tbuckley/cabot-search huggingface dataset:
Shamanism and efficacious exceptionalism
Authors: Aaron D. Blackwell, Benjamin Grant Purzycki
Journal: Behavioral and Brain Sciences (2018)

Abstract Shamans can have efficacy at healing through botanical remedies and in observational and advisory functions through cognitive strengths, while shamanic acts of strangeness are likely honest signals of these qualities. Given this potential for shamanic practices to have true efficacy and the capacity for honest signaling, we expect efficacy will influence the spread, persistence, and loss of shamanic practices.
Stratification by interferon-γ release assay level predicts risk of incident TB
Authors: Brita Askeland Winje, Richard White, Heidi Syre, Dag Harald Skutlaberg, Fredrik Oftung, Anne Torunn Mengshoel, Hege Salvesen Blix, Arne Broch Brantsæter, Ellen Kristine Holter, Nina Handal, Gunnar Skov Simonsen, Jan Egil Afset, Anne Marte Bakken Kran
Journal: Thorax (2018)

Introduction Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. Methods In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009–30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. Results The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to &lt;1.00, 1.00 to &lt;4.00 and &gt;4.00 IU/mL, respectively, compared with negative tests (&lt;0.35 IU/mL). Conclusions Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.
Genomics of Parallel Ecological Speciation in Lake Victoria Cichlids
Authors: Joana Isabel Meier, David Alexander Marques, Catherine Elise Wagner, Laurent Excoffier, Ole Seehausen
Journal: Molecular Biology and Evolution (2018)

The genetic basis of parallel evolution of similar species is of great interest in evolutionary biology. In the adaptive radiation of Lake Victoria cichlid fishes, sister species with either blue or red-back male nuptial coloration have evolved repeatedly, often associated with shallower and deeper water, respectively. One such case is blue and red-backed Pundamilia species, for which we recently showed that a young species pair may have evolved through "hybrid parallel speciation". Coalescent simulations suggested that the older species P. pundamilia (blue) and P. nyererei (red-back) admixed in the Mwanza Gulf and that new "nyererei-like" and "pundamilia-like" species evolved from the admixed population. Here, we use genome scans to study the genomic architecture of differentiation, and assess the influence of hybridization on the evolution of the younger species pair. For each of the two species pairs, we find over 300 genomic regions, widespread across the genome, which are highly differentiated. A subset of the most strongly differentiated regions of the older pair are also differentiated in the younger pair. These shared differentiated regions often show parallel allele frequency differences, consistent with the hypothesis that admixture-derived alleles were targeted by divergent selection in the hybrid population. However, two-thirds of the genomic regions that are highly differentiated between the younger species are not highly differentiated between the older species, suggesting independent evolutionary responses to selection pressures. Our analyses reveal how divergent selection on admixture-derived genetic variation can facilitate new speciation events.
Abstract 17697: Impacts of Postdischarge Physical Activity and its Change During the First 3 Months After Discharge on Long-term Prognosis in Older Japanese Patients With Heart Failure
Authors: Naoki Fujimoto, So Miyahara, Kaoru Dohi, Emiyo Sugiura, Keishi Moriwaki, Taku Omori, Naoto Kumagai, Norikazu Yamada, Masaaki Ito
Journal: Circulation (2016)

Introduction: Impacts of postdischarge physical activity (PA) and its change in a short period of time on rehospitalization remain unclear in older heart failure (HF). Methods: Forty-one patients (...
Continuous Glucose Monitors for Insulin Dosing—Reply
Authors: Alan R. Shapiro
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Targeting Tumor Vasculature with TNF Leads Effector T Cells to the Tumor and Enhances Therapeutic Efficacy of Immune Checkpoint Blockers in Combination with Adoptive Cell Therapy
Authors: Angela Rita Elia, Matteo Grioni, Veronica Basso, Flavio Curnis, Massimo Freschi, Angelo Corti, Anna Mondino, Matteo Bellone
Journal: Clinical Cancer Research (2018)

Purpose: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTL). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the tumor vasculature, and improving intratumor infiltration by activated CTLs, could sensitize tumors to ICB with antibodies specific for the PD-1 and CTLA-4 receptors.Experimental Design: Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with autochthonous prostate cancer and C57BL/6 mice with orthotopic B16 melanoma were treated with NGR-TNF, adoptive T-cell therapy (ACT), and ICB, and monitored for immune surveillance and disease progression.Results: The combination of ACT, NGR-TNF, and ICB was the most effective in delaying disease progression, and in improving overall survival of mice bearing ICB-resistant prostate cancer or melanoma. Mechanistically, the therapeutic effects were associated with potent tumor infiltration, especially by endogenous but also by adoptively transferred PD-1+, granzyme B+, and interferon-γ+ CTLs. The therapeutic effects were also associated with favorable T-effector/regulatory T cell ratios.Conclusions: Targeting the tumor vasculature with low-dose TNF in association with ACT may represent a novel strategy for enhancing T-cell infiltration in tumors and overcoming resistance to immune checkpoint blockers. Clin Cancer Res; 24(9); 2171-81. ©2018 AACR.
pH protective Y1 receptor ligand functionalized antiphagocytosis BPLP-WPU micelles for enhanced tumor imaging and therapy with prolonged survival time
Authors: Zhenqi Jiang, Yuchen Tian, Dingying Shan, Yinjie Wang, Ethan Gerhard, Jianbi Xia, Rong Huang, Yan He, Aiguo Li, Jianchao Tang, Huimin Ruan, Yong Li, Juan Li, Jian Yang, Aiguo Wu
Journal: Biomaterials (2018)
Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study
Authors: Lorenza Rimassa, Eric Assenat, Markus Peck-Radosavljevic, Marc Pracht, Vittorina Zagonel, Philippe Mathurin, Elena Rota Caremoli, Camillo Porta, Bruno Daniele, Luigi Bolondi, Vincenzo Mazzaferro, William Harris, Nevena Damjanov, Davide Pastorelli, María Reig, Jennifer Knox, Francesca Negri, Jörg Trojan, Carlos López López, Nicola Personeni, Thomas Decaens, Marie Dupuy, Wolfgang Sieghart, Giovanni Abbadessa, Brian Schwartz, Maria Lamar, Terri Goldberg, Dale Shuster, Armando Santoro, Jordi Bruix
Journal: The Lancet Oncology (2018)
<i>Notes from the Field</i>: Pharmacy Needs After a Natural Disaster — Puerto Rico, September–October 2017
Authors: Amy M. Lavery, Anita Patel, Tegan K. Boehmer, Leslie Lee, Tina Bhavsar, Jacqueline Thomas, Lori Hall, Suzanne Beavers, Maria Murray, Satish K. Pillai
Journal: MMWR Morbidity and Mortality Weekly Report (2018)
Plasma ICAM-1 (pICAM-1) and plasma IL-8 (pIL-8) level as biomarker of metastatic colorectal cancer patients (mCRC) treated with mFOLFOX6/XELOX plus bevacizumab (BV) (WJOG7612GTR).
Authors: Yoshiyuki Yamamoto, Wataru Okamoto, Akitaka Makiyama, Kohei Shitara, Tadamichi Denda, Takashi Ogura, Yasuyuki Nakano, Tomohiro Nishina, Masato Komoda, Hiroki Hara, Yukinori Ozaki, HIsato Kawakami, Narikazu Boku, Ichinosuke Hyodo, Kentaro Yamazaki, Shuichi Hironaka, Kazuko Sakai, Takeharu Yamanaka, Kei Muro, Kazuto Nishio
Journal: Journal of Clinical Oncology (2018)

670 Background: Bevacizumab (BV)-containing chemotherapy has been established as the standard first-line treatment for metastatic colorectal cancer (mCRC). However, no biomarkers have been established to predict the clinical benefit of BV for patients (pts) with mCRC. Methods: Blood samples were collected in EDTA before the first-line treatment with BV+mFOLFOX6 or +XELOX for mCRC. Plasma samples were analyzed at Roche Diagnostics Ltd. (Penzberg, Germany) using IMPACT-2 (Roche proprietary multiplex enzyme-linked immunosorbent assay platform). Median values of pICAM-1 and pIL-8 were used as cut-off points to categorize pts into the low and high groups. Progression free survival (PFS) and overall survival (OS) were compared between two groups, using Cox proportional hazards model. Results: Among 102 pts enrolled between January 2014 and April 2015, 100 (53 BV+mFOLFOX6 and 47 BV+XELOX) were eligible. Median PFS was 11.4 months [95% CI, 9.5-13.0]. Response rate was 64.6 % [53.3-74.9]. pICAM-1 and pIL-8 were measured in 99 pts and the median values were 190.0 ng/ml [range, 58.0- 1080.1] and 311.5 pg/ml [range, 83.2-4541.4], respectively. The hazard ratios of PFS and OS between the high and low pICAM-1 groups were 2.08 [95%CI, 1.28-3.40, p = 0.003] and 2.04 [0.92-4.50, p = 0.079], respectively. The hazard ratios of PFS and OS between the high and low pIL-8 groups were 1.63 [95%CI, 1.00-2.65, p = 0.048] and 3.42[1.57-7.44, p = 0.002], respectively. Conclusions: High pICAM-1 and pIL-8 were associated with short PFS and OS of mCRC pts treated with BV-containing chemotherapy, suggesting that pICAM-1 and pIL-8 could be predictive markers for prognosis of mCRC treated with BV. Clinical trial information: UMIN000012442.
Effect of matched therapy in metastatic colorectal cancer on progression free survival in the phase I setting.
Authors: Michael Lam, Allan Andresson Lima Pereira, Jonathan M. Loree, Shailesh M Advani, Michael J. Overman, Ann Bailey, Amber Johnson, Vijaykumar Holla, Nora Sylvia Sanchez, Yekaterina Khotskaya, Funda Meric-Bernstam, Scott Kopetz, Shubham Pant
Journal: Journal of Clinical Oncology (2018)

619 Background: The benefits of matching targeted treatments to aberrations identified by molecular profiling (MP) is unclear. Outcomes in phase 1 settings have been traditionally reported across tumor histologies. We report outcomes based on a metastatic colorectal cancer (mCRC) population. Methods: Patients (pts) with mCRC receiving at least one dose of treatment on a phase 1 study were annotated for variants detected by MP. A precision oncology decision support (PODS) team determined variant function and actionability. A matched therapy (MT) was defined as allocation to a novel agent that targeted the aberration or predicted pathway deemed actionable by PODS. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to estimate hazard ratios (HR). Results: A total of 370 patients enrolled onto 467 phase 1 trials were identified from January 2012 to April 2017. 106 enrolments were assigned to MT. Pts with microsatellite instability-high (MSI-H), BRAF V600E , PIK3CA mutation were more likely to be assigned a MT, while left-sided tumors and RAS mutant patients were less likely to be treated with a MT. Molecularly-targeted regimens (MTR) were utilized more frequently in MT while immune-targeting MTR was more common in non-MT. BRAF V600E mutations and HER2 amplification/overexpression made up 44.3% of MT. There was a significant difference in PFS between the MT vs non-MT group (HR 0.65, 95% CI 0.51-0.83, p = 0.016) in univariate analysis. The 6-month PFS probability was 31% (95% CI; 23-41%) versus 13% (95% CI; 10-17%) respectively. Other significant factors in univariate analysis associated with longer PFS were MSI-H, BRAF V600E and use of a regimen containing cytotoxic chemotherapy while RAS mutations were associated with shorter PFS. In multivariate analysis, after correcting for mutation status, allocation to a MT was associated with improved PFS (HR = 0.72, 95% CI 0.50-0.99, p = 0.043). Conclusions: Matching clinical trial enrollment to MP based on dedicated decision support is associated with improved outcomes in mCRC patients. The MT strategy is still hampered by a limited number of actionable variants, and is driven by a small number of active MTs.
By using a core outcome set we measure what matters to patients
Authors: C.A.C. Prinsen, P.I. Spuls, C.B. Terwee
Journal: British Journal of Dermatology (2018)

Linked Articles:Horbach. Br J Dermatol 2018; 178:473–481. Thorlacius et al. Br J Dermatol 2018; 178:715–721.
Prospective study in bullous pemphigoid: association of high serum anti-BP180 IgG levels with increased mortality and reduced Karnofsky score
Authors: M.M. Holtsche, S. Goletz, N. van Beek, D. Zillikens, S. Benoit, K. Harman, S. Walton, J. English, M. Sticherling, A. Chapman, N.J. Levell, R. Groves, H.C. Williams, I.R. König, E. Schmidt
Journal: British Journal of Dermatology (2018)

Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. The multicentre prospective BLISTER (Bullous Pemphigoid Steroids and Tetracyclines) trial randomized 253 patients with BP to compare the benefits and harms between initial treatment with doxycycline or prednisolone.To analyse distinct autoantibody profiles for the prediction of the disease course in a well-characterized cohort of BP sera.One hundred and forty-three patients of the BLISTER trial consented to participate in this serological study. Sera taken at baseline were analysed by (i) indirect immunofluorescence, (ii) anti-BP180 NC16A (16th noncollagenous domain) and anti-BP230 enzyme-linked immunosorbent assay and (iii) immunoblotting with various substrates. Results were then linked with clinical parameters including age, Karnofsky score, number of blisters, related adverse events and mortality.Disease activity correlated with immunoglobulin (Ig)G anti-BP180 levels but not with levels of anti-BP230 IgG and anti-BP180 IgE. High levels of both anti-BP180 IgG and anti-BP230 IgG were associated with a low Karnofsky score. The presence of anti-BP230 IgG was more frequent in older patients. Those with higher total IgE serum levels suffered from fewer adverse events. Higher IgG anti-BP180 levels were associated with an increased 1-year mortality rate.Analysis of the autoantibody profile is not only of diagnostic relevance but may also be helpful in predicting the course of the disease.
Implications of prolonged time to pancreaticoduodenectomy after neoadjuvant chemoradiation: Analysis of the National Cancer Database.
Authors: Annabelle Teng, Trang Nguyen, Anton Bilchik, Victoria O'Connor, David Y Lee
Journal: Journal of Clinical Oncology (2018)

473 Background: For patients with pancreatic adenocarcinoma (PA), the optimal time interval between neoadjuvant chemoradiation (CR) to surgical resection has not been well established. The National Cancer Database (NCDB) was used to evaluate the impact of radiation-surgery (RS) interval on outcomes. Methods: The NCDB from 2006-2014 was queried for patients ≥18 years old diagnosed with PA who received CR prior to surgery. Survival and short-term outcomes were compared between patients who had a Whipple procedure performed ≤12 weeks and &gt; 12 weeks after completion of CR therapy. Results: 1610 patients met selection criteria. Average RS interval was 58.2 ± 39.5 days. 1419 patients had RS interval ≤12 weeks (mean 47.4 days) and 191 had RS interval &gt; 12 weeks (mean 138.8 days). Age, race, gender, income, type of treatment facility, CA 19-9 levels, types of chemotherapy and radiation dosage administered were similar between the two groups. Mean tumor size was 32.2 mm in the ≤12 week group and 34.9 mm in the &gt; 12 week group (p = 0.021). There was a higher proportion of patients with clinical stage III cancers in the &gt; 12 weeks group than in the ≤12 weeks group (33.5% vs 14%). Short-term morbidity and mortality was not significantly different between the two groups in terms of length of stay, readmission within 30 days, 30-day and 90-day mortality. However, a long-term survival benefit was observed in the &gt; 12 week group (median 25.8 months in ≤12 weeks vs 30.2 months in &gt; 12 weeks, p = 0.049) that appears to persist. An interval &gt; 12 weeks was associated with significantly prolonged survival on multivariate analysis (HR 0.80 (0.65-0.99 95% CI, p = 0.042)). Higher clinical stage and positive surgical margins were independently associated with worse survival. Conclusions: Surgical resection beyond 12 weeks after CR for PA did not worsen surgical outcomes. Waiting may contribute to better patient selection, especially those with larger tumors and higher clinical stage. In the absence of progressive disease, patients need to be continuously evaluated for surgical resection after CR.
Promoting respiratory public health through epigenetics research: an ERS Environment Health Committee workshop report
Authors: Erik Melén, Robert Barouki, Maeve Barry, H. Marike Boezen, Barbara Hoffmann, Susanne Krauss-Etschmann, Gerard H. Koppelman, Bertil Forsberg
Journal: European Respiratory Journal (2018)

Epigenetics is a rapidly developing research field that is expected to unravel the complex interplay between genes and environmental exposures relevant for health and disease. Epigenetics is classically referred to as heritable phenotypic changes that cannot be explained by changes in DNA sequence. DNA methylation, which is the covalent binding of a methyl group to a cytosine followed by a guanine (CpG), is the most commonly used epigenetic marker in human studies to date. Epigenetics also refers to hydroxymethylation, chromatin remodelling, histone modifications and expression of noncoding RNAs. Recent epidemiological and experimental studies have shown that epigenetic changes are influenced by genetic factors, environmental exposures, ageing and disease processes. In particular, early-life events and exposures seem to strongly influence epigenetic processes such as DNA methylation [1, 2]. From the definition of epigenetics, heritable changes are implied and observations from pre-conceptual exposure studies raise the question whether epigenetic changes really can be inherited at the individual level from one generation to the next [3]. If so, this would have immense public health implications, since generations to come may have to face health consequences of the life their parents and grandparents lived, the diseases they had or the environmental factors they were exposed to. There are, however, many question marks around potential epigenetic effects across generations; from epidemiological and experimental evidence to mechanisms and potential health effects. Here, we report on an European Respiratory Society (ERS) Environment and Health Committee workshop held in March 2017 where epigenetics and transgenerational effects in the field of respiratory research were discussed. The aim of the meeting was to examine the role of ERS advocacy in promoting public health policy in relation to epigenetic mechanisms and to identify future research activities. Time to bridge public health actions for respiratory disease with findings from recent epigenetics research <http://ow.ly/iQoD30iyt7I>
Clinical and Pathological Characteristics of <i>KEAP1</i>- and <i>NFE2L2</i>-Mutated Non–Small Cell Lung Carcinoma (NSCLC)
Authors: Rieke Frank, Matthias Scheffler, Sabine Merkelbach-Bruse, Michaela A. Ihle, Anna Kron, Michael Rauer, Frank Ueckeroth, Katharina König, Sebastian Michels, Rieke Fischer, Anna Eisert, Jana Fassunke, Carina Heydt, Monika Serke, Yon-Dschun Ko, Ulrich Gerigk, Thomas Geist, Britta Kaminsky, Lukas C. Heukamp, Mathieu Clement-Ziza, Reinhard Büttner, Jürgen Wolf
Journal: Clinical Cancer Research (2018)

Purpose:KEAP1 and NFE2L2 mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non-small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC.Experimental Design: Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed.Results:KEAP1 mutations occurred with a frequency of 11.3% (n = 157) and NFE2L2 mutations with a frequency of 3.5% (n = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD; 72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC; 59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with KEAP1 mutation had a response on systemic treatment in first-, second-, or third-line setting. Of NFE2L2-mutated patients, none responded to second- or third-line therapy.Conclusions:KEAP1- and NFE2L2-mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance. Clin Cancer Res; 24(13); 3087-96. ©2018 AACR.