tbuckley/cabot-search huggingface dataset:
Atopic Dermatitis Biomarker Analysis Points to Elevation of TSLP and IL-33 Signaling and Suggests a Role for Type 2 Innate Lymphoid Cells
Authors: Janet Griffiths, Sriram Sridhar, Monica Gavala, Tuyet-Hang Pham, Yoichiro Ohne, Melissa De Los Reyes, Fernanda Pilataxi, Ioannis Kagiampakis, Jane Parnes, STEVEN KOMJATHY, Caroline Bronchick, Donald Leung, Elena Goleva
Journal: Journal of Allergy and Clinical Immunology (2020)
Clinical criteria predicting an overall survival benefit to platinum rechallenge (PR) in metastatic urothelial cancer (mUC).
Authors: Elodie Mussat, Anne Jouinot, Carolina Saldana, Charlotte Joly, Yves Allory, Maya Nourieh, Dimitri Vordos, Laurent Salomon, Alexandre de la TAILLE, Christophe Tournigand, Benoit Rousseau
Journal: Journal of Clinical Oncology (2020)

490 Background: In mUC, 2nd line treatments after platinum-based regimen have limited efficacy, such as vinca-alkaloid, taxan or immune checkpoint inhibitors. PR is proposed by ESMO guidelines if progression occurs &gt;12 months after initial exposure with low level of evidence. Our objectives were to assess if PR was associated with better outcomes compared to other regimens and to identify parameters predicting its benefit in mUC. Methods: From a large monocentric cohort of mUC pts pretreated by 1st line platinum-based regimen, we retrospectively included pts who received a second line (PR, other cytotoxic drugs, immunotherapy). The primary end point was overall survival (OS). Survival analyses were performed using Cox models, weighted on a propension score to ensure groups comparability. Results: Among 155 consecutive pts firstly treated between 2006 and 2017, 55 pts were then treated by PR and 45 pts treated by other chemotherapy (n=37), immunotherapy (n=6) or targeted therapy (n=2). As PR is used in pts who benefited from platinum therapy, we restricted the analyses to pts who did not progressed during 1st line, resulting in 43 PR pts and 25 pts treated by other regimens. Univariate analyses identified main factors impairing OS at 2nd line initiation: time from prior chemotherapy &lt;6 months, non-complete response to 1st line treatment and 2nd line treatment without platinum. These factors were subsequently used in a propension score to weigh survival analyses. PR was significantly associated with better OS than other regimens (HR=0.57, CI95% [0.37-0 .88], p=0.011). Median OS, median PFS and ORR were 16.5 vs 9.0 months (P=0.012), 5.8 vs 2.4 months (P=0.012) and 45 vs 15% (P=0.048) for PR and other regimens respectively. The most common grade 3 to 4 adverse events were hematologic toxicities: 54% for PR vs 22% for other treatments. ROC curve analysis of the best delay for PR since the end of 1st line was 5.7 months (sensitivity 60%, specificity 84%). Conclusions: PR is feasible and associated with significant OS improvement in second line treatment of mUC in pts that benefited initially from 1st line platinum and with Platinum-free interval &gt;6 months. These results should be confirmed prospectively.
Analysis of Kansas Water Well Policies and Proposal of Nonpublic Household Water Well Recommendations
Authors: Elizabeth Ablah, Mary Winston Marrow, Jack Brown, Allison Honn
Journal: Environmental Health Perspectives (2020)

Background: Many nonpublic water well users unknowingly consume contaminated groundwater containing unsafe levels of pollutants. This has important implications for more than 13 million households in the United States that rely upon nonpublic water wells for drinking, cooking, and other household uses. Although public water quality is regulated through the Safe Drinking Water Act, there are no drinking water standards for nonpublic water well quality in Kansas, nor is there an adequate public health infrastructure in place to prevent or address potential exposures to contamination. Objectives: This project was conducted to identify promising action steps that would protect Kansans relying on nonpublic water wells for drinking, cooking, and other household purposes. Methods: The project team consisted of public health, environmental health, and legal professionals with experience working on groundwater quality issues impacting nonpublic water wells in Kansas. From 2015 through 2018, the team established and convened an advisory group; reviewed relevant state statutes and regulations, all Kansas county environmental codes, and a representative sample of 23 city water well codes; conducted an extensive review of academic literature to identify best practices; conducted dozens of key informant interviews; proposed recommendations; engaged dozens of stakeholders through a survey of these proposed recommendations; and conducted interactive webinars to identify which organizations need to lead each of the recommendations. Discussion: The project team developed 18 recommendations. The recommendations are organized by survey respondents’ perceptions of potential public health impact. There are very few standard practices in Kansas that ensure safe water for nonpublic household water wells. Although not all of the 18 recommendations may be applicable to other communities and states, many likely would be useful for governmental agencies, academic institutions, nonprofit organizations, and others to consider. These recommendations offer more protections for nonpublic household water well users than any resource we have found. https://doi.org/10.1289/EHP5507
iNOS Regulates the Therapeutic Response of Pancreatic Cancer Cells to Radiotherapy
Authors: Patricia M.R. Pereira, Kimberly J. Edwards, Komal Mandleywala, Lukas M. Carter, Freddy E. Escorcia, Luis Felipe Campesato, Mike Cornejo, Lolkje Abma, Abu-Akeel Mohsen, Christine A. Iacobuzio-Donahue, Taha Merghoub, Jason S. Lewis
Journal: Cancer Research (2020)

Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to radiotherapy, chemotherapy, or a combination of these modalities, and surgery remains the only curative intervention for localized disease. Although cancer-associated fibroblasts (CAF) are abundant in PDAC tumors, the effects of radiotherapy on CAFs and the response of PDAC cells to radiotherapy are unknown. Using patient samples and orthotopic PDAC biological models, we showed that radiotherapy increased inducible nitric oxide synthase (iNOS) in the tumor tissues. Mechanistic in vitro studies showed that, although undetectable in radiotherapy-activated tumor cells, iNOS expression and nitric oxide (NO) secretion were significantly increased in CAFs secretome following radiotherapy. Culture of PDAC cells with conditioned media from radiotherapy-activated CAFs increased iNOS/NO signaling in tumor cells through NF-κB, which, in turn, elevated the release of inflammatory cytokines by the tumor cells. Increased NO after radiotherapy in PDAC contributed to an acidic microenvironment that was detectable using the radiolabeled pH (low) insertion peptide (pHLIP). In murine orthotopic PDAC models, pancreatic tumor growth was delayed when iNOS inhibition was combined with radiotherapy. These data show the important role that iNOS/NO signaling plays in the effectiveness of radiotherapy to treat PDAC tumors. SIGNIFICANCE: A radiolabeled pH-targeted peptide can be used as a PET imaging tool to assess therapy response within PDAC and blocking iNOS/NO signaling may improve radiotherapy outcomes.
Persistent CD8 T cell restricted aberrant IL-7 signaling in an atypical (T-B+NK+) SCID patient with compound heterozygous JAK3 mutations
Authors: Aaruni Khanolkar, Jeffrey Wilks, Guorong Liu, Bridget Simpson, Edward Caparelli, Dawn Kirschmann, Jenna Bergerson, Ramsay Fuleihan
Journal: Journal of Allergy and Clinical Immunology (2020)
Identification of genomic aberrations associated with overall survival in metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Adam Kessel, Summer Tran, Zachary Rivers, Andrew W Hahn, Roberto Nussenzveig, Nityam Rathi, Benjamin Louis Maughan, Deepika Sirohi, David D. Stenehjem, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2020)

745 Background: Tumor comprehensive genomic profiling (CGP) in addition to risk stratification by IMDC criteria may aid in improving risk stratification. The objective of this study was to assess the prognostic impact of somatic mutations in addition to IMDC risk criteria. Methods: All patients with mccRCC treated with first line with VEGFR-TKI with CGP data available through a CLIA certified lab were included. Kaplan-Meier methodology and Cox proportional hazard ratios were used to test the association of overall survival with genomic alterations present in at least 7% of the population in this dataset. Genomic data were correlated with outcome by univariate analysis and subsequent multivariate testing, integrating genomic data with IMDC risk criteria. Results: A total of 58 patients met eligibly. The presence of any mutation in VHL, PBRM1, and MLL2 were prognostic in terms of overall survival (Table). The mutation status for these three prognostic genes was added to the IMDC risk model to test for the prognostic correlation. The mutations status of these 3 genes significantly correlated with overall survival (VHL: 0.32 [95% CI 0.11-0.95], PBRM1: 0.36 [0.14-0.96], and MLL2: 7.60 [1.35-24.6]) independent of the IMDC risk criteria. Conclusions: In mccRCC, VHL, PBRM1, and MLL2 mutations each predict overall survival independent of IMDC criteria. Further studies are warranted to assess alterations with low prevalence in this data set. Upon external validation, these data provide the rationale for integration of mutation status of these three genes in to the IMDC risk criteria.[Table: see text]
Increasing Capacity and Improving Quality in Substance Use Disorder Training
Authors: Gregg C. Lund
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
In vitro proliferation assays do not fully predict the MCF-7 tumor growth response to lignan lariciresinol in vivo
Authors: Maarit Airio, Anni Wärri, Sari Mäkelä, Niina M. Saarinen
Journal: Cancer Research (2005)

5183  Lariciresinol (LAR) is a lignan found in edible plants. When ingested, LAR is converted to mammalian lignans e.g. enterodiol (END) and enterolactone (ENL) by intestinal microbiota. ENL is suggested to be biologically active in hormonally dependent diseases such as breast cancer. In epidemiological studies ENL is linked with reduced breast cancer risk in premenopausal women. In experimental mammary cancer model we have shown that ENL inhibits the tumor growth in the presence of ovarian hormones. Objective: In this study we investigated the effects of LAR and its mammalian metabolites on MCF-7 proliferation in vitro and in vivo in the presence of estrogen (“premenopausal” estrogen milieu). Experimental: In vitro the effects on cell proliferation of 1-10μM LAR and its mammalian metabolites in the presence and absence of 1 nM estradiol (E2) were measured by using the MTT/WST assay. In vivo effects of dietary LAR (20 and 100 ppm) were studied in ovariectomized E2 pelleted (1.7 mg, 60-day release) athymic Balb/c nu/nu female mice bearing MCF-7 tumors in mammary fat pads (4 sites per mouse). When tumors reached an area of approx. 20 mm2, the mice were implanted with a new E2 pellet and divided into 3 treatment groups: 1) Control group fed AIN-93G diet (BD), 2) LAR 20 group fed BD supplemented with 20 ppm of LAR, and 3) LAR 100 group fed BD supplemented with 100 ppm of LAR. The hormone responsiveness of the established tumors was verified in a group of mice fed BD by replacing the E2 pellet with a placebo pellet (negative control group). Results: In vitro, LAR and its metabolites secoisolariciresinol and ENL increased the MCF-7 cell proliferation in the presence and absence of E2. The MCF-7 cell proliferation stimulating effect of the lignans was antagonized by antiestrogens such as tamoxifen and ICI 182.780 suggesting estrogen receptor mediated mechanism(s). However, in MCF-7 tumor bearing mice dietary LAR (20 or 100 ppm) did not increase the growth of the tumors. Instead a trend for a decreased tumor growth (volume and weight) was measured. Accordingly, the uterine weight of the LAR fed mice was lower compared to mice having BD suggesting antiestrogenic effect of LAR diet in vivo. No significant differences in body weights, food consumption or other organ weights were observed between dietary treatment groups. Conclusions: These results indicate that lignans may have distinct effects on human breast cancer cell growth in vitro and in vivo. LAR and its metabolites stimulated the proliferation of MCF-7 cells in vitro while in athymic mice a trend for a decreased MCF-7 tumor growth was observed. Thus in vivo other tumor growth modulating mechanisms than estrogenicity of LAR and/or its mammalian metabolites may be dominating.
Does detection of KIT D816V mutation in peripheral blood benefit the recognition of clonal mast cell disease in patients with anaphylaxis?
Authors: Leander De Puysseleyr, Didier Ebo, Katrien Vermeulen, Jessy Elst, Athina Van Gasse, Michel Van Houdt, Christel Mertens, Margaretha Faber, Margo Hagendorens, Luc De Clerck, Vito Sabato
Journal: Journal of Allergy and Clinical Immunology (2020)
Association of early life circulating TSLP differs by race among children with atopic dermatitis in the Mechanisms of Progression from Atopic Dermatitis to Asthma in Children (MPAACH) cohort
Authors: Liza Murrison, Xiaomeng Ren, Lisa Martin, Hua He, John Kroner, Asel Baatyrbek Kyzy, Angelo Bucci, Jocelyn Biagini Myers, Gurjit Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2020)
In coma after cardiac arrest with nonshockable rhythm, therapeutic hypothermia improved 90-d neurologic outcome
Authors: Benton R. Hunter, Jonathan M. Kirschner
Journal: Annals of Internal Medicine (2020)

ACP Journal Club18 February 2020In coma after cardiac arrest with nonshockable rhythm, therapeutic hypothermia improved 90-d neurologic outcomeBenton R. Hunter, MD, Jonathan M. Kirschner, MDBenton R. Hunter, MDIndiana University School of Medicine, Indianapolis, Indiana, USA (B.R.H., J.M.K.)Search for more papers by this author, Jonathan M. Kirschner, MDIndiana University School of Medicine, Indianapolis, Indiana, USA (B.R.H., J.M.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202002180-017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLascarrou JB, Merdji H, Le Gouge A, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med. 2019;381:2327-37. https://pubmed.ncbi.nlm.nih.gov/31577396Clinical Impact RatingsEmergency Med: Hospitalists: Cardiology: Critical Care: References1 Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369:2197-206. [PMID: 24237006] Google Scholar2 Donnino MW, Andersen LW, Berg KM, et al. Temperature management after cardiac arrest. Circulation. 2015;132:2448-56. [PMID: 26434495] Google Scholar Author, Article, and Disclosure InformationAffiliations: Indiana University School of Medicine, Indianapolis, Indiana, USA (B.R.H., J.M.K.)Disclosures: The commentators have disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-3039.This article was published at Annals.org on 4 February 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: JC17KeywordsCardiopulmonary resuscitationComaDisabilitiesHeartHypothermiaIntensive care unitsNumber needed to treatPatientsResuscitationTemperature ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Options for Addressing the Dilemma of Managing Dense Breasts
Authors: Lisa A. Newman, Cheng-Har Yip
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials
Authors: David S Hong, Steven G DuBois, Shivaani Kummar, Anna F Farago, Catherine M Albert, Kristoffer S Rohrberg, Cornelis M van Tilburg, Ramamoorthy Nagasubramanian, Jordan D Berlin, Noah Federman, Leo Mascarenhas, Birgit Geoerger, Afshin Dowlati, Alberto S Pappo, Stefan Bielack, François Doz, Ray McDermott, Jyoti D Patel, Russell J Schilder, Makoto Tahara, Stefan M Pfister, Olaf Witt, Marc Ladanyi, Erin R Rudzinski, Shivani Nanda, Barrett H Childs, Theodore W Laetsch, David M Hyman, Alexander Drilon
Journal: The Lancet Oncology (2020)
A Qualitative Exploration of Food Allergy Management among a Medicaid-Insured Population
Authors: Alexandria Bozen, Justin Zaslavsky, Dara Cohn, Neha Agnihotri, Stephannie Davies, Waheeda Samady, Lisa Lombard, Kari Nadeau, Ruchi Gupta, Mary Tobin
Journal: Journal of Allergy and Clinical Immunology (2020)
Simultaneous Endocardial and Epicardial Delineation of 3D Reentrant Ventricular Tachycardia
Authors: Roderick Tung, Michael Raiman, Hongtao Liao, Xianzhang Zhan, Fa Po Chung, Rich Nagel, Hongde Hu, Jiang Jian, Dalise Y. Shatz, Stephanie A. Besser, Zaid A. Aziz, Andrew D. Beaser, Gaurav A. Upadhyay, Hemal M. Nayak, Takuro Nishimura, Yumei Xue, Shulin Wu
Journal: Journal of the American College of Cardiology (2020)
An unexpected finding on a chest radiograph
Authors: Chris J Kapelios, Maria Bonou, John Barbetseas, Konstantinos Makrilakis
Journal: BMJ (2020)

A 92 year old man presented with recent onset of productive cough and fever up to 38.2°C.

He had a history of atrial fibrillation and symptomatic tachycardia-bradycardia syndrome, for which he had undergone percutaneous implantation of a single chamber cardiac pacemaker six months earlier.

At presentation he was afebrile and had a systemic arterial pressure of 130/75 mm Hg, regular heart rate (60 beats/min) and rhythm, and normal lung sounds. Jugular venous pressure was normal, he had no peripheral oedema, and his extremities were warm. There were no signs or symptoms of pacemaker dysfunction (dizziness, syncope, palpitations, dyspnoea, or thoracic or abdominal muscle twitching).

Table 1 shows his laboratory results.

View this table:

Table 1 
Relevant blood results



Electrocardiogram (ECG) …
Overcoming sociodemographic factors in the care of testicular cancer patients at a safety net hospital.
Authors: Nathan Chertack, Rashed Ghandour, Nirmish Singla, Yuval N. Freifeld, Ryan C. Hutchinson, Kevin Dale Courtney, Joseph Allen Moore, Ahmet Aydin, Vitaly Margulis, Yair Lotan, Solomon L. Woldu, Aditya Bagrodia
Journal: Journal of Clinical Oncology (2020)

398 Background: Optimal treatment of GCT in underserved populations is subject to barriers that are associated with worse clinical outcomes. We determine whether standardized treatment of GCT can overcome such sociodemographic factors limiting patient care. Methods: The records of all patients undergoing primary treatment for GCT were analyzed from both a public safety net hospital and an academic tertiary care center in the same metropolitan area. Patients at both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center and clinicopathologic features, practice patterns, and outcomes were analyzed. Results: 106 and 95 patients underwent initial treatment for GCT between 2006 and 2018 in the safety net hospital and tertiary care center, respectively. Safety net patients were younger (29 vs 33 years, p=0.005), more likely to be Hispanic (79% vs 11%), more likely to be uninsured (80% vs 12%, p&lt;0.001), and present via the emergency department (76% vs 8%, p&lt;0.001). They were more likely to have metastatic (stage II/III) disease (42% vs 26%, p=0.025). On multivariable analysis, presence of lymphovascular invasion (OR=0.30, p=0.008) and embryonal carcinoma component (OR=0.36, p=0.02) were associated with surveillance vs adjuvant treatment for Stage I patients; hospital setting was not (OR=0.67, p=0.55). For patients with Stage II/III NSGCT, there was no difference in performance of PC-RPLND at the safety net hospital vs tertiary care center (52% vs 64%, p=0.53). No difference in recurrence rates between cohorts (5% vs 6%, p=0.76) was observed. Conclusions: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCT; this may be overcome with integrated, standardized management of testicular cancer.