tbuckley/cabot-search huggingface dataset:
Plasma Biomarkers of Tubular Injury and Inflammation Are Associated with CKD Progression in Children
Authors: Jason H. Greenberg, Alison G. Abraham, Yunwen Xu, Jeffrey R. Schelling, Harold I. Feldman, Venkata S. Sabbisetti, Mariana Cardenas Gonzalez, Steven Coca, Sarah J. Schrauben, Sushrut S. Waikar, Vasan S. Ramachandran, Michael G. Shlipak, Bradley Warady, Paul L. Kimmel, Joseph V. Bonventre, Michelle Denburg, Chirag R. Parikh, Susan Furth
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Identifying novel biomarkers of kidney function decline in children may have clinical value and help elucidate the biologic mechanisms of CKD progression. In the CKiD prospective cohort study, the authors evaluated 651 children with CKD and measured biomarkers in plasma collected 5 months after enrollment. After multivariable adjustment, risk of CKD progression was significantly higher among children with concentrations of a biomarker of tubular injury (KIM-1) or either of two biomarkers of inflammation (TNF receptor–1 [TNFR-1] and TNFR-2) in the highest quartile compared with those with concentrations in the lowest quartile for the respective biomarker. Use of plasma KIM-1, TNFR-1, and TNFR-2 as biomarkers of ongoing tubular damage and inflammation may identify children at increased risk of CKD progression. Background After accounting for known risk factors for CKD progression in children, clinical outcomes among children with CKD still vary substantially. Biomarkers of tubular injury (such as KIM-1), repair (such as YKL-40), or inflammation (such as MCP-1, suPAR, TNF receptor-1 [TNFR-1], and TNFR-2) may identify children with CKD at risk for GFR decline. Methods We investigated whether plasma KIM-1, YKL-40, MCP-1, suPAR, TNFR-1, and TNFR-2 are associated with GFR decline in children with CKD and in subgroups defined by glomerular versus nonglomerular cause of CKD. We studied participants of the prospective CKiD Cohort Study which enrolled children with an eGFR of 30–90 ml/min per 1.73 m 2 and then assessed eGFR annually. Biomarkers were measured in plasma collected 5 months after study enrollment. The primary endpoint was CKD progression, defined as a composite of a 50% decline in eGFR or incident ESKD. Results Of the 651 children evaluated (median age 11 years; median baseline eGFR of 53 ml/min per 1.73 m 2 ), 195 (30%) had a glomerular cause of CKD. Over a median follow-up of 5.7 years, 223 children (34%) experienced CKD progression to the composite endpoint. After multivariable adjustment, children with a plasma KIM-1, TNFR-1, or TNFR-2 concentration in the highest quartile were at significantly higher risk of CKD progression compared with children with a concentration for the respective biomarker in the lowest quartile (a 4-fold higher risk for KIM-1 and TNFR-1 and a 2-fold higher risk for TNFR-2). Plasma MCP-1, suPAR, and YKL-40 were not independently associated with progression. When stratified by glomerular versus nonglomerular etiology of CKD, effect estimates did not differ significantly. Conclusions Higher plasma KIM-1, TNFR-1, and TNFR-2 are independently associated with CKD progression in children.
The Conundrum and Opportunity of Gender Equity for Evidence Generators
Authors: Rebecca F. Ortega, Roxana Mehran, Pamela S. Douglas
Journal: JAMA Cardiology (2020)

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 Cardiology 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 Cardiology journal
Diffuse Telangiectatic Rash Associated With Novel Antibody Drug Conjugate Therapies
Authors: Eric P. Sorensen, Justin Thrush, Nancy L. Bartlett, Ilana S. Rosman, Milan J. Anadkat, Heather A. Jones
Journal: JAMA Dermatology (2020)

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 Dermatology 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 Dermatology journal
Role of CX3CR1 signaling in malignant transformation of gliomas
Authors: Sungho Lee, Khatri Latha, Ganiraju Manyam, Yuhui Yang, Arvind Rao, Ganesh Rao
Journal: Neuro-Oncology (2020)

Abstract Background Chemokine signaling may contribute to progression of low-grade gliomas (LGGs) by altering tumor behavior or impacting the tumor microenvironment. In this study, we investigated the role of CX3C chemokine receptor 1 (CX3CR1) signaling in malignant transformation of LGGs. Methods Ninety patients with LGGs were genotyped for the presence of common CX3CR1 V249I polymorphism and examined for genotype-dependent alterations in survival, gene expression, and tumor microenvironment. A genetically engineered mouse model was leveraged to model endogenous intracranial gliomas with targeted expression of CX3C ligand 1 (CX3CL1) and CX3CR1, individually or in combination. Results LGG patients who were heterozygous (V/I; n = 43) or homozygous (I/I; n = 2) for the CX3CR1 V249I polymorphism had significantly improved median overall (14.8 vs 9.8 y, P &amp;lt; 0.05) and progression-free survival (8.6 vs 6.5 y, P &amp;lt; 0.05) compared with those with the wild type genotype (V/V; n = 45). Tumors from the V/I + I/I group exhibited significantly decreased levels of CCL2 and MMP9 transcripts, correlating with reduced intratumoral M2 macrophage infiltration and microvessel density. In an immunocompetent mouse model of LGGs, coexpression of CX3CL1 and CX3CR1 promoted a more malignant tumor phenotype characterized by increased microglia/macrophage infiltration and microvessel density, resulting in shorter survival. Conclusions CX3CR1 V249I polymorphism is associated with improved overall and progression-free survival in LGGs. CX3CR1 signaling enhances accumulation of tumor associated microglia/macrophages and angiogenesis during malignant transformation.
Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure
Authors: Julio A. Chirinos, Lei Zhao, Yi Jia, Cecilia Frej, Luigi Adamo, Douglas Mann, Swapnil V. Shewale, John S. Millar, Daniel J. Rader, Benjamin French, Jeff Brandimarto, Kenneth B. Margulies, John S. Parks, Zhaoqing Wang, Dietmar A. Seiffert, James Fang, Nancy Sweitzer, Christina Chistoffersen, Björn Dahlbäck, Bruce D. Car, David A. Gordon, Thomas P. Cappola, Ali Javaheri
Journal: Circulation (2020)

Background: Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models. Methods: In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography–mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure. Results: In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51–0.61]; P &lt;0.0001) and the composite of death/ventricular assist device implantation/heart transplantation (standardized hazard ratio, 0.62 [95% CI, 0.58–0.67]; P &lt;0.0001). This relationship was independent of HDL cholesterol or apo AI levels. Apo M remained associated with death (hazard ratio, 0.78 [95% CI, 0.69–0.88]; P &lt;0.0001) and the composite of death/ventricular assist device/heart transplantation (hazard ratio, 0.85 [95% CI, 0.76–0.94]; P =0.001) in models that adjusted for multiple confounders. This association was present in both heart failure with reduced and preserved ejection fraction and was replicated in the Washington University cohort and a cohort with heart failure with preserved ejection fraction only (TOPCAT). The S1P and apo M content of isolated HDL particles strongly correlated ( R =0.81, P &lt;0.0001). The top canonical pathways associated with apo M were inflammation (negative association), the coagulation system (negative association), and liver X receptor/retinoid X receptor activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.
Immune escape and immunotherapy of acute myeloid leukemia
Authors: Luca Vago, Ivana Gojo
Journal: Journal of Clinical Investigation (2020)

In spite of the recent approval of new promising targeted therapies, the clinical outcome of patients with acute myeloid leukemia (AML) remains suboptimal, prompting the search for additional and synergistic therapeutic rationales. It is increasingly evident that the bone marrow immune environment of AML patients is profoundly altered, contributing to the severity of the disease but also providing several windows of opportunity to prompt or rewire a proficient antitumor immune surveillance. In this Review, we present current evidence on immune defects in AML, discuss the challenges with selective targeting of AML cells, and summarize the clinical results and immunologic insights from studies that are testing the latest immunotherapy approaches to specifically target AML cells (antibodies, cellular therapies) or more broadly reactivate antileukemia immunity (vaccines, checkpoint blockade). Given the complex interactions between AML cells and the many components of their environment, it is reasonable to surmise that the future of immunotherapy in AML lies in the rational combination of complementary immunotherapeutic strategies with chemotherapeutics or other oncogenic pathway inhibitors. Identifying reliable biomarkers of response to improve patient selection and avoid toxicities will be critical in this process.
<i>TP53</i> Mutations Predict Sensitivity to Adjuvant Gemcitabine in Patients with Pancreatic Ductal Adenocarcinoma: Next-Generation Sequencing Results from the CONKO-001 Trial
Authors: Marianne Sinn, Bruno V. Sinn, Denise Treue, Ulrich Keilholz, Frederik Damm, Rosa Schmuck, Philipp Lohneis, Frederick Klauschen, Jana K. Striefler, Marcus Bahra, Hendrik Bläker, Sven Bischoff, Uwe Pelzer, Helmut Oettle, Hanno Riess, Jan Budczies, Carsten Denkert
Journal: Clinical Cancer Research (2020)

We performed next-generation sequencing (NGS) in the CONKO-001 phase III trial to identify clinically relevant prognostic and predictive mutations and conducted a functional validation in The Cancer Genome Atlas (TCGA) sequencing data.Patients of the CONKO-001 trial received curatively intended surgery for pancreatic adenocarcinoma (PDAC) followed by adjuvant chemotherapy with gemcitabine (Gem) or observation only (Obs). Tissue samples of 101 patients were evaluated by NGS of 37 genes. Cox proportional hazard models were applied for survival analysis. In addition, functional genomic analyses were performed in an NGS and RNA-sequencing dataset of 146 pancreatic tumors from TCGA.The most common mutations in the CONKO cohort were KRAS (75%), TP53 (60%), SMAD4 (10%), CDKNA2 (9%), as well as SWI/SNF (12%) complex alterations. In untreated patients, TP53 mutations were a negative prognostic factor for disease-free survival (DFS; HR mut vs. WT 2.434, P = 0.005). With respect to gemcitabine treatment, TP53 mutations were a positive predictive factor for gemcitabine efficacy [TP53mut: HR for DFS Gem vs. Obs, 0.235 (0.130 - 0.423; P < 0.001); TP53wt: HR for DFS Gem vs. Obs, 0.794 (0.417 - 1.513; P = 0.483)] with a significant test for interaction (P = 0.003). In the TCGA dataset, TP53 mutations were associated with shortened DFS.In CONKO-001, the benefit from adjuvant gemcitabine was confined to the TP53mut patient group. This potentially clinical relevant observation needs to be confirmed in independent prospective studies. The sensitivity of TP53mut PDAC to gemcitabine in CONKO-001 provides a lead for further mechanistic investigations.
Managing clinical trials for covid-19: the importance of ethics committees
Authors: Qiankun Luo, Tao Qin
Journal: BMJ (2020)

In the global outbreak of covid-19, people are self-isolating at home, cities are blocked, and schools, museums, and stores are closed.1 Medical students and retired doctors are convened to deal with covid-19,23 but there are still no effective drugs or vaccines.

The World Health Organization’s 2016 guidance on ethical issues in infectious diseases …
Smartphone Application to Reinforce Education Increases High-Quality Preparation for Colorectal Cancer Screening Colonoscopies in a Randomized Trial
Authors: Benjamin Walter, Rena Frank, Leopold Ludwig, Nektarios Dikopoulos, Martina Mayr, Bruno Neu, Benjamin Mayer, Alexander Hann, Benjamin Meier, Karel Caca, Thomas Seufferlein, Alexander Meining
Journal: Clinical Gastroenterology and Hepatology (2020)
Abstract #1262: Dual pulse labeling of S-phase population using click chemistry to measure changes in cell proliferation
Authors: Jolene Bradford, Scott Clarke
Journal: Cancer Research (2009)

The measurement of cellular proliferation is fundamental to the assessment of cell health, genotoxicity, and in the evaluation of drug efficacy. Changes in cell proliferation can give insights into mechanisms of cell growth, development, and cell cycle kinetics. A standard method for monitoring time dependant changes of cell proliferation is through the use of multiple pulse labeling of DNA based on the incorporation of nucleoside analogs. Typically, halogenated derivatives of deoxyuridine are used and detected with antibodies which have selective affinity for the specific halogen modified base. Although there are several halogen modified bases to use, antibody selectivity must be carefully evaluated to achieve correct labeling. By augmenting the antibody approach with a non-antibody method of detection using a click chemistry modified deoxyuridine analog, another specific label can be added to the tools used for examining changes in proliferation rates. Here, examples are shown combining click chemistry with traditional BrdU antibody labeling using flow cytometry in Jurkat T-cell leukemia, TF-1 erythroleukemia, and THP-1 monocytic leukemia cells. Click chemistry labeling uses 5-ethynyl 2\#8242;-deoxyuridine (EdU) incorporation and detection with copper catalyzed dye-azide to form a stable covalent triazole ring. Use with selected bromodeoxyuridine (BrdU) antibody results in unambiguous double labeling without cross-reactivity. An unanticipated benefit is observed when using these two nucleoside analogs in combination. Simultaneous addition of BrdU and EdU is shown to only incorporate BrdU into the newly synthesized DNA, while a first pulse of EdU followed by sequential addition of BrdU without prior removal of the EdU results in four population of cells: first, those labeled only with EdU during the first pulse are cells which have exited S-phase prior to BrdU addition; second, those labeled with both BrdU and EdU are cells which have remained in S-phase during the duration of the two pulses; third, those labeled only with BrdU are cells which entered S-phase after BrdU addition; and fourth, those cells which have not labeled with either EdU or BrdU indicating these cells were not synthesizing DNA during either pulse. Examples of both long and short pulses of double labeling are given and the complex labeling patterns are interpreted through the use of appropriate population gating. Rapid changes in proliferation rate induced by drugs or treatment can be monitored using this no wash pulse labeling method. This method has broad applications and demonstrates the value of click chemistry combined with other antibody based methods for measuring changes in cell proliferation.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1262.
The Health of Undocumented Latinx Immigrants: What We Know and Future Directions
Authors: India J. Ornelas, Thespina J. Yamanis, Raymond A. Ruiz
Journal: Annual Review of Public Health (2020)

Undocumented Latinx immigrants experience unique factors prior to migration, during migration, and after migration that shape their health. Our review summarizes the limited but growing literature highlighting how exposure to trauma, immigration enforcement, changes to social networks, and discrimination negatively affect the mental and physical health of undocumented Latinx immigrants. We also discuss how policies and social ties can promote their health. We focus on areas of particular concern, including health care, mental health, and HIV. Future research should use interdisciplinary approaches and intersectional frameworks to understand and address health inequities. Conducting research with undocumented Latinx immigrant communities requires community engagement, assurance of confidentiality, and creative recruitment and retention strategies. Recommendations for public health practice include investing in community health centers and organizations to ensure access to health and social services; presenting results with sufficient contextualization to interpret their generalizability; and advocating for federal-, state-, and local-level policy changes that reduce the negative health consequences associated with being undocumented.
Crizotinib in <i>ROS1</i> and <i>MET</i> Deregulated NSCLC—Letter
Authors: Marcel Wiesweg, Martin Schuler, Hans-Ulrich Schildhaus
Journal: Clinical Cancer Research (2020)

In the METROS trial, Landi and colleagues evaluated the efficacy of crizotinib in advanced non–small cell lung cancer (NSCLC) harboring ROS1 rearrangements or MET dysregulation ([1][1]). A total of 505 patients were screened and 10 patients entered the trial with cancers harboring MET exon 14
A new way to measure the extent of patients’ hidradenitis suppurativa
Authors: J.S. Kirby, M. Butt, T. King
Journal: British Journal of Dermatology (2020)

Hidradenitis suppurativa (HS) is a skin disease that causes large boils and pustules to form. It usually affects skin folds of the body, such as the armpits and groin, and can cause significant inflammation, pain, itch, scarring, and disfigurement. About 0.1‐1% of people have HS in the U.S.A. and Europe. HS is more common in females. When studies measure HS on the skin, they often need a clinician (e.g. a doctor) to count the number of each type of HS lesion (affected patch of skin). This can be difficult and, because of this, one clinician may count a different number to another. If clinicians don't agree when they should, then this isn't an accurate measurement tool. This study was done by researchers in the U.S.A. to find how well clinicians could measure HS using a different approach. The authors interviewed clinicians who treat HS, to find out what skin changes they noticed to decide if HS was better or worse. From this, the researchers developed a new HS measure based on the size of the area with HS and the amount of redness, swelling, and broken skin. Next, the authors had 10 clinicians examine 23 people with HS and they completed the new measure and the existing measures. The new measure had more agreement among the clinicians than the existing methods of measuring HS. Also, a clinician was more likely to be consistent with himself/herself when measuring the same person with HS. This study showed that counting HS lesions is hard and a different approach might help improve HS measurement. This is a summary of the study: Severity and Area Score for Hidradenitis (SASH): a novel outcome measurement for hidradenitis suppurativa
TH1/TH17 cell recognition of desmoglein 3 and bullous pemphigoid antigen 180 in patients with lichen planus
Authors: Thomas Schmidt, Farzan Solimani, Robert Pollmann, Ronja Stein, Ansgar Schmidt, Inna Stulberg, Katja Kühn, Rüdiger Eming, Verena Eubel, Peter Kind, Nicole Arweiler, Cassian Sitaru, Michael Hertl
Journal: Journal of Allergy and Clinical Immunology (2018)