tbuckley/cabot-search huggingface dataset:
Mapping and Epidemiological analysis of types of Congenital Malformations in a Teaching Hospital
Authors: Cobo Daniel L
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Introduction: The World Health Organization (WHO) defines as congenital malformation, all anomalies triggered by the alteration of normal development resulting in a deficient formation from the initial stage of the fetus still in intrauterine, whose origin occurs before birth, having causes genetic, environmental or unknown, whether structural or functional, these disorders can be seen in prenatal care, childbirth, or even manifested in childhood. Background: To map and analyze epidemiological data on congenital malformations in children at a Teaching Hospital in the interior of the State of São Paulo. Materials and Methods: Data were collected from children with congenital malformations between the years 2010 and 2017, searched through the International Disease Code (ICD 10) with codes from Q00 to Q89. During the analysis of the medical records, 30,309 male and female children with congenital malformations were identified, aged between 1 day and 12 years. Results: 30,309 male and female children with congenital malformations were identified (16,956 male or 54.75% and 13,713 female or 45.25%) aged between 1 day and 12 years (19,587 from 0 to 4 years or 64.63 %; 5,780 from 5 to 8 years or 19.07% and 4,942 from 9 to 12 years or 16.30%). The main types of congenital malformations were found: cardiac and circulatory or 42.32%; spinal cord or 12.34%; congenital clubfoot or 11.07%; male and female genitals and urinary tracts or 8.97% which add up to 74.70%. Conclusion: Congenital malformations are rare anomalies and this study concluded that they are mostly associated with male gender, early age and with a predominance of cardiac and circulatory alterations.
Peak Absolute Lymphocyte Count Post CAR-T Is Associated with Clinical Response and Survival Outcome in Aggressive Lymphoma
Authors: Radhika Bansal, Anatilde Gonzalez Guerrico, Henan Zhang, Zuoyi Shao, Elham Babadi, Kodi E Marinez, Gabrielle Gonzalez McCoy, Matthew A Hathcock, Arushi Khurana, N. Nora Bennani, Jonas Paludo, Yucai Wang, Stephen M. Ansell, Patrick B. Johnston, Jose C Villasboas, Yi Lin
Journal: Blood (2021)
Bone Marrow GZMK +IL7R + Progenitor-Exhausted CD8 + T Cells Correlate with Sustained Clinical Remission in Patients with Acute Myeloid Leukemia (AML) Undergoing Chemotherapy
Authors: Francesco Mazziotta, Luca Biavati, Rupkatha Mukhopadhyay, Hanna A. Knaus, Ivan M. Borrello, Ivana Gojo, Leo Luznik
Journal: Blood (2021)
Role of Pulmonary Vasodilators in Ameliorating Primary Graft Dysfunction Following Lung Transplant
Authors: Emily Cerier, Kalvin Lung, Ankit Bharat
Journal: JAMA Surgery (2021)

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RCGP disputes health secretary’s claim that A&amp;E pressure is due to lack of GP appointments
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The Royal College of General Practitioners has disputed a claim by the health and social care secretary for England that pressure on emergency departments was being caused by a lack of GP appointments.

In a letter to Sajid Javid, shared with The BMJ, the college’s chair, Martin Marshall, said that there was no evidence to support the claim made by the health secretary when he gave evidence to the House of Commons Health and Social Care Committee on 2 November.

Marshall wrote “We are dismayed and disappointed at the media coverage of your evidence session, which suggested that lack of face-to-face GP …
Clinical Outcomes at 3 and 6 Months of Fedratinib Therapy Following Prior Ruxolitinib Failure: Real-World Assessment of Spleen, Symptoms, and Hematologic Response
Authors: John Mascarenhas, Aaron T. Gerds, Arianna Kee, Jonathan K. Kish, Pranav Abraham, Alexandrina Balanean, Jose Alberto Nadal, Djibril Liassou, Bruce A. Feinberg, Ali McBride, Claire N. Harrison
Journal: Blood (2021)
Association of Self-reported COVID-19 Infection and SARS-CoV-2 Serology Test Results With Persistent Physical Symptoms Among French Adults During the COVID-19 Pandemic
Authors: Joane Matta, Emmanuel Wiernik, Olivier Robineau, Fabrice Carrat, Mathilde Touvier, Gianluca Severi, Xavier de Lamballerie, Hélène Blanché, Jean-François Deleuze, Clément Gouraud, Nicolas Hoertel, Brigitte Ranque, Marcel Goldberg, Marie Zins, Cédric Lemogne, Sofiane Kab, Adeline Renuy, Stephane Le-Got, Celine Ribet, Emmanuel Wiernik, Marcel Goldberg, Marie Zins, Fanny Artaud, Pascale Gerbouin-Rérolle, Mélody Enguix, Camille Laplanche, Roselyn Gomes-Rima, Lyan Hoang, Emmanuelle Correia, Alpha Amadou Barry, Nadège Senina, Gianluca Severi, Julien Allegre, Fabien Szabo de Edelenyi, Nathalie Druesne-Pecollo, Younes Esseddik, Serge Hercberg, Mathilde Touvier, Marie-Aline Charles, Pierre-Yves Ancel, Valérie Benhammou, Anass Ritmi, Laetitia Marchand, Cécile Zaros, Elodie Lordmi, Adriana Candea, Sophie de Visme, Thierry Simeon, Xavier Thierry, Bertrand Geay, Marie-Noelle Dufourg, Karen Milcent, Delphine Rahib, Nathalie Lydie, Clovis Lusivika-Nzinga, Gregory Pannetier, Nathanael Lapidus, Isabelle Goderel, Céline Dorival, Jérôme Nicol, Fabrice Carrat, Cindy Lai, Liza Belhadji, Hélène Esperou, Sandrine Couffin-Cadiergues, Jean-Marie Gagliolo, Hélène Blanché, Jean-Marc Sébaoun, Jean-Christophe Beaudoin, Laetitia Gressin, Valérie Morel, Ouissam Ouili, Jean-François Deleuze, Laetitia Ninove, Stéphane Priet, Paola Mariela Saba Villarroel, Toscane Fourié, Souand Mohamed Ali, Abdenour Amroun, Morgan Seston, Nazli Ayhan, Boris Pastorino, Xavier de Lamballerie
Journal: JAMA Internal Medicine (2021)

After an infection by SARS-CoV-2, many patients present with persistent physical symptoms that may impair their quality of life. Beliefs regarding the causes of these symptoms may influence their perception and promote maladaptive health behaviors.
SPLUNC1 comes of age? Predicting acute exacerbations in cystic fibrosis
Authors: Colin D. Bingle, Lynne Bingle
Journal: European Respiratory Journal (2021)

Cystic fibrosis (CF) was first recognised as a specific disease in 1938 in an autopsy study of malnourished infants who displayed mucus plugging of glandular ducts [1]. The disease was characterised by malabsorption of fat and protein, steatorrhea, growth failure and pulmonary infection, which was ultimately fatal [1, 2]. Since that time, life expectancy for patients with CF has steadily improved from around 6 months to more than 40 years [3]. In many countries, the number of adults with CF now exceeds the number of children [3, 4]. Initially, improvement in survival occurred without any knowledge of the basic disease defect, using treatments directed at nutritional repletion, relief of airway obstruction, and antibiotic therapy of lung infection [2, 3]. The discovery of the CFTR gene in 1989 marked an important milestone in the history of CF [5] and led directly to the development of an array of targeted therapeutics that have shown great efficacy in modifying the disease [6, 7]. Although therapies have changed, aggressive treatment remains the foundation of clinical care. Measurement of the levels of SPLUNC1 in sputum may be a useful biomarker of cystic fibrosis exacerbations <https://bit.ly/2TBfaB9>
Safety and Efficacy of Tenalisib Given in Combination with Romidepsin in Patients with Relapsed/Refractory T-Cell Lymphoma: Final Results from a Phase I/II Open Label Multi-Center Study
Authors: Swaminathan P Iyer, Auris Huen, Weiyun Z. Ai, Deepa Jagadeesh, Mary Jo Lechowicz, Craig Okada, Tatyana A. Feldman, Suchitra Sundaram, Juan Pablo Alderuccio, Nishitha Reddy, Don Stevens, Timothy M. Kuzel, Ann Mohrbacher, Kasi Viswanath Routhu, Prajak Barde, Ajit Mohanchandran Nair, Brad M. Haverkos
Journal: Blood (2021)
Collagen Linearization within Tumors
Authors: Craig E. Barcus, Gregory D. Longmore
Journal: Cancer Research (2021)

Abstract It is now well appreciated that the tumor microenvironment (TME) surrounding primary tumors impacts tumor growth, progression (invasion and migration), and response to therapy. Broadly speaking, the TME is composed of cells (immune cells, activated fibroblasts, adipocytes, endothelial cells), acellular extracellular matrix (ECM), and cytokines or growth factors, some of which are bound or tethered to the ECM proteins. All these compartments undergo significant changes during tumor development and progression. Changes to the ECM, in particular, can dramatically influence cancer biology. This has stimulated the development of therapies that directly reverse or prevent the structural changes in the TME ECM that facilitate cancer progression. But to do so, in a rational manner, we need to understand how structural changes to tumor ECM arise, are remodeled, and function to facilitate tumor cell invasion and migration that give rise to metastatic disease, which is the main cause of cancer-related deaths. In this issue of Cancer Research, Janjanam and colleagues show that the ratio of WISP1/WISP2 in tumors is critical for ECM collagen fiber linearization and important for metastasis. WISP2 binds ECM collagen directly and can inhibit WISP1-mediated collagen linearization. These new results offer a new approach for targeting the altered collagen ECM in tumors by preventing or reversing collagen linearization. See related article by Janjanam et al., p. 5666
62 Applying machine vision to empower preclinical development of cell engager and adoptive cell therapeutics in patient-derived organoid models of solid tumors
Authors: Sonal Khare, Chi-Sing Ho, Madhavi Kannan, Brian Larsen, Brandon Mapes, Jenna Shaxted, Jagadish Venkataraman, Ameen Salahudeen
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Cell engager and adoptive cell therapeutics have emerged as efficacious and durable treatments in patients with B-cell malignancies. Though many analogous strategies are under development in solid tumors, none have received approval. Preclinical development of these therapies requires cell labeling of immortalized cell lines and/or primary expanded T cells to distinguish target and effector cells. However, cell engager and adoptive cell therapies have had limited evidence of reproducibility in primary patient-derived models such as tumor organoid cultures thus far. Here, we build upon our tumor organoid platform 1 to measure organoid specific responses to these therapies. Utilizing machine vision coupled with time-lapse-microscopy, we obtain multiparameter kinetic readouts of patient-derived tumor organoid cell killing and allogeneic MHC-matched primary peripheral blood mononuclear cells (PBMCs). Methods The patient-derived tumor organoids were co-cultured with PBMCs in the presence of engagers/activators and vital dyes and incubated for 96 hrs. Cell death was measured by quantifying the caspase 3/7 vital dye pixel intensities at different time points using high throughput imaging. As a first step, a fully convolutional neural network was trained to segment out organoids from brightfield images comprised of organoids, immune cells and potential background artifacts. This segmentation mask was then transferred over to registered caspase 3/7 images to quantify tumor cell specific phenotypes in a rapid and automated manner. Results The time-lapse imaging assay allowed for both the tracking of the organoid growth over time as well as the quantification of the kinetics of engagers/activators in comparison to controls resulting in accurate and precise technical reproducibility. Further, this assay allowed for the co-localization of the organoids and the immune cells over time, thus, enabling a spatiotemporal summary of dose dependent efficacy of candidate therapeutics. Conclusions We demonstrate the scalability and throughput of a machine vision tumor organoid immune co-culture platform across multiple unique patient-derived tumor organoid lines bearing a target of interest, enabling future discovery of biomarkers of therapeutic response and resistance. Reference Larsen B, Kannan M, Langer LF, Khan AA, Salahudeen AA, A pan-cancer organoid platform for precision medicine. Cell Reports 2021; 36 :109429
Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed By BV Consolidation in Patients with CD30-Expressing Peripheral T-Cell Lymphomas
Authors: Alex F. Herrera, Jasmine Zain, Kerry J. Savage, Tatyana A. Feldman, Jonathan E Brammer, Lu Chen, Leslie L. Popplewell, Lihua E Budde, Matthew Mei, Lori A. Leslie, Ranjit Nair, Chitra Hosing, Lacolle Peters, Stephen J Forman, Steven T. Rosen, Larry W. Kwak, Swaminathan P Iyer
Journal: Blood (2021)
Treatment of Relapsed/Refractory Waldenström Macroglobulinemia Patients: Final Clinical and Molecular Results of the Phase II Brb (Bendamustine, Rituximab and Bortezomib) Trial of the Fondazione Italiana Linfomi (FIL)
Authors: Giulia Benevolo, Simone Ferrero, Nicoletta Villivà, Anna Castiglione, Federico Monaco, Carola Boccomini, Maria Giuseppina Cabras, Catello Califano, Paolo Casula, Federica Cavallo, Annarita Conconi, Daniela Drandi, Gianluca Gaidano, Anna Ines Gregorini, Stefano Felici, Martina Ferrante, Donato Mannina, Anna Lia Molinari, Pellegrino Musto, Gerardo Musuraca, Michele Merli, Roberto Sartori, Monica Tani, Marzia Varettoni, Umberto Vitolo, Lorella Orsucci
Journal: Blood (2021)
A phase I imaging and pharmacodynamic trial of CS-1008 in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: Marika Ciprotti, Niall C Tebbutt, Fook T Lee, Sze T Lee, Dave C McKee, Graeme J O'Keefe, Sylvia J Gong, Geoffrey Chong, Hui K Gan, Wendie Hopkins, Bridget Chappell, Nancy Y Guo, Fiona E Smyth, Archie N Tse, Mendel Jansen, Manabu Matsumura, Rira Watanabe, Robert A Beckman, Jon Greenberg, Andrew M Scott
Journal: Cancer Research (2013)
Aurora Kinase Inhibition Overcomes Primary Venetoclax Failure and Leads to Synthetic Lethality in BCL2-Positive Lymphomas Via Upregulation of P53/P21/BAX Axis
Authors: Rajeswaran Mani, Samon Benrashid, Sarah E Teague, Scott C Jaros, Hsih-Te Yang, Lawrence J Druhan, David M Foureau, Nury M Steuerwald, Nilanjan Ghosh, Edward A. Copelan, Donald L. Durden, Belinda Avalos, Steven I. Park
Journal: Blood (2021)
Efficacy of Dapagliflozin in Black Versus White Patients With Heart Failure and Reduced Ejection Fraction
Authors: Kieran F. Docherty, Modele O. Ogunniyi, Inder S. Anand, Akshay S. Desai, Mirta Diez, Jonathan G. Howlett, Jose C. Nicolau, Eileen O’Meara, Subodh Verma, Silvio E. Inzucchi, Lars Køber, Mikhail N. Kosiborod, Daniel Lindholm, Felipe A. Martinez, Olof Bengtsson, Piotr Ponikowski, Marc S. Sabatine, Mikaela Sjöstrand, Scott D. Solomon, Anna Maria Langkilde, Pardeep S. Jhund, John J.V. McMurray
Journal: JACC Heart Failure (2021)

This study sought to investigate the efficacy and safety of dapagliflozin in Black and White patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure).Black patients may respond differently to certain treatments for HFrEF than White patients.Patients with New York Heart Association functional class II to IV with an ejection fraction of ≤40% and elevated N-terminal pro-B-type natriuretic peptide were eligible for DAPA-HF. Because >99% of Black patients were randomized in the Americas, this post hoc analysis considered Black and White patients enrolled only in North and South America. The primary outcome was the composite of a worsening HF event (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death.Of the 4,744 patients randomized in DAPA-HF, 1,494 (31.5%) were enrolled in the Americas. Of these, 1,181 (79.0%) were White, and 225 (15.1%) were Black. Black patients had a higher rate of worsening HF events, but not mortality, compared with White patients. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint similarly in Black patients (HR: 0.62; 95% CI: 0.37-1.03) and White patients (HR: 0.68; 95% CI: 0.52-0.90; P-interaction = 0.70). Consistent benefits were observed for other prespecified outcomes, including the composite of total (first and repeat) HF hospitalizations and cardiovascular death (P-interaction = 0.43) and Kansas City Cardiomyopathy Questionnaire total symptom score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either Black or White patients.Dapagliflozin reduced the risk of worsening HF and cardiovascular death, and it improved symptoms, similarly in Black and White patients without an increase in adverse events. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
Abstract 9368: Concordance of LDL-Cholesterol Levels Between the Friedewald, Martin/Hopkins, and Sampson Equations in Patients With Atherosclerotic Cardiovascular Disease
Authors: Aparna Sajja, Hsin-Fang Li, Kateri Spinelli, Salim S Virani, Seth S Martin, Ty Gluckman
Journal: Circulation (2021)

Introduction: Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is important for cardiovascular risk assessment and guiding cholesterol-lowering therapy. Different methods currently exist to estimate LDL-C. There is limited data in patients with atherosclerotic cardiovascular disease (ASCVD) in prior studies. Objectives: To assess concordance of estimated LDL-C using the Friedewald, Martin/Hopkins, and Sampson equations. Methods: We performed a retrospective analysis of electronic health record data from a large multistate healthcare system. Patients with ASCVD and triglycerides (TG) &lt;400 mg/dL between October 1, 2015 and June 30, 2019 were included. LDL-C was estimated using the Friedewald equation (with a fixed TG to very LDL-C [VLDL-C] ratio of 5:1), Martin/Hopkins equation (with a flexible ratio), and Sampson equation (with estimation of VLDL-C by multiple least squares regression). Pairwise comparisons were performed, with patients categorized as concordant if the LDL-C was &lt;70 mg/dL using both equations and discordant if the LDL-C was &lt;70 mg/dL for the reference equation and ≥70 mg/dL for the comparator. Results: The study included 146,106 patients with ASCVD (median age 68 years, 56% male, and 91% White). Discordance rates were 15% for the Friedewald vs Martin/Hopkins comparison, 9% for the Friedewald vs Sampson comparison, and 7% for the Sampson vs Martin/Hopkins comparison. Estimated LDL-C was lower for the Friedewald and Sampson equations compared to the Martin/Hopkins equation. Discordance was more pronounced at lower LDL-C cut points and in those with TG ≥150 mg/dL. Conclusions: Important differences in estimated LDL-C exist between the three equations, particularly among those with TG ≥150 mg/dL. These results in ASCVD patients, synthesized with prior evidence, raise concern that reliance upon the Friedewald and Sampson equations may result in underestimation and thus, undertreatment of LDL-C in those at increased risk.
Abstract 13152: Circulating Endothelial Extracellular Microvesicles Increase With Advancing Age And Are Associated With Endothelial Dysfunction
Authors: Christian DeSouza, Kelly A Stockelman, Tyler D Bammert, Jamie G Hijmans, Grace Lincenberg, Jared Greiner, Brian L Stauffer, Christopher Desouza
Journal: Circulation (2021)

Background: Aging is associated with a progressive increase in risk and prevalence of cardiovascular disease (CVD). Endothelial cell dysfunction is considered to be a central mechanism underlying the age-related increase in vascular risk and disease. However, the direct, and indirect, effects of aging on endothelial cell biology are diverse and not completely understood.Clinical interest in circulating extracellular vesicles, particularly endothelial cell-derived microvesicles (EMVs), has intensified due to their involvement in the development and progression of endothelial dysfunction and CVD. The purpose of this study was to determine: 1) if circulating EMV levels increase with age, independent of other cardiometabolic risk factors; and if so, 2) whether circulating EMVs are associated with age-related endothelial vasodilator dysfunction. Methods: Thirty-six healthy, non-obese, normotensive, sedentary men were studied: 12 young (age: 27 + 1 yr); 12 middle-aged (51 + 1 yr) and 12 older (67 + 2 yr). EMV identification (CD31 + /42b - ) and concentration in peripheral blood was determined by flow cytometry. Forearm blood flow (FBF: via plethysmography) was assessed in response to intra-arterial infusions of acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) in 8 young, 8 middle-aged and 8 older men. Results: Circulating EMV levels were significantly and progressively higher across the young, middle-aged and older groups (57 + 5 vs 102 + 9 vs 134 + 16 EMV/μL, respectively). FBF response to acetylcholine was significantly and progressively lower (~35%) in the young (from 5.2±0.4 to 17.2±1.8 mL/100 mL tissue/min) vs middle-aged (4.5±0.3 to 13.2±1.2 mL/100 mL tissue/min) vs older (4.2±0.3 to 11.3±0.8 mL/100 mL tissue/min) group. Circulating EMVs were positively associated with age (r=0.67; P&lt;0.01) and inversely associated with the vasodilator response to acetylcholine (r=-0.43; P&lt;0.01). Conclusions: Aging, independent of other cardiometabolic risk factors, is associated with progressive elevated circulating levels of EMVs. Circulating EMVs may serve as a biomarker of, and contributor to, age-related endothelial dysfunction and vascular disease risk.
Immune Checkpoint Inhibitors (ICI) Enhance Cancer Associated Thrombosis (CAT) in Murine Model of Colon Carcinoma
Authors: Shadi Swaidani, Young Jun Shim, Patricia Rayman, Paul G. Pavicic, C. Marcela Diaz-Montero, Alok A Khorana, Keith R. McCrae
Journal: Blood (2021)
Suppressing Synthesis of the Long Isoform of the Prolactin Receptor Is a Targeted Strategy to Prevent and Treat B Cell Malignancies
Authors: Adeleh Taghi Khani, Anil Kumar, Kelly Radecki, Sung June Lee, Mary Lorenson, Xiwei Wu, Zhaohui Gu, Ameae Walker, Srividya Swaminathan
Journal: Blood (2021)
Acute and Post-Acute COVID-19 Severity and Mortality in Patients with Hematologic Malignancies: A Population-Based Registry Study
Authors: Joaquin Martinez-Lopez, Javier De La Cruz, Rodrigo Gil-Manso, Angel Cedillo, Adrian Alegre, Maria Pilar Llamas Sillero, Rafael F. Duarte, Víctor Jiménez-Yuste, jose Angel Hernandez, Mi Kwon, Pedro Sanchez Godoy, Pilar Martinez-Barranco, Blanca Colás Lahuerta, Pilar Herrera Puente, Lauren Benito, Alberto Velasco, Arturo Matilla, Concha Alaez, Rafael Martos, Carmen Martínez-Chamorro, Keina Quiroz, Juan F del Campo, Adolfo De La Fuente, Maria Regina Herraez, Adriana Pascual, Elvira Gomez, Jaime Perez De Oteyza, Elena Ruiz, Jose Luis Diez Martin, Julio Garcia-Suarez
Journal: Blood (2021)