bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the Rotavirus Vaccination Program in Norway After Four Years With High Coverage
Authors: Bruun Tone , Salamanca Beatriz Valcarcel , Bekkevold Terese , Døllner Henrik , Gibory Moustafa , Gilje Ann Marit , Haarr Elisebet , Kran Anne-Marte Bakken , Leegaard Truls M. , Nakstad Britt , Nordbø Svein Arne , Rojahn Astrid , Størdal Ketil , Flem Elmira 
Published: January 2021

Background:
Use of rotavirus vaccines worldwide since 2006 has led to a significant impact on the burden of rotavirus disease. However, only a third of European countries have introduced rotavirus vaccination in their immunization programs. In October 2014, rotavirus vaccination was introduced for Norwegian infants under strict age restrictions. Exclusive use of the monovalent rotavirus vaccine (RV1) and high vaccination coverage from the beginning enabled evaluation of the impact of this vaccine during the first 4 years after introduction.

Methods:
Prospective laboratory-based surveillance among children <5 years of age hospitalized for acute gastroenteritis at 5 Norwegian hospitals was used to assess the vaccine effectiveness of 2 vaccine doses against rotavirus hospitalization in a case-control study. We used community controls selected from the national population-based immunization registry, and test-negative controls recruited through hospital surveillance. We also assessed the vaccine impact by using time-series analysis of retrospectively collected registry data on acute gastroenteritis in primary and hospital care during 2009–2018.

Results:
Vaccine effectiveness against rotavirus-confirmed hospitalization was 76% (95% confidence interval [CI]: 34%–91%) using test-negative controls, and 75% (95% CI: 44%–88%) using community controls. In the postvaccine period, acute gastroenteritis hospitalizations in children <5 years were reduced by 45% compared with the prevaccine years (adjusted incidence rate ratios 0.55; 95% CI: 0.49–0.61). Reduction in hospitalizations was also seen in cohorts not eligible for vaccination. Rates in primary care decreased to a lesser degree.

Conclusions:
Four years after introduction of rotavirus vaccination in the national childhood immunization program, we recorded a substantial reduction in the number of children hospitalized for acute gastroenteritis in Norway, attributable to a high vaccine effectiveness.
Natural variants in SARS-CoV-2 S protein pinpoint structural and functional hotspots: implications for prophylaxis and therapeutic strategies
Authors: Pokhrel Suman , Kraemer Benjamin R. , Burkholz Scott , Mochly-Rosen Daria 
Published: January 2021

AbstractIn December 2019, a novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of pneumonia with severe respiratory distress and outbreaks in Wuhan, China. The rapid and global spread of SARS-CoV-2 resulted in the coronavirus 2019 (COVID-19) pandemic. Earlier during the pandemic, there were limited genetic viral variations. As millions of people became infected, multiple single amino acid substitutions emerged. Many of these substitutions have no consequences. However, some of the new variants show a greater infection rate, more severe disease, and reduced sensitivity to current prophylaxes and treatments. Of particular importance in SARS-CoV-2 transmission are mutations that occur in the Spike (S) protein, the protein on the viral outer envelope that binds to the human angiotensin-converting enzyme receptor (hACE2). Here, we conducted a comprehensive analysis of 441,168 individual virus sequences isolated from humans throughout the world. From the individual sequences, we identified 3,540 unique amino acid substitutions in the S protein. Analysis of these different variants in the S protein pinpointed important functional and structural sites in the protein. This information may guide the development of effective vaccines and therapeutics to help arrest the spread of the COVID-19 pandemic.
Evaluation of at-home methods for N95 filtering facepiece respirator decontamination
Authors: Chen T.X. , Pinharanda A. , Steinemann N. A. , Yasuma-Mitobe K. , Lee E. , Hahn J. , Wu L. , Fanourakis S. , Peterka D. S. , Hillman E.M.C 
Published: January 2021

AbstractN95 filtering facepiece respirators (FFRs) are essential for the protection of healthcare professionals and other high-risk groups against Coronavirus Disease of 2019 (COVID-19). In response to shortages in FFRs during the ongoing COVID-19 pandemic, the Food and Drug Administration issued an Emergency Use Authorization permitting FFR decontamination and reuse. However, although industrial decontamination services are available at some large institutions, FFR decontamination is not widely accessible.To be effective, FFR decontamination must 1) inactivate the virus; 2) preserve FFR integrity, specifically fit and filtering capability; and 3) be non-toxic and safe. Here we identify and test at-home heat-based methods for FFR decontamination that meet these requirements using common household appliances. Our results identify potential protocols for simple and accessible FFR decontamination, while also highlighting unsuitable methods that may jeopardize FFR integrity.One sentence summarySurvey of at-home methods for N95 respirator decontamination using heat and evaluation of their effects on N95 respirator integrity.
Binding and activation of serotonergic G-protein coupled receptors by the multimodal antidepressant vortioxetine
Authors: Ladefoged Lucy Kate , Koch Rebekka , Biggin Philip C. , Schiøtt Birgit 
Published: January 2021

AbstractG-protein coupled receptors are important pharmacological targets. Despite substantial progress, important questions still remain concerning the details of activation: how can a ligand act as an agonist in one receptor, but as an antagonist in a homologous receptor, and how can agonists activate a receptor despite lacking polar functional groups able to interact with helix 5? Studying vortioxetine, an important multimodal antidepressant drug, may elucidate both questions. Herein, we present a thoroughin silicoanalysis of vortioxetine binding to 5-HT1A, 5-HT1B, and 5-HT7receptors and compare to available experimental data. We are able to rationalize the differential mode of action of vortioxetine at different receptors, but also, in the case of the 5-HT1Areceptor, we observe the initial steps of activation suggesting that interaction with helix 5 does not necessarily require a hydrogen bond as previously suggested. The results extend our current understanding of agonist and antagonist action at GPCRs.
In-depth computational analysis of natural and artificial carbon fixation pathways
Authors: Löwe Hannes , Kremling Andreas 
Published: January 2021

AbstractIn the recent years, engineering new-to-nature CO2 and C1 fixing metabolic pathways made a leap forward. These new, artificial pathways promise higher yields and activity than natural ones like the Calvin-Benson-Bassham cycle. The question remains how to best predict theirin vivoperformance and what actually makes one pathway “better” than another.In this context, we explore aerobic carbon fixation pathways by a computational approach and compare them based on their ATP-efficiency and specific activity considering the kinetics and thermodynamics of the reactions. Beside natural pathways, this included the artificial Reductive Glycine Pathway, the CETCH cycle and two completely new cycles with superior stoichiometry: The Reductive Citramalyl-CoA cycle and the 2-Hydroxyglutarate-Reverse Tricarboxylic Acid cycle. A comprehensive kinetic data set was collected for all enzymes of all pathways and missing kinetic data was sampled with the Parameter Balancing algorithm. Kinetic and thermodynamic data were fed to the Enzyme Cost Minimization algorithm to check for respective inconsistencies and calculate pathway specific activities.We found that the Reductive Glycine Pathway, the CETCH cycle and the new Reductive Citramalyl-CoA cycle were predicted to have higher ATP-efficiencies and specific activities than the natural cycles. The Calvin Cycle performed better than previously thought, however. It can be concluded that the weaker overall characteristics in the design of the Calvin Cycle might be compensated by other benefits like robustness, low nutrient demand and a good compatibility with the host’s physiological requirements. Nevertheless, the artificial carbon fixation cycles hold great potential for future applications in Industrial Biotechnology and Synthetic Biology.
The spread of breathing air from wind instruments and singers using schlieren techniques
Authors: Becher Lia , Gena Amayu W. , Alsaad Hayder , Richter Bernhard , Spahn Claudia , Voelker Conrad 
Published: January 2021

AbstractIn this article, the spread of breathing air when playing wind instruments and singing was investigated and visualized using two methods: (1) schlieren imaging with a schlieren mirror and (2) background-oriented schlieren (BOS). These methods visualize airflow by visualizing density gradients in transparent media. The playing of professional woodwind and brass instrument players, as well as professional classical trained singers, were investigated to estimate the spread distances of the breathing air. For a better comparison and consistent measurement series, a single high and a single low note as well as an extract of a musical piece were investigated. Additionally, anemometry was used to determine the velocity of the spreading breathing air and the extent to which it was still quantifiable. The results presented in this article show there is no airflow escaping from the instruments, which is transported farther than 1.2 m into the room. However, differences in the various instruments have to be considered to assess properly the spread of the breathing air. The findings discussed below help to estimate the risk of cross-infection for wind instrument players and singers and to develop efficacious safety precautions, which is essential during critical health periods such as the current COVID-19 pandemic.
Meta-Analysis of Adenoviral p53 Gene Therapy Clinical Trials in Recurrent Head and Neck Squamous Cell Carcinoma
Authors: Sobol Robert E. , Menander Kerstin B. , Chada Sunil , Wiederhold Dora , Sellman Beatha , Talbott Max , Nemunaitis John J. 
Published: January 2021

AbstractBackgroundWe conducted a meta-analysis of previous adenoviral p53 (Ad-p53) treatment data in recurrent head and neck squamous cell carcinoma (HNSCC) patients to identify optimal Ad-p53 treatment methods for future clinical trials.MethodsThe meta-analysis involved recurrent HNSCC patients treated with Ad-p53 for whom p53 genotyping and immunohistochemistry tumor biomarker studies had been performed (n = 70). Ad-p53 tumor treatment responses defined by RECIST 1.1 criteria were correlated with Ad-p53 dose and tumor p53 biomarkers. Gene expression profiles induced by Ad-p53 treatment were evaluated using the Nanostring IO 360 panel.ResultsAd-p53 dose based upon the injected tumor volume had a critical effect on tumor responses. All responders had received Ad-p53 doses greater than 7 × 1010viral particles/cm3of tumor volume. There was a statistically significant difference in tumor responses between patients treated with greater than 7 × 1010viral particles/cm3compared to patients treated at lower Ad-p53 doses (Tumor Response 31% (9/29) for Ad-p53 > 7 × 1010viral particles/cm3versus 0% (0/25) for Ad-p53 < 7 × 1010viral particles/cm3; p = 0.0023). All responders were found to have favorable p53 biomarker profiles defined by less than 20% p53 positive tumor cells by immunohistochemistry (IHC), wild type p53 gene sequence or p53 deletions, truncations, or frame-shift mutations without functional p53 tetramerization domains. Preliminary gene expression profiling results revealed that Ad-p53 treatment increased Type I Interferon signaling, decreased TGF-beta and beta-catenin signaling resulting in an increased CD8+ T cell signature which are associated with increased responses to immune checkpoint blockade.ConclusionsOur findings have important implications for future p53 targeted cancer treatments and identify fundamental principles to guide Ad-p53 gene therapy. We discovered that previous Ad-p53 clinical trials were negatively impacted by the inclusion of patients with unfavorable p53 biomarker profiles and by under dosing of Ad-p53 treatment. Future Ad-p53 clinical trials should have favorable p53 biomarker profiles inclusion criteria and Ad-p53 dosing above 7 × 1010viral particles/cm3of injected tumor volume. Preliminary gene expression profiling identified p53 mechanisms of action associated with responses to immune checkpoint blockade supporting evaluation of Ad-p53 in combination with immune checkpoint inhibitors.
An engineered lactate responding promoter system operating in glucose-rich and anaerobic environments
Authors: Zúñiga Ana , Chang Hung-Ju , Fristot Elsa , Bonnet Jerome 
Published: January 2021

AbstractBacteria equipped with genetically-encoded lactate biosensors would support several applications in biopharmaceutical production, diagnosis, or therapeutics. However, many applications involve glucose-rich and anaerobic environments, in which current whole-cell lactate biosensors have low performance. Here we engineered a synthetic lactate biosensor system by repurposing the natural LldPRD promoter regulated by the LldR transcriptional regulator. We removed glucose catabolite repression by designing a hybrid promoter, containing LldR operators and tuned both regulator and reporter gene expression to optimize biosensor signal-to-noise ratio. The resulting lactate biosensor, termed ALPaGA (ALactatePromoter Operating inGlucose andAnaerobia) can operate in glucose rich, aerobic and anaerobic conditions. Our work provides a versatile lactate biosensing platform suitable for many environmental conditions.
Pixelwise H-score: a novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images
Authors: Ram Sripad , Vizcarra Pamela , Whalen Pamela , Deng Shibing , Painter CL , Jackson-Fisher Amy , Pirie-Shepherd Steven , Xia Xiaoling , Powell Eric L. 
Published: January 2021

ABSTRACTImmunohistochemistry (IHC) assays play a central role in evaluating biomarker expression in tissue sections for diagnostic and research applications. Manual scoring of IHC images, which is the current standard of practice, is known to have several shortcomings in terms of reproducibility and scalability to large scale studies. Here, by using a digital image analysis-based approach, we introduce a new metric called the pixelwise H-score (pix H-score) that quantifies biomarker expression from whole-slide scanned IHC images. The pix H-score is an unsupervised algorithm that only requires the specification of intensity thresholds for the biomarker and the nuclear-counterstain channels. We present the detailed implementation of the pix H-score in two different whole-slide image analysis software packages Visiopharm and HALO. We consider three biomarkers P-cadherin, PD-L1, and 5T4, and show how the pix H-score exhibits tight concordance to multiple orthogonal measurements of biomarker abundance such as the biomarker mRNA transcript and the pathologist H-score. We also compare the pix H-score to existing automated image analysis algorithms and demonstrate that the pix H-score provides either comparable or significantly better performance over these methodologies. We also present results of an empirical resampling approach to assess the performance of the pix H-score in estimating biomarker abundance from select regions within the tumor tissue relative to the whole tumor resection. We anticipate that the new metric will be broadly applicable to quantify biomarker expression from a wide variety of IHC images. Moreover, these results underscore the benefit of digital image analysis-based approaches which offer an objective, reproducible, and highly scalable strategy to quantitatively analyze IHC images.
Heterogeneity versus the COVID-19 Pandemic
Authors: Shanmugam Ramalingam , Ledlow Gerald , Singh Karan P. 
Published: January 2021

AbstractIn this paper, heterogeneity is formally defined, and its properties are explored. We define and distinguish observable versus non-observable heterogeneity. It is proposed thatheterogeneityamong the vulnerable is a significant factor in the contagion impact of COVID-19, as demonstrated with incidence rates on a Diamond Princess Cruise ship in February 2020. Given the nature of the disease, its heterogeneity and human social norms, pre-voyage and post-voyage quick testing procedures may become the new standard for cruise ship passengers and crew. The technological advances in testing available today would facilitate more humanistic treatment as compared to more archaic quarantine and isolation practices for all onboard ship. With quick testing, identification of those infected and thus not allowed to embark on a cruise or quarantining those disembarking and other mitigation strategies, the popular cruise adventure could be available safely again. Whatever the procedures implemented, the methodological purpose of this study should add valuable insight in the modeling of disease and specifically, the COVID-19 virus.
Genome-wide screening of circadian and non-circadian impact of Neat1 genetic deletion
Authors: Jacq Audrey , Becquet Denis , Bello-Goutierrez Maria-Montserrat , Boyer Bénédicte , Guillen Séverine , Franc Jean-Louis , François-Bellan Anne-Marie 
Published: January 2021

AbstractThe functions of the long non-coding RNA, Nuclear enriched abundant transcript 1 (Neat1), are poorly understood. Neat1 is required for the formation of paraspeckles, but its respective paraspeckle-dependent or independent functions are unknown. Several studies including ours reported that Neat1 is involved in the regulation of circadian rhythms. We characterized the impact of Neat1 genetic deletion in a rat pituitary cell line. The mRNAs whose circadian expression pattern or expression level is regulated by Neat1 were identified after high-throughput RNA sequencing of the circadian transcriptome of wild-type cells compared to cells in which Neat1 was deleted by CRISPR/Cas9. The numerous RNAs affected by Neat1 deletion were found to be circadian or non-circadian, targets or non-targets of paraspeckles, and to be associated with many key biological processes showing that Neat1, interacting or independently of the circadian system, could play crucial roles in key physiological functions through diverse mechanisms.
Integrin β3 Targeting Biomaterial Preferentially Promotes Secretion of bFGF and Proliferation of iPSC-Derived Vascular Smooth Muscle Cells
Authors: Dash Biraja C. , Duan Kaiti , Kyriakides Themis R. , Hsia Henry C. 
Published: January 2021

AbstractHuman-induced pluripotent stem cell-derived-vascular smooth muscle cells (hiPSC-VSMC) have been shown to promote angiogenesis and wound healing. However, there is a paucity of research on how the extracellular matrix (ECM) microenvironment may impact the hiPSC-VSMC’s function. In this study, our objective was to understand the effect of specific ECM ligand-integrin interaction on hiPSC- VSMC’s paracrine secretion, cell proliferation, and morphology. We here showed a precise modulation of hiPSC-VSMC in a fibronectin functionalized fibrillar collagen scaffold by targeting their integrin β3. The secretion of proangiogenic growth factor, basic fibroblast growth factor (bFGF) was found to be fibronectin dependent via αvβ3 integrin interactions. Also, our data indicate the possible role of a positive feedback loop between integrin β3, bFGF, and matrix metalloproteinase-2 in regulating hiPSC- VSMC’s morphology and cell proliferation. Finally, the secretome with improved proangiogenic activity shows potential for future regenerative applications.
The Ran pathway uniquely regulates cytokinesis in cells with different fates in the earlyC. elegansembryo
Authors: Ozugergin Imge , Mastronardi Karina , Law Chris , Piekny Alisa 
Published: January 2021

ABSTRACTCytokinesis occurs at the end of mitosis and occurs due to the ingression of a contractile ring that cleaves the daughter cells. This process is tightly controlled to prevent cell fate changes or aneuploidy, and the core machinery is highly conserved among metazoans. Multiple mechanisms regulate cytokinesis, but their requirement in different cell types is not known. Here, we show that differently fated AB and P1cells in the earlyC. elegansembryo have unique cytokinesis kinetics supported by distinct levels and cortical patterning of myosin. Through perturbation of polarity regulators and the generation of stable tetraploid strains, we demonstrate that these differences depend on both cell fate and size. Additionally, these parameters could influence the Ran pathway, which coordinates the contractile ring with chromatin position, and controls cytokinesis differently in AB and P1cells. Our findings demonstrate the need to consider multiple parameters when modeling ring kinetics.
A synthetic gene circuit for imaging-free detection of dynamic cell signaling
Authors: Ravindran Pavithran T. , McFann Sarah , Toettcher Jared E. 
Published: January 2021

AbstractCells employ intracellular signaling pathways to sense and respond to changes in their external environment. In recent years, live-cell biosensors have revealed complex pulsatile dynamics in many pathways, but studies of these signaling dynamics are limited by the necessity of live-cell imaging at high spatiotemporal resolution1. Here, we describe an approach to infer pulsatile signaling dynamics from just a single measurement in fixed cells using a pulse-detecting gene circuit. We computationally screened for circuit with pulse detecting capability, revealing an incoherent feedforward topology that robustly performs this computation. We then implemented the motif experimentally for the Erk signaling pathway using a single engineered transcription factor and fluorescent protein reporter. Our ‘recorder of Erk activity dynamics’ (READer) responds sensitively to both spontaneous and stimulus-driven Erk pulses. READer circuits thus open the door to permanently labeling transient, dynamic cell populations to elucidate the mechanistic underpinnings and biological consequences of signaling dynamics.
Gender differences in the Israeli academia: a bibliometric analysis of different disciplines
Authors: Cooper Tzipi , Aharony Noa , Bar-Ilan Judit 
Published: January 2021

PurposeThis study explores faculty members' outputs and citations by gender and academic rank in Israeli academia. The study focuses on the connection between research productivity and underrepresentation of women in academia. To this end, four fields were chosen, each representing a different discipline: Psychology (social sciences), Public Health (health sciences), Linguistics (humanities), and Chemistry (Exact sciences).Design/methodology/approachThe name, the rank and the gender of the researchers were collected from the researchers' websites and those of their departments. The number of publications and citations were retrieved from Scopus.FindingsFindings revealed that there is a significant difference between the median number of men and women in Chemistry concerning publications and citations and in Psychology concerning citations. Moreover, in all four disciplines, females' average number of publications was lower than that of males', and that in three out of the four disciplines (Psychology, Public Health and Chemistry), men published more in top journals (the top 5%) than females, while the reverse was true of Linguistics. Furthermore, in three disciplines (Public Health, Linguistics and Chemistry), there is an increase in the average citations per female researchers between 2015 and 2019. Further, in all disciplines, women collaborated more than men.Originality/valueAs only a few studies in Israel have explored faculty members' outputs and citations, this study contributes and enlarges the Israeli research concerning this topic.