bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicompartmental Non-invasive Sensing of Postprandial Lipemia in Humans with Multispectral Optoacoustic Tomography
Authors: Fasoula Nikolina-Alexia , Karlas Angelos , Kallmayer Michael , Milik Anamaria Beatrice , Pelisek Jaroslav , Eckstein Hans-Henning , Klingenspor Martin , Ntziachristos Vasilis 
Published: June 2020

AbstractDisturbed blood lipid profiles after food intake have been associated with increased risk for cardiovascular and metabolic disease. Postprandial lipid profiling (PLP) can be used as a risk factor for cardiovascular disease, insulin resistance and other metabolic diseases but is based today on frequent blood sampling over several hours after a meal, an approach that is invasive and inconvenient for patients. Non-invasive PLP may offer a favorable alternative for disseminated monitoring in humans. In this study, we investigate the use of localized lipid sensing guided by Multispectral Optoacoustic Tomography (MSOT) for non-invasive, label-free assessment of postprandial lipemia in human vasculature and in soft tissues. For penetrating deep in human tissue, we utilize measurements at 930 nm, where lipids exhibit strong light absorption in the near-infrared spectral range (NIR). In a pilot study, we longitudinally measured postprandial lipemia in healthy subjects over 6 hours following consumption of a high-fat meal. Localized measurements were obtained from four anatomical structures: the radial artery, the cephalic vein, the brachioradialis muscle and the subcutaneous fat of the forearm. Analysis of optoacoustic signals demonstrated a 63.4% mean lipid increase in intra-arterial lipids at approximately 4 hours postprandially, a 89.7% mean increase in intra-venous lipids at 3-hours, a 120.8% mean increase in intra-muscular lipids at 3-hours and a 30.5% mean increase in subcutaneous fat lipids at 4-hours. We discuss how portable MSOT offers unprecedented potential to study lipid metabolism that could lead to novel diagnostics and prevention strategies by offering label-free and non-invasive detection of tissue biomarkers implicated in cardiometabolic diseases.
Thin Film Metallization Stacks Serve as Reliable Conductors on Ceramic-based Substrates for Active Implants
Authors: Kiele Patrick , Čvančara Paul , Langenmair Michael , Mueller Matthias , Stieglitz Thomas 
Published: June 2020

AbstractHermetic and non-hermetic packages of active implantable medical devices are often fabricated of ceramics like alumina. Screen printed PtAu paste is the state of the art metallization for functional structures. Due to solid state and liquid diffusion of Au at thermal exposure, solder times are limited; otherwise metal structures tend to delaminate. Moreover, it was shown that PtAu with solder fails after 37.4 years. We established a thin film metallization on alumina process to overcome these disadvantages. The metallization consists of sputtered platinum with an underlying adhesion layer made of tungsten-titanium to increase the adhesion strength to the alumina substrate. We avoided using gold in this work due to its high diffusion tendency. Instead, the materials in use provide relatively low diffusion properties, which potentially increases the long term mechanical performance and usability during assembly and packaging.Utilizing the Design of Experiment (DoE) methodology, we derived an optimal Pt thickness of 500 nm with 43 nm of WTi as adhesion promoting layer. After accelerated aging at 150 °C, corresponding to 125 years at body temperature (37 °C), the contact pad adhesion strength was with 32.75 MPa ± 7.08 MPa still significantly higher than the safety limit of 17 MPa, following the recommendations for a robust screen-printing metallization process. Moreover, soldering times of up to 120 s did not influence the adhesive strength. The new process reduced the minimum track distance to 50% of screen printing values and is capable of rapid prototyping. It helps to make the assembly process independent of the manufacturing person, to increase the yield of device fabrication and -most important in implantable device manufacturing-to make it more robust and thereby more safe for the patient.
Transgressive segregation for salt tolerance in rice due to physiological coupling and uncoupling and genetic network rewiring
Authors: Pabuayon Isaiah C.M. , Kitazumi Ai , Cushman Kevin R. , Singh Rakesh Kumar , Gregorio Glenn B. , Dhatt Balpreet , Zabet-Moghaddam Masoud , Walia Harkamal , de los Reyes Benildo G. 
Published: June 2020

AbstractTransgressive segregation is common in plant breeding populations, where a small minority of recombinants are outliers relative to parental phenotypes. While this phenomenon has been attributed to complementation and epistatic effects, the physiological, biochemical, and molecular bases have not been fully illuminated. By systems-level scrutiny of the IR29 x Pokkali recombinant inbred population of rice, we addressed the hypothesis that novel salt tolerance phenotypes are created by positive or negative coupling or uncoupling effects and novel regulatory networks. Hyperspectral profiling distinguished the transgressive individuals in terms of stress penalty to growth. Non-parental network signatures that led to either optimal or non-optimal integration of developmental with stress-related mechanisms were evident at the macro-physiological, biochemical, metabolic, and transcriptomic levels. The large positive net gain in super-tolerant progeny was due to ideal complementation of beneficial traits, while shedding antagonistic traits. Super-sensitivity was explained by the stacking of multiple antagonistic traits and loss of major beneficial traits. The mechanisms elucidated in this study are consistent with the Omnigenic Theory, emphasizing the synergy or lack thereof between core and peripheral components. This study supports a breeding paradigm based on genomic modeling to create the novel adaptive phenotypes for the crops of the 21stcentury.
A survivin-driven tumour-activatable minicircle system for prostate cancer theranostics
Authors: Wang TianDuo , Chen Yuanxin , Goodale David , Allan Alison L. , Ronald John A. 
Published: June 2020

AbstractGene vectors driven by tumour-specific promoters to express reporter genes and therapeutic genes are an emerging approach for improved cancer diagnosis and treatment. Minicircles (MCs) are shortened plasmids stripped of prokaryotic sequences and have potency and safety characteristics that are beneficial for clinical translation. We previously developed survivin-driven, tumour-activatable MCs for cancer detection via a secreted blood reporter assay. Here we present a novel theranostic system for prostate cancer featuring a pair of survivin-driven MCs, combining selective detection of aggressive tumours via a urinary reporter test and subsequent tumour treatment with gene-directed enzyme prodrug therapy.MethodsWe engineered both diagnostic and therapeutic survivin-driven MCs expressing Gaussia luciferase, a secreted reporter that is detectable in the urine, and cytosine deaminase:uracil phosphoribosyltransferase fusion, respectively. Diagnostic MCs were evaluated in mice carrying orthotopic prostate tumours with varying survivin levels, measuring reporter activity in serial urine samples. Therapeutic MCs were evaluated in mice receiving prodrug using bioluminescence imaging to assess cancer cell viability over time.ResultsDiagnostic MCs revealed mice with aggressive prostate tumours exhibited significantly higher urine reporter activity than mice with non-aggressive tumours and tumour-free mice. Combined with 5-fluorocytosine prodrug treatment, therapeutic MCs resulted in reduced bioluminescence signal in mice with aggressive prostate tumours compared to control mice.ConclusionSequential use of these MCs may be used to first identify patients carrying aggressive prostate cancer by a urinary reporter test, followed by stringent treatment in stratified individuals identified to have high-risk lesions. This work serves to highlight tumour-activatable MCs as a viable platform for development of gene-based tumour-activatable theranostics.
Heterogeneous adaptation of cysteine reactivity to a covalent oncometabolite
Authors: Perez Minervo , Bak Daniel W. , Bergholtz Sarah E. , Crooks Daniel R. , Yang Youfeng , Weerapana Eranthie , Linehan W. Marston , Meier Jordan L. 
Published: June 2020

ABSTRACTMetabolism and signaling intersect in the genetic cancer syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a disease in which mutation of the TCA cycle enzyme fumarate hydratase (FH) causes hyperaccumulation of fumarate. This electrophilic oncometabolite can alter gene activity at the level of transcription, via reversible inhibition of epigenetic dioxygenases, as well as posttranslationally, via covalent modification of cysteine residues. To better understand how metabolites function as covalent signals, here we report a chemoproteomic analysis of a kidney-derived HLRCC cell line. Building on previous studies, we applied a general reactivity probe to compile a dataset of cysteine residues sensitive to rescue of cellular FH activity. This revealed a broad upregulation of cysteine reactivity upon FH rescue, caused by an approximately equal proportion of transcriptional and posttranslational regulation in the rescue cell line. Gene ontology analysis highlights new targets and pathways potentially modulated by FH mutation. Comparison of the new dataset to literature studies highlights considerable heterogeneity in the adaptive response of cysteine-containing proteins in different models of HLRCC. Our analysis provides a resource for understanding the proteomic adaptation to fumarate accumulation, and a foundation for future efforts to exploit this knowledge for cancer therapy.
Patient-derived xenograft culture-transplant system for investigation of human breast cancer metastasis
Authors: Ma Dennis , Hernandez Grace A. , Lefebvre Austin E.Y.T. , Alshetaiwi Hamad , Blake Kerrigan , Dave Kushal R. , Rauf Maha , Williams Justice W. , Davis Ryan T. , Evans Katrina T. , Masoud Madona Y.G. , Lee Regis , Edwards Robert A. , Digman Michelle A. , Kessenbrock Kai , Lawson Devon A. 
Published: June 2020

AbstractMetastasis is a fatal disease where research progress has been hindered by a lack of authentic experimental models. Here, we develop a 3D tumor sphere culture-transplant system that facilitates the expansion and engineering of patient-derived xenograft (PDX) tumor cells for functional metastasis assaysin vivo. Orthotopic transplantation and RNA sequencing analyses show that PDX tumor spheres maintain tumorigenic potential, and the molecular marker and global transcriptome signatures of native tumor cells. Tumor spheres display robust capacity for lentiviral engineering and dissemination in spontaneous and experimental metastasis assaysin vivo. Inhibition of pathways previously reported to attenuate metastasis also inhibit metastasis after sphere culture, validating our approach for authentic investigations of metastasis. Finally, we demonstrate a new role for the metabolic enzyme NME1 in promoting breast cancer metastasis, providing proof-of-principle that our culture-transplant system can be used for authentic propagation and engineering of patient tumor cells for functional studies of metastasis.
Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor
Authors: Zhao Peng , Praissman Jeremy L. , Grant Oliver C. , Cai Yongfei , Xiao Tianshu , Rosenbalm Katelyn E. , Aoki Kazuhiro , Kellman Benjamin P. , Bridger Robert , Barouch Dan H. , Brindley Melinda A. , Lewis Nathan E. , Tiemeyer Michael , Chen Bing , Woods Robert J. , Wells Lance 
Published: June 2020

SUMMARYThe current COVID-19 pandemic is caused by the SARS-CoV-2 betacoronavirus, which utilizes its highly glycosylated trimeric Spike protein to bind to the cell surface receptor ACE2 glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatic analyses of natural variants and with existing 3D-structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation that, taken together, can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.
Megakaryopoiesis in Dengue virus infected K562 cell promotes viral replication which inhibits endomitosis and accumulation of ROS associated with differentiation
Authors: Kaur Jaskaran , Rawat Yogita , Sood Vikas , Rathore Deepak K. , Kumar Shrikant K. , Kumar Niraj K. , Bhattacharyya Sankar 
Published: June 2020

AbstractIn the human host blood Monocytes and bone marrow Megakaryocytes are implicated as major sites supporting high replication. The human K562 cell line supports DENV replication and represent Megakaryocyte-Erythrocyte progenitors (MEP), replicating features ofin vivoMegakaryopoiesis upon stimulation with Phorbol esters. In this article, we report results that indicate the mutual influence of Megakaryopoiesis and DENV replication on each other, through comparison of PMA-induced differentiation of either mock-infected or DENV-infected K562 cells. We present data showing PMA-induced differentiation to drastically increase DENV replication and a concomitant augmented secretion of infectious virus. Although the mechanism is not clear yet, we show that it is not through an increased uptake of virus by differentiated cells. On the other hand, DENV replication in cells undergoing PMA-induced differentiation, interferes with major differentiation markers of Megakaryopoiesis including activation of ERK1/2 MAP Kinase, endomitosis and surface expression of platelet-specific proteins without any drastic effect on cell death. Among signaling intermediaries of the JAK-STAT pathway, we observed infection associated degradation of SOC3 protein similar to earlier observations with STAT2. DENV infection leads to accumulation of Reactive-oxygen species (ROS) in different cells including K562. PMA-induced differentiation of uninfected K562 cells also leads to intracellular ROS accumulation. Interestingly, we observed ROS accumulation to be suppressed by concomitant DENV replication in K562 cells undergoing PMA-induced differentiation. This is the first report of a model system where DENV replication suppresses intracellular ROS accumulation. The implications of these results for Megakaryopoiesis and viral replication would be discussed.
In-vitro study of the activity of some medicinal plant leaf extracts on urinary tract infection causing bacterial pathogens isolated from indigenous people of Bolangir district, Odisha, India
Authors: Saha Mirkashim H. , Dash Saumya , Mishra Abhisek , Satpathy Jyotismita , Mishra Sujit K. 
Published: June 2020

ABSTRACTThousands of people over the world are suffering from Urinary tract infection (UTI) each day. Side effects associated with the most preferred allopathic treatment for UTI and antibiotic resistance shown by the pathogens has evolved as major challenge. Owing to this, the present study was carried out to identify the bacterial UTI pathogens among indigenous people of Bolangir district, Odisha, Indiavis-à-visexplore the alternative source of natural therapeutics. Bacterial pathogens causing the UTIs were identified using the colony morphology, Gram’s staining and biochemical characterization techniques. Microbial inhibitory test of antibiotics and leaf extracts were performed using the disc diffusion and well diffusion techniques respectively. MIC and MLC were determined by broth dilution method. Binary probit model was used to determine the prevalence of UTI across people of different age group and gender. Four bacterial strains namelyEscherichia coli,Enterococcus faecalis,Staphylococcus aureus, andKlebsiella pneumoniaewere identified as the causative agents of UTI among the people. TheE. coliwas identified as most infectious whileS. aureusas the least infectious pathogen. Females in the age group of ‘16-30 years’ and male within ‘61-75 years’ were more susceptible to UTI. Among the tested leaf extracts,Tamarindus indicaandClitoria ternateawere more effective to treat UTI as compared to the tested antibiotics Ceftriaxone and Piperacillin. The leaf extracts ofT. indicaandC. ternateamay effectively be utilized for herbal drug development for treatment of UTI.
In Vitroefficacy comparison of linezolid, tedizolid, sutezolid and delpazolid against rapid growing Mycobacteria isolated in Beijing, China
Authors: Wen Shuan , Gao Xiaopan , Zhao Weijie , Huo Fengmin , Jiang Guanglu , Dong Lingling , Zhao Liping , Wang Fen , Yu Xia , Huang Hairong 
Published: June 2020

ABSTRACTThe natural resistance of rapid growth Mycobacterium (RGM) against multiple antibiotics renders the treatment of caused infections less successful and time consuming. Therefore, new effective agents are urgently needed. The aim of this study was to evaluate thein vitrosusceptibility of 115 isolates, constituting different RGM species, against four oxazolidinones i.e. delpazolid, sutezolid, tedizolid and linezolid. Additionally, 32 reference strains of different RGM species were also tested. The four oxazolidinones exhibited potentin vitroactivity against the recruited RGM reference strains, 24 out of 32 RGM species had MICs ≤ 8 μg/mL against all four oxazolidinones whereas tedizolid and delpazolid generally presented lower MICs than linezolid or sutezolid. Tedizolid showed the strongest activity against clinical isolates ofM. abscessuswith MIC50=1μg/mL and MIC90=2μg/mL. MIC values for tedizolid were usually 4- to 8-fold less than the MICs of linezolid forM. abscessussubsp.abscessus. The MIC distributions of sutezolid and linezolid were similar, while delpazolid showed 2-fold lower MIC as compared with linezolid. Linezolid was not active against most of the testedM. fortuitumisolates, 22 out of the 25M. fortuitumwere resistant against linezolid. However, delpazolid exhibited better antimicrobial activity against these isolates with 4-fold lower MIC values, in contrast with linezolid. In addition, the protein alignment of RplC and RplD and structure based analysis showed that there may be no correlation between oxazolidinones resistance and mutationsin rplC, rplDand23 srRNAgenes in tested RGM. This study showed tedizolid harbors the strongest inhibitory activity againstM. abscessus in vitro, while delpazolid presented the best activity againstM. fortuitum, which provided important insights on the potential clinical application of oxazolidinones to treat RGM infections.
A link between zinc uptake, bile salts, and a capsule required for virulence of a mastitis-associated extraintestinal pathogenicEscherichia colistrain
Authors: Olson Michael A. , Grimsrud Aleksander , Richards Amanda C. , Mulvey Matthew A. , Wilson Eric , Erickson David L. 
Published: June 2020

ABSTRACTExtraintestinal pathogenicEscherichia coli(ExPEC) are major causes of urinary and bloodstream infections. ExPEC reservoirs are not completely understood. Some mastitis-associatedE. coli(MAEC) strains carry genes associated with ExPEC virulence, including metal scavenging, immune avoidance, and host attachment functions. In this study, we investigated the role of the high-affinity zinc uptake (znuABC) system in the MAEC strain M12. Elimination ofznuABCmoderately decreased fitness during mouse mammary gland infections. The ΔznuABCmutant strain exhibited an unexpected growth delay in the presence of bile salts, which was alleviated by the addition of excess zinc. We isolated ΔznuABCmutant suppressor mutants with improved growth of in bile salts, several of which no longer produced the K96 capsule made by strain M12. Addition of bile salts also reduced capsule production by strain M12 and ExPEC strain CP9, suggesting that capsule synthesis may be detrimental when bile salts are present. To better understand the role of the capsule, we compared the virulence of mastitis strain M12 with its unencapsulated ΔkpsCSmutant in two models of ExPEC disease. The wild type strain successfully colonized mouse bladders and kidneys and was highly virulent in intraperitoneal infections. Conversely, the ΔkpsCSmutant was unable to colonize kidneys and was unable to cause sepsis. These results demonstrate that some MAEC may be capable of causing human ExPEC illness. Virulence of strain M12 in these infections is dependent on its capsule. However, capsule may interfere with zinc homeostasis in the presence of bile salts while in the digestive tract.
Covid-19 Pandemic Data Analysis and Forecasting using Machine Learning Algorithms
Authors: Sengupta Sohini , Mugde Sareeta , Sharma Garima 
Published: June 2020

AbstractIndia reported its first Covid-19 case on 30th Jan 2020 and the number of cases reported heavily escalated from March, 2020. This research paper analyses COVID -19 data initially at a global level and then drills down to the scenario obtained in India. Data is gathered from multiple data sources-several authentic government websites. The need of the hour is to accurately forecast when the numbers will reach at its peak and then diminish. It will be of huge help to public welfare professionals to plan the preventive measures to be taken keeping the economic balance of the country as well. Variables such as gender, geographical location, age etc. have been represented using Python and Data Visualization techniques. Time Series Forecasting techniques including Machine Learning models like Linear Regression, Support Vector Regression, Polynomial Regression and Deep Learning Forecasting Model like LSTM(Long short-term memory) are deployed to study the probable hike in cases and in the near future. A comparative analysis is also done to understand which model fits the best for our data. Data is considered till 30thJuly, 2020. The results show that a statistical model named sigmoid model is outperforming other models. Also the Sigmoid model is giving an estimate of the day on which we can expect the number of active cases to reach its peak and also when the curve will start to flatten. Strength of Sigmoid model lies in providing a count of date that no other model offers and thus it is the best model to predict Covid cases counts –this is unique feature of analysis in this paper. Certain feature engineering techniques have been used to transfer data into logarithmic scale as is affords better comparison removing any data extremities or outliers. Based on the predictions of the short-term interval, our model can be tuned to forecast long time intervals.