bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects on Driving Behavior When Using a Head-mounted Display in a Dynamic Driving Simulator
Authors: Blissing Björn , Bruzelius Fredrik , Eriksson Olle 
Published: January 2022

Driving simulators are established tools used during automotive development and research. Most simulators use either monitors or projectors as their primary display system. However, the emergence of a new generation of head-mounted displays has triggered interest in using these as the primary display type. The general benefits and drawbacks of head-mounted displays are well researched, but their effect on driving behavior in a simulator has not been sufficiently quantified.
This article presents a study of driving behavior differences between projector-based graphics and head-mounted display in a large dynamic driving simulator. This study has selected five specific driving maneuvers suspected of affecting driving behavior differently depending on the choice of display technology. Some of these maneuvers were chosen to reveal changes in lateral and longitudinal driving behavior. Others were picked for their ability to highlight the benefits and drawbacks of head-mounted displays in a driving context.
The results show minor changes in lateral and longitudinal driver behavior changes when comparing projectors and a head-mounted display. The most noticeable difference in favor of projectors was seen when the display resolution is critical to the driving task. The choice of display type did not affect simulator sickness nor the realism rated by the subjects.
Small-Molecule NSC59984 Induces Mutant p53 Degradation through a ROS-ERK2-MDM2 Axis in Cancer Cells
Authors: Zhang Shengliang , Zhou Lanlan , El-Deiry Wafik S. 
Published: January 2022

Abstract

Increased reactive oxygen species (ROS) and hyperstabilized mutant p53 are common in cancer. Hyperstabilized mutant p53 contributes to its gain of function (GOF) which confers resistance to chemotherapy and radiotherapy. Targeting mutant p53 degradation is a promising cancer therapeutic strategy. We used a small-molecule NSC59984 to explore elimination of mutant p53 in cancer cells, and identified an inducible ROS-ERK2-MDM2 axis as a vulnerability for induction of mutant p53 degradation in cancer cells. NSC59984 treatment promotes a constitutive phosphorylation of ERK2 via ROS in cancer cells. The NSC59984-sustained ERK2 activation is required for MDM2 phosphorylation at serine-166. NSC59984 enhances phosphorylated-MDM2 binding to mutant p53, which leads to mutant p53 ubiquitination and degradation. High cellular ROS increases the efficacy of NSC59984 targeting mutant p53 degradation and antitumor effects. Our data suggest that mutant p53 stabilization has a vulnerability under high ROS cellular conditions, which can be exploited by compounds to target mutant p53 protein degradation through the activation of a ROS-ERK2-MDM2 axis in cancer cells.

Implications:
An inducible ROS-ERK2-MDM2 axis exposes a vulnerability in mutant p53 stabilization and can be exploited by small-molecule compounds to induce mutant p53 degradation for cancer therapy.
MIRO2 Regulates Prostate Cancer Cell Growth via GCN1-Dependent Stress Signaling
Authors: Furnish Madison , Boulton Dillon P. , Genther Victoria , Grofova Denisa , Ellinwood Mitchell Lee , Romero Lina , Lucia M. Scott , Cramer Scott D. , Caino M. Cecilia 
Published: January 2022

Abstract

There is a continued need to identify novel therapeutic targets to prevent the mortality associated with prostate cancer. In this context, mitochondrial Rho GTPase 2 (MIRO2) mRNA was upregulated in metastatic prostate cancer compared with localized tumors, and higher MIRO2 levels were correlated with poor patient survival. Using human cell lines that represent androgen-independent or -sensitive prostate cancer, we showed that MIRO2 depletion impaired cell growth, colony formation, and tumor growth in mice. Network analysis of MIRO2′s binding partners identified metabolism and cellular responses to extracellular stimuli as top overrepresented pathways. The top hit on our screen, General Control Nonderepressible 1 (GCN1), was overexpressed in prostate cancer, and interacted with MIRO2 in prostate cancer cell lines and in primary prostate cancer cells. Functional analysis of MIRO2 mutations present in patients with prostate cancer led to the identification of MIRO2 159L, which increased GCN1 binding. Importantly, MIRO2 was necessary for efficient GCN1-mediated GCN2 kinase signaling and induction of the transcription factor activating transcription factor 4 (ATF4) levels. Further, MIRO2′s effect on regulating prostate cancer cell growth was mediated by ATF4. Finally, levels of activated GCN2 and ATF4 were correlated with MIRO2 expression in prostate cancer xenografts. Both MIRO2 and activated GCN2 levels were higher in hypoxic areas of prostate cancer xenografts. Overall, we propose that targeting the MIRO2-GCN1 axis may be a valuable strategy to halt prostate cancer growth.

Implications:
MIRO2/GCN1/GCN2 constitute a novel mitochondrial signaling pathway that controls androgen-independent and androgen-sensitive prostate cancer cell growth.
The First Lady Presses for Cancer Screening to Get Back On Track
Authors: DuBois Lisa A. , DuBois Raymond N. 
Published: January 2022

Abstract
The First Lady of the United States, Dr. Jill Biden, visited the Hollings Cancer Center at the Medical University of South Carolina on October 25, 2021. This Commentary remarks on the administration's goal of directing public attention to cancer screening and prevention as part of an overall effort to recover ground lost in the COVID-19 pandemic, particularly in underserved communities.
AnIn VivoScreen to Identify Short Peptide Mimotopes with Enhanced Antitumor Immunogenicity
Authors: He Xuedan , Zhou Shiqi , Quinn Breandan , Jahagirdar Dushyant , Ortega Joaquin , Long Mark D. , Abrams Scott I. , Lovell Jonathan F. 
Published: January 2022

AbstractTumor-associated self-antigens are potential cancer vaccine targets but suffer from limited immunogenicity. There are examples of mutated, short self-peptides inducing epitope-specific CD8+ T cells more efficiently than the wild-type epitope, but current approaches cannot yet reliably identify such epitopes, which are referred to as enhanced mimotopes (“e-mimotopes”). Here, we present a generalized strategy to develop e-mimotopes, using the tyrosinase-related protein 2 (Trp2) peptide Trp2180–188, which is a murine MHC class I (MHC-I) epitope, as a test case. Using a vaccine adjuvant that induces peptide particle formation and strong cellular responses with nanogram antigen doses, a two-step method systematically identified e-mimotope candidates with murine immunization. First, position-scanning peptide microlibraries were generated in which each position of the wild-type epitope sequence was randomized. Randomization of only one specific residue of the Trp2 epitope increased antitumor immunogenicity. Second, all 20 amino acids were individually substituted and tested at that position, enabling the identification of two e-mimotopes with single amino acid mutations. Despite similar MHC-I affinity compared with the wild-type epitope, e-mimotope immunization elicited improved Trp2-specific cytotoxic T-cell phenotypes and improved T-cell receptor affinity for both the e-mimotopes and the native epitope, resulting in better outcomes in multiple prophylactic and therapeutic tumor models. The screening method was also applied to other targets with other murine MHC-I restriction elements, including epitopes within glycoprotein 70 and Wilms' Tumor Gene 1, to identify additional e-mimotopes with enhanced potency.
A interseccionalidade como base do feminismo negro
Authors: Leal Halina Macedo 
Published: January 2022

A análise de processos de opressão de gênero começa a emergir nas reflexões filosóficas, seja pelo foco no funcionamento do sistema patriarcal ou pelo foco na intersecção do patriarcado com relações de dominação a partir de origens etnicorraciais. Em geral, tais reflexões buscam examinar os fundamentos dos sistemas opressivos e a reação das mulheres a tais sistemas. São localizadas diferentes formas e demandas dos movimentos feministas e os modos como estes procuram, por meio da discussão sobre gênero, fortalecer o papel social e político das mulheres. Neste contexto, o presente artigo visa examinar o lugar do feminismo negro no debate e suas bases de sustentação, tendo em vista as peculiaridades das necessidades das mulheres negras. Estas peculiaridades estão relacionadas à inseparabilidade estrutural entre patriarcado, sexismo, racismo esuas articulações que implicam em múltiplas situações de opressão sofridas por este grupo de mulheres. Em outras palavras, busca-se analisar a centralidade do conceito de interseccionalidade para a compreensão da atuação do feminismo negro nas reflexões filosóficas acerca da condição da mulher negra na sociedade.
IL-1β Impacts Vascular Integrity and Lymphatic Function in the Embryonic Omentum
Authors: Menendez Matthew , Drozd Anna , Borawska Katarzyna , Chmielewska Joanna J. , Wu Meng-Ling , Griffin Courtney T. 
Published: January 2022

Background:
The chromatin-remodeling enzyme BRG1 (brahma-related gene 1) regulates gene expression in a variety of rapidly differentiating cells during embryonic development. However, the critical genes that BRG1 regulates during lymphatic vascular development are unknown.

Methods:
We used genetic and imaging techniques to define the role of BRG1 in murine embryonic lymphatic development, although this approach inadvertently expanded our study to multiple interacting cell types.

Results:
We found that omental macrophages fine-tune an unexpected developmental process by which erythrocytes escaping from naturally discontinuous omental blood vessels are collected by nearby lymphatic vessels. Our data indicate that circulating fibrin(ogen) leaking from gaps in omental blood vessels can trigger inflammasome-mediated IL-1β (interleukin-1β) production and secretion from nearby macrophages. IL-1β destabilizes adherens junctions in omental blood and lymphatic vessels, contributing to both extravasation of erythrocytes and their uptake by lymphatics. BRG1 regulates IL-1β production in omental macrophages by transcriptionally suppressing the inflammasome trigger RIPK3 (receptor interacting protein kinase 3).

Conclusions:

Genetic deletion of
Brg1
in embryonic macrophages leads to excessive IL-1β production, erythrocyte leakage from blood vessels, and blood-filled lymphatics in the developing omentum. Altogether, these results highlight a novel context for epigenetically regulated crosstalk between macrophages, blood vessels, and lymphatics.
Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?
Authors: Samargandy Saad , Matthews Karen A. , Brooks Maria M. , Barinas-Mitchell Emma , Magnani Jared W. , Thurston Rebecca C. , El Khoudary Samar R. 
Published: January 2022

Background:
Whether changes in blood pressure (BP) over women’s midlife are more driven by chronological aging or the menopause transition has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic BP (SBP), diastolic BP, pulse pressure (PP), and mean arterial pressure (MAP) over the menopause transition, and to assess whether menopause-related factors predict the group and level of BP measures.

Methods:
Participants were from the SWAN (Study of Women’s Health Across the Nation). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution.

Results:
The study included 3302 multiracial and multiethnic women with BP measures over 17 follow-up visits (baseline age [SD]: 46.3 [2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure.

Conclusions:
Distinct BP trajectories over the menopause transition exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the menopause transition.
Blood parasites in sympatric lizards: what is their impact on hosts’ immune system?
Authors: Damas-Moreira Isabel , Maia João P. , Tomé Beatriz , Salvi Daniele , Perera Ana , Harris D. James 
Published: January 2022

Abstract
Assessment of parasites and their pathogenicity is essential for studying the ecology of populations and understanding their dynamics. In this study, we investigate the prevalence and intensity of infection of haemogregarines (phylum Apicomplexa) in two sympatric lizard species, Podarcis vaucheri and Scelarcis perspicillata, across three localities in Morocco, and their effect on host immune response. We used the Phytohaemagglutinin (PHA) skin testing technique to relate the level of immune response with parasite infection. Prevalence and intensity levels were estimated with microscopy, and 18S rRNA gene sequences were used to confirm parasite identity. All parasites belong to the haemogregarine lineage found in other North African reptiles. There were differences in prevalence between localities and sexes. Overall, infected lizards were larger than uninfected ones, although we did not detect differences in parasitaemia across species, sex or locality. The swelling response was not related to the presence or number of haemogregarines, or to host body size, body condition, sex or species. We found no evidence of impact for these parasites on the circulating blood cells or the hosts’ immune system, but more data is needed to assess the potential impact of mixed infections, and the possibility of cryptic parasite species.
The complete mitochondrial genomes of Notiophilus quadripunctatus Dejean, 1826 and Omophron limbatum (Fabricius, 1777): New insights into the mitogenome phylogeny of the Carabidae (Insecta, Coleoptera)
Authors: Raupach Michael J. , Deister Fabian , Villastrigo Adrián , Balke Michael 
Published: January 2022

Abstract
The Carabidae is by far the largest family of the Adephaga, with more than 40,000 described species. Whereas their phylogeny has been extensively studied, convergences and reversals in morphological traits prevent a robust phylogenetic concept so far. In this study, we sequenced the complete mitochondrial genomes of Notiophilus quadripunctatus (Nebriinae) and Omophrom limbatum (Omophroninae) using high-throughput sequencing. Both mitogenomes consisted of a single circular DNA molecule that encoded the typical 13 protein-coding genes, two subunits of mitochondrial RNAs, 22 tRNAs and a putative control region. Our phylogenetic study placed Omophrom limbatum as sister taxon to all other analyzed ground beetle species whereas Notiophilus quadripunctatus was identified as sister to Nebria brevicollis as part of the Nebriinae. The analyses also support the monophyly of the Cicindelidae but place Trachypachus holmbergi (Trachypachidae) within the Carabidae. Nevertheless, almost all carabid subfamilies with more than one analyzed species were identified as monophyla.
GEFSv12 Reforecast Dataset for Supporting Subseasonal and Hydrometeorological Applications
Authors: Guan Hong , Zhu Yuejian , Sinsky Eric , Fu Bing , Li Wei , Zhou Xiaqiong , Xue Xianwu , Hou Dingchen , Peng Jiayi , Nageswararao M. M. , Tallapragada Vijay , Hamill Thomas M. , Whitaker Jeffrey S. , Bates Gary , Pegion Philip , Frederick Sherrie , Rosencrans Matthew , Kumar Arun 
Published: January 2022

Abstract
For the newly implemented Global Ensemble Forecast System, version 12 (GEFSv12), a 31-yr (1989–2019) ensemble reforecast dataset has been generated at the National Centers for Environmental Prediction (NCEP). The reforecast system is based on NCEP’s Global Forecast System, version 15.1, and GEFSv12, which uses the Finite Volume 3 dynamical core. The resolution of the forecast system is ∼25 km with 64 vertical hybrid levels. The Climate Forecast System (CFS) reanalysis and GEFSv12 reanalysis serve as initial conditions for the Phase 1 (1989–99) and Phase 2 (2000–19) reforecasts, respectively. The perturbations were produced using breeding vectors and ensemble transforms with a rescaling technique for Phase 1 and ensemble Kalman filter 6-h forecasts for Phase 2. The reforecasts were initialized at 0000 (0300) UTC once per day out to 16 days with 5 ensemble members for Phase 1 (Phase 2), except on Wednesdays when the integrations were extended to 35 days with 11 members. The reforecast dataset was produced on NOAA’s Weather and Climate Operational Supercomputing System at NCEP. This study summarizes the configuration and dataset of the GEFSv12 reforecast and presents some preliminary evaluations of 500-hPa geopotential height, tropical storm track, precipitation, 2-m temperature, and MJO forecasts. The results were also compared with GEFSv10 or GEFS Subseasonal Experiment reforecasts. In addition to supporting calibration and validation for the National Water Center, NCEP Climate Prediction Center, and other National Weather Service stakeholders, this high-resolution subseasonal dataset also serves as a useful tool for the broader research community in different applications.
The Unpredictable Truth: A Proposed Road Map for a Reflect-Then-Act Approach to Climate Uncertainties and Lessons Learned from Norwegian Municipalities
Authors: Aall Carlo , Groven Kyrre 
Published: January 2022

Abstract
Through the years, several papers have criticized climate policy decision-making for being naïve with respect to how it views climate model outputs as objective facts and uses the outputs directly to program policies. From this and similar observations, many of the papers conclude that there is a need for shifting to a new approach on how climate policy makers may relate to climate change uncertainties. The article proposes such a shift by presenting a road map on how to address uncertainties in climate change adaptation. It consists of three major elements: first, to accept that in many cases we will not be able to reduce climate change uncertainties; second, to diversify the way in which we describe climate change uncertainties, moving from a one-dimensional technical perspective to a multidimensional perspective that applies uncertainties also to social and political processes and systems; and third, to change the way we address climate change uncertainties by moving from a predict-then-act to a reflect-then-act approach, implying that we must adapt to climate change even under high and varied forms of uncertainties. Embedded in this last point is to accept that, unlike for climate change mitigation, the precautionary principle will apply in many situations of climate change adaptation. In the last part of the article the usability of the proposed road map is demonstrated post ante on four Norwegian cases of climate-related natural hazard events.

Significance Statement
The article sums up the international policy and scientific climate change uncertainty discourses and presents a road map on how to improve the way uncertainties are addressed in local efforts of adapting to climate change. The underlying logic of the proposed road map is to expand from the so far prevailing logic of adapting only when uncertainties are low with an additional logic that is applicable in situations with high uncertainties. The road map consists of seven questions to be addressed and seven alternative adaptation options to follow. A selection of recent practical cases on local climate change adaptation efforts in Norway is then presented to demonstrate the applicability of the proposed road map.
Coexisting Morbidity Burden in Hospitalized Elderly Patients with New-Onset Heart Failure vs Acutely Decompensated Chronic Heart Failure
Authors: Xanthopoulos Andrew , Tryposkiadis Konstantinos , Giamouzis Grigorios , Dimos Apostolos , Bourazana Angeliki , Papamichalis Michail , Zagouras Alexandros , Iakovis Nikolaos , Kitai Takeshi , Skoularigis John , Starling Randall C. , Triposkiadis Filippos 
Published: January 2022

Coexisting morbidities (CM) are common in patients with heart failure (HF). This study evaluated the CM burden and its clinical significance in elderly hospitalized patients with new-onset (De-novo) HF (n = 84) and acutely decompensated chronic HF (ADCHF) (n = 122). All had HF symptoms associated with: (a) LVEF <50%, or, (b) left ventricular ejection fraction (LVEF) ≥50% and NT-proBNP ≥300 pg/mL. The primary endpoint was the composite of all-cause death/HF rehospitalization at 6 months. Age was similar between patients with new-onset HF and ADCHF [82 (12.5) vs 80 (11) years, respectively; P = .549]. The CM burden was high in both groups. However, the number of CM [3 (2) vs 4 (1.75)] and the prevalence of multimorbidity [CM ≥2; 65 (77.4%) vs 108 (88.5%)] were lower in new-onset HF ( P = .016 and P = .035, respectively). The survival probability without the primary endpoint was higher in new-onset HF than in ADCHF ( P = .001) driven by less rehospitalizations ( P = .001). In the total study population significant primary endpoint predictors were red blood cell distribution width (RDW), urea, and coronary artery disease (CAD) prevalence (AUC of the model =.7685), whereas significant death predictors were RDW, urea, and the number of CM (AUC = .7859), all higher in ADCHF. Thus, the higher CM burden in ADCHF than in new-onset HF most likely contributed to the worse outcome.
Acid freezes uricolysis in addition to glycolysis: Utility of fluoride-EDTA-citrate tube in the measurement of uric acid for patients administered rasburicase
Authors: Kalaria Tejas , Fenn Jonathan , Whitmill Richard , Ford Clare , Gama Rousseau 
Published: January 2022

Background In samples from patients administered rasburicase, ex vivo uricolysis leads to spuriously low uric acid results. The manufacturer’s recommendation of storing the sample in ice-water until analysis, however, does not fully arrest uricolysis. Since uricase activity is affected by pH and metal chelators, we assessed uricolysis inhibition in sodium fluoride-ethylenediaminetetraacetic acid (EDTA)-citrate sample tube (FC Mix tube, Greiner) used primarily for plasma glucose. Method A serum pool was spiked with rasburicase and uric acid measured at 15, 45, 90, 150, 240 and 1080 min in a lithium heparin tube in ice-water, plain tube at room temperature (RT), EDTA tube at RT, FC Mix tube in ice-water, FC Mix tube at RT and FC Mix tube at RT prepared by dissolving FC Mix in serum. Results The rate of urate decay was lowest in the FC Mix tube independent of temperature, then lithium heparin tube in ice-water, then EDTA tube at RT and highest in the plain tube at RT. Uric acid concentrations in the prepared FC Mix tube at RT and heparin tube in ice-water were, respectively, 98.2% and 93.8% of control values at 90 min, 97.1% and 89.3% of control values at 4 h, and remained higher in the prepared FC Mix tube at all time points. Conclusion NaF-EDTA-citrate mixture largely arrested rasburicase mediated ex vivo uricolysis without the need for sample cooling. We propose that sample tubes containing NaF-EDTA-citrate be used for the measurement of uric acid in patients administered rasburicase.