-2 emerged in China at the end of 2019 and caused the global pandemic of COVID-19, a disease with high morbidity and mortality. While our understanding of this new virus is rapidly increasing, gaps remain in our understanding of how SARS-CoV-2 can effectively suppress host cell antiviral responses. Recent work on other viruses has demonstrated a novel mechanism through which viral proteins can mimic critical regions of human histone proteins. Histone proteins are responsible for governing genome accessibility and their precise regulation is critical for a cell’s ability to control transcription and respond to viral threats. Here, we show that the protein encoded by ORF8 (Orf8) in SARS-CoV-2 functions as a histone mimic of the ARKS motif in histone 3. Orf8 is associated with chromatin, binds to numerous histone-associated proteins, and is itself acetylated within the histone mimic site. Orf8 expression in cells disrupts multiple critical histone post-translational modifications (PTMs) including H3K9ac, H3K9me3, and H3K27me3 and promotes chromatin compaction while Orf8 lacking the histone mimic motif does not. Further, SARS-CoV-2 infection in human cell lines and postmortem patient lung tissue cause these same disruptions to chromatin. However, deletion of the Orf8 gene from SARS-CoV-2 largely blocks its ability to disrupt host-cell chromatin indicating that Orf8 is responsible for these effects. Finally, deletion of the ORF8 gene affects the host-cell transcriptional response to SARS-CoV-2 infection in multiple cell types and decreases the replication of SARS-CoV-2 in human induced pluripotent stem cell-derived lung alveolar type 2 (iAT2) pulmonary cells. These findings demonstrate a novel function for the poorly understood ORF8-encoded protein and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Finally, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19.
Measuring metabolic rate in single flies during sleep and waking states
Authors: Brown Elizabeth B. , Klok Jaco , Keene Alex C. 
Published: November 2021

ABSTRACTDrosophila melanogaster is a leading genetic model for studying the neural regulation of sleep. Sleep is associated with changes in behavior and physiological state that are largely conserved across species. The investigation of sleep in flies has predominantly focused on behavioral readouts of sleep because physiological measurements, including changes in brain activity and metabolic rate are less accessible. We have previously used stop-flow indirect calorimetry to measure whole body metabolic rate in single flies and have shown that in flies, like mammals, metabolic rate is reduced during sleep. Here, we describe a modified version of this system that allows for efficient and highly sensitive acquisition of CO2 output from single flies. We also describe a modification that allows for simultaneous acquisition of CO2 and O2 levels, providing a respiratory quotient that quantifies how metabolic stores are utilized. Finally, we show that sleep-dependent changes in metabolic rate are diminished in aging flies, supporting the notion that sleep quality is reduced as flies age. Taken together, the use of indirect calorimetry provides a physiological measure of sleep with broad applications to genetic studies in flies.
Rapid, Reliable and Robust approach for extraction-free RT-PCR based detection of SARS-CoV-2 in clinical setting to expedite large scale screening
Authors: Dubey Abhilasha , Upadhyay Sanjay , Mehta Manjeet 
Published: November 2021

AbstractRapid, reliable and robust method for the detection of SARS-CoV-2 is an indispensable need for diagnostics. The development of diagnostic method will aid to address further waves of the pandemic potentially with rapid surveillance of disease; and to allay the fears. To meet this challenge, we have developed a rapid RT-qPCR method for the detection of 3 target genes or confirmatory genes in less than 30 minutes. The assay showed 100% sensitivity and 100% specificity when tested on 120 samples. We compared a conventional extraction based method with extraction-free method, and then further reduced the run time of extraction free method. Additionally, we have validated our rapid RT-qPCR method for the assessment of pooled sample. We hereby propose a most reliable approach for the mass screening of samples with ease of operation at low cost. Finally we designed a single tube analysis method which provides qualitative as well as quantitative results in minimum time.
Crystal structure of oligoribonuclease from Vibrio cholerae O1 El Tor with bound peptide
Authors: Zhang Jianyu , Sun Liyuan , Zhang Qionglin , Bartlam Mark 
Published: November 2021

Oligoribonuclease (Orn), a member of the DEDDh superfamily, can hydrolyse 2–5 nt nanoRNAs to mononucleotides. It is involved in maintaining the intracellular levels of RNA, c-di-GMP signalling and transcription initiation in many bacterial species. Here, the crystal structure of Orn from Vibrio cholerae O1 El Tor (VcOrn) is reported at a resolution of 1.7 Å. VcOrn, which consists of nine α-helices and six β-strands, crystallizes with a single monomer in the asymmetric unit but forms a homodimer via crystallographic twofold symmetry. Electron density is observed in the active pocket that corresponds to an intersubunit N-terminal expression tag with sequence GPLGSHHH. The positively charged N-terminal tag binds in the negatively charged nucleotide-binding pocket with a buried surface area of ∼500 Å2. The N-terminal tag interacts with VcOrn via π–π stacking with two conserved residues involved in nucleotide binding, as well as via salt bridges and hydrogen bonds. The structure reported here reveals that the active pocket can accommodate polypeptides in addition to nucleotides, thus providing an important starting point for investigation into substrate modification and inhibitor design targeting VcOrn.
The experiences of autistic adults during the COVID-19 pandemic in the UK and implications for autism services development
Authors: Riese Bettina , Mukherjee Raja A.S. 
Published: November 2021

Purpose
COVID-19 has been challenging for many in the UK. This is no different to many with autism spectrum disorder. Based on the experiences and issues raised by a small group of autistic women in an ongoing support group, consideration if this holds true for the wider adult autistic community across further lockdowns and restrictions to public life was explored.

Design/methodology/approach
An online questionnaire was created based on the issues raised. Participants indicated the degree to which they agreed or disagreed with each statement.

Findings
Autistic adults experienced an increase in anxiety and poor mental health, which in turn has exacerbated autistic features, such as rigidity. The data indicates that autistic adults can adapt to change provided there is support in maintaining routines.

Research limitations/implications
The research is limited due to the small number of participants (N = 120), as well as national variations in service provision.

Practical implications
Our data raises wider questions about the nature of support for autistic adults without cognitive impairments during times of crises and how services can respond and may even be shaped in the future to provide support that is cost-effective and relevant to autistic adults.

Social implications
To ensure that services have an awareness of how crises impact on autistic adults and how relatively simple changes may avert poor mental health.

Originality/value
That the creation of local support networks, and the ability to access these, is a key feature of autism-specific support.
The open-access telecommunication transmission network in the Canary Islands: an alternative proposal to the current management model?
Authors: Krawietz Ramos Eduardo , Aguilar Chinea Rosa María , Baquero Pérez Pedro Juan 
Published: November 2021

Purpose
This paper aims to study the competition problems and market failures in the Canary Islands and propose an alternative management model for the telecommunication transmission network. This model is based on a wholesale-only open-access transmission network, available to all the retail service providers of this region, and managed by a unique entity subject to regulation with cost-based prices. The proposal hopefully will help to debate about the implementation of certain regulatory models in the network industries, concerning telecommunication submarine cables connecting archipelagos.

Design/methodology/approach
An empirical approach has been used, based on the observation and analysis of the regulatory policies applied to the wholesale transmission networks in the Canary Islands, Azores and Madeira archipelagos.

Findings
Results show a persistent margin squeeze situation on the retail broadband market in the Canary Islands, due to the pricing strategy on the Spanish mainland-Canaries wholesale market, which is, in turn, delaying the entry of alternatives and the level of development and efficiency of competition. The risk of duopoly collusion is also present on this wholesale market. Additionally, public aids will be needed to replace the systems connecting with the non-capital islands and to provide redundancy to El Hierro. The alternative proposal might help preventing the above. Eventually, several insights are considered for further investigation.

Originality/value
Little attention has been paid to this topic in the literature, regarding the analysis of regulatory policies applied over fiber optic submarine cable infrastructures in fragmented territories like archipelagos. Consequently, an empirical analysis has been accomplished to emphasize this research work, based on the regulatory policies adopted.