tbuckley/cabot-search huggingface dataset:
Elevated bilirubin, alkaline phosphatase at onset, and drug metabolism are associated with prolonged recovery from DILI
Authors: Kristin Ashby, Wei Zhuang, Andres González-Jimenez, Ismael Alvarez-Alvarez, M. Isabel Lucena, Raúl J. Andrade, Guruprasad P. Aithal, Ayako Suzuki, Minjun Chen
Journal: Journal of Hepatology (2021)

Although most drug-induced liver injury (DILI) cases resolve after the offending medication is discontinued, time to recovery varies among patients, with 6 -12% developing a chronic disease. Herein, we investigated clinical factors and drug properties as potential risk determinants that influence the time course for DILI recovery and developed a model to predict its trajectory.We applied an accelerated failure time model to 294 cases collected by the International Drug-Induced Liver Network Consortium (iDILIC). Factors included in the multivariate recovery score model were selected through univariate analysis. The model was externally validated using 257 cases from the Spanish DILI Registry and 191 cases from the LiverTox database.Higher serum bilirubin and alkaline phosphatase (ALP) at DILI onset, a longer time to onset, and non-significant drug metabolism were associated with a longer recovery and were included in the recovery score model. We defined high- and low-risk groups based on the scores assigned by the model. The estimated probability of recovery by 6 months was 0.46 (95% CI 0.26-0.61) for the high-risk group and 0.93 (95% CI 0.58-0.99) for the low-risk group in the iDILIC. Model performance was validated in both validation sets. The high- and low-risk cases identified by the model showed a significantly different time course for recovery, with a majority of low-risk cases recovering sooner.The trajectory of biochemical recovery from DILI is predicted by the extent of drug metabolism, serum bilirubin and ALP at DILI onset. The model can be used to compute an estimated DILI recovery and, when a significant delay is predicted, clinicians may consider additional investigations such as histologic evaluation or extended follow-up.In this study, we investigated whether drug properties and clinical factors are associated with the time it takes to recover from drug-induced liver injury (DILI). We found that total bilirubin, alkaline phosphatase level at DILI onset, time to onset, and extent of drug metabolism were consistently associated with recovery time. Using these factors, we built a model to predict the trajectory of recovery from DILI and validated this model in 2 independent cohorts. Our findings offer important insights into the factors influencing the trajectory of recovery from DILI. Additional investigations and longer follow-ups can be planned in those for whom a delayed recovery is predicted.
Treating Inflammation and Fibrosis in Chronic GVHD: Two Birds, One ROCK
Authors: Corey Cutler
Journal: Journal of Clinical Oncology (2021)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease. April 20, 2021 ARTICLE CITATION DOI: 10.1200/JCO.21.00214 Journal of Clinical Oncology - published online before print April 20, 2021 PMID: 33877859 Treating Inflammation and Fibrosis in Chronic GVHD: Two Birds, One ROCK Corey Cutler , MD, MPH1xCorey CutlerSearch for articles by this author Show More 1Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.21.00214 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyAUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTTreating Inflammation and Fibrosis in Chronic GVHD: Two Birds, One ROCKThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Corey CutlerStock and Other Ownership Interests: Bluebird Bio, Idera, Verastem, Northwest Biotherapeutics, Actinium PharmaceuticalsHonoraria: Omeros, PfizerConsulting or Advisory Role: Incyte, Jazz Pharmaceuticals, CareDX, Mesoblast, Syndax, MedsenicNo other potential conflicts of interest were reported. Companion ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease
Reply to Zhongzhong Chen, Hua Xie, and Fang Chen’s Letter to the Editor re: Vuthy Ea, Anne Bergougnoux, Pascal Philibert, et al. How Far Should We Explore Hypospadias? Next-generation Sequencing Applied to a Large Cohort of Hypospadiac Patients. Eur Urol 2021;79:507–15
Authors: Anne Bergougnoux, Vuthy Ea, Françoise Paris, Nicolas Kalfa
Journal: European Urology (2021)
Abstract 258: Endothelium-Dependent Vasodilation in Conduit and Resistance Vessels in Relation to the Endothelial Nitric Oxide Synthase Gene
Authors: Erik Ingelsson, Ann-Christine Syvänen, Lars Lind
Journal: Circulation (2007)

Background: The role of nitric oxide in vasodilation, and in cardiovascular disease in general, has been of intense interest recent years. Prior community-based studies relating single nucleotide p...
Global estimates of expected and preventable cervical cancers among girls born between 2005 and 2014: a birth cohort analysis
Authors: Maxime Bonjour, Hadrien Charvat, Eduardo L Franco, Marion Piñeros, Gary M Clifford, Freddie Bray, Iacopo Baussano
Journal: The Lancet Public Health (2021)

BackgroundWHO has launched an initiative aiming to eliminate cervical cancer as a public health problem. Elimination is a long-term target that needs long-lasting commitment. To support local authorities in implementing human papillomavirus (HPV) vaccination, we provide regional and country-specific estimates of cervical cancer burden and the projected impact of HPV vaccination among today's young girls who could develop cervical cancer if not vaccinated.MethodsThe expected number of cervical cancer cases in the absence of vaccination among girls born between 2005 and 2014 was quantified by combining age-specific incidence rates from GLOBOCAN 2018 and cohort-specific mortality rates by age from UN demographic projections. Preventable cancers were estimated on the basis of HPV prevalence reduction attributable to vaccination and the relative contribution of each HPV type to cervical cancer incidence. We assessed the number of cervical cancer cases preventable through vaccines targeting HPV types 16 and 18, with and without cross-protection, and through vaccines targeting HPV types 16, 18, 31, 33, 45, 52, and 58.FindingsGlobally, without vaccination, the burden of cervical cancer in these birth cohorts is expected to reach 11·6 million (95% uncertainty interval 11·4–12·0) cases by 2094. Approximately 75% of the burden will be concentrated in 25 countries mostly located in Africa and Asia, where the future number of cases is expected to increase manyfold, reaching 5·6 million (5·4–6·0) cases in Africa and 4·5 million (4·4–4·6) cases in Asia. Worldwide immunisation with an HPV vaccine targeted to HPV types 16 and 18, with cross-protection against HPV types 31, 33, and 45, could prevent about 8·7 million (8·5–9·0) cases.InterpretationDetailed estimates of the increasing burden of cervical cancer and projected impact of HPV vaccination is of immediate relevance to public health decision makers. Shifting the focus of projections towards recently born girls who could develop cervical cancer if not vaccinated is fundamental to overcome stakeholders' hesitancy towards HPV vaccination.FundingBill & Melinda Gates Foundation, Canadian Institutes of Health Research.
Airport Traveler Testing Program for SARS-CoV-2 — Alaska, June–November 2020
Authors: Elizabeth C. Ohlsen, Kimberly A. Porter, Eric Mooring, Coleman Cutchins, Anne Zink, Joseph McLaughlin
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Travel can facilitate SARS-CoV-2 introduction.To reduce introduction of SARS-CoV-2 infections, the state of Alaska implemented a program on June 6, 2020, for arriving air, sea, and road travelers that required either molecular testing for SARS-CoV-2, the virus that causes COVID-19, or a 14-day self-quarantine after arrival.The Alaska Department of Health and Social Services (DHSS) used weekly standardized reports submitted by 10 participating Alaska airports to evaluate air traveler choices to undergo testing or self-quarantine, traveler test results, and airport personnel experiences while implementing the program.Among 386,435 air travelers who arrived in Alaska during June 6-November 14, 2020, a total of 184,438 (48%) chose to be tested within 72 hours before arrival, 111,370 (29%) chose to be tested on arrival, and 39,685 (10%) chose to self-quarantine without testing after arrival.An additional 15,112 persons received testing at airport testing sites; these were primarily travelers obtaining a second test 7-14 days after arrival, per state guidance.Of the 126,482 airport tests performed in Alaska, 951 (0.8%) results were positive, or one per 406 arriving travelers.Airport testing program administrators reported that clear communication, preparation, and organization were vital for operational success; challenges included managing travelers' expectations and ensuring that sufficient personnel and physical space were available to conduct testing.Expected mitigation measures such as vaccination, physical distancing, mask wearing, and avoidance of gatherings after arrival might also help limit postarrival transmission.Posttravel self-quarantine and testing programs might reduce travel-associated SARS-CoV-2 transmission and importation, even without enforcement.Traveler education and community and industry partnerships might help ensure success.To assess the airport traveler testing program, Alaska DHSS reviewed Alaska's COVID-19 requirements and testing operations for arriving air travelers during June 6-November 14, 2020.Although travelers entering Alaska by road and sea were also subject to these requirements, entry by road and sea was minimal after Canada began restricting nonessential transit on March 20, 2020 (1), and these ports of entry neither provided weekly briefs nor routinely offered onsite testing; therefore, this report is limited to an analysis of the air traveler program.Airport programs were asked to provide weekly reports on the numbers of incoming flights, passengers screened for symptoms, passengers tested within 72 hours before arrival, passengers who chose to self-quarantine for 14 days after arrival, passengers tested at the airport, and positive test results.In
Everything That Wenckebachs Is Not the AV Node
Authors: Tharian S. Cherian, Saman Nazarian, David S. Frankel
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
PMN-derived netrin-1 attenuates cardiac ischemia-reperfusion injury via myeloid ADORA2B signaling
Authors: Jiwen Li, Catharina Conrad, Tingting W. Mills, Nathaniel K. Berg, Boyun Kim, Wei Ruan, Jae W. Lee, Xu Zhang, Xiaoyi Yuan, Holger K. Eltzschig
Journal: The Journal of Experimental Medicine (2021)

Previous studies implicated the neuronal guidance molecule netrin-1 in attenuating myocardial ischemia-reperfusion injury. However, the tissue-specific sources and receptor signaling events remain elusive. Neutrophils are among the first cells responding to an ischemic insult and can be associated with tissue injury or rescue. We found netrin-1 levels were elevated in the blood of patients with myocardial infarction, as well as in mice exposed to myocardial ischemia-reperfusion. Selectively increased infarct sizes and troponin levels were found in Ntn1loxP/loxP Lyz2 Cre+ mice, but not in mice with conditional netrin-1 deletion in other tissue compartments. In vivo studies using neutrophil depletion identified neutrophils as the main source for elevated blood netrin-1 during myocardial injury. Finally, pharmacologic studies using treatment with recombinant netrin-1 revealed a functional role for purinergic signaling events through the myeloid adenosine A2b receptor in mediating netrin-1–elicited cardioprotection. These findings suggest an autocrine signaling loop with a functional role for neutrophil-derived netrin-1 in attenuating myocardial ischemia-reperfusion injury through myeloid adenosine A2b signaling.
High-Density Lipoprotein Anti-Inflammatory Capacity and Incident Cardiovascular Events
Authors: Congzhuo Jia, Josephine L.C. Anderson, Eke G. Gruppen, Yu Lei, Stephan J.L. Bakker, Robin P.F. Dullaart, Uwe J.F. Tietge
Journal: Circulation (2021)

The role of high-density lipoprotein (HDL) function in cardiovascular disease represents an important emerging concept. The present study investigated whether HDL anti-inflammatory capacity is prospectively associated with first cardiovascular events in the general population.HDL anti-inflammatory capacity was determined as its ability to suppress TNFα (tumor necrosis factor α)-induced VCAM-1 (vascular cell adhesion molecule-1) mRNA expression in endothelial cells in vitro (results expressed as achieved percent reduction by individual HDL related to the maximum TNFα effect with no HDL present). In a nested case-control design of the PREVEND (Prevention of Renal and Vascular End Stage Disease) study, 369 cases experiencing a first cardiovascular event (combined end point of death from cardiovascular causes, ischemic heart disease, nonfatal myocardial infarction, and coronary revascularization) during a median of 10.5 years of follow-up were identified and individually matched to 369 controls with respect to age, sex, smoking status, and HDL cholesterol. Baseline samples were available in 340 cases and 340 matched controls.HDL anti-inflammatory capacity was not correlated with HDL cholesterol or hsCRP (high-sensitivity C-reactive protein). HDL anti-inflammatory capacity was significantly lower in cases compared with controls (31.6% [15.7-44.2] versus 27.0% [7.4-36.1]; P<0.001) and was inversely associated with incident CVD in a fully adjusted model (odds ratio [OR] per 1 SD, 0.74 [CI, 0.61-0.90]; P=0.002). Furthermore, this association was approximately similar with all individual components of the cardiovascular disease end point. The HDL anti-inflammatory was not correlated with cholesterol efflux capacity (r=-0.02; P>0.05). When combining these 2 HDL function metrics in 1 model, both were significantly and independently associated with incident cardiovascular disease in a fully adjusted model (efflux: OR per 1 SD, 0.74; P=0.002; anti-inflammatory capacity: OR per 1 SD, 0.66; P<0.001). Adding HDL anti-inflammatory capacity improved risk prediction by the Framingham risk score, with a model likelihood-ratio statistic increase from 10.50 to 20.40 (P=0.002).The HDL anti-inflammatory capacity, reflecting vascular protection against key steps in atherogenesis, was inversely associated with incident cardiovascular events in a general population cohort, independent of HDL cholesterol and HDL cholesterol efflux capacity. Adding HDL anti-inflammatory capacity to the Framingham risk score improves risk prediction.
Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD
Authors: Masaomi Nangaku, Kazuoki Kondo, Yoshimasa Kokado, Kiichiro Ueta, Genki Kaneko, Tsubasa Tandai, Yutaka Kawaguchi, Yasuhiro Komatsu
Journal: Journal of the American Society of Nephrology (2021)

Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular morbidity and mortality. Previous studies in patients with anemia and nondialysis-dependent CKD (NDD-CKD) found significantly elevated hemoglobin levels with use of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, compared with placebo.In this phase 3, open-label, active-controlled noninferiority trial, we randomized 304 Japanese adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users and nonusers) to oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks. The primary efficacy end point was average hemoglobin at weeks 20 and 24. Safety data included adverse events (AEs) and serious AEs.A total of 151 participants received vadadustat and 153 received darbepoetin alfa. Least squares mean of the average hemoglobin at weeks 20 and 24 was 11.66 (95% confidence interval [95% CI], 11.49 to 11.84) g/dl for vadadustat and 11.93 (95% CI, 11.76 to 12.10) g/dl for darbepoetin alfa. The 95% CIs for both treatments were within the target hemoglobin range (11.0-13.0 g/dl), and the lower 95% confidence limit for the difference between groups (-0.50 g/dl) was above the predefined noninferiority margin (-0.75 g/dl), demonstrating noninferiority of vadadustat to darbepoetin alfa. Similar proportions of patients in each group reported AEs and serious AEs. The most frequent AEs with vadadustat were nasopharyngitis, diarrhea, and constipation.In Japanese patients with NDD-CKD, vadadustat was noninferior to darbepoetin alfa, was effective up to week 52 in terms of average hemoglobin, and was generally well tolerated. These results suggest that vadadustat may be a potential treatment for anemia in this patient population.
Tumor-derived exosomes: Nanovesicles made by cancer cells to promote cancer metastasis
Authors: Hongwei Chen, Venkata Chengalvala, Hongxiang Hu, Duxin Sun
Journal: Acta Pharmaceutica Sinica B (2021)

Nanomedicine usually refers to nanoparticles that deliver the functional drugs and siRNAs to treat cancer. Recent research has suggested that cancer cells can also make nanoparticles that also deliver functional molecules in promoting cancer metastasis, which is the leading cause of various cancer mortalities. This nanoparticle is called tumor-derived vesicles, or better-known as tumor-derived exosomes (TEXs). TEXs are nanoscale membrane vesicles (30-140 nm) that are released continuously by various types of cancer cells and contain tumor-derived functional biomolecules, including lipids, proteins, and genetic molecules. These endogenous TEXs can interact with host immune cells and epithelial cells locally and systemically. More importantly, they can reprogram the recipient cells in favor of promoting metastasis through facilitating tumor cell local invasion, intravasation, immune evasion, extravasation, and survival and growth in distant organs. Growing evidence suggests that TEXs play a key role in cancer metastasis. Here, we will review the most recent findings of how cancer cells harness TEXs to promote cancer metastasis through modulating vascular permeability, suppressing systemic immune surveillance, and creating metastatic niches. We will also summarize recent research in targeting TEXs to treat cancer metastasis.
Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon
Authors: Yoshitaka Toyama, Rudolf A Werner, Camilo A Ruiz-Bedoya, Alvaro A Ordonez, Kei Takase, Constantin Lapa, Sanjay K Jain, Martin G Pomper, Steven P Rowe, Takahiro Higuchi
Journal: Theranostics (2021)

In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear oncology. Although PET-based molecular imaging of the kidneys is still in its infancy, such a trend has emerged in the field of functional renal radionuclide imaging. Potentially allowing for precise and thorough evaluation of renal radiotracer urodynamics, PET radionuclide imaging has numerous advantages including precise anatomical co-registration with CT images and dynamic three-dimensional imaging capability. In addition, relative to scintigraphic approaches, PET can allow for significantly reduced scan time enabling high-throughput in a busy PET practice and further reduces radiation exposure, which may have a clinical impact in pediatric populations. In recent years, multiple renal PET radiotracers labeled with
Targeted Therapy with BET Protein and β Catenin Antagonists Against Ruxolitinib Resistant Post-Myeloproliferative Neoplasm (MPN) Secondary (s) AML Cells
Authors: Dyana T. Saenz, Warren Fiskus, Taghi Manshouri, Yimin Qian, Kanak Raina, David N Saenz, Christopher Peter Mill, Agnieszka J Nowak, Baohua Sun, Srdan Verstovsek, Craig M Crews, Kapil N. Bhalla
Journal: Blood (2017)
Familial chilblain lupus in a child with heterozygous mutation in <i>SAMHD1</i> and normal interferon signature
Authors: D.W. Linggonegoro, H. Song, K.M. Jones, P.Y. Lee, B. Schmidt, R.A. Vleugels, J.T. Huang
Journal: British Journal of Dermatology (2021)

The type I interferonopathies comprise a growing group of genetically determined disorders that result in an abnormal upregulation of type I interferon (IFN).1 Familial chilblain lupus is a type I interferonopathy that is inherited as an autosomal dominant trait. It manifests early in childhood and is characterized by dusky purple patches, papules, and plaques that are exacerbated by cold exposure. Here we present a child with familial chilblain lupus, found to have a heterozygous SAMHD1 mutation with a unique interferon signature.
The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition
Authors: Xuanji Li, Jakob Stokholm, Asker Brejnrod, Gisle Alberg Vestergaard, Jakob Russel, Urvish Trivedi, Jonathan Thorsen, Shashank Gupta, Mathis Hjort Hjelmsø, Shiraz A. Shah, Morten Arendt Rasmussen, Hans Bisgaard, Søren Johannes Sørensen
Journal: Cell Host & Microbe (2021)
Human brain region-specific variably methylated regions are enriched for heritability of distinct neuropsychiatric traits
Authors: Lindsay F Rizzardi, Peter F Hickey, Adrian Idrizi, Rakel Tryggvadóttir, Colin M Callahan, Kimberly E Stephens, Sean D Taverna, Hao Zhang, Sinan Ramazanoglu, Kasper D Hansen, Andrew P Feinberg
Journal: Genome biology (2021)
Inherited Gene Regulation Unifies Molecular Approaches to Nongenetic Inheritance: Response to Edelaar et al.
Authors: Irene Adrian-Kalchhauser, Sonia E. Sultan, Lisa Shama, Helen Spence-Jones, Stefano Tiso, Claudia Isabelle Keller Valsecchi, Franz J. Weissing
Journal: Trends in Ecology & Evolution (2021)