tbuckley/cabot-search huggingface dataset:
Non-granular laterally spreading tumors: potential superficial cancers that artificial intelligence does not easily detect
Authors: Pierre Lafeuille, Jérôme Rivory, Thomas Lambin, Clara Yzet, El Houcine Latif, Adrien Bartoli, Mathieu Pioche
Journal: Endoscopy (2021)

Artificial intelligence (AI) and especially deep learning have recently shown promising results in various medical fields involving endoscopic images [1] [2]. However, as AI becomes more and more powerful, we must remain careful and attentive in detection. We showed recently in a case report that a real-time computer-aided detection system (CADe) may have difficulties in detecting flat colorectal sessile serrated adenomas/polyps (SSA/Ps) [3]. Among the difficult lesions to detect, non-granular laterally spreading tumors (LST-NGs) represent a challenge because, in addition to their flat macroscopic form, which is difficult to identify, they are associated with advanced histology, with 27 % of invasive cancers being found in the elevated non-granular forms and 47 % in the pseudodepressed ones [4]. It is therefore a major challenge for diagnostic endoscopy that these are not missed, as they are potential interval cancers that will have become advanced by the next surveillance colonoscopy 3 or 5 years later.
COVID-19 Outbreaks at Youth Summer Camps — Louisiana, June–July 2021
Authors: Julius L. Tonzel, Theresa Sokol
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

According to sequencing data reported by CDC, the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, has been the predominant lineage circulating in Louisiana since the week of June 20, 2021 (1). In Louisiana, the increased spread of the Delta variant corresponded with the start of the state's fourth and largest increase in average daily COVID-19 incidence to date (1,2). This report describes COVID-19 outbreaks in Louisiana youth summer camps as the Delta variant became the predominant lineage during June-July 2021. This activity was reviewed by the Louisiana Department of Health (LDH) and was conducted consistent with applicable state law and LDH policy.
Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis
Authors: William J. Sandborn, Brian G. Feagan, Geert D’Haens, Douglas C. Wolf, Igor Jovanovic, Stephen B. Hanauer, Subrata Ghosh, AnnKatrin Petersen, Steven Y. Hua, Ji Hwan Lee, Lorna Charles, Denesh Chitkara, Keith Usiskin, Jean-Frederic Colombel, Loren Laine, Silvio Danese
Journal: New England Journal of Medicine (2021)

Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease.We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner, and patients in cohort 2 received open-label ozanimod at the same daily dose. At 10 weeks, patients with a clinical response to ozanimod in either cohort underwent randomization again to receive double-blind ozanimod or placebo for the maintenance period (through week 52). The primary end point for both periods was the percentage of patients with clinical remission, as assessed with the three-component Mayo score. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. Safety was also assessed.In the induction period, 645 patients were included in cohort 1 and 367 in cohort 2; a total of 457 patients were included in the maintenance period. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P<0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], P<0.001). The incidence of clinical response was also significantly higher with ozanimod than with placebo during induction (47.8% vs. 25.9%, P<0.001) and maintenance (60.0% vs. 41.0%, P<0.001). All other key secondary end points were significantly improved with ozanimod as compared with placebo in both periods. The incidence of infection (of any severity) with ozanimod was similar to that with placebo during induction and higher than that with placebo during maintenance. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. Elevated liver aminotransferase levels were more common with ozanimod.Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Funded by Bristol Myers Squibb; True North ClinicalTrials.gov number, NCT02435992.).
The role of transjugular intrahepatic portosystemic shunt in patients with portal hypertension: Advantages and pitfalls
Authors: Hae Lim Lee, Sung Won Lee
Journal: Clinical and Molecular Hepatology (2021)

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective interventional procedure to relieve portal hypertension, which is a main mechanism for the development of complications of liver cirrhosis (LC), such as variceal hemorrhage, ascites, and hepatorenal syndrome. However, the high incidence of adverse events after TIPS implementation limits its application in clinical practice. Esophageal variceal hemorrhage is one of the major indications for TIPS. Recently, preemptively performed TIPS has been recommended, as several studies have shown that TIPS significantly reduced mortality as well as rebleeding or failure to control bleeding in patients who are at high risk of treatment failure for bleeding control with endoscopic variceal ligation and vasoactive drugs. Meanwhile, recurrent ascites is another indication for TIPS with a proven survival benefit. TIPS may also be considered as an effective treatment for other LC complications, usually as an alternative therapy. Although there are concerns about the development of hepatic encephalopathy and hepatic dysfunction after TIPS implementation, careful patient selection using prognostic scores can lead to excellent outcomes. Assessments of cardiac and renal function prior to TIPS may also be considered to improve patient prognosis.
Testing Practices, Interpretation, and Diagnostic Evaluation of Iron Deficiency Anemia by US Primary Care Physicians
Authors: Andrew J. Read, Akbar K. Waljee, Jeremy B. Sussman, Hardeep Singh, Grace Y. Chen, Sandeep Vijan, Sameer D. Saini
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Recognition of iron deficiency anemia (IDA) is important to initiate timely evaluation for gastrointestinal tract cancer. Retrospective studies have reported delays in diagnostic evaluation of IDA as a common factor associated with delayed diagnosis of colorectal cancer. <h3>Objective</h3> To assess how US primary care physicians (PCPs) approach testing for anemia, interpret iron laboratory studies, and refer patients with IDA for gastrointestinal endoscopy. <h3>Design, Setting, and Participants</h3> This survey study, conducted in August 2019, included members of the American College of Physicians Internal Medicine Insiders Panel, a nationally representative group of American College of Physicians membership, who self-identified as PCPs. Participants completed a vignette-based survey to assess practices related to screening for anemia, interpretation of laboratory-based iron studies, and appropriate diagnostic evaluation of IDA. <h3>Main Outcomes and Measures</h3> Descriptive statistics based on survey responses were evaluated for frequency of anemia screening, correct interpretation of iron laboratory studies, and proportion of patients with new-onset IDA referred for gastrointestinal tract evaluation. <h3>Results</h3> Of 631 PCPs who received an invitation to participate in the survey, 356 (56.4%) responded and 31 (4.9%) were excluded, for an adjusted eligible sample size of 600, yielding 325 completed surveys (response rate, 54.2%). Of the 325 participants who completed surveys, 180 (55.4%) were men; age of participants was not assessed. The mean (SD) duration of clinical experience was 19.8 (11.2) years (range, 1.0-45.0 years). A total of 250 participants (76.9%) screened at least some patients for anemia. Interpretation of iron studies was least accurate in a scenario of a borderline low ferritin level (40 ng/mL) with low transferrin saturation (2%); 86 participants (26.5%) incorrectly responded that this scenario did not indicate IDA, and 239 (73.5%) correctly identified this scenario as IDA. Of 312 participants, 170 (54.5%) recommended bidirectional endoscopy (upper endoscopy and colonoscopy) for new IDA for women aged 65 years; of 305 respondents, 168 (55.1%) recommended bidirectional endoscopy for men aged 65 years. <h3>Conclusions and Relevance</h3> In this survey study, US PCPs' self-reported testing practices for anemia suggest overuse of screening laboratory tests, misinterpretation of iron studies, and underuse of bidirectional endoscopy for evaluation of new-onset IDA. Both misinterpretation of iron studies and underuse of bidirectional endoscopy can lead to delayed diagnosis of gastrointestinal tract cancers and warrant additional interventions.
Patient derived organoids in prostate cancer: improving therapeutic efficacy in precision medicine
Authors: Sahithi Pamarthy, Hatem E. Sabaawy
Journal: Molecular Cancer (2021)

Abstract With advances in the discovery of the clinical and molecular landscapes of prostate cancer (PCa), implementation of precision medicine-guided therapeutic testing in the clinic has become a priority. Patient derived organoids (PDOs) are three-dimensional (3D) tissue cultures that promise to enable the validation of preclinical drug testing in precision medicine and coclinical trials by modeling PCa for predicting therapeutic responses with a reliable efficacy. We evaluate the advances in 3D culture and PDO use to model clonal heterogeneity and screen for effective targeted therapies, with a focus on the technological advances in generating PDOs. Recent innovations include the utilization of PDOs both in original research and/or correlative studies in clinical trials to examine drug effects within the PCa tumor microenvironment (TME). There has also been a significant improvement with the utilization of various extracellular matrices and single cell assays for the generation and long-term propagation of PDOs. Single cell derived PDOs could faithfully recapitulate the original tumor and reflect the heterogeneity features. While most PDO use for precision medicine understandably involved tissues derived from metastatic patients, we envision that the generation of PDOs from localized PCa along with the incorporation of cells of the TME in tissue models would fulfill the great potential of PDOs in predicting drug clinical benefits. We conclude that single cell derived PDOs reiterate the molecular features of the original tumor and represent a reliable pre-clinical PCa model to understand individual tumors and design tailored targeted therapies.
1209P RELAY, ramucirumab plus erlotinib (RAM+ERL) in untreated metastatic EGFR-mutant NSCLC (EGFR+NSCLC): Association between TP53 status and clinical outcome
Authors: M. Nishio, L. Paz-Ares, M. Reck, K. Nakagawa, E.B. Garon, M. Ceccarelli, S.R. Wijayawardana, C. Visseren-Grul, S. Novello
Journal: Annals of Oncology (2021)
416P Randomized phase II trial of second-line FOLFIRI-panitumumab vs FOLFIRI alone in Ras wild type (wt) metastatic colorectal cancer (mCRC) patients beyond progression to first-line FOLFOX-panitumumab: BEYOND study (GEMCAD 17-01)
Authors: J. Aparicio, A.C. Virgili Manrique, J. Capdevila, F. Muñoz Boza, P. Galván, P. Richart, H. Oliveres, D. Paez, J. Hernando, S. Garcia Serrano, R. Vera, X. Hernandez, R. Alvarez Gallego, M.C. Riesco-Martinez, X. García de Albeniz, J. Maurel
Journal: Annals of Oncology (2021)
Blood Serum Therapy and Antitoxins.
Journal: JAMA (1895)

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349P The amount of cancer stem cells and the sensitivity to anticancer drugs in glioblastoma primary cell culture
Authors: O. Susova, A. Poletaeva, A. Lupatov, I. Kholodenko, A. Karamysheva, A.A. Mitrofanov, D. Naskhletashvili, T. Nasedkina, A. Bekyashev
Journal: Annals of Oncology (2021)
Controlled temperature-mediated curcumin release from magneto-thermal nanocarriers to kill bone tumors
Authors: A. Khodaei, F. Jahanmard, H.R. Madaah Hosseini, R. Bagheri, A. Dabbagh, H. Weinans, S. Amin Yavari
Journal: Bioactive Materials (2021)

Systemic chemotherapy has lost its position to treat cancer over the past years mainly due to drug resistance, side effects, and limited survival ratio. Among a plethora of local drug delivery systems to solve this issue, the combinatorial strategy of chemo-hyperthermia has recently received attention. Herein we developed a magneto-thermal nanocarrier consisted of superparamagnetic iron oxide nanoparticles (SPIONs) coated by a blend formulation of a three-block copolymer Pluronic F127 and F68 on the oleic acid (OA) in which Curcumin as a natural and chemical anti-cancer agent was loaded. The subsequent nanocarrier SPION@OA-F127/F68-Cur was designed with a controlled gelation temperature of the shell, which could consequently control the release of curcumin. The release was systematically studied as a function of temperature and pH, via response surface methodology (RSM). The bone tumor killing efficacy of the released curcumin from the carrier in combination with the hyperthermia was studied on MG-63 osteosarcoma cells through Alamar blue assay, live-dead staining and apoptosis caspase 3/7 activation kit. It was found that the shrinkage of the F127/F68 layer stimulated by elevated temperature in an alternative magnetic field caused the curcumin release. Although the maximum release concentration and cell death took place at 45 °C, treatment at 41 °C was chosen as the optimum condition due to considerable cell apoptosis and lower side effects of mild hyperthermia. The cell metabolic activity results confirmed the synergistic effects of curcumin and hyperthermia in killing MG-63 osteosarcoma cells.
Activated PI3Kδ signals compromise plasma cell survival via limiting autophagy and increasing ER stress
Authors: Fahd Al Qureshah, Sara Sagadiev, Christopher D. Thouvenel, Shuozhi Liu, Zhaolin Hua, Baidong Hou, Mridu Acharya, Richard G. James, David J. Rawlings
Journal: The Journal of Experimental Medicine (2021)

While phosphatidylinositide 3-kinase delta (PI3Kδ) plays a critical role in humoral immunity, the requirement for PI3Kδ signaling in plasma cells remains poorly understood. Here, we used a conditional mouse model of activated PI3Kδ syndrome (APDS), to interrogate the function of PI3Kδ in plasma cell biology. Mice expressing a PIK3CD gain-of-function mutation (aPIK3CD) in B cells generated increased numbers of memory B cells and mounted an enhanced secondary response but exhibited a rapid decay of antibody levels over time. Consistent with these findings, aPIK3CD expression markedly impaired plasma cell generation, and expression of aPIK3CD intrinsically in plasma cells was sufficient to diminish humoral responses. Mechanistically, aPIK3CD disrupted ER proteostasis and autophagy, which led to increased plasma cell death. Notably, this defect was driven primarily by elevated mTORC1 signaling and modulated by treatment with PI3Kδ-specific inhibitors. Our findings establish an essential role for PI3Kδ in plasma cell homeostasis and suggest that modulating PI3Kδ activity may be useful for promoting and/or thwarting specific immune responses.
1431P Descriptive analysis and prognostic factors of microsatellite instability (MSI) gastric cancer patients (pts) compared to microsatellite stable (MSS) pts in a tertiary hospital
Authors: O. Mirallas, D. López-Valbuena, D. García-Illescas, B. Martin Cullell, N. Rodriguez, A. Gantxegi, D.H. Marmolejo Castaneda, A.A. Valdivia, M.A. Rezqallah Aron, G. Villacampa Javierre, D. Gómez-Puerto, K.S. Vega, G. Molina, C. Salva-Torres, M. Jofre, M. Alsina, S. Castro, J. Tabernero, M. Diez, T. Macarulla Mercade
Journal: Annals of Oncology (2021)
240P A real-world data analysis: The first United Kingdom experience of cyclin-dependent kinase 4/6 inhibitor in advanced breast cancer in the National Health Service within an access program
Authors: C. Palmieri, A. Musson, C. Harper-wynne, D. Wheatley, G. Bertelli, I. MacPherson, M. Nathan, M. Verrill, J. Eva, C. Doody, R. Chowdhury
Journal: Annals of Oncology (2021)
Temporal Trends in Suicide Attempts Among Children in the Decade Before and During the COVID-19 Pandemic in Paris, France
Authors: Anthony Cousien, Eric Acquaviva, Solen Kernéis, Yazdan Yazdanpanah, Richard Delorme
Journal: JAMA Network Open (2021)

This cross-sectional study uses surveillance data to assess temporal trends in suicide attempts among children admitted to a pediatric emergency department in Paris, France, in the decade before and during the COVID-19 pandemic.
983P Phase I dose escalation study in patients (pts) with advanced solid tumours receiving first-in-class BI 765063, a selective signal-regulatory protein α (SIRPα) inhibitor, in combination with ezabenlimab (BI 754091), a programmed cell death protein 1 (PD-1) inhibitor
Authors: N. Kotecki, S. Champiat, J-P. Delord, A. Vinceneux, C. Jungels, A. Marabelle, I. Korakis, S. Wojciekowski, E. Block, N. Clarke, C. Fromond, N. Poirier, D. Costantini, B. Vasseur, P.A. Cassier
Journal: Annals of Oncology (2021)
Leveraging the Treg-intrinsic CTLA4–PKCη signaling pathway for cancer immunotherapy
Authors: Hsin-Yu Liu, Christophe Pedros, Kok-Fai Kong, Ann J Canonigo-Balancio, Wen Xue, Amnon Altman
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Our previous studies revealed a critical role of a novel CTLA4-protein kinase C-eta (PKCη) signaling axis in mediating the suppressive activity of regulatory T cells (Tregs) in antitumor immunity. These studies have employed adoptive transfer of germline PKCη-deficient ( Prkch −/− ) Tregs into Prkch +/+ mice prior to tumor implantation. Here, we extended these findings into a biologically and clinically more relevant context. Methods We have analyzed the role of PKCη in antitumor immunity and the tumor microenvironment (TME) in intact tumor-bearing mice with Treg-specific or CD8 + T cell-specific Prkch deletion, including in a therapeutic model of combinatorial treatment. In addition to measuring tumor growth, we analyzed the phenotype and functional attributes of tumor-infiltrating immune cells, particularly Tregs and dendritic cells (DCs). Results Using two models of mouse transplantable cancer and a genetically engineered autochthonous hepatocellular carcinoma (HCC) model, we found, first, that mice with Treg-specific Prkch deletion displayed a significantly reduced growth of B16–F10 melanoma and TRAMP-C1 adenocarcinoma tumors. Tumor growth reduction was associated with a less immunosuppressive TME, indicated by increased numbers and function of tumor-infiltrating CD8 + effector T cells and elevated expression of the costimulatory ligand CD86 on intratumoral DCs. In contrast, CD8 + T cell-specific Prkch deletion had no effect on tumor growth or the abundance and functionality of CD8 + effector T cells, consistent with findings that Prkch −/− CD8 + T cells proliferated normally in response to in vitro polyclonal or specific antigen stimulation. Similar beneficial antitumor effects were found in mice with germline or Treg-specific Prkch deletion that were induced to develop an autochthonous HCC. Lastly, using a therapeutic model, we found that monotherapies consisting of Treg-specific Prkch deletion or vaccination with irradiated Fms-like tyrosine kinase 3 ligand (Flt3L)-expressing B16–F10 tumor cells post-tumor implantation significantly delayed tumor growth. This effect was more pronounced in mice receiving a combination of the two immunotherapies. Conclusion These findings demonstrate the potential utility of PKCη inhibition as a viable clinical approach to treat patients with cancer, especially when combined with adjuvant therapies.
537P-SC Exposure-response analysis of cabozantinib in patients with metastatic renal cell cancer treated in routine care
Authors: S.D. Krens, N.P. van Erp, S. Groenland, D.J.A. Moes, I.M.E. Desar, S.F. Mulder, T. Van Der Hulle, N. Steeghs, C.M. Van Herpen
Journal: Annals of Oncology (2021)