tbuckley/cabot-search huggingface dataset:
Differences in the genomic landscape of advanced prostate cancer (aPC) patients (pts) with BRCA1 versus BRCA2 mutations as detected by machine learning analysis of the comprehensive genomic profile (CGP) of cell-free DNA (cfDNA).
Authors: Raquel Reisinger, Sergiusz Wesolowski, Umang Swami, Pedro C. Barata, Edgar Javier Hernandez, Roberto Nussenzveig, Gordon Lemmon, Bennet Peterson, Chuck Hensel, Mehmet Asim Bilen, Elisabeth I. Heath, Lakshminarayanan Nandagopal, Philip James Saylor, Hani M. Babiker, Manish Kohli, Sumanta K. Pal, Michael B. Lilly, Mark Yandell, A. Oliver Sartor, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2021)

162 Background: PARP inhibitors (PARPi) provide significant clinical benefit for men with aPC with BRCA 1 and BRCA 2 mutations. However, in clinical trials, pts with BRCA1 mutations appeared to derive less benefit than pts with BRCA2 (De Bono et al., 2020). Probabilistic Graphical Models (PGMs) are artificial intelligence (AI) algorithms that capture multivariate, multi-level dependencies in complex patterns in large datasets while retaining human interpretability. We hypothesize that PGMs can reveal variants in BRCA1 and 2 that co-segregate with other known pathogenic variants and may explain the difference in response to PARPi therapy. Methods: Multilevel gene interdependencies between BRCA1 or BRCA2 were assessed using a Bayesian Network (BN) machine learning approach and Fisher’s exact test. CGP was performed by a validated cfDNA NGS panel that sequenced 74 clinically relevant cancer genes (Guardant360, Redwood City, CA). Only variants of known significance and those of unknown significance with a pathogenic REVEL score were included in the analysis. Results: Of 4671 men with aPC undergoing cfDNA CGP, 1248 men with somatic mutations in BRCA1, BRCA2, ATM, or combinations of the three were included in the analysis. The Bayesian network analysis demonstrated positive interdependencies between pathogenic variants in BRCA1 and 7 other genes. A positive interdependency between BRCA2 and 2 genes was present (table). ATM displayed negative interdependency with both BRCA 1 and 2. Conclusions: Our results demonstrate a decreased association of BRCA2 versus BRCA1 with known or predicted pathogenic variants at other loci. This may explain increased sensitivity of aPC with BRCA2 mutations to PARPi due to fewer concurrent resistance pathways. For example, alteration of ERBB2, which segregates strongly with BRCA1, is known to induce tumor progression and invasion in aPC and is associated with castration-resistance. These hypothesis-generating data reveal differential genomic signatures associated with BRCA1 as compared to BRCA2 and may inform development of future combinatorial treatment regimens for these pts. [Table: see text]
Correction: Article on Phosphatidylinositol 3-Kinase in Breast Cancer
Journal: Clinical Cancer Research (2008)

In the article on phosphatidylinositol 3-kinase in breast cancer in the October 15, 2007 issue of Clinical Cancer Research, the names of the authors, Angelo Paradiso, Anita Mangia, Amalia Azzariti, and Stefania Tommasi, were listed incorrectly.Paradiso A, Mangia A, Azzariti A, Tommasi S. Phosphatidylinositol 3-Kinase in Breast Cancer: Where from Here? Clin Cancer Res 2007;13:5988–90.
The equilibrative nucleoside transporter ENT1 is critical for nucleotide homeostasis and optimal erythropoiesis
Authors: Mahmoud Mikdar, Pedro González-Menéndez, Xiaoli Cai, Yujin Zhang, Marion Serra, Abdoul K. Dembele, Anne-Claire Boschat, Sylvia Sanquer, Cerina Chhuon, Ida Chiara Guerrera, Marc Sitbon, Olivier Hermine, Yves Colin, Caroline Le Van Kim, Sandrina Kinet, Narla Mohandas, Yang Xia, Thierry Peyrard, Naomi Taylor, Slim Azouzi
Journal: Blood (2021)
Melanoma‐associated glycosyltransferase GCNT2 as an emerging biomarker and therapeutic target*
Authors: M. Perez, A. Chakraborty, L.S. Lau, N.B.B. Mohammed, C.J. Dimitroff
Journal: British Journal of Dermatology (2021)

In metastatic melanoma, with a dismal survival rate and propensity for treatment resistance and recurrence, it is critical to establish biomarkers that better predict treatment response and disease severity. The melanoma glycome, composed of complex carbohydrates termed glycans, is an under-investigated area of research, although it is gaining momentum in the cancer biomarker and therapeutics field. Novel findings suggest that glycans play a major role in influencing melanoma progression and could be exploited for prognosticating metastatic activity and/or as therapeutic targets. In this review, we discuss the role of aberrant glycosylation, particularly the specialized function of β1,6 N-acetylglucosaminyltransferase 2 (GCNT2), in melanoma pathogenesis and summarize mechanisms of GCNT2 regulation to illuminate its potential as a predictive marker and therapeutic target.
Quantifying publication rates and time to publication for urologic oncology podium presentations.
Authors: Mark Mikhail, Kevin Chua, Hiren V. Patel, Alexandra L. Tabakin, Sai Krishnaraya Doppalapudi, Saum Ghodoussipour, Isaac Yi Kim, Thomas L Jang, Arnav Srivastava, Eric A. Singer
Journal: Journal of Clinical Oncology (2021)

357 Background: The American Urological Association (AUA) annual meetings serve as a large platform for unpublished research. Among the selected abstracts, podium presentations represent the most impactful submissions. Furthermore, between large meeting attendance and social media promotion, authors can disseminate their findings to a potentially large audience prior to final manuscript publication. While all AUA abstracts do undergo peer review, it is not with the same level of scrutiny that full-length manuscripts receive. Thus, we investigated the publication rates, impact factors, and time to publication of urologic oncology podium presentations at the AUA. Methods: Of 875 podium presentation abstracts from the 2017 AUA Annual meeting, 394 (45.0%) were classified as urologic oncology. We chose 2017 to allow for a three-year window for publication. Abstracts were assessed for subsequent publication between January 1, 2015 and May 31, 2020 with a pre-determined PubMed search protocol. Abstract authors were searched for individually, with key terms being added sequentially until &lt;30 results were generated in PubMed. Each search result was then reviewed until a matching publication was found. Abstracts were deemed published if at least one author of the presented abstract was a manuscript author and/or at least one conclusion in the presented abstract was included in the conclusions of the publication. Publication rates, time to publication, and 2019 journal impact factors were collected. Results: Of 394 urologic oncology podium presentations at the 2017 AUA, 228 (57.9%) focused on prostate cancer, while 81 (20.6%) and 58 (14.7%) presentations focused on kidney and bladder cancer, respectively (table). Overall, 211 (53.6%) podium presentations were published. Median time from presentation to publication was 13.6 months (IQR: 7.5-21.5). There were 9 (2.3%) publications that were published prior to the submission deadline and 57 (14.5%) podium presentations that were published prior to the 2017 AUA meeting. The number of articles published at one, two and three years after the meeting was 90, 170 and 202, respectively. The median journal impact factor of all published works was 3.4 (IQR: 2.7-5.9). Conclusions: While AUA podium presentations disseminate valuable data, approximately half of these presentations were not published in peer-reviewed journals within three years. Therefore, care must be taken when promoting data or adopting new practices based on these presentations alone. [Table: see text]
Audio Interview: The Implications of Changes in the Structural Biology of SARS-CoV-2
Authors: Eric J. Rubin, Lindsey R. Baden, Jonathan Abraham, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

The Implications of Changes in the Structural Biology of SARS-CoV-2 In this audio interview conducted on March 9, 2021, the editors are joined by structural biologist Jonathan Abraham to talk about...
Health disparities in allergic and immunologic conditions in racial and ethnic underserved populations: A Work Group Report of the AAAAI Committee on the Underserved
Authors: Carla M. Davis, Andrea J. Apter, Adrian Casillas, Michael B. Foggs, Margee Louisias, Elsie C. Morris, Anil Nanda, Michael R. Nelson, Princess U. Ogbogu, Cheryl Lynn Walker-McGill, Julie Wang, Tamara T. Perry
Journal: Journal of Allergy and Clinical Immunology (2021)
Extraperitoneal versus transperitoneal approach for robot-assisted radical prostatectomy: An updated systematic review and meta-analysis.
Authors: Michael Uy, Raees Cassim, Jaehoon Kim, Jennifer Hoogenes, Bobby Shayegan, Edward Matsumoto
Journal: Journal of Clinical Oncology (2021)

261 Background: Extraperitoneal RARP (EP-RARP) has recently become a popular surgical approach and is often compared to the transperitoneal RARP (TP-RARP). We conducted a systematic review and meta-analysis of the available literature to evaluate the differences in peri-operative characteristics, oncological and functional control, and surgical complications between EP-RARP and TP-RARP. Methods: A comprehensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Google Scholar, and select conference abstract publications was performed for eligible studies comparing outcomes between EP-RARP versus TP-RARP. This was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered with PROSPERO. A leave-one-out sensitivity analyses was performed to control for heterogeneity and risk of bias. Results: A total of 16 studies (three randomized controlled trials, five prospective, and eight retrospective studies) were included with a total pooled population of 3897 patients including 2201 (56.5%) EP-RARPs and 1696 (43.5%) TP-RARPs. When compared to TP-RARP, EP-RARP offers faster operative time (MD: -14.4 minutes; 95% CI: -26.3, -2.3; p = 0.02), decreased length of post-operative stay (MD: -0.9 days, 95% CI: -1.3, -0.4, p &lt; 0.0001), decreased rates of post-operative ileus (RR: 0.2, 95% CI: 0.1, 0.7, p = 0.009) and inguinal hernia formation (RR: 0.2, 95% CI: 0.1, 0.5, p = 0.001). There were no significant differences in total complications, estimated blood loss, positive surgical margins, or urinary continence at 6 months post-RARP. Conclusions: Based on the available evidence, EP-RARP delivered similar oncological and functional outcomes, while also offering faster operative time, decreased length of post-operative stay, and decreased rates of post-operative ileus and inguinal hernia formation when compared to the TP-RARP. These findings provide evidence-based data for surgical approach optimization and prompts future research to examine whether these findings hold true with recent advances in single-port RARP and outpatient RARP.
Off-label Use of Direct Oral Anticoagulants in Patients Receiving Surgical Mechanical and Bioprosthetic Heart Valves
Authors: Ankur Kalra, Sajjad Raza, Baqir Hasan Jafry, Harley E. King, Joseph A. Lahorra, Lars G. Svensson, Samir R. Kapadia
Journal: JAMA Network Open (2021)

This cohort study assesses direct oral anticoagulant use in patients with surgical prosthetic heart valves in the United States and evaluates differences in preoperative and postoperative profiles in patients discharged while receiving direct oral anticoagulant vs warfarin.
Abstract 11751: Paradoxical Low-flow Low-gradient Aortic Stenosis: Improvement in Indexed Stroke Volume After Trans-catheter Aortic Valve Replacement is Inversely Related to the Number of Conditions Contributing to Low Transvalvular Flow
Authors: Nisha Hosadurg, Dou Huang, Kristen Brown, Andrew R Weintraub, Ayan R Patel, Benjamin S Wessler
Journal: Circulation (2019)

Introduction: Paradoxical low-flow low-gradient aortic stenosis (P-LFLG AS) is associated with high mortality after transcatheter aortic valve replacement (TAVR). Failure to increase SVi after TAVR...
Electrically Conductive and 3D‐Printable Oxidized Alginate‐Gelatin Polypyrrole:PSS Hydrogels for Tissue Engineering
Authors: Thomas Distler, Christian Polley, Fukun Shi, Dominik Schneidereit, Mark. D. Ashton, Oliver Friedrich, Jürgen F. Kolb, John G. Hardy, Rainer Detsch, Hermann Seitz, Aldo R. Boccaccini
Journal: Advanced Healthcare Materials (2021)

Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli-responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin-content oxidized alginate-gelatin (ADA-GEL) hydrogel is reported, offering 3D-printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA-GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D-printability, and cytocompatibility. It is possible to prepare open-porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D-printable ADA-GEL can be rendered conductive (ADA-GEL-PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical-stimulation assisted tissue engineering.
Fluoroquinolones and Aortic Disease
Authors: Milo Gatti, Emanuel Raschi, Fabrizio De Ponti
Journal: JAMA Internal Medicine (2021)

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Ileoileal intussusception treated by polypectomy with spiral enteroscopy in Peutz–Jeghers syndrome
Authors: Pierre Lafeuille, Laura Calavas, Olivier Ragi, Thomas Lambin, Mathieu Pioche, Jean-Christophe Saurin
Journal: Endoscopy (2021)

For two decades, deep enteroscopy using instruments such as double-balloon systems (Fujifilm, Tokyo, Japan) has enabled resection of small-bowel polyps in patients with Peutz–Jeghers syndrome [1]. However, these techniques are time consuming, which has been a major limitation. Motorized spiral enteroscopy (MSE; Olympus Medical, Tokyo, Japan) is a recent advancement in this field; however, very limited data on the efficacy of MSE are available [2] [3]. In a recent European prospective study in patients with suspected small-bowel disease, MSE showed a diagnostic yield of 74 %, a total enteroscopy rate of 10 %, and a low rate of major adverse events (1.5 %) [2].
Correspondence on ‘Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement’
Authors: Aaqib Zaffar Banday, Ankur Kumar Jindal, Surjit Singh
Journal: Annals of the Rheumatic Diseases (2021)

Correspondenceof transcription 1 (STAT1) GOF-an IEI characterised by chronic mucocutaneous candidiasis, autoimmunity and elevated type I interferon signature. 20Forbes et al used ruxolitinib (maximum dose 40 mg/day (adults)) for management of treatment-refractory autoimmune manifestations, including cytopenia, hepatitis, lupus-like manifestations and enteropathy in 11 patients with STAT1 GOF.During 4-34 months of JAKi therapy, improvement was noted in ~80%.The adverse events reported were herpes zoster (requiring antiviral drugs and temporary cessation of ruxolitinib), mild pancreatitis and mild cytopenia. 21Recently, baricitinib (maximum 20 mg/ day) has been reported to result in improvement of pulmonary, cutaneous and neurological manifestations in a young child with USP18 deficiency. 22o conclude, JAKis have emerged as targeted therapy for several monogenic type I interferonopathies, though the data are still not plenitude.
Long-term effectiveness of population-wide multifaceted interventions for hepatocellular carcinoma in Taiwan
Authors: Sih-Han Liao, Chi-Ling Chen, Chen-Yang Hsu, Kuo-Liong Chien, Jia-Horng Kao, Pei-Jer Chen, Tony Hsiu-Hsi Chen, Chien-Hung Chen
Journal: Journal of Hepatology (2021)

Taiwan has launched a series of population-wide interventions to prevent hepatocellular carcinoma (HCC) related to hepatitis B and C virus infection since 1984. We took this opportunity to investigate the impact of each intervention on the incidence and case-fatality rate of HCC, and assessed their relative contributions to the overall reduction in mortality during this period.Population-based registry data on HCC mortality and incidence from individuals aged 0 to 84 years between 1979 and 2016 were collected before (Period 1) and after universal hepatitis B vaccination from 1984 (Period 2), universal health care from 1995 (Period 3), and viral hepatitis therapy from 2003 (Period 4). A Bayesian Poisson regression model was used for mortality decomposition analysis to estimate the respective contributions of these interventions to the reduction in age-specific incidence and case-fatality rates.Mortality declined substantially in children, young- and middle-aged groups, but only slightly decreased in the elderly group. The declining trends in mortality were in part explained by incidence reduction and in part by a remarkable decline in case-fatality rate attributed to universal health care. Hepatitis B vaccination led to a 35.9% (26.8% to 44.4%) reduction in incidence for individuals aged 30 years or below, whereas antiviral therapy reduced the incidence of HCC by 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for individuals aged 30-49 years and 50-69 years, respectively.Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.Since 1984, a series of population-wide interventions have been launched in Taiwan to prevent viral hepatitis-related hepatocellular carcinoma, including a universal hepatitis B vaccination program (from 1984), universal health care (from 1995), and a national viral hepatitis therapy program (from 2004). Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.
Intrinsic Immunogenicity of Small Cell Lung Carcinoma Revealed by Its Cellular Plasticity
Authors: Navin R. Mahadevan, Erik H. Knelson, Jacquelyn O. Wolff, Amir Vajdi, Maria Saigí, Marco Campisi, Deli Hong, Tran C. Thai, Brandon Piel, Saemi Han, Bruce B. Reinhold, Jonathan S. Duke-Cohan, Michael J. Poitras, Luke J. Taus, Patrick H. Lizotte, Andrew Portell, Victor Quadros, Alison D. Santucci, Takahiko Murayama, Israel Cañadas, Shunsuke Kitajima, Aoi Akitsu, Maya Fridrikh, Hideo Watanabe, Brendan Reardon, Prafulla C. Gokhale, Cloud P. Paweletz, Mark M. Awad, Eliezer M. Van Allen, Ana Lako, Xi-Tao Wang, Benjamin Chen, Fangxin Hong, Lynette M. Sholl, Michael Y. Tolstorukov, Kathleen Pfaff, Pasi A. Jänne, Evisa Gjini, Robin Edwards, Scott Rodig, Ellis L. Reinherz, Matthew G. Oser, David A. Barbie
Journal: Cancer Discovery (2021)

Abstract Small cell lung carcinoma (SCLC) is highly mutated, yet durable response to immune checkpoint blockade (ICB) is rare. SCLC also exhibits cellular plasticity, which could influence its immunobiology. Here we discover that a distinct subset of SCLC uniquely upregulates MHC I, enriching for durable ICB benefit. In vitro modeling confirms epigenetic recovery of MHC I in SCLC following loss of neuroendocrine differentiation, which tracks with derepression of STING. Transient EZH2 inhibition expands these nonneuroendocrine cells, which display intrinsic innate immune signaling and basally restored antigen presentation. Consistent with these findings, murine nonneuroendocrine SCLC tumors are rejected in a syngeneic model, with clonal expansion of immunodominant effector CD8 T cells. Therapeutically, EZH2 inhibition followed by STING agonism enhances T-cell recognition and rejection of SCLC in mice. Together, these data identify MHC I as a novel biomarker of SCLC immune responsiveness and suggest novel immunotherapeutic approaches to co-opt SCLC's intrinsic immunogenicity. Significance: SCLC is poorly immunogenic, displaying modest ICB responsiveness with rare durable activity. In profiling its plasticity, we uncover intrinsically immunogenic MHC Ihi subpopulations of nonneuroendocrine SCLC associated with durable ICB benefit. We also find that combined EZH2 inhibition and STING agonism uncovers this cell state, priming cells for immune rejection. This article is highlighted in the In This Issue feature, p. 1861
Seroprevalence and Determinants of Helicobacter pylori Infection in the Hispanic Community Health Study/Study of Latinos
Authors: Sabrina H. Tsang, M. Larissa Avilés-Santa, Christian C. Abnet, Maximo O. Brito, Martha L. Daviglus, Sylvia Wassertheil-Smoller, Sheila F. Castañeda, Sharon Minnerath, Gregory A. Talavera, Barry I. Graubard, Bharat Thyagarajan, M. Constanza Camargo
Journal: Clinical Gastroenterology and Hepatology (2021)