tbuckley/cabot-search huggingface dataset:
Characterization of urine metabolic profiles of farnesoid X receptor-null mice exhibiting spontaneous hepatocarcinogenesis using mass spectrometry-based metabolomics
Authors: John Tyburski, Insook Kim, Sung-Hoon Ahn, Jeffrey Idle, Frank Gonzalez
Journal: Cancer Research (2008)

1218  INTRODUCTION: The farnesoid X receptor (FXR, NR1H4), a member of the nuclear receptor superfamily, controls the synthesis and transport of bile acids (BA). Previous studies with Fxr-null mice revealed a high incidence of spontaneous liver tumors by twelve months of age, perhaps resulting from BA-related inflammation. The mechanism by which these mice develop liver tumors is unknown. The purpose of this study was to characterize the urine metabolite profiles of Fxr-null versus wild-type (WT) mice to gain insight into metabolic pathways that are altered in the absence of FXR. METHODS: Twelve male WT and twelve age- and strain-matched Fxr-null mice were used for collection of 24-hour urine samples at two, six, eight, ten, eleven, and twelve months of age. Sample volumes and body weights were recorded for comparison according to genotype, and the animals were necropsied at twelve months after urine collection concluded. Urine samples were analyzed by ultra-performance® liquid chromatography-time of flight mass spectrometry. Data matrices were first normalized by urine creatinine levels and then analyzed by principal components analysis. Urine ions that differed in relative normalized concentration by genotype were identified from contributions and loadings plots. The chemical identities of the ions were predicted from their exact masses and confirmed by tandem mass spectrogram comparisons using authentic standards. RESULTS: Mean body weight of Fxr-null mice are statistically significantly lower by six months as compared with WT mice. Principal components analysis reveals dramatic separation in the first component of the scores space according to genotype as early as two months of age. This separation is indicative of distinct urine metabolite profiles exhibiting ions that are both elevated and attenuated in urine from Fxr-null versus WT mice. Moreover, these metabolite profile differences change over time. All Fxr-null mice had liver tumors by twelve months of age, whereas the no liver tumors were observed in WT mice. CONCLUSIONS: Urine metabolic profiles of male Fxr-null mice differ from age- and gender-matched WT mice in the first twelve months of life. Several large (>500 mass/charge) metabolites are substantially elevated in the urine of Fxr-null mice at all timepoints tested. In addition, the relative concentrations of a subset of urine metabolites differ according to genotype in an age- and/or disease-dependent manner. These results provide insight into the perturbations in metabolic pathways that prevail in the absence of FXR during spontaneous liver tumorigenesis and mark the first metabolomics study into FXR function.
2S albumins and 11S globulins, two storage proteins involved in pumpkin seeds allergy
Authors: Cristina Bueno‐Díaz, Laura Martín‐Pedraza, Laura León, Elisa Haroun‐Díaz, Carlos Pastor‐Vargas, Esther Muñoz‐García, Manuel de las Heras, Eva Batanero, Javier Cuesta‐Herranz, Mayte Villalba
Journal: Allergy (2020)
Abstract 16091: Female Rats Have Better Right Ventricular (RV) Systolic Function Than Male Rats in Pressure Overload Despite Comparable RV Afterload
Authors: Tik-Chee Cheng, Diana M Tabima, Timothy A Hacker, Naomi C Chesler
Journal: Circulation (2019)

Background: Women are more susceptible to pulmonary arterial hypertension (PAH) than men, however, PAH females exhibit better RV systolic function and survival than male counterparts. We sought to ...
Stepwise Implementation Is Effective In Lowering Oxygenation Targets
Authors: H.J.F. Helmerhorst, M.J. Schultz, P.H. van der Voort, R.J. Bosman, A. Abu-Hanna, D.J. van Westerloo, E. de Jonge, Oxytar Study Grp
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
NIDDK initiatives addressing health disparities in chronic diseases
Authors: B. Tibor Roberts, Griffin P. Rodgers
Journal: Journal of Clinical Investigation (2020)

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focuses on many diseases that place disparate burdens on minority groups and the poor, such as obesity, diabetes, and kidney disease. Here, we highlight the NIDDK's commitment to combating health disparities through basic, translational, and clinical research.
Abstract 14280: Can Telemedicine-Assisted Paramedicine Reduce Emergency Department Visits and 30-Day Readmissions Among High-Risk Heart Failure Patients? a Pilot Study
Authors: Brock Daniels, Cristina Del Toro, Michael Zelenetz, Kriti Gogia, Baria Hafeez, Peter Greenwald, Sunday Clark, Peter Steel, Hanson Hsu, Parag Goyal, Evelyn Horn, Rahul Sharma
Journal: Circulation (2018)

Introduction: Heart failure (HF) patients have high rates of 30-day readmission and emergency department (ED) utilization. Early physician contact within 7 days of discharge is optimal, but success...
Sequencing Therapy for Patients With Lung Cancer
Authors: Gregory J. Riely
Journal: Journal of the National Comprehensive Cancer Network (2020)

Non–small cell lung cancer (NSCLC) can no longer be considered as one disease, nor can it be treated as one. Understanding tumor histology in NSCLC is critical to understanding optimal biomarker evaluation and initial therapy. Proper biomarker evaluation includes both evaluation of PD-L1 status, as well as testing for actionable oncogenic drivers such as EGFR , ALK , ROS1 , BRAF , Met Exon 14 , RET , and NTRK . For patients with NSCLC and a driver oncogene, preferred treatment is targeted therapy. Conversely, for those without an oncogenic driver, preferred initial treatment is pembrolizumab in combination with chemotherapy for patients with low PD-L1 expression (1%–49%) or as a single-agent for high PD-L1 expression (≥50%). For small cell lung cancer (SCLC), the first major NCCN Guideline changes occurred in 2019, with the addition of either atezolizumab or durvalumab to platinum-based chemotherapy and etoposide as first-line therapy for patients with extensive-stage SCLC.
Moving Beyond One-Size-Fits-All Treatment for Patients After Cardiac Arrest
Authors: Romergryko G. Geocadin
Journal: JAMA Network Open (2020)

Clifton W. Callaway, MD, PhD; Patrick J. Coppler, PA-C; John Faro, BS; Jacob S. Puyana, BS; Pawan Solanki, MD; Cameron Dezfulian, MD; Ankur A. Doshi, MD; Jonathan Elmer, MD, MS; Adam Frisch, MD; Francis X. Guyette, MD, MPH; Masashi Okubo, MD, MS; Jon C. Rittenberger, MD, MS; Alexandra Weissman, MD, MS, MPH
Covid-19: Acts of omission
Authors: Kamran Abbasi
Journal: BMJ (2020)

The UK government is becoming known for acts of omission.No evidence exists of Russian interference in the 2016 Brexit referendum because the government didn't and won't look for it.Nor does it seek lessons from an immediate public inquiry to inform a future surge of covid-19. 1Nothing predicts behaviour like behaviour, and if over 60 000 excess deaths in six months will not force behaviour change then perhaps nothing will?The pandemic is at its global height and anything but in retreat, exploiting a philosophical battle between prioritising health or banking on the economy.In the UK and US, the economy has won out.Wealth before health.Elsewhere, the role of health in generating wealth, and the emerging evidence behind it, is better understood. 2 The European Union, for example, has announced a €750bn (£680bn; $860bn) coronavirus recovery fund. 3 Out of the EU, England is marginalising independent scientific advice. 4 5 Acts of commission are faring little better, as the persistent struggles with testing, contact tracing, and local data flows demonstrate. 6 7Positive talk doesn't paper over the burden on health professionals and their need to rest and recuperate, or the lack of public confidence in seeking urgent care during a pandemic. 8 9A genuine opportunity exists to build back better by reducing unnecessary healthcare or making better use of hospital medicines data. 10 11 Clinicians can at least focus on clinical skills.Anosmia is among the myriad clinical presentations of covid-19, and one of the most talked about.Half of all patients with covid-19 lose their sense of smell, but most recover it within four weeks. 12 The key challenge is staying alert for an alternative explanation.At the other end of the clinical spectrum, severely ill patients with breathlessness and agitation require palliation and clear communication about prospects with family and carers. 13 As the system flails, health professionals are relied on to hold it together.Despite encouraging reports about a possible covid-19 vaccine, 14 expert consensus is that the winter will bring another surge of cases.Covid-19 is no mere political power game.Further mishandling of the response will lead to more excess deaths, and premature death is a losing game for both people and the economy.
AB0186 Changes in bone turnover markers and vitamin d receptor (vdr) genotype during glucocorticoid therapy
Authors: M Gantes, A Arteaga, Y Barrios, I Ferraz, A Alvarez, B Rodríguez-Lozano, D Batista, E Trujillo, T González
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Adverse effects of glucocorticoids (GCT) upon the skeleton and markers of bone turnover have been documented but the mechanisms remain unclear. <h3>Objectives</h3> To test of early changes in markers of bone turnover for three months of GCT and the influence of VDR. <h3>Methods</h3> In fifty three patients (age 41,7 SD 12,6) with inflammatory diseases who received a dose greater than 5 mg of prednisone or equivalent (mean dose 1,9 g) for 3 months, the serum levels of parathyroid hormone (PTHi), 25-dihydroxyvitamin D, (Vit D), osteocalcin, alkaline phosphatase, and urine ratios of calcium/creatinine and deoxypyridinoline/creatinine, were determined baseline and 3 months after GCT. VDR genotypes were determined by PCR to demonstrate the presence (b) or absence (B) of a restriction target for Bsm I, in intron 7. <h3>Results</h3> The patients with high baseline levels of PTHi showing lower levels of baseline VitD, (p = 0,003) and 3 months after of GCT the patients with lower levels of PTH have the higher levels of Vit D, (p = 0,001, r = 0,54). There were no significant differences in biochemical markers of bone remodelling between the three genotypes: bb, BB, and Bb VDR before and 3 months after GCT. <h3>Conclusion</h3> These preliminary results suggest not effect of VDR genotype in the changes of the biochemical markers of bone remodelling for glucocorticoid therapy.
Disruption of cancer care in Canada during COVID-19
Authors: Sherene Chen-See
Journal: The Lancet Oncology (2020)

Cancer never waits, but during the COVID-19 pandemic, its diagnosis and treatment had to. According to a survey commissioned by the Canadian Cancer Survivor Network (CCSN), many cancer diagnostic tests and treatments were cancelled or postponed because of COVID-19. These delays led to increased fear and anxiety among patients and caregivers, which continue today.
Cytotoxicity Burst? Differentiating Specific from Nonspecific Effects in Tox21 <i>in Vitro</i> Reporter Gene Assays
Authors: Beate I. Escher, Luise Henneberger, Maria König, Rita Schlichting, Fabian C. Fischer
Journal: Environmental Health Perspectives (2020)

High-throughput screening of chemicals with in vitro reporter gene assays in Tox21 has produced a large database on cytotoxicity and specific modes of action. However, the validity of some of the reported activities is questionable due to the "cytotoxicity burst," which refers to the supposition that many stress responses are activated in a nonspecific way at concentrations close to cell death.We propose a pragmatic method to identify whether reporter gene activation is specific or cytotoxicity-triggered by comparing the measured effects with baseline toxicity.Baseline toxicity, also termed narcosis, is the minimal toxicity any chemical causes. Quantitative structure-activity relationships (QSARs) developed for baseline toxicity in mammalian reporter gene cell lines served as anchors to define the chemical-specific threshold for the cytotoxicity burst and to evaluate the degree of specificity of the reporter gene activation. Measured 10% effect concentrations were related to measured or QSAR-predicted 10% cytotoxicity concentrations yielding specificity ratios (SR). We applied this approach to our own experimental data and to ∼8,000 chemicals that were tested in six of the high-throughput Tox21 reporter gene assays.Confirmed baseline toxicants activated reporter gene activity around cytotoxic concentrations triggered by the cytotoxicity burst. In six Tox21 assays, 37%-87% of the active hits were presumably caused by the cytotoxicity burst (SR<1) and only 2%-14% were specific with SR≥10 against experimental cytotoxicity but 75%-97% were specific against baseline toxicity. This difference was caused by a large fraction of chemicals showing excess cytotoxicity.The specificity analysis for measured in vitro effects identified whether a cytotoxicity burst had likely occurred. The SR-analysis not only prevented false positives, but it may also serve as measure for relative effect potency and can be used for quantitative in vitro-in vivo extrapolation and risk assessment of chemicals. https://doi.org/10.1289/EHP6664.
Measurement of Novel, Drinking Water-Associated PFAS in Blood from Adults and Children in Wilmington, North Carolina
Authors: Nadine Kotlarz, James McCord, David Collier, C. Suzanne Lea, Mark Strynar, Andrew B. Lindstrom, Adrien A. Wilkie, Jessica Y. Islam, Katelyn Matney, Phillip Tarte, M.E. Polera, Kemp Burdette, Jamie DeWitt, Katlyn May, Robert C. Smart, Detlef R.U. Knappe, Jane A. Hoppin
Journal: Environmental Health Perspectives (2020)

From 1980 to 2017, a fluorochemical manufacturing facility discharged wastewater containing poorly understood per- and polyfluoroalkyl substances (PFAS) to the Cape Fear River, the primary drinking water source for Wilmington, North Carolina, residents. Those PFAS included several fluoroethers including HFPO-DA also known as GenX. Little is known about the bioaccumulation potential of these fluoroethers.
Intraductal Transplantation Models of Human Pancreatic Ductal Adenocarcinoma Reveal Progressive Transition of Molecular Subtypes
Authors: Koji Miyabayashi, Lindsey A. Baker, Astrid Deschênes, Benno Traub, Giuseppina Caligiuri, Dennis Plenker, Brinda Alagesan, Pascal Belleau, Siran Li, Jude Kendall, Gun Ho Jang, Risa Karakida Kawaguchi, Tim D.D. Somerville, Hervé Tiriac, Chang-Il Hwang, Richard A. Burkhart, Nicholas J. Roberts, Laura D. Wood, Ralph H. Hruban, Jesse Gillis, Alexander Krasnitz, Christopher R. Vakoc, Michael Wigler, Faiyaz Notta, Steven Gallinger, Youngkyu Park, David A. Tuveson
Journal: Cancer Discovery (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common malignancy, with little improvement in patient outcomes over the past decades. Recently, subtypes of pancreatic cancer with different prognoses have been elaborated; however, the inability to model these subtypes has precluded mechanistic investigation of their origins. Here, we present a xenotransplantation model of PDAC in which neoplasms originate from patient-derived organoids injected directly into murine pancreatic ducts. Our model enables distinction of the two main PDAC subtypes: intraepithelial neoplasms from this model progress in an indolent or invasive manner representing the classical or basal-like subtypes of PDAC, respectively. Parameters that influence PDAC subtype specification in this intraductal model include cell plasticity and hyperactivation of the RAS pathway. Finally, through intratumoral dissection and the direct manipulation of RAS gene dosage, we identify a suite of RAS-regulated secreted and membrane-bound proteins that may represent potential candidates for therapeutic intervention in patients with PDAC. Significance: Accurate modeling of the molecular subtypes of pancreatic cancer is crucial to facilitate the generation of effective therapies. We report the development of an intraductal organoid transplantation model of pancreatic cancer that models the progressive switching of subtypes, and identify stochastic and RAS-driven mechanisms that determine subtype specification. See related commentary by Pickering and Morton, p. 1448. This article is highlighted in the In This Issue feature, p. 1426
MED13L integrates Mediator-regulated epigenetic control into lung cancer radiosensitivity
Authors: Nasha Zhang, Yemei Song, Yeyang Xu, Jiandong Liu, Yue Shen, Liqing Zhou, Jinming Yu, Ming Yang
Journal: Theranostics (2020)

To date, efforts to improve non-small-cell lung cancer (NSCLC) outcomes with increased radiation dose have not been successful. Identification of novel druggable targets that are capable to modulate NSCLC radiosensitivity may provide a way forward. Mediator complex is implicated in gene expression control, but it remains unclear how Mediator dysfunction is involved in cancer radiotherapy. Methods: The biologic functions of miR-4497, MED13L and PRKCA in NSCLC radiosensitivity were examined through biochemical assays including gene expression profilling, cell proliferation assay, colony formation assay, wound healing assay, transwell assay, dual luciferase reporter assay, xenograft models, immunoprecipitation, and chromatin immunoprecipitation sequencing. Clinical implications of miR-4497, MED13L and PRKCA in radiosensitivity were evaluated in NSCLC patients treated with concurrent chemoradiotherapy or radiotherapy alone. Results: We found that radiation can trigger disassemble of Mediator complex via silencing of MED13L by miR-4497 in NSCLC. Although not interrupting structure integrity of the core Mediator or the CDK8 kinase module, suppression of MED13L attenuated their physical interactions and reduced recruitment of acetyltransferase P300 to chromatin via Mediator. Silencing of MED13L therefore diminishes global H3K27ac signals written by P300, activities of enhancer and/or promoters and expression of multiple oncogenes, especially PRKCA. Inhibition of PRKCA expression potentiates the killing effect of radiotherapy in vitro and in vivo. Remarkably, high PRKCA expression in NSCLC tissues is correlated with poor prognosis of patients received radiotherapy. Conclusions: Our study linking PRKCA to radiosensitivity through a novel mechanism may enable the rational targeting of PRKCA to unlock therapeutic potentials of NSCLC.
Diagnosis of Hypersensitivity Pneumonitis in Adults: An Official ATS/JRS/ALAT Clinical Practice Guideline
Authors: Ganesh Raghu, Martine Remy-Jardin, Christopher J. Ryerson, Jeffrey L. Myers, Michael Kreuter, Martina Vasakova, Elena Bargagli, Jonathan H. Chung, Bridget F. Collins, Elisabeth Bendstrup, Hassan A. Chami, Abigail T. Chua, Tamera J. Corte, Jean-Charles Dalphin, Sonye K. Danoff, Javier Diaz-Mendoza, Abhijit Duggal, Ryoko Egashira, Thomas Ewing, Mridu Gulati, Yoshikazu Inoue, Alex R. Jenkins, Kerri A. Johannson, Takeshi Johkoh, Maximiliano Tamae-Kakazu, Masanori Kitaichi, Shandra L. Knight, Dirk Koschel, David J. Lederer, Yolanda Mageto, Lisa A. Maier, Carlos Matiz, Ferran Morell, Andrew G. Nicholson, Setu Patolia, Carlos A. Pereira, Elisabetta A. Renzoni, Margaret L. Salisbury, Moises Selman, Simon L. F. Walsh, Wim A. Wuyts, Kevin C. Wilson
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Section:ChooseTop of pageAbstract <<ContentsSummary of Recommendation...IntroductionHow to Use These Guidelin...MethodsDefinitionClinical ManifestationsPathogenesisRadiological FeaturesHistopathological Feature...Diagnostic CriteriaDiagnostic InterventionsFuture DirectionsConclusionsReferencesCITING ARTICLES
Lung-targeting lentiviral vector for passive immunisation against influenza
Authors: Tiong Kit Tan, Toby P E Gamlen, Pramila Rijal, Alain R Townsend, Deborah R Gill, Stephen C Hyde
Journal: Thorax (2020)

When recombinant simian immunodeficiency virus (SIV) is pseudotyped with the F and HN glycoproteins from murine respiratory Sendai virus (rSIV.F/HN), it provides efficient lung cell targeting and lifelong transgene expression in the murine airways. We have shown that a single dose of rSIV.F/HN can direct stable expression of neutralising antibody against influenza in the murine airways and systemic circulation, and protects mice against two different influenza strains in lethal challenge experiments. These data suggest that rSIV.F/HN could be used as a vector for passive immunisation against influenza and other respiratory pathogens.
Covid-19 associated chilblain-like lesions in an asymptomatic doctor
Authors: Sofia Hadjieconomou, Jenny Hughes
Journal: BMJ (2020)

These (fig 1) are chilblain-like lesions in a woman in her late 20s.



Fig 1 

She presented with a two week history of burning and itching of her fingers and toes, with erythematous and purple papules. Erosions were present on her …
Hybrid Telerehabilitation and Telecare is More Efffective Than Usual Care in Improving Peak Vo2 and 6-Minute Walk Distance but is Not Associated With Reduction of 24-Months Mortality Except in the Most Experienced Center - Result of the First Randomized, Prospective, Open- Label, Parallel Group, Controlled, Multi-Center - Telereh-Hf Study
Authors: Ewa Piotrowicz, Ryszard Piotrowicz, Grzegorz Opolski, Piotr Orzechowski, Sławomir Pluta, Renata Główczyńska, Dominika Szalewska, Robert Irzmański, Michael Pencina, Ilona Kowalik, Tomasz Krauze, Anna Mierzynska, Maciej Banach, Wojciech Zaręba
Journal: Circulation (2019)
Trends in US Heart Transplant Waitlist Activity and Volume During the Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Ersilia M. DeFilippis, Lauren Sinnenberg, Nosheen Reza, Michael M. Givertz, Michelle M. Kittleson, Veli K. Topkara, Maryjane A. Farr
Journal: JAMA Cardiology (2020)

Solid organ transplants have declined significantly during the coronavirus disease (COVID-19) pandemic in the US. Limited data exist regarding changes in heart transplant (HT).
Molecular Underpinnings of Severe Coronavirus Disease 2019
Authors: Robert M. Plenge
Journal: JAMA (2020)

Caspar I. van der Made, MD; Annet Simons, PhD; Janneke Schuurs-Hoeijmakers, MD, PhD; Guus van den Heuvel, MD; Tuomo Mantere, PhD; Simone Kersten, MSc; Rosanne C. van Deuren, MSc; Marloes Steehouwer, BSc; Simon V. van Reijmersdal, BSc; Martin Jaeger, PhD; Tom Hofste, BSc; Galuh Astuti, PhD; Jordi Corominas Galbany, PhD; Vyne van der Schoot, MD, PhD; Hans van der Hoeven, MD, PhD; Wanda Hagmolen of ten Have, MD, PhD; Eva Klijn, MD, PhD; Catrien van den Meer, MD; Jeroen Fiddelaers, MD; Quirijn de Mast, MD, PhD; Chantal P. Bleeker-Rovers, MD, PhD; Leo A. B. Joosten, PhD; Helger G. Yntema, PhD; Christian Gilissen, PhD; Marcel Nelen, PhD; Jos W. M. van der Meer, MD, PhD; Han G. Brunner, MD, PhD; Mihai G. Netea, MD, PhD; Frank L. van de Veerdonk, MD, PhD; Alexander Hoischen, PhD