bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-ResistantStaphylococcus aureus(MRSA)
Authors: Huang David B. , Gaukel Eric , Kerzee Nancy , Borroto-Esoda Katyna , Lowry Simon , Xiong Yan Q. , Abdelhady Wessam , Bayer Arnold S. 
Published: March 2021

AbstractMRSA endovascular infections are frequently recalcitrant to treatment with standard-of-care antibiotics. Anti-staphylococcal phage lysins represent important candidate adjunctive agents against invasive MRSA infections because of both their microbicidal and anti-biofilm properties. We utilized the rabbit model of aortic valve infective endocarditis (using the prototype MRSA strain, MW2) to examine the combined efficacy of the lysin, LSVT-1701, plus daptomycin. LSVT-1701 was given at two dose-regimens (32.5 mg/kg and 50 mg/kg) with different dose-durations (single dose vs daily dose for 2 d vs daily dose for 4 d); daptomycin was given at a sub-lethal daily dose of 4 mg/kg for 4 d to maximize potential synergistic interaction outcomes. The combination of LSVT-1701 plus daptomycin was highly effective at reducing target tissue MRSA counts (cardiac vegetations, kidneys, and spleen), especially when the lysin was given for multiple days and/or at higher daily doses. Of importance, when given for four daily doses, both lysin dose-regimens in combination with daptomycin sterilized all target tissues. These findings suggest that LSVT-1701 warrants further clinical evaluation as adjunctive therapy for the treatment of invasive MRSA infections.
Hypothyroidism and its influence in the development of Metabolic Syndrome (MetS)
Authors: Pinheiro D. J. L. L. , Santos T. C. , Spacini G. R. , Guerra A. P. S. , Bacci M. C. L , Nemecek M. G , Oliveira J. R. C. , Dantas R. L. M. , Cortez P. J. O. , Faber J. 
Published: March 2021

AbstractBackgroundMetabolic syndrome (MetS) is a complex disorder that affects the cardiovascular system and it is generally associated with mental and metabolic health issues. To diagnose MetS it is essential to identify certain comorbidities related to cardiovascular diseases. Hypothyroidism, for instance, is a common disorder that reduces the basal metabolism, leading to the development of other diseases. Therefore, it is important to know how hypothyroidism can increase the chances of MetS.ObjectivesTo assess whether there is an increased risk of patients with hypothyroidism developing MetS given the association of different comorbidities in a sample of an urban Brazilian population.MethodsThis was an observational, exploratory and retrospective study of patients diagnosed with hypothyroidism (using levothyroxine for hormonal reposition therapy).The incidence and prevalence of four specific comorbidities were quantified by histograms, and all comparisons were performed by using joint and conditional probabilities with their respective confident intervals.ResultsConsistent with the literature, our results also showed that there is a prevalence in women (79%) and in elderly patients (80%). Moreover, it also indicated that around 64% of the patients were women aged over 60 years and at least one comorbidity was associated with them. By analyzing the risk group for MetS, with two comorbidities, the combination with higher chances of acquiring a new comorbidity were Systemic arterial hypertension (SAH) and Diabetes Mellitus (DM), in this sample.ConclusionOur results indicate that hypothyroidism can increase the chances to develop MetS or may worsen its effects due to the association of common comorbidities present in both cases. Keywords: metabolic syndrome, hypothyroidism, comorbidities, statistical analysis.
Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes
Authors: Vuong Nguyen Lam , Lam Phung Khanh , Ming Damien Keng Yen , Duyen Huynh Thi Le , Nguyen Nguyet Minh , Tam Dong Thi Hoai , Kien Duong Thi Hue , Chau Nguyen Van Vinh , Chanpheaktra Ngoun , Lum Lucy Chai See , Pleités Ernesto , Simmons Cameron P. , Rosenberger Kerstin , Jaenisch Thomas , Bell David , Acestor Nathalie , Halleux Christine , Olliaro Piero L. , Wills Bridget A. , Geskus Ronald B. , Yacoub Sophie 
Published: March 2021

AbstractBackgroundEarly identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).MethodsWe performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.ResultsOn days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.ConclusionsOur findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.Summary of the main pointHigher levels of any of VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, and CRP on illness days 1-3 increased the risk of developing severe/moderate dengue. The relationships differed between children and adults and some changed when assessed together.
Youth-oriented packaging and the demand for e-liquids: Evidence from data scraped from Amazon in the United Kingdom
Authors: Lawani Abdelaziz , Georgette Owusu-Amankwah , Anna-Liisa Ihuhwa 
Published: March 2021

AbstractTo address the threat e-cigarettes poses to public health, especially among youths, the Food and Drug Administration (FDA) issued a policy in 2020 that regulates the sale and distribution of e-cigarettes with fruit and mint flavors. Such flavors are alleged to lure youth into smoking and can increase the likelihood for addiction to other drugs. However, this regulation does not address packaging that can have a similar effect on the demand for e-cigarettes products. Indeed, certain e-liquids use youth-oriented (kiddish, cartoonish, and colorful) packaging which are attractive to youth but may also induce a no-harm perception among e-liquids users. In this paper, we examine the impact of the youth-oriented packaging on e-liquid sales. Using data scraped from Amazon, the results of our analysis reveal that youth-oriented packaging increases the sale of e-liquids. In addition, the demand for e-liquids is inelastic and the percentage of propylene glycol (PG), the rating, and the sentiment in the online reviews left by previous buyers also influence the sale of e-liquids. This research suggests that besides fruit and mint flavors, the policy goal of reducing use among youth should also include packaging. The analysis finds that taxation policies to raise prices of e-liquids will not affect appreciably the demand for e-liquids. Policies for e-liquids control should focus on designing packaging that reduces the no- or low-risk perception.
The effect of CYP3A4 genetic polymorphisms on the pharmacokinetics of calcineurin inhibitors in renal transplant recipients: a systematic review and meta-analysis protocol
Authors: Salehi Saeedeh , Abedini Fateme , Shahi Abbas , Afzali Shima , Dashti-Khavidaki Simin , Amirzargar Ali Akbar 
Published: March 2021

AbstractBackgroundCalcineurin inhibitors (CNIs) are metabolized by CYP3A4. Polymorphisms in the CYP3A4 gene alter the activity of CYP3A4 protein and therefore affect the CNIs concentrations. Results of studies that investigated the association between CYP3A4 polymorphisms and CNIs pharmacokinetics are controversial. Therefore, this systematic review and meta-analysis will evaluate the effect of CYP3A4 polymorphisms on the pharmacokinetics of CNIs in renal transplant recipients.MethodThis protocol is developed according to the PRISMA-P guideline and registered in PROSPERO (CRD42020145219). The MeSH/Emtree terms of CYP3A4 polymorphisms and CNIs pharmacokinetics in PECO-based question will be obtained from the comprehensive literature search on PubMed/MEDLINE, Scopus, Web of Science, Embase, CENTRAL, and ProQuest without any language limitation from 1 January 1998 to 31 March 2021. Google Scholar search engine, registries, conference papers, and key journals will also be searched. Screening, selection, quality assessment, and data extraction will be performed by two independent reviewers. Statistical heterogeneity will be calculated by the Q Cochrane test and I2statistic. Publication bias and sensitivity analysis will be evaluated by appropriate tests.Results and conclusionAccording to the meta-analysis of the aggregated data from the relevant primary studies, the association between CYP3A4 polymorphisms and CNIs pharmacokinetics will be reported, which possibly help the pharmacogenetic-guided dosing approach.
Cell cycle-independent integration of stress signals promotes Non-G1/G0 quiescence entry
Authors: Argüello-Miranda Orlando , Marchand Ashley , Kennedy Taylor , Russo Marielle AX , Noh Jungsik 
Published: March 2021

AbstractCellular quiescence is a non-proliferative state required for cell survival under stress and during development. In most quiescent cells, proliferation is stopped in a reversible state of low Cdk1 kinase activity; in many organisms, however, quiescent states with high Cdk1 activity can also be established through still uncharacterized stress or developmental mechanisms. Here, we used a microfluidics approach coupled to phenotypic classification by machine learning to identify stress pathways associated with starvation-triggered high-Cdk1 quiescent states inSaccharomyces cerevisiae. We found that low- and high-Cdk1 quiescent states shared a core of stress-associated processes, such as autophagy, protein aggregation, and mitochondrial upregulation, but differed in the nuclear accumulation of the stress transcription factors Xbp1, Gln3, and Sfp1. The decision between low- or high-Cdk1 quiescence was controlled by cell cycle-independent accumulation of Xbp1, which acted as a time-delayed integrator of the duration of stress stimuli. Our results show how cell cycle-independent stress-activated factors promote cellular quiescence outside of G1/G0.
GPR15 in colon cancer development and anti-tumor immune responses
Authors: NamKoong Hong , Lee Bomi , Swaminathan Gayathri , Koh Seong-Joon , Rogalla Stephan , Mikhail David , Habtezion Aida 
Published: March 2021

AbstractG protein-coupled receptor 15 (GPR15) is a chemoattractant receptor which in response to its ligand, C10orf99/GPR15L, promotes colon homing of T cells in health and colitis. The functional role of GPR15 in colon cancer is largely unexplored, motivating our current studies using murine colon cancer models and human colorectal cancer (CRC) tissues. Our initial analysis of human CRC specimen revealed significant reduction in GPR15 expression and frequency of GPR15+immune cells in tumors compared to ‘tumor-free’ surgical margins. In the AOM/DSS murine model of colitis associated colon cancer (CAC), we observed increased colonic polyps/tumor burden and lower survival rate inGpr15-deficient (KO) compared toGpr15-sufficient (Het) mice. Analysis of immune cell infiltrates in the colonic polyps showed significantly decreased CD8+T cells and increased IL-17+CD4+and IL-17+CD8+T cells inGpr15-KO than in Het mice. GPR15 deficiency thus alters the immune environment in colonic polyps to mitigate T cell-mediated anti-tumor responses resulting in severe disease. Consistent with a protective role of GPR15, administration of GPR15L to established tumors in the MC38 CRC mouse model increased CD45+cell infiltration, enhanced TNFαexpression on CD4+and CD8+T cells at the tumor site and dramatically reduced tumor burden. Our findings highlight an important, unidentified role of the GPR15-GPR15L axis in promoting a tumor-suppressive immune microenvironment and unveils a novel, colon-specific therapeutic target for CRC.
Increased Risk for Cerebral Small Vessel Disease is Associated with Quantitative Susceptibility Mapping in HIV Infected and Uninfected Individuals
Authors: Murray Kyle D. , Uddin Md Nasir , Tivarus Madalina E. , Sahin Bogachan , Wang Henry Z. , Singh Meera V. , Qiu Xing , Wang Lu , Spincemaille Pascal , Wang Yi , Maggirwar Sanjay B. , Zhong Jianhui , Schifitto Giovanni 
Published: March 2021

ABSTRACTThe aim of this study was to assess in the context of cerebral small vessel disease (CSVD), cardiovascular risk factors and white matter hyperintensities (WMHs) were associated with brain tissue susceptibility as measured by quantitative susceptibility mapping (QSM). Given that CSVD is diagnosed by the presence of lacunar strokes, periventricular and deep WMHs, increased perivascular spaces, and microbleeds, we expected that QSM could capture changes in brain tissue due to underlying CSVD pathology. We compared a cohort of 101 HIV-infected individuals (mean age (SD) = 53.2 (10.9) years) with mild to moderate cardiovascular risk scores, as measured by the Reynold’s risk score, to 102 age-matched controls (mean age (SD) = 50.3 (15.7) years) with similar Reynold scores. We performed brain MRI to assess CSVD burden by acquiring 3D T1-MPRAGE, 3D FLAIR, 2D T2-TSE, and mGRE for QSM. We found that signs of CSVD are significantly higher in individuals with HIV-infection compared to controls and that WMH volumes are significantly correlated with age and cardiovascular risk scores. Regional QSM was associated with cardiovascular risk factors, age, sex, and WMH volumes but not HIV status. These results suggest that QSM may be an early imaging marker reflective of alterations in brain microcirculation.
Svep1 stabilizes developmental vascular anastomosis in reduced flow conditions
Authors: Coxam Baptiste , Padberg Yvonne , Maier Katja , Jung Simone , Bartels-Klein Eireen , Szymborska Anna , Finotto Lise , Helker Christian S.M. , Stainier Didier Y.R. , Schulte-Merker Stefan , Gerhardt Holger 
Published: March 2021

AbstractWe report the discovery that flow and Svep1 are modulator of vessel anastomosis during developmental angiogenesis in zebrafish embryos. We show that loss of Svep1 and blood flow reduction both contribute to defective anastomosis of intersegmental vessels. We show that this defect in primary angiogenic sprouts is associated with an expansion of Apelin-positive tip cells and with reduced formation and lumenisation of the dorsal longitudinal anastomotic vessel. Mechanistically, our results suggest that flow and Svep1 act synergistically to modulate vascular network formation in the zebrafish trunk.
Profiling epigenetic age in single cells
Authors: Trapp Alexandre , Kerepesi Csaba , Gladyshev Vadim N. 
Published: March 2021

ABSTRACTDNA methylation of a defined set of CpG dinucleotides emerged as a critical and precise biomarker of the aging process. Multi-variate machine learning models, known as epigenetic clocks, can exploit quantitative changes in the methylome to predict the age of bulk tissue with remarkable accuracy. However, intrinsic sparsity and digitized methylation in individual cells have so far precluded the assessment of aging in single cell data. Here, we present scAge, a probabilistic approach to determine the epigenetic age of single cells, and validate our results in mice. scAge tissue-specific and multi-cell type single cell clocks correctly recapitulate chronological age of the original tissue, while uncovering the inherent heterogeneity that exists at the single-cell level. The data suggest that while tissues age in a coordinated fashion, some cells age more or less rapidly than others. We show that individual embryonic stem cells exhibit an age close to zero, that certain stem cells in a tissue show a reduced age compared to their chronological age, and that early embryogenesis is associated with the reduction of epigenetic age of individual cells, the latter supporting a natural rejuvenation event during gastrulation. scAge is both robust against the low coverage that is characteristic of single cell sequencing techniques and is flexible for studying any cell type and vertebrate organism of interest. This study demonstrates for the first time the potential for accurate epigenetic age profiling at single-cell resolution.
Heat wave event facilitates defensive responses in invasive C3 plant Ambrosia artemisiifolia L. under elevated CO2concentration to the detriment of insect herbivores
Authors: Tian Zhenya , Ma Chao , Zhao Chenchen , Zhang Yan , Gao Xuyuan , Tian Zhenqi , Chen Hongsong , Guo Jianying , Zhou Zhongshi 
Published: March 2021

AbstractTo predict and mitigate the effects of climate change on communities and ecosystems, the joint effects of extreme climatic events on species interactions need to be understood. Using the common ragweed (Ambrosia artemisiifoliaL.)—leaf beetle (Ophraella communa) system, we investigated the effects of heat wave and elevated CO2on common ragweed growth, secondary metabolism, and the consequent impacts on the beetle. The results showed that elevated CO2and heat wave facilitatedA. Artemisiifoliagrowth; further,A. artemisiifoliaaccumulated large amounts of defensive secondary metabolites. Being fed onA. artemisiifoliagrown under elevated CO2and heat wave conditions resulted in the poor performance ofO. communa(high mortality, long development period, and low reproduction). Overall, under elevated CO2, heat wave improved the defensive ability ofA. artemisiifoliaagainst herbivores. This implies that heat wave event will relieve harm ofA. artemisiifoliato human under elevated CO2. On the other hand, super adaptability to climatic changes may aggravate invasive plant distribution, posing a challenge to the control of invasive plants in the future.
Independent mechanisms underlie the protective effect of dietary polyunsaturated fatty acid supplementation and Gαzdeficiency on the early type 1 diabetes phenotype of Non-obese diabetic (NOD) mice
Authors: Fenske Rachel J. , Wienkes Haley N. , Peter Darby C. , Schaid Michael D. , Pennati Andrea , Galipeau Jacques , Kimple Michelle E. 
Published: March 2021

AbstractNon-obese diabetic (NOD) mice deficient in Gzalpha subunit (Gαz) are protected from developing hyperglycemia, even with early islet insulitis similar to wild-type mice. Similarly, wild-type (WT) NOD mice are protected from glucose intolerance when fed a diet enriched in eicosapentaneoic acid (EPA). In the beta-cell, Prostaglandin EP3 receptor (EP3), whose primary endogenous ligand is the arachidonic acid (AA) metabolite, prostaglandin E2, is specifically coupled to Gαz. In this work, we tested whether dietary EPA supplementation, thereby reducing systemic PGE2levels, would complement Gαzloss in the NOD mouse model. WT and Gαz-null NOD mice were fed an AA-enriched diet, EPA-enriched diet, or control diet upon weaning. After 12 weeks of diet feeding, glucose tolerance tests were performed and pancreatic islets and whole pancreas collected forex vivoanalyses, with the longer-term effect of an EPA-enriched diet on splenic T-cell populations quantified via flow cytometry. Our results reveal a polyunsaturated fatty acid-enriched diet, whether AA or EPA, improves wild-type NOD glucose tolerance by the same magnitude as Gαzloss, but through almost completely different physiological and cellular mechanisms. Our results shed critical light on future research into novel pharmacological and dietary adjuvant therapies for T1D.
Using synthetic MR images for distortion correction
Authors: Montez David F. , Van Andrew N. , Miller Ryland L. , Seider Nicole A. , Marek Scott , Zheng Annie , Newbold Dillan J. , Scheidter Kristen , Feczko Eric , Perrone Anders J. , Miranda-Dominguez Oscar , Earl Eric A. , Kay Benjamin P. , Jha Abhinav K. , Sotiras Aristeidis , Laumann Timothy O. , Greene Deanna J. , Gordon Evan M. , Tisdall M. Dylan , van der Kouwe Andre , Fair Damien A. , Dosenbach Nico U.F. 
Published: March 2021

AbstractFunctional MRI (fMRI) data acquired using echo-planar imaging (EPI) are highly distorted by magnetic field inhomogeneities. Distortion combined with underlying differences in image contrast between EPI and T1-weighted and T2-weighted (T1w/T2w) structural images makes the alignment of functional and anatomical images a challenge. Typically, separately acquired field map data are used to correct fMRI distortions and a flexible cost function insensitive to cross-modal differences in image contrast and intensity is used for aligning fMRI and anatomical images. The quality of alignment achieved with this approach can vary greatly and depends on the quality of field map data. In addition, many publicly available datasets lack field map data entirely. To address this issue, we developedSynth, a software package for distortion correction and cross-modal image registration that does not require separately acquired field map data.Synthcombines information from T1w and T2w anatomical images to construct an idealized undistorted synthetic image that has similar contrast properties to fMRI data. The undistorted synthetic image then serves as an effective reference for individual-specific nonlinear unwarping to correct fMRI distortions. We demonstrate, in both pediatric (ABCD: Adolescent Brain Cognitive Development) and adult (MSC: Midnight Scan Club) data thatSynthperforms comparably well to other leading distortion correction approaches that utilize field map data, and often outperforms them. Field map-less distortion correction withSynthallows accurate and precise registration of fMRI data with missing or corrupted field map information.
Updating the steady state model of C4photosynthesis
Authors: von Caemmerer Susanne 
Published: March 2021

AbstractC4plants play a key role in world agriculture. For example, C4crops such as maize and sorghum are major contributors to both first and third world food production and the C4grasses sugarcane; miscanthus and switchgrass are major plant sources of bioenergy. In the challenge to manipulate and enhance C4photosynthesis, steady state models of leaf photosynthesis provide and important tool for gas exchange analysis and thought experiments that can explore photosynthetic pathway changes. Here the C4photosynthetic model by von Caemmerer and Furbank (1999) has been updated with new kinetic parameterisation and temperature dependencies added. The parameterisation was derived from experiments on the C4monocot,Setaria viridis, which for the first time provides a cohesive parametrisation. Mesophyll conductance and its temperature dependence have also been included, as this is an important step in the quantitative correlation between the initial slope of the CO2response curve of CO2assimilation and in vitro PEP carboxylase activity. Furthermore, the equations for chloroplast electron transport have been updated to include cyclic electron transport flow and equations have been added to calculate electron transport rate from measured CO2assimilation rates.HighlightThe C4photosynthesis model by von Caemmerer and Furbank (1999) has been updated. It now includes temperature dependencies and equations to calculate electron transport rate from measured CO2assimilation rates.