tbuckley/cabot-search huggingface dataset:
Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8+ T cells
Authors: Kamila Hladíková, Vladimír Koucký, Jan Bouček, Jan Laco, Marek Grega, Miroslav Hodek, Michal Zábrodský, Milan Vošmik, Kateřina Rozkošová, Hana Vošmiková, Petr Čelakovský, Viktor Chrobok, Aleš Ryška, Radek Špíšek, Anna Fialová
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Standard treatment of oropharyngeal squamous cell carcinoma (OPSCC) is associated with high morbidity, whereas immunotherapeutic approaches using PD-1:PD-L1 checkpoint blockade only show moderate response rates in OPSCC patients. Therefore, a better stratification of patients and the development of novel therapeutic protocols are crucially needed. The importance of tumor-infiltrating B cells (TIL-Bs) in shaping antitumor immunity remains unclear; therefore, we analyzed frequency, phenotype, prognostic value and possible roles of TIL-Bs in OPSCC. <h3>Methods</h3> We utilized transcriptomic analysis of immune response-related genes in 18 OPSCC samples with respect to human papillomavirus (HPV) status. The density and localization of CD20<sup>+</sup>, CD8<sup>+</sup> and DC-LAMP<sup>+</sup> cells were subsequently analyzed in 72 tissue sections of primary OPSCC samples in relation to patients' prognosis. The immunohistochemical approach was supplemented by flow cytometry-based analysis of phenotype and functionality of TIL-Bs in freshly resected primary OPSCC tissues. <h3>Results</h3> We observed significantly higher expression of B cell-related genes and higher densities of CD20<sup>+</sup> B cells in HPV-associated OPSCC samples. Interestingly, CD20<sup>+</sup> TIL-Bs and CD8<sup>+</sup> T cells formed non-organized aggregates with interacting cells within the tumor tissue. The densities of both intraepithelial CD20<sup>+</sup> B cells and B cell/CD8<sup>+</sup> T cell interactions showed prognostic significance, which surpassed HPV positivity and CD8<sup>+</sup> TIL density in stratification of OPSCC patients. High density of TIL-Bs was associated with an activated B cell phenotype, high CXCL9 production and high levels of tumor-infiltrating CD8<sup>+</sup> T cells. Importantly, the abundance of direct B cell/CD8<sup>+</sup> T cell interactions positively correlated with the frequency of HPV16-specific CD8<sup>+</sup> T cells, whereas the absence of B cells in tumor-derived cell cultures markedly reduced CD8<sup>+</sup> T cell survival. <h3>Conclusions</h3> Our results indicate that high abundance of TIL-Bs and high density of direct B cell/CD8<sup>+</sup> T cell interactions can predict patients with excellent prognosis, who would benefit from less invasive treatment. We propose that in extensively infiltrated tumors, TIL-Bs might recruit CD8<sup>+</sup> T cells via CXCL9 and due to a highly activated phenotype contribute by secondary costimulation to the maintenance of CD8<sup>+</sup> T cells in the tumor microenvironment.
The Role of Class II Human Leukocyte Antigens (cII-HLAs) in Determining the Immunogenic Potential of Therapeutic Factor VIII Proteins in Hemophilia Patients: The "Gate Keeper" Hypothesis
Authors: Vincent P. Diego, Bernadette W. Luu, Marco Hofmann, Marcio A. Almeida, Jose Antonio G. Hernandez, Juan Peralta, Joanne Curran, Jerry S. Powell, Raja Rajalingam, Long V. Dinh, Sarah Williams-Blangero, Miguel A Escobar, Eugene Maraskovsky, John Blangero, Tom E. Howard
Journal: Blood (2018)
Diverse cardiopulmonary diseases are associated with distinct xenon magnetic resonance imaging signatures
Authors: Ziyi Wang, Elianna A. Bier, Aparna Swaminathan, Kishan Parikh, John Nouls, Mu He, Joseph G. Mammarappallil, Sheng Luo, Bastiaan Driehuys, Sudarshan Rajagopal
Journal: European Respiratory Journal (2019)

As an increasing number of patients exhibit concomitant cardiac and pulmonary disease, limitations of standard diagnostic criteria are more frequently encountered. Here, we apply noninvasive 129Xe magnetic resonance imaging (MRI) and spectroscopy to identify patterns of regional gas transfer impairment and haemodynamics that are uniquely associated with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), left heart failure (LHF) and pulmonary arterial hypertension (PAH).Healthy volunteers (n=23) and patients with COPD (n=8), IPF (n=12), LHF (n=6) and PAH (n=10) underwent 129Xe gas transfer imaging and dynamic spectroscopy. For each patient, three-dimensional maps were generated to depict ventilation, barrier uptake (129Xe dissolved in interstitial tissue) and red blood cell (RBC) transfer (129Xe dissolved in RBCs). Dynamic 129Xe spectroscopy was used to quantify cardiogenic oscillations in the RBC signal amplitude and frequency shift.Compared with healthy volunteers, all patient groups exhibited decreased ventilation and RBC transfer (both p≤0.01). Patients with COPD demonstrated more ventilation and barrier defects compared with all other groups (both p≤0.02). In contrast, IPF patients demonstrated elevated barrier uptake compared with all other groups (p≤0.007), and increased RBC amplitude and shift oscillations compared with healthy volunteers (p=0.007 and p≤0.01, respectively). Patients with COPD and PAH both exhibited decreased RBC amplitude oscillations (p=0.02 and p=0.005, respectively) compared with healthy volunteers. LHF was distinguishable from PAH by enhanced RBC amplitude oscillations (p=0.01).COPD, IPF, LHF and PAH each exhibit unique 129Xe MRI and dynamic spectroscopy signatures. These metrics may help with diagnostic challenges in cardiopulmonary disease and increase understanding of regional lung function and haemodynamics at the alveolar-capillary level.
Optimizing the Timing of Allogeneic Blood or Marrow Transplantation (BMT) in a Prospective Cohort of Relapsed or Refractory Acute Myeloid Leukemia (AML)
Authors: Hong Liu, Yali Zhang, Theresa Hahn, Julie Thomas, Meir Wetzler, Eunice S. Wang, Lise Hernandez, Maureen Ross, George L. Chen, Philip L. McCarthy
Journal: Blood (2011)
The Cost of Applying to Medical School — A Barrier to Diversifying the Profession
Authors: Lorena Millo, Noelani Ho, Peter A. Ubel
Journal: New England Journal of Medicine (2019)

Applying to medical school may be prohibitively expensive for some people. Need-based financial aid helps low-income students afford tuition, but it doesn't help people who can't afford to apply to medical school in the first place. Other solutions may be needed.
Hypometilating Agents (HMA) As Salvage Therapy in Relapsed or Refractory AML: A 5-Center Retrospective Study
Authors: Marica Laurino, Federica Lessi, Antonio Branca, Silvia Imbergamo, Elena Crisà, Anna Candoni, Davide Lazzarotto, Michele Gottardi, Cristina Papayannidis, Gianpietro Semenzato
Journal: Blood (2017)
Integrating spiritual care into an ambulatory cancer center.
Authors: Karen Terry, Sophia Tsesmelis Piccolino, Alaysia Williams, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2019)

205 Background: Spiritual care is identified as a core component of quality oncologic care. Unmet spiritual needs can lead to worse quality of life, lower satisfaction with care, and greater psychological distress. Despite increasing evidence that cancer outpatients also have unmet spiritual needs, professional spiritual care is often limited in the ambulatory setting. Many cancer centers provide access to professional chaplains only while patients are hospitalized. Where chaplain services are available to outpatients, access is often limited. At Mount Sinai, we embedded a full-time professional chaplain in our ambulatory cancer center. This presentation will describe our methods, results, and conclusions from a year of data on outpatient spiritual care referrals. Methods: We identified three sources of referrals to spiritual care: direct referrals from patients’ primary oncology teams, direct referrals from Supportive Oncology/Palliative Care, and automatic referrals through a question about meaning and purpose on our distress screen. We also included the opportunity for patients to self-refer to spiritual care through our distress screen. We collected data on the number of patients identified through these referral sources, time to initial contact, and the validity of the referral as assessed by our chaplain. Results: These three sources resulted in 454 referrals to spiritual care. We screened 1,410 patients through our distress screen and 16% (226) triggered a referral to spiritual care. Distress screen referrals comprised nearly 50% of all spiritual care referrals. In addition, 32% (144) of our referrals came from the patients’ clinical teams and 10% (46) from the Supportive Oncology team. Our chaplain assessed that 31% (141) had a spiritual need that required regular follow-up and 12% (56) required monitoring. Conclusions: Using multiple referral methods we were able to identify a significant number of ambulatory cancer patients with an identified spiritual need. Future projects will look at specific metrics for patient experience, improving chaplain ability to connect with patients, validating our screening question for spiritual distress, and determining an appropriate patient load for an outpatient chaplain.
Iron Deficiency Anemia, a Rare and Potentially Underestimated Cause of Thrombocytopenia and a Differential Diagnosis of Immune Thrombocytopenia (ITP): Results from a Retrospective Case-Controlled Study
Authors: Tessa Huscenot, Darnige Luc, Orianne Wagner Ballon, Loustau Valentine, Delphine Gobert, Marie Le cann, Caroline Morbieu, Marc Michel
Journal: Blood (2018)
Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers
Authors: Felix Stickel, Philipp Lutz, Stephan Buch, Hans Dieter Nischalke, Ines Silva, Vanessa Rausch, Janett Fischer, Karl Heinz Weiss, Daniel Gotthardt, Jonas Rosendahl, Astrid Marot, Mona Elamly, Marcin Krawczyk, Markus Casper, Frank Lammert, Thomas W. M. Buckley, Andrew McQuillin, Ulrich Spengler, Florian Eyer, Arndt Vogel, Silke Marhenke, Johann von Felden, Henning Wege, Rohini Sharma, Stephen Atkinson, Andre Franke, Sophie Nehring, Vincent Moser, Clemens Schafmayer, Laurent Spahr, Carolin Lackner, Rudolf E. Stauber, Ali Canbay, Alexander Link, Luca Valenti, Jane I. Grove, Guruprasad P. Aithal, Jens U. Marquardt, Waleed Fateen, Steffen Zopf, Jean‐Francois Dufour, Jonel Trebicka, Christian Datz, Pierre Deltenre, Sebastian Mueller, Thomas Berg, Jochen Hampe, Marsha Y. Morgan
Journal: Hepatology (2019)

Background and Aims Carriage of rs738409:G in patatin‐like phospholipase domain containing 3 ( PNPLA3 ) is associated with an increased risk for developing alcohol‐related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17‐beta dehydrogenase 13 ( HSD17B13 ) was shown to be associated with a reduced risk for developing alcohol‐related liver disease and to attenuate the risk associated with carriage of PNPLA3 rs738409:G. This study explores the risk associations between these two genetic variants and the development of alcohol‐related cirrhosis and HCC. Approach and Results Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including 1,031 with alcohol‐related cirrhosis and HCC, 1,653 with alcohol‐related cirrhosis without HCC, 2,588 alcohol misusers with no liver disease, and 899 healthy controls. Genetic associations with the risks for developing alcohol‐related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for developing both cirrhosis (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72‐0.88; P = 8.13 × 10 −6 ) and HCC (OR, 0.77; 95% CI, 0.68‐0.89; P = 2.27 × 10 −4 ), whereas carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR, 1.70; 95% CI, 1.54‐1.88; P = 1.52 × 10 −26 ) and HCC (OR, 1.77; 95% CI, 1.58‐1.98; P = 2.31 × 10 −23 ). These associations remained significant after adjusting for age, sex, body mass index, type 2 diabetes, and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women, but the protective effect against the subsequent development of HCC was only observed in men (OR allelic , 0.75; 95% CI, 0.64‐0.87; P = 1.72 × 10 −4 ). Conclusions Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol‐related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population.
Re: Veeru Kasivisvanathan, Armando Stabile, Joana B. Neves, et al. Magnetic Resonance Imaging-targeted Biopsy Versus Systematic Biopsy in the Detection of Prostate Cancer: A Systematic Review And Meta-analysis. Eur Urol 2019;76:284–303
Authors: Francesco Montorsi, Giorgio Gandaglia, Alberto Briganti
Journal: European Urology (2019)
The non-canonical NF-kappaB Signaling Pathway Contributes to the Expansion and Lymphomagenesis of CD40-activated B Cells
Authors: Laura Bernhardine Kuhn, Stefanie Zapf, Djermanovic Kristina, Daniel C. Strobl, Falk Weih, Helmut Blum, Oliver Weigert, Lothar J. Strobl, Zimber-Strobl Ursula
Journal: Blood (2018)
Combining Imatinib-Following-Nilotinib Treatment in First Line Therapy for Chronic Phase Chronic Myeloid Leukemia. Update from the PhilosoPhi34 Study at 24 Months of Follow-up
Authors: Maria Luisa Pioltelli, Ester Pungolino, Mariella D'adda, Chiara Elena, Lorenza Maria Borin, Alessandra Perego, Alessandra Iurlo, Alessandra Trojani, Mauro Turrini, Marianna Caramella, Pierangelo Spedini, Simona Malato, Francesco Spina, Salvatore Artale, Mariacristina Carraro, Nicola Orofino, Michela Anghilieri, Mirko Farina, Maria Luisa Latargia, Giuseppe Rossi, Enrica Morra, Roberto Cairoli
Journal: Blood (2018)
Worry about quality of life for younger versus older adult thyroid cancer survivors.
Authors: Stefanie Marie Thomas, David Reyes-Gastelum, Joel Milam, Kimberly Ann Miller, Anamara Ritt-Olson, Ann S. Hamilton, Kevin C. Ward, Brittany L. Gay, Sarah T. Hawley, Megan Rist Haymart
Journal: Journal of Clinical Oncology (2019)

157 Background: Thyroid cancer is one of the most common cancers in young adults, age 18-39 years. Since this population has distinct medical and developmental needs, it is important to understand age differences in worry about quality of life. Methods: Thyroid cancer patients diagnosed between 2014-15 were accrued from the Surveillance, Epidemiology and End Results Program (SEER) registries of Georgia and Los Angeles County and surveyed between 2017-18. The primary outcome was patient reported worry about quality of life. Covariates for this analysis included age (categorized 18-25, 26-39, 40-64, and 65-79), involvement in surgical decision making (low, just right, high) and amount of information received on treatment side effects (low, just right, high). Race/ethnicity, sex, and tumor characteristics were also evaluated. Multivariable analyses were used to assess associations between worry about quality of life and independent variables. Results: In the cohort of 2,632 patients, 39.8% were somewhat to very much worried about quality of life not being the same as before thyroid cancer diagnosis, 15.1% reported low involvement in surgical decision making, and 32.6% reported low amount of information regarding side effects. Younger age was associated with high worry about quality of life (p &lt; 0.001), low involvement in decision making (p &lt; 0.001) and low amount of information on treatment side effects (p &lt; 0.001). In multivariable analyses, high worry was significantly associated with female sex (Odds ratio [OR]: 1.29 95% confidence Interval [CI]:1.04-1.59), non-white, non-Hispanic race/ethnicity (OR: 1.64 CI: 1.38-1.95), positive lymph nodes (OR: 1.41 CI: 1.14-1.75) and younger age (ages 18-25 years OR: 2.34 CI: 1.45-3.76; ages 26-39 years OR: 2.26 CI: 1.68-3.05; and ages 40-64 years OR:1.94 CI 1.50-2.51). Age differences remained significant after adding either involvement in decision-making or information received. Conclusions: Young adults report higher worry about quality of life. Controlling for decision-making involvement or information received about side effects did not eliminate age differences in worry. Ongoing psychosocial support addressing quality of life worries among younger survivors is needed.
Abstract 348: Homeobox A4 Suppresses Vascular Smooth Muscle Cell Phenotypic Switching as a Novel Regulator of YAP/TEAD Transcriptional Activity
Authors: Masahiro Kimura, Takahiro Horie, Takeshi Kimura, Koh Ono
Journal: Circulation Research (2019)

The Hippo signaling pathway is involved in the pathophysiology of various cardiovascular diseases. Yes-associated protein (YAP) and transcriptional enhancer activator domain (TEAD) transcriptional factors, the main transcriptional complex of the Hippo pathway, were recently identified as modulators of phenotypic switching of vascular smooth muscle cells (VSMCs). However, the intrinsic regulator of YAP/TEAD-mediated gene expressions in VSMCs remains to be elucidated, then we sought to investigate a novel regulator of YAP/TEAD transactivation involved in vascular diseases. We first investigated novel YAP/TEAD regulators using lentiviral shRNA library in HEK 293T-based TEAD-responsive reporter cell line and detected Homeobox A4 (HOXA4) as a potent repressor of YAP/TEAD transcriptional activity. HOXA4 attenuated YAP/TEAD-mediated gene expression independently of YAP phosphorylation, and co-immunoprecipitation assays revealed that HOXA4 interacts with TEADs but not YAP. Mechanistically, HOXA4 attenuated YAP/TEAD-mediated transcription by competing with YAP for TEAD binding. We also clarified that the expression of HOXA4 is relatively abundant in the vasculature, especially in VSMCs. In vitro experiments in human VSMCs showed HOXA4 maintains the differentiation state of VSMCs via inhibition of YAP/TEAD-induced phenotypic switching characterized by cell morphology, cell proliferation, and gene expression patterns. We generated Hoxa4-decifient mice and confirmed the downregulation of smooth muscle-specific contractile genes and the exacerbation of vascular remodeling after carotid artery ligation in vivo. Our results demonstrate HOXA4 is a novel repressor of VSMC phenotypic switching by inhibiting YAP/TEAD-mediated transcription. These findings give us a better understanding of the vascular pathophysiology and a novel therapeutic approach for vascular remodeling.
A Real World Resistance Profile of Virologic Failures Collected from an International Collaboration (SHARED)
Authors: Anita Howe, Valeria Cento, Nathaniel Knight, Julia Dietz, Velia Chiara Di Maio, Adolfo De Salazar, Stephanie Popping, Slim Fourati, Elena Knops, Midori Kjellin, Murat Sayan, Orna Mor, Robert J. De Knegt, Robert Mitchell, Edward V. Tam, Rohit Pai, Oscar Octavio Cruz Pereira, Johan Lennerstrand, Gary P. Wang, Alexander Wong, Milosz Parczewski, Tanya Applegate, Alnoor Ramji, Carlo Federico Perno, Rolf Kaiser, Charles A. B. Boucher, Jordan J. Feld, Jean-Michel Pawlotsky, Federico Garcia, Francesca Ceccherini-Silberstein, Christoph Sarrazin, Richard Harrigan
Journal: Hepatology (2018)

A Real World Resistance Profile of Virologic Failures Collected from an International Collaboration (SHARED)
Confirmation of a New Statistical Method for Comprehensively Dissecting QTLs Using In Vitro Transcription, the Model Factor VII Gene and a Novel Modification of the G-Free Cassette.
Authors: Maria Sabater, Jose Manuel Soria, Manana Khachidze, Xiaoping Meng, Laura Almasy, Juan Carlos Souto, Jordi Fontcuberta, John Blangero, Tom Howard
Journal: Blood (2004)
Targeting Semaphorin 4D in Cancer: A Look from Different Perspectives
Authors: Luca Tamagnone, Giulia Franzolin
Journal: Cancer Research (2019)

Abstract Semaphorin 4D (Sema4D) plays a role in various cell types including B lymphocytes, differentiating neurons, endothelial cells, and cancer cells. Preclinical and in vitro studies have shown that Sema4D-directed antibodies in combination with immune checkpoint inhibitors reshape the tumor microenvironment by promoting recruitment of effector lymphocytes and antigen-presenting cells, while reducing immunosuppressive cell types, which ultimately leads to tumor rejection. Hence, early-stage clinical trials with combination therapies including anti-Sema4D antibodies are ongoing. In this issue of Cancer Research, Zuazo-Gaztelu and colleagues report an unexpected proinvasive effect induced by anti-Sema4D antibodies in a preclinical model of neuroendocrine pancreatic cancer (Rip1-Tag2), mediated by retrograde signaling of transmembrane Sema4D in macrophages, which increases their recruitment to tumors, SDF-1 secretion, and metastasis-promoting phenotype. See related article by Zuazo-Gaztelu et al., p. 5328
Abstract 645: CUBIC as an Alternative “Clearing” Method for Creating Hydrogel-based Structure in Organs
Authors: Meghana Tallam, Qize Yuan, Meg Greer, Matthew W Kay
Journal: Circulation Research (2019)

Cardiac nerves have a major influence on cardiac health, heart failure, and sudden cardiac death. Understanding the impact of the cardiac nervous system requires in depth cell-specific analysis of the heart, which can be done using tissue clearing followed by 3D microscopic imaging. “Clearing” is the creation of hydrogel-based structures of organs where the lipids are removed without damaging the proteins of the organ. We are interested in using clearing to analyze cardiac neural anatomic pathways with high accuracy. Recently the CUBIC clearing method has gained momentum since it can clear tissue quicker than other methods. While previous research has shown qualitative images and descriptions to describe CUBIC efficacy, quantification of the clearing performance is lacking. The purpose of this study was to compare sequential images of cardiac tissue immersed in CUBIC solution alongside tissue absorbance spectra to measure the efficiency of the CUBIC method. To visualize cardiac neurons, we selectively expressed a fluorescent probe: an enhanced yellow fluorescent protein (EYFP) conjugated with the light-activated channel (channelrhodopsin (ChR2). Mice were crossbred to express EYFP+ChR2 in parasympathetic cardiac neurons which was driven by a choline acetyltransferase (ChAT) promoter using the Cre-Lox system. Hearts from these mice were excised and perfused with PFA as a fixative and perfused with the CUBIC solution. The tissue then was immersed in CUBIC solution and kept in an insulated shaker at 37°C. Each day, the tissue holder that held the cardiac tissue was taken out of the CUBIC solution and a white light from an LED was directed through the heart and the light intensity was recorded by a spectrometer. Beer-Lambert’s Law related light intensity and transmittance to absorbance to measure daily changes in the absorbance spectrum. Finally, we imaged the right atria of a cleared heart to capture the parasympathetic neural anatomic pathways using 2-photon confocal microscopy. We found that, that over the course of 14 days, the absorbance spectrum of the heart sample decreased over time, with the greatest reduction occurring between days 1 and 4. Future work would include decreasing environmental factors when measuring light intensity.
A Gene Variant in IRF3 Impacts On the Clinical Outcome of Acute Myeloid Leukemia (AML) Patients Submitted to Allogeneic Stem Cell Transplantation (allo-SCT)
Authors: Beatriz Martin-Antonio, Maria Suarez-LLedo, Montserrat Arroyes, Francesc Fernandez-Avilés, Carmen Martinez, Montserrat Rovira, Ildefonso Espigado, David Gallardo, Anna Bosch, Ismael Buno, Carolina Martinez-Laperche, Antonio Jimenez-Velasco, Rafael De La Camara, Salut Brunet, Jose B. Nieto, Alvaro Urbano-Ispizua
Journal: Blood (2012)
Healthcare Utilization and Imputed Costs of Acute Myeloid Leukemia Patients By FLT3 Status and Early Midostaurin Use at a Comprehensive Cancer Center
Authors: Minkyoung Yoo, Jyothi Menon, Connor Willis, Sudhir Unni, Trang Au, Joseph Biskupiak, Briana Ndife, George J Joseph, Gaetano J Bonifacio, Eytan M. Stein, Srinivas K. Tantravahi, Paul J. Shami, Tibor Kovacsovics, Diana Brixner, David Dean Stenehjem
Journal: Blood (2018)