tbuckley/cabot-search huggingface dataset:
The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial
Authors: R. Barroso-Sousa, W.T. Barry, H. Guo, D. Dillon, Y.B. Tan, K. Fuhrman, W. Osmani, A. Getz, M. Baltay, C. Dang, D. Yardley, B. Moy, P.K. Marcom, E.A. Mittendorf, I.E. Krop, E.P. Winer, S.M. Tolaney
Journal: Annals of Oncology (2019)

Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics.
Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity
Authors: Kevin H. Lin, Abigail Xie, Justine C. Rutter, Yeong-ran Ahn, Julia M. Lloyd-Cowden, Amanda G. Nichols, Ryan S. Soderquist, Timothy R. Koves, Deborah M. Muoio, Nancie J. MacIver, Jatinder K. Lamba, Timothy S. Pardee, Chad M. McCall, David A. Rizzieri, Kris C. Wood
Journal: Cell Metabolism (2019)
Recruiting CD33 on mast cells to inhibit IgE-mediated mast cell–dependent anaphylaxis
Authors: Stephen J. Galli
Journal: Journal of Clinical Investigation (2019)

IgE-mediated activation of mast cells is a hallmark of an anaphylactic reaction to allergen. In this issue of the JCI, Duan et al. describe an approach for suppressing IgE-dependent mast cell activation, thereby suppressing anaphylaxis. Specifically, the authors show that delivery of liposomes containing both the specific antigen recognized by the mast cell–bound IgE and a high-affinity glycan ligand of the inhibitory receptor CD33 (CD33L) to targeted mast cells inhibits antigen-induced, FcεRI-dependent spleen tyrosine kinase (Syk) phosphorylation and downstream protein tyrosine kinase (PTK) phosphorylation, Ca++ flux, and β-hexosaminidase release (i.e., degranulation). However, this strategy only worked if both the antigen (reactive with the mast cell–bound IgE) and CD33L were on the same liposome. This approach promises to rapidly reduce IgE-dependent mast cell activation in response to challenge with offending allergens.
T-cell–inflamed gene expression profile (GEP) and PD-L1 expression in patients (pts) with esophageal cancer (EC).
Authors: Torben Steiniche, Sun Young Rha, Hyun Cheol Chung, Jeanette Bæhr Georgsen, Morten Ladekarl, Marianne Nordsmark, Marie Louise Jespersen, Hyo Song Kim, Hyunki Kim, Carly Fein, Ting Wu, Mary J. Savage, Matthew John Marton, S. Peter Kang, Senaka A. Peter, David Paul Kelsen, Geoffrey Yuyat Ku
Journal: Journal of Clinical Oncology (2019)

26 Background: GEP and PD-L1 expression have been associated with anti–PD-1/PD-L1 therapy. In this retrospective observational study we explored the prognostic value of GEP and PD-L1 expression in pts with EC receiving standard-of-care therapy (SOC). Methods: Tumor tissue samples collected from 2005 to 2017 were procured from Yonsei Cancer Center (South Korea), Memorial Sloan Kettering Cancer Center (USA) and Aarhus University Hospital (Denmark). GEP score was derived from an 18-gene signature using extracted tumor RNA analyzed by NanoString nCounter; GEP high/intermediate (GEP-H/I) and low were defined by a cutoff of –1.540, consistent with pembrolizumab clinical trials. PD-L1 expression was assessed by PD-L1 IHC 22C3 pharmDx assay (Agilent); positive was defined as combined positive score (CPS) ≥ 10, where CPS is the the number of PD-L1–positive cells (tumor cells, lymphocytes and macrophages) divided by the total number of viable tumor cells, multiplied by 100. Associations of GEP score and PD-L1 expression with clinicopathologic variables were analyzed by chi-square test and multiple logistic regression models. Overall survival (OS) from diagnosis date to death date/last follow-up was analyzed using Cox proportional hazards models adjusting for age, sex, stage, region and ECOG performance status (PS). Results: 294 samples with both PD-L1 and GEP data were analyzed. Median age was 65 y (range 33-88); 85% were from men, 58% were stage IV, 63% were esophageal adenocarcinoma (EAC) and 37% were esophageal squamous cell carcinoma (ESCC). Overall 36% of tumors were GEP-H/I: 46% in EAC vs 18% in ESCC. GEP was not associated with OS overall (adjusted hazard ratio [aHR] –0.90; 95% CI 0.68-1.18) or in pts with EAC (aHR 0.93; 95% CI 0.68-1.27) or ESCC (aHR 0.76; 95% CI 0.40-1.44). 21% of tumors were PD-L1-CPS ≥ 10: 18% in EAC and 26% in ESCC. PD-L1 expression was associated with ECOG PS (adjusted odds ratio 0.520; 95% CI 0.309-0.875; P = 0.014) but was not associated with OS overall (aHR 0.89; 95% CI 0.64-1.24) or in pts with EAC (aHR 0.97; 95% CI 0.63-1.49) or ESCC (aHR 1.31; 95% CI 0.73-2.34). Conclusions: Our results suggest that T-cell–inflamed GEP and PD-L1 expression may not be prognostic in pts with EC who received SOC.
Hypertensive Disorders of Pregnancy and Recurrent Wheezing: 12 Month Follow-up of a Birth Cohort Study
Authors: Mariana Abduch Rahal, Luiza Ribeiro Magalhães, Juliana Rinaldis Silva, Fernanda Taniguchi Falleiros, Etienne Larissa Duim, Francisco Lazaro Pereira Sousa, Maria Celia Cunha Ciaccia, Vera E. Rullo
Journal: Journal of Allergy and Clinical Immunology (2019)
Ectonucleosidase CD39 Is Highly Expressed on ATLL Cells and Suppresses the Immune Response through the Adenosine Pathway
Authors: Yasuhiro Nagate, Sachiko Ezoe, Jiro Fujita, Takafumi Yokota, Michiko Ichii, Akira Tanimura, Yukiko Doi, Tomoaki Ueda, Jun Toda, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
Journal: Blood (2018)
Abstract 17440: Non-Invasive Classification of Pulmonary Hypertension Using 4D Flow MRI and Random Forests
Authors: Matthew D Antalek, Kenichiro Suwa, Michael Schaffer, Brett Fenster, Michael Markl, Benjamin Freed, Jeremy Collins, Alex Barker
Journal: Circulation (2017)

Introduction: The gold standard to diagnose pulmonary hypertension (PH) is invasive right heart catheterization (RHC). However, data from cardiac and 4D flow MRI with modern machine learning models...
Presence of TP53 Mutation and Monosomal Karyotype Predict the Outcome of Patients with Acute Myeloid Leukemia in Non-Remission at Allogeneic Stem Cell Transplantation
Authors: Yuho Najima, Daichi Sadato, Yuka Harada, Chizuko Hirama, Keisuke Oboki, Takashi Toya, Noriko Doki, Kyoko Haraguchi, Kota Yoshifuji, Megumi Akiyama, Kyoko Inamoto, Aiko Igarashi, Takeshi Kobayashi, Kazuhiko Kakihana, Yoshiki Okuyama, Hisashi Sakamaki, Hironori Harada, Kazuteru Ohashi
Journal: Blood (2018)
Left Ventricular Function as a Predictor of Noncardiac Surgical Procedural Outcome
Authors: John S. Ikonomidis
Journal: JAMA Surgery (2019)

Benjamin J. Lerman, BS; Rita A. Popat, PhD; Themistocles L. Assimes, MD, PhD; Paul A. Heidenreich, MD, MS; Sherry M. Wren, MD
Abstract 10412: The Effect of Positive Remodeling Area Index and Large Plaque Burden over Fractional Flow Reserve
Authors: Shunsuke Imai, Takeshi Kondoh, Yoshiaki Kawase, Hitoshi Matsuo
Journal: Circulation (2015)

Introduction: Coronary angiographic anatomical stenosis has not been well correlated with physiological fractional flow reserve (FFR), however, the mechanism of the discordance remains poorly understood. We focused on the patients who had no anatomical significant stenosis by coronary angiogram (CAG) but physiological significant stenosis by FFR (reverse mismatch) in the proximal or mid left anterior descending artery (LAD). We explored what coronary CT angiography (CCTA) findings of the target lesion of the LAD predict abnormal FFR. Methods: ECG-gated CCTA was performed using SOMATOM Definition AS+ (128 slice Siemens) and CAG underwent within 4 weeks. FFR was measured using a pressure guide wire (verrata, Volcano) during ATP infusion. Forty consecutive reverse mismatch (with no anatomical stenosis and FFR≦0.8) pts and 40 no mismatch (with no anatomical stenosis and FFR&gt;0.8) pts were selected. Results: There were no significant differences in mean age (72±10y vs 74±8y), gender (M/F 21/19 vs 28/12), coronary risk factors (DM (9 vs 17), HT(32 vs 30), dyslipidemia (23 vs 18), Smoking (5 vs 4)), angle of LAD and LCX (70±21vs71±20 deg.), proximal reference lumen area (0.14±0.14 vs 0.14±0.11 mm2) and vessel area (0.15±0.04 vs 0.15±0.06mm2), distal reference lumen area (0.11±0.12 vs 0.10±0.04mm2) and vessel area (0.14±0.13 vs 0.12±0.04mm2), grade of plaque calcification, and presence of low density plaque (8 vs 7 pts) between no mismatch and reverse mismatch groups. However, vessel area (0.21±0.07mm2, P=0.0004) and positive remodeling area index (1.40±0.26, P&lt;0.0001) at the minimum lumen area (MLA) in reverse mismatch group were higher than those (0.16±0.05mm2, 1.01±0.18) in no mismatch groups, respectively. AUC of remodeling area index was 0.924 for diagnosis of reverse mismatch on ROC analysis. Sensitivity was 82.5%, specificity was 84.6% when the remodeling area index was 1.13. Conclusions: Even if anatomical significant stenosis is not observed, FFR was depressed in patients with large vessel area and positive remodeling area index derived from CCTA at MLA. Large plaque at MLA may be one of the mechanisms of reverse mismatch.
Abstract 17620: Does Doppler E/e’ Ratio Reliably Estimate Diastolic Filling Pressures in Stress Cardiomyopathy?: A Validation Study in Apical and non-Apical Phenotypes
Authors: Aline Iskandar, Gerard P Aurigemma, Timothy P Fitzgibbons, Mohammed Ahmed, Dennis Tighe
Journal: Circulation (2014)

BACKGROUND: We have recently shown that mean LV end diastolic pressure (LVEDP) is commonly elevated in apical ("Tako-tsubo") stress cardiomyopathy (SCM) and likely contributes to heart failure in this syndrome. The assessment of diastolic filling pressures by use of E/e’ ratio (early diastolic transmitral E to tissue Doppler e') has been applied to many forms of heart disease, but has not been validated in SCM, and has not been studied in the apical sparing variant. METHODS: We identified 62 patients with SCM, 43 patients with apical/Tako-tsubo SCM and 19 patients with apical sparing (basal and midventricular) variant of SCM, who underwent measurement of E/e', using the average of lateral and septal e’ (cm/s), within 48 hours of direct invasive measurement of LVEDP (mm Hg). RESULTS: LVEDP was significantly higher in apical sparing SCM compared to apical SCM (28 ± 6 mmHg vs. 22 ± 7 mmHg, p&lt;0.002). LVEDP directly correlated with E/e’ ratio in apical SCM (r = 0.64, p &lt; 0.0001, Figure 1). When individual data were examined, we found that of the apical SCM group, 3 pts had normal LVEDP and were correctly identified with normal E/e’ ratio (&lt; 8). All apical SCM patients with elevated LVEDP (16 mm Hg or greater) had E/e’ &gt; 8, and fifteen of these had E/e’ ratio &gt; 15. By contrast, all apical sparing SCM had elevated LVEDP. In this group, E/e’ did not predict LVEDP: the overall correlation between E/e’ and LVEDP (r = 0.27, p = 0.26, Figure 2) was poor. When individual data were examined, 5 patients with elevated LVEDP had normal E/e’ and, of the remaining 14 patients with elevated LVEDP, only 1 patient had E/e’ &gt;15. CONCLUSION: Our results demonstrate: 1. Elevated LVEDP is found among 95% of SCM, regardless of the phenotype. 2. Unexpectedly, apical sparing SCM appears to have worse impairment of diastolic function and higher LVEDP than apical variant SCM 3. E/e’ ratio reliably predicts LVEDP in pts with apical variant SCM; by contrast, this index underestimates LVEDP among patients with apical sparing SCM.
Abstract #3248: Anti-tumor activity of a T cell-engaging MCSP-specific BiTE antibody at very low effector to target ratios: A new approach to treat metastatic melanoma
Authors: Hitoe Torisu-Itakura, Hans Schoellhammer, Young Huynh, Susanne Hausmann, Ralf Lutterbuese, Peter Kufer, Patrick Baeuerle, Donald Morton
Journal: Cancer Research (2009)

Introduction:  There is no standard immunotherapy for advanced melanoma. Bispecific T-cell engager (BiTE) antibodies redirect cytotoxic T cells to malignant cells and have shown impressive efficacy in patients with non-Hodgkin9s lymphoma (Bargou et al., Science 321: 974, 2008). We here investigated a new BiTE antibody specific for melanoma-associated chondroitin sulfate proteoglycan (MCSP), one of the best characterized surface antigens on melanoma cells, and for the CD3 complex on T cells. Thereby, T cells are stimulated to initiate serial lysis of MCSP-expressing melanoma cells via redirected lysis. In this study, we examined MCSP expression and the effect of MCSP-BiTE antibody in 32 human melanoma cell lines established from metastatic tissue of patients.  Methods:  Peripheral blood mononuclear cells (PBMCs) were obtained from healthy donors. Twenty-five melanoma cell lines were co-cultured with PBMCs with or without MCSP-BiTE antibody (0, 10, 100 or 1,000 ng/ml). The percentage of live cells, dead cells, and the total cells was determined by flow cytometry using PKH67 and propidium  iodide. The effector:target (E:T) ratios of PBMCs to melanoma cells tested were 1:1, 1:5 or 1:10.  Results:  Of the 32 melanoma lines, 30 expressed MCSP.  A 6-7 day co-culture of 25 cell lines with PBMCs caused the decrease in the number of alive MSCP-positive cells at all E:T ratios. The degree of cell lysis varied between the cell lines but correlated in all cases with increasing MCSP-specific BiTE antibody concentrations and E:T ratios. For instance, with treatment at 10, 100 or 1,000 ng/ml of MCSP-BiTE the percentage of dead cells was significantly (p Conclusions:  MCSP is expressed in over 90% of melanoma cell lines. With MCSP-specific BiTE antibody, PBMCs can kill MCSP-positive melanoma cells, even at the very low E:T ratio of 1:10. Because MCSP-specific BiTE antibodies can broadly activate the anti-tumor activity of T cells, this immunotherapeutic approach merits clinical investigation in patients with MCSP-positive metastatic melanoma.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3248.
Development of a Bifunctional Checkpoint Inhibitory T Cell Engager (CiTE) to Reverse Adaptive Immune Escape in AML
Authors: Monika Herrmann, Christina Krupka, Katrin Deiser, Bettina Lindl, Ralph Mocikat, Klaus H. Metzeler, Karsten Spiekermann, Sebastian Kobold, Nadja Fenn, Karl-Peter Hopfner, Marion Subklewe
Journal: Blood (2018)
Decolonization to Reduce Postdischarge Infection Risk among MRSA Carriers
Authors: Susan S. Huang, Raveena Singh, James A. McKinnell, Steven Park, Adrijana Gombosev, Samantha J. Eells, Daniel L. Gillen, Diane Kim, Syma Rashid, Raul Macias-Gil, Michael A. Bolaris, Thomas Tjoa, Chenghua Cao, Suzie S. Hong, Jennifer Lequieu, Eric Cui, Justin Chang, Jiayi He, Kaye Evans, Ellena Peterson, Gail Simpson, Philip Robinson, Chester Choi, Charles C. Bailey, James D. Leo, Alpesh Amin, Donald Goldmann, John A. Jernigan, Richard Platt, Edward Septimus, Robert A. Weinstein, Mary K. Hayden, Loren G. Miller
Journal: New England Journal of Medicine (2019)

Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge.
Recombinant Antibodies Expressed In Mammalian Cells For Analysis Of Antigenic Determinants On Mite Allergens
Authors: Crystal M. Richardson, Jill Glesner, Jacob L. Daniel, Jillian L. Bracaglia, Bryan R.E. Smith, Martin D. Chapman, Scott A. Smith, Anna Pomes
Journal: Journal of Allergy and Clinical Immunology (2019)
Active surveillance for nodular lymphocyte-predominant Hodgkin lymphoma
Authors: Sven Borchmann, Erel Joffe, Craig H. Moskowitz, Andrew D. Zelenetz, Ariela Noy, Carol S. Portlock, John F. Gerecitano, Connie L. Batlevi, Philip C. Caron, Pamela Drullinsky, Audrey Hamilton, Paul A. Hamlin, Steven M. Horwitz, Anita Kumar, Matthew J. Matasar, Alison J. Moskowitz, Colette N. Owens, M. Lia Palomba, Anas Younes, David J. Straus
Journal: Blood (2019)
Clinical characteristics and predictors of outcomes in patients with fibrolamellar carcinoma: An eleven-year analysis of the National Cancer Database (NCDB).
Authors: Hussein Assi, Hassan Hatoum, Sarbajit Mukherjee, Michael Machiorlatti, Sara Vesely, Vipul Pareek
Journal: Journal of Clinical Oncology (2019)

413 Background: Fibrolamellar carcinoma (FLC) is a very rare liver tumor, comprising only 1% of all primary liver tumors in the United Sates. There is no standard of care for unresectable disease. Current practices are based on small retrospective studies and case series. We aim to analyze the clinicopathologic factors and treatment modalities affecting overall survival (OS) in FLC. Methods: Using the National Cancer Data Base (NCDB), we identified 496 patients diagnosed with FLC between 2004 and 2015. Simple descriptive statistics were created for all covariates. Survival data was available on 461 patients. Kaplan Meier Survival analysis was used for unadjusted results, and Cox proportional hazards model was used for multivariable analysis. The objective of the study is to identify predictors of survival in FLC. Results: The median age at diagnosis was 32 (range 18-90) years. Fifty-six percent were males. Stage distribution included 114 (31.2%), 43 (11.8%), 89 (24.3%) and 120 (32.8%) patients for stages I, II, III and IV, respectively. Median follow-up was 24 months. Surgery of the primary site was performed on 282 (56.9%) of patients, 146 (51.2%) of which had regional lymph node dissection. Seventy (47.9%) patients had pN+ disease. Among patients with available serum alpha fetoprotein (AFP) data, 146 (42.5%) had abnormal AFP levels (&gt; 20 ng/mL). Median OS by stage were 78.5, 87.2, 18.6, and 10.6 months for stages I, II, III, and IV, respectively. Multivariate analysis showed that age (HR 1.01, p &lt; 0.0001), pN+ (HR 2.31, p = 0.0003), and abnormal AFP (HR 1.69, p = 0.0003) were negative predictors of survival. Among metastatic patients, 57 (11.4%) had metastatectomy. Metastatectomy improved overall survival in stage IV FLC, HR 0.51 (95% CI 0.29-0.89). Conclusions: Independent predictors of decreased OS in patients with FLC include age, pN+ and abnormal AFP. Metastatectomy improved OS. FLC is a rare disease entity that warrants further investigations to better delineate optimal treatment approaches.
Toward a more comprehensive theory of self-sacrificial violence
Authors: Jordan Kiper, Richard Sosis
Journal: Behavioral and Brain Sciences (2018)

Abstract We argue that limiting the theory of extreme self-sacrifice to two determinants, namely, identity fusion and group threats, results in logical and conceptual difficulties. To strengthen Whitehouse's theory, we encourage a more holistic approach. In particular, we suggest that the theory include exogenous sociopolitical factors and constituents of the religious system as additional predictors of extreme self-sacrifice.
Homocysteine, folate and vitamin B12 in psoriasis
Authors: T.‐Y. Tsai, H. Yen, Y.‐C. Huang
Journal: British Journal of Dermatology (2019)

Patients with psoriasis have an increased risk of coronary heart disease and stroke. It has been suggested that psoriasis causes raised blood levels of homocysteine. High levels of homocysteine are linked to atherosclerosis (“furring up” of the arteries). The breakdown of homocysteine is dependent on folic acid and vitamin B12. Low blood levels of folic acid have been reported in psoriasis, partly due to its consumption by increased cell turnover in the skin and partly due to reduced absorption in the gut. The authors, based in Taiwan, reviewed the published studies and confirmed that patients with psoriasis indeed had high levels of homocysteine and low levels of folic acid in their blood compared with controls (people without psoriasis). There was no difference in the blood levels of vitamin B12 between psoriasis patients and controls. The authors express a note of caution, since many other confounding factors may affect the results. However, they recommend testing homocysteine blood levels in psoriatic patients to identify those at risk of cardiovascular disease. Further studies are recommended, particularly to investigate whether giving folic acid or vitamin B12 reduces the risk of these complications.
The Rise of Wearable Technology in Health Care
Authors: Thomas M. Krummel
Journal: JAMA Network Open (2019)

Timothy J. Daskivich, MD, MSHPM; Justin Houman, MD; Mayra Lopez, MPH; Michael Luu, MPH; Philip Fleshner, MD; Karen Zaghiyan, MD; Scott Cunneen, MD; Miguel Burch, MD; Christine Walsh, MD; Guy Paiement, MD; Thomas Kremen, MD; Harmik Soukiasian, MD; Andrew Spitzer, MD; Titus Jackson, PA; Hyung L. Kim, MD; Andrew Li, MD; Brennan Spiegel, MD
State Preemption to Prevent Local Taxation of Sugar-Sweetened Beverages
Authors: Eric Crosbie, Dean Schillinger, Laura A. Schmidt
Journal: JAMA Internal Medicine (2019)

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