tbuckley/cabot-search huggingface dataset:
Pathology: Hub and Integrator of Modern, Multidisciplinary [Precision] Oncology
Authors: Carolyn C. Compton, Angelo M. De Marzo, Jayanta Debnath, Keith D. Eaton, Kojo Elenitoba-Johnson, Michelangelo Fiorentino, Christopher A. French, Thomas J. Fuchs, Felice Giangaspero, Jiaoti Huang, A. John Iafrate, Michael M. Ittmann, Roy A. Jensen, Annette S. Kim, Massimo Loda, Robin G. Lorenz, Tamara L. Lotan, Anirban Maitra, Gerrit A. Meijer, Richard N. Mitchell, Anil V. Parwani, Francesco Pezzella, Eli Pikarsky, Jorge S. Reis-Filho, Andrea L. Richardson, Mark A. Rubin, Lawrence D. True
Journal: Clinical Cancer Research (2021)

Abstract Every profession has an essential, behind-the-scenes component without which it cannot function. Medicine is no exception. Pathologists are one of medicine's group of specialists whose work as diagnosticians is critical for patient care. This article describes the multifaceted role that pathologists play in oncology practice and cancer research. To do so, we will highlight the role of pathologists in a typical “day-in-the-life” of a patient's journey in cancer care. Clinicians, clinical trialists, radiologists, researchers, and pathologists, all work together to provide optimal, multidisciplinary care for patients with cancer.
Abstract 17085: An Anomalous Outcome Of Renal Transplant
Authors: Pooja Prasad, Kristian Enestvedt, Rehman Shehzad, Harsh Golwala
Journal: Circulation (2021)

Case Presentation: A 65 year old man with diabetic renal disease developed acute dyspnea at rest on the first post-operative day after an uncomplicated deceased donor renal transplant. He was hypertensive, tachycardic, and hypoxemic. His electrocardiogram showed anterior ST elevations with reciprocal inferior ST depressions and his chest x-ray revealed pulmonary edema. He was given anti-platelet therapy, nitroglycerin, beta blocker and taken emergently for angiography. He had a thrombotic occlusion of a co-dominant anomalous left circumflex artery arising from the ostium of a moderate caliber right coronary artery. He underwent successful percutaneous coronary intervention. His post-revascularization echocardiogram showed a hypokinetic to akinetic inferior wall with preserved global left ventricular systolic function. Coronary CT for further assessment of the course of the anomalous artery was not pursued given minimal benefit and the risk of worsening graft function. He was discharged on dual anti-platelet therapy, beta blocker and a statin. Discussion: There is no consensus about risk stratification before renal transplant. Our patient’s pre-operative exercise treadmill test (ETT) showed reduced functional capacity at 5.6 metabolic equivalents, failure to reach target heart rate, with 1.0 mm down sloping ST depression in infero-lateral leads with no ischemic symptoms. While our patient had an equivocal ETT, his lack of angina argued against further work-up. Post-operatively, a pro-inflammatory state, increased shear stress, acquired thrombophilia and immunosuppressive medications can all contribute to plaque rupture with thrombus formation. Atherosclerosis due to diabetes and renal disease coupled with mechanical factors such as passive compression at the intraarterial course, acute angle take-off or valve-like closure of the slit orifice may have subjected our patient with an anomalous left circumflex artery to an acute ST-elevation MI.
Thirty years of the International Banff Classification for Allograft Pathology: the past, present, and future of kidney transplant diagnostics
Authors: Alexandre Loupy, Michael Mengel, Mark Haas
Journal: Kidney International (2021)

2021 marks the 30th anniversary of the original development of the Banff Classification of Kidney Allograft Pathology, when in August 1991 a group of pathologists and transplant clinicians led by Kim Solez and Lorraine Racusen met in Banff, Alberta, Canada, and established the first widely accepted criteria for the diagnosis of kidney transplant rejection and other lesions seen on kidney allograft biopsies. Since that time, Banff conferences have been held every 2 years at many sites around the world, resulting in several major revisions to the classification and expansion well beyond pure histopathology of kidney allografts to encompass other solid organ transplants, and with involvement of immunogeneticists, immunologists, other basic scientists, biostatisticians, and data scientists defining a very diverse and integrated Banff community. This approach with multidisciplinary international input, constantly incorporating new evidence from the scientific literature and from studies performed by Banff working groups while still maintaining the importance of a long-standing consensus process, has resulted in the Banff classification gaining overwhelming international acceptance as the main reference used for the scoring of kidney allograft biopsies in research studies, routine practice, and clinical trials. This review focuses on the major milestones in the development of the Banff classification of kidney allograft pathology and the evolution of the Banff process over the past 3 decades, with prospects for future advances and refinements.
A global approach to improving penile cancer care
Authors: Marco Bandini, Mohamed Ahmed, Giuseppe Basile, Nicholas Watkin, Viraj Master, Yao Zhu, Gagan Prakash, Alejandro Rodriguez, Mbaaga K. Ssebakumba, Riccardo Leni, Giuseppe Ottone Cirulli, Ben Ayres, Rachel Compitello, Filippo Pederzoli, Pankaj M. Joshi, Sanjay B. Kulkarni, Francesco Montorsi, Guru Sonpavde, Andrea Necchi, Philippe E. Spiess
Journal: Nature Reviews Urology (2021)
The role of estrogen receptor signaling in suppressing the immune response to cancer
Authors: James M. Rae, Marc E. Lippman
Journal: Journal of Clinical Investigation (2021)

Immune checkpoint blockade (ICB) therapies are standard of care for the treatment of many solid tumors. While some patients with cancer experience exceptional and long-term responses, intrinsic and acquired mechanisms of resistance limit the clinical efficacy of ICBs. In addition, ICBs can elicit life-threatening side effects. Alternative options that can increase ICB responses without added toxicities are needed. In this issue of the JCI, Chakraborty et al. explored the role of estrogen receptor α (ERα) in modulating ICB activity. Using transcriptomics and preclinical melanoma models, the authors show that ERα signaling in tumor-associated macrophages contributed to an immune-suppressive state within the tumor microenvironment (TME) by promoting CD8+ T cell dysfunction and exhaustion. Further, in murine melanoma models, the addition of fulvestrant, a selective estrogen receptor downregulator (SERD) approved for the treatment of breast cancer, enhanced the antitumor effects of ICB. These results provide a rationale for human trials to test the combination of antiestrogens with ICBs.
Uncoupled biological and chronological aging of neutrophils in cancer promotes tumor progression
Authors: Laura A Mittmann, Florian Haring, Johanna B Schaubächer, Roman Hennel, Bojan Smiljanov, Gabriele Zuchtriegel, Martin Canis, Olivier Gires, Fritz Krombach, Lesca Holdt, Sven Brandau, Thomas Vogl, Kirsten Lauber, Bernd Uhl, Christoph A Reichel
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Beyond their fundamental role in homeostasis and host defense, neutrophilic granulocytes (neutrophils) are increasingly recognized to contribute to the pathogenesis of malignant tumors. Recently, aging of mature neutrophils in the systemic circulation has been identified to be critical for these immune cells to properly unfold their homeostatic and anti-infectious functional properties. The role of neutrophil aging in cancer remains largely obscure. Methods Employing advanced in vivo microscopy techniques in different animal models of cancer as well as utilizing pulse-labeling and cell transfer approaches, various ex vivo / in vitro assays, and human data, we sought to define the functional relevance of neutrophil aging in cancer. Results Here, we show that signals released during early tumor growth accelerate biological aging of circulating neutrophils, hence uncoupling biological from chronological aging of these immune cells. This facilitates the accumulation of highly reactive neutrophils in malignant lesions and endows them with potent protumorigenic functions, thus promoting tumor progression. Counteracting uncoupled biological aging of circulating neutrophils by blocking the chemokine receptor CXCR2 effectively suppressed tumor growth. Conclusions Our data uncover a self-sustaining mechanism of malignant neoplasms in fostering protumorigenic phenotypic and functional changes in circulating neutrophils. Interference with this aberrant process might therefore provide a novel, already pharmacologically targetable strategy for cancer immunotherapy.
Abstract 9876: Optimizing Public Naloxone Kit Locations Through Mathematical Modeling
Authors: K.H. Benjamin Leung, Brian Grunau, May K Lee, Jane Buxton, Jennie Helmer, Sean Van Diepen, Jim Christenson, Timothy Chan
Journal: Circulation (2021)

Introduction: Use of bystander-administered naloxone may lead to improved likelihood of recovery from opioid overdose. We sought to determine the accessibility of public access naloxone kits on nearby opioid overdose incidents if placed at public transit stops, compared to placing kits outside pharmacies or with existing public access automated external defibrillators (PADs). Methods: We included all incidents in Metro Vancouver, British Columbia responded to by British Columbia Emergency Health Services coded as a drug overdose with naloxone administered on-scene (Dec. 2014 to Aug. 2020). We geo-coded all public transit bus stops and used a mathematical optimization model to select bus stops where publicly accessible naloxone kits could be placed to maximize accessibility (defined as ≤100 m walking distance) to opioid overdoses. We evaluated accessibility on out-of-sample OHCAs using five-fold cross validation and compared against two baseline policies: placing publicly accessible naloxone kits at all pharmacies identified by the College of Pharmacists of British Columbia, and placing kits at all PADs identified by the British Columbia AED Registry. Statistical analysis was conducted using McNemar’s test. Results: We identified 14,318 opioid overdoses, 8,972 bus stops, 736 pharmacies, and 425 PADs. Accessibility of public naloxone kits for opioid overdose locations was 5.1% when placed at all pharmacies and 3.5% when placed with all existing PADs. Optimized naloxone kit placement using bus stops as candidate locations resulted in significantly higher accessibility than both pharmacy and PAD-based placement at 14.8% with 10 optimized locations (P&lt;0.001), increasing to 36.7% with 500 locations (P&lt;0.001). Conclusion: Optimizing placement of public access naloxone kits at select public transit locations can provide significantly higher accessibility to opioid overdose locations compared to placement at pharmacies or at existing PAD locations.
Evaluation of a novel CFTR potentiator in COPD ferrets with acquired CFTR dysfunction
Authors: Niroop Kaza, Vivian Y. Lin, Denise Stanford, Shah S. Hussain, Emily Falk Libby, Harrison Kim, Monica Borgonovi, Katja Conrath, Venkateshwar Mutyam, Stephen A. Byzek, Li Ping Tang, John E. Trombley, Lawrence Rasmussen, Trenton Schoeb, Hui Min Leung, Guillermo J. Tearney, S. Vamsee Raju, Steven M. Rowe
Journal: European Respiratory Journal (2021)

Rationale The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been tested in vivo, given limitations to rodent models of COPD. Ferrets exhibit cystic fibrosis-related lung pathology when CFTR is absent and COPD with bronchitis following cigarette smoke exposure. Objectives To evaluate CFTR dysfunction induced by smoking and test its pharmacological reversal by a novel CFTR potentiator, GLPG2196, in a ferret model of COPD with chronic bronchitis. Methods Ferrets were exposed for 6 months to cigarette smoke to induce COPD and chronic bronchitis and then treated with enteral GLPG2196 once daily for 1 month. Electrophysiological measurements of ion transport and CFTR function, assessment of mucociliary function by one-micron optical coherence tomography imaging and particle-tracking microrheology, microcomputed tomography imaging, histopathological analysis and quantification of CFTR protein and mRNA expression were used to evaluate mechanistic and pathophysiological changes. Measurements and main results Following cigarette smoke exposure, ferrets exhibited CFTR dysfunction, increased mucus viscosity, delayed mucociliary clearance, airway wall thickening and airway epithelial hypertrophy. In COPD ferrets, GLPG2196 treatment reversed CFTR dysfunction, increased mucus transport by decreasing mucus viscosity, and reduced bronchial wall thickening and airway epithelial hypertrophy. Conclusions The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathological features of chronic bronchitis in a COPD ferret model.
Corrigendum to: Deep learning-based automatic tumor burden assessment of pediatric high-grade gliomas, medulloblastomas, and other leptomeningeal seeding tumors
Authors: Jian Peng, Daniel D Kim, Jay B Patel, Xiaowei Zeng, Jiaer Huang, Ken Chang, Xinping Xun, Chen Zhang, John Sollee, Jing Wu, Deepa J Dalal, Xue Feng, Hao Zhou, Chengzhang Zhu, Beiji Zou, Ke Jin, Patrick Y Wen, Jerrold L Boxerman, Katherine E Warren, Tina Y Poussaint, Lisa J States, Jayashree Kalpathy-Cramer, Li Yang, Raymond Y Huang, Harrison X Bai
Journal: Neuro-Oncology (2021)
SARS-CoV-2 infection in fully vaccinated patients with multiple myeloma
Authors: Nicola Sgherza, Paola Curci, Rita Rizzi, Immacolata Attolico, Daniela Loconsole, Anna Mestice, Maria Chironna, Pellegrino Musto
Journal: Blood Cancer Journal (2021)

SARS-CoV-2 Variant of Concern Anti-spike IgG b before infection/days from fully vaccination Anti-spike IgG b post infection/days from fully vaccination Anti SARS-CoV-2 c IgM/ IgG days from infection 1 76 F Hypertension Severe obesity Chronic obstructive bronchopathy Chronic renal failure SMM, IgA λ
Classification of Soft Tissue Sarcoma Specimens with Raman Spectroscopy as Smart Sensing Technology
Authors: Liming Li, Vamiq M. Mustahsan, Guangyu He, Felix B. Tavernier, Gurtej Singh, Brendan F. Boyce, Fazel Khan, Imin Kao
Journal: Cyborg and Bionic Systems (2021)

Intraoperative confirmation of negative resection margins is an essential component of soft tissue sarcoma surgery. Frozen section examination of samples from the resection bed after excision of sarcomas is the gold standard for intraoperative assessment of margin status. However, it takes time to complete histologic examination of these samples, and the technique does not provide real-time diagnosis in the operating room (OR), which delays completion of the operation. This paper presents a study and development of sensing technology using Raman spectroscopy that could be used for detection and classification of the tumor after resection with negative sarcoma margins in real time. We acquired Raman spectra from samples of sarcoma and surrounding benign muscle, fat, and dermis during surgery and developed (i) a quantitative method (QM) and (ii) a machine learning method (MLM) to assess the spectral patterns and determine if they could accurately identify these tissue types when compared to findings in adjacent H&amp;E-stained frozen sections. High classification accuracy (&gt;85%) was achieved with both methods, indicating that these four types of tissue can be identified using the analytical methodology. A hand-held Raman probe could be employed to further develop the methodology to obtain spectra in the OR to provide real-time in vivo capability for the assessment of sarcoma resection margin status.
Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities
Authors: John S. Kim, Gísli Thor Axelsson, Matthew Moll, Michaela R. Anderson, Elana J. Bernstein, Rachel K. Putman, Tomoyuki Hida, Hiroto Hatabu, Eric A. Hoffman, Ganesh Raghu, Steven M. Kawut, Margaret F. Doyle, Russell Tracy, Lenore J. Launer, Ani Manichaikul, Stephen S. Rich, David J. Lederer, Vilmundur Gudnason, Brian D. Hobbs, Michael H. Cho, Gary M. Hunninghake, Christine Kim Garcia, Gunnar Gudmundsson, R. Graham Barr, Anna J. Podolanczuk
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n = 3,547), COPDGene (Genetic Epidemiology of COPD, n = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0–1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1–1.3), COPDGene (OR, 1.3; 95% CI, 1.2–1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0–1.4). A higher monocyte count was associated with ILA progression over 5 years in AGES-Reykjavik (OR, 1.2; 95% CI, 1.0–1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.
Abstract 10618: A Head up CPR Based Care Bundle Improves the Likelihood of Survival to Hospital Discharge After Out of Hospital Cardiac Arrest
Authors: Johanna C Moore, José Labarere, Charles Lick, Sue Duval, Joe Holley, Kenneth Scheppke, Michael Jacobs, Bayert Salverda, Carolina Rojas-Salvador, Paul Nystrom, Ryan Quinn, Paul Adams, Guillaume P Debaty, Mack Hutchison, Charles Mason, Eduardo Martinez, Steven Mason, Armando Clift, Peter Antevy, Eric Grizzard, Sebastian Garay, Keith G Lurie, Paul E Pepe
Journal: Circulation (2021)

Introduction: Survival rates after out-of-hospital cardiac arrest (OHCA) remain poor with widespread use of conventional (C) CPR. Based on pre-clinical studies showing improved cerebral flow and neurologically-intact survival, a FDA approved automated Head Up Positioning (AHUP) device for CPR was developed for use with an impedance threshold device (ITD), and manual and/or automated suction cup-based CPR. A prospective observational IRB approved registry was created to track use and clinical outcomes with this AHUP device based bundle. Hypothesis: Faster time to use of an AHUP CPR bundle improves survival to hospital discharge after OHCA versus historical controls treated with C-CPR. Methods: Registry patients from sites routinely recording time from 911 call to AHUP device placement (T 911 ) were included. C-CPR controls were from 3 prior randomized prospective CPR trials: 1) Resuscitation Outcomes Consortium Prehospital Resuscitation using an IMpedance valve and Early versus Delayed (ROC PRIMED) Study, 2) Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study (ROC-ALPS), 3) The ResQTrial. Propensity score analysis was performed using logistic regression for baseline characteristics including age, sex, witnessed arrest, bystander CPR, shockable rhythm, and time to first responder CPR. Each AHUP patient was matched with up to 4 C-CPR patients. Results: Of 11 U.S. sites reporting AHUP CPR outcomes, 6 had time from 911 call to AHUP device placement recorded (n = 227). The model yielded a c-statistic of 0.76. Stratified by T 911 , the odds of survival with AHUP CPR were significantly higher than with C-CPR between T 911 &lt; 7 minutes (OR 4.57, 95% CI 1.3-16.0) and T 911 &lt; 15 minutes (OR 2.01, 95% CI 1.1-3.8). There was a time dependent effect of AHUP device placement on survival (See Figure). Conclusions: More rapid initiation of an AHUP CPR bundle resulted in improved survival to hospital discharge versus historical controls treated with C-CPR in OHCA.
Phenotype, genotype, treatment, and survival outcomes in patients with X-linked inhibitor of apoptosis deficiency
Authors: Linlin Yang, Claire Booth, Carsten Speckmann, Markus G. Seidel, Austen J.J. Worth, Gerhard Kindle, Arjan C. Lankester, Bodo Grimbacher, Andrew R. Gennery, Mikko R.J. Seppanen, Emma C. Morris, Siobhan O. Burns, Anna Sediva, Benedicte Neven, Fabian Hauck, Klaus Warnatz, Malgorzata Pac, Maria Carrabba, Pere Palacin, Peter Jandus, Ann Gardulf, Nizar Mahlaoui, Martine Pergent, Catharina Schutz, Svetlana Sharapova, Lougaris Vassilios, Fabio Candotti, Stephano Volpi
Journal: Journal of Allergy and Clinical Immunology (2021)
Governance of Emerging Biotechnologies: Lessons from Two Chinese Cases
Authors: Hui Zhang, Cuilian Zhang, Jing Wang, Yongguang Yang, Yubao Wei, Zhenxiang Zhang, Yuming Wang
Journal: The American Journal of Bioethics (2021)

This article is referred to by:Response to Open Peer Commentaries on "Developing a Reflexive, Anticipatory, and Deliberative Approach to Unanticipated Discoveries: Ethical Lessons from iBlastoids"
A041702: A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (≥ 70 Years of Age) with Chronic Lymphocytic Leukemia (CLL)
Authors: Jennifer A. Woyach, Amy S. Ruppert, Gabriela Perez, Allison M Booth, Diane Feldman, Elie G Dib, Aminah Jatoi, Jennifer Le-Rademacher, Nyla A. Heerema, Cecelia Miller, Gerard Lozanski, Richard F. Little, Brian T. Hill, Wei Ding, Richard M. Stone, Sumithra J Mandrekar, John C. Byrd
Journal: Blood (2021)
The number sense represents multitudes and magnitudes
Authors: Oliver R Marshall
Journal: Behavioral and Brain Sciences (2021)

Abstract Clarke and Beck's view that numbers are both second-order and sensible is based on an empirically dubious claim, which is required to show that what they call the “weak sensitivity principle” is satisfied. The explanatory benefits that they say are gained by positing a sensory relation to numbers are also gained by positing such a relation to multitudes of objects.