tbuckley/cabot-search huggingface dataset:
Transfer learning between preclinical models and human tumors identifies a conserved NK cell activation signature in anti-CTLA-4 responsive tumors
Authors: Emily F. Davis-Marcisak, Allison A. Fitzgerald, Michael D. Kessler, Ludmila Danilova, Elizabeth M. Jaffee, Neeha Zaidi, Louis M. Weiner, Elana J. Fertig
Journal: Genome Medicine (2021)

Abstract Background Tumor response to therapy is affected by both the cell types and the cell states present in the tumor microenvironment. This is true for many cancer treatments, including immune checkpoint inhibitors (ICIs). While it is well-established that ICIs promote T cell activation, their broader impact on other intratumoral immune cells is unclear; this information is needed to identify new mechanisms of action and improve ICI efficacy. Many preclinical studies have begun using single-cell analysis to delineate therapeutic responses in individual immune cell types within tumors. One major limitation to this approach is that therapeutic mechanisms identified in preclinical models have failed to fully translate to human disease, restraining efforts to improve ICI efficacy in translational research. Method We previously developed a computational transfer learning approach called projectR to identify shared biology between independent high-throughput single-cell RNA-sequencing (scRNA-seq) datasets. In the present study, we test this algorithm’s ability to identify conserved and clinically relevant transcriptional changes in complex tumor scRNA-seq data and expand its application to the comparison of scRNA-seq datasets with additional data types such as bulk RNA-seq and mass cytometry. Results We found a conserved signature of NK cell activation in anti-CTLA-4 responsive mouse and human tumors. In human metastatic melanoma, we found that the NK cell activation signature associates with longer overall survival and is predictive of anti-CTLA-4 (ipilimumab) response. Additional molecular approaches to confirm the computational findings demonstrated that human NK cells express CTLA-4 and bind anti-CTLA-4 antibodies independent of the antibody binding receptor (FcR) and that similar to T cells, CTLA-4 expression by NK cells is modified by cytokine-mediated and target cell-mediated NK cell activation. Conclusions These data demonstrate a novel application of our transfer learning approach, which was able to identify cell state transitions conserved in preclinical models and human tumors. This approach can be adapted to explore many questions in cancer therapeutics, enhance translational research, and enable better understanding and treatment of disease.
Antimicrobial resistance genes and clonal success in Escherichia coli isolates causing bloodstream infection
Authors: Sam Lipworth, Timothy Ea Peto, Derrick W Crook, A Sarah Walker, Nicole Stoesser
Journal: The Lancet Microbe (2021)

We read with interest the study by Gladstone and colleagues1 describing a large, longitudinal survey of Escherichia coli bacteraemia isolates from Norway from 2002 to 2017. The authors’ central hypothesis is that antimicrobial resistance does not explain clonal success, using the example of the early and sustained growth of the predominantly antimicrobial susceptible clonal complex 131 (CC131) clade A versus the multidrug resistant clade C2. However, the authors characterised clade A as being drug susceptible based on the presence or absence of blaCTX-M and fluoroquinolone resistance mechanisms only.
Prescribing Trends of Antidiabetes Medications in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A Cohort Study
Authors: Samantha T. Harris, Elisabetta Patorno, Min Zhuo, Seoyoung C. Kim, Julie M. Paik
Journal: Diabetes Care (2021)

OBJECTIVE To assess changes in antidiabetes medication class prescriptions over time among patients with diabetic kidney disease (DKD), characteristics of patients prescribed these medications, and prescribers’ specialty. RESEARCH DESIGN AND METHODS We conducted a cohort study design using insurance claims data between 2013 and the first quarter of 2020 (2020Q1). Included are adult patients with DKD who initiated a new antidiabetes medication between 2013 and 2020Q1 (N = 160,489 patients). The primary outcome is the yearly and quarterly percent of medication initiation for each antidiabetes medication class over all antidiabetes medication initiations. RESULTS For patients with DKD, sodium–glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide 1 receptor agonist (GLP-1RA) initiations steadily increased between 2013 and 2020Q1. Internists and endocrinologists were the most frequent prescriber specialties. Patients &amp;lt;65 years of age had a larger percentage of all initiations that were SGLT2i or GLP-1RA, 16% and 23%, respectively, in 2019, and patients &amp;gt;75 years of age had a smaller percentage of all initiations that were SGLT2i or GLP-1RA, 11% and 13%, in 2019. CONCLUSIONS For patients with DKD, SGLT2i and GLP-1RA prescriptions have increased over time, likely reflecting evolving prescribing patterns in response to the results of recent clinical trials and new clinical guidelines.
潜在的前軟骨形成性,抗炎症性二重機能性疾患修飾性変形性関節症薬物としての神経EGFP様1【JST・京大機械翻訳】
Authors: Li Chenshuang, Zheng Zhong, Ha Pin, Jiang Wenlu, A Berthiaume Emily, Lee Seungjun, Mills Zane, Pan Hsinchuan, C Chen Eric, Jiang Jie, T Culiat Cymbeline, Zhang Xinli, Ting Kang, Soo Chia
Journal: Biomaterials (2020)
Molecular Epidemiology of Acute Myeloid Leukemia (AML): Novel Association of Clinical Epidemiologic Exposures with Unique Mutation Groups on Exome Sequencing of Leukemia DNA in the Mayo Clinic AML Epidemiology Cohort
Authors: James M. Foran, Michael Heckman, Rhett P. Ketterling, Lisa Sproat, Liuyan Jennifer Jiang, Bruce Eckloff, Nancy Diehl, Laura E. Finn, Keith Robertson, Raoul Tibes, James R. Cerhan, Yan W Asmann
Journal: Blood (2017)
P-150 Insights into the gastric and oesophageal cancer patient experience: Results of a pan-European patient survey
Authors: Z. Maravic, V. Fotaki, O. Mesalles Naranjo, E. Gasenko, I. Rawicka, P. Ruiz Aguilar, C. Santangelo, L. Wyrwicz, M. Leja
Journal: Annals of Oncology (2021)
Face-to-face with Sports Medicine Australia. Welcome back!
Authors: Andrea Britt Mosler, Myles Calder Murphy
Journal: British Journal of Sports Medicine (2021)

As the world continues to deal with the devasting impact of the COVID-19 pandemic, Sports Medicine Australia (SMA) has resumed face-to-face education events… with an innovative virtual spin. SMA is excited to present the annual conference in Australia’s premier sporting city of Melbourne from 6 to 9 October 2021. While Australia’s borders remain closed, we welcome high profile international keynote speakers presenting virtually, complemented by an array of high calibre Australian keynote and invited speakers interacting face-to-face. All the usual educational and social components we love about the annual SMA conference will be there to enjoy.

The adaptation and resurgence of outdoor forms of exercise during the COVID-19 pandemic has put a spotlight on sports like running and rowing which can be performed with relatively safe physical distancing. Many of Australia’s Olympic Gold medal winning rowers trained on Melbourne’s Yarra river leaving their medical teams to manage the long-recognised high prevalence of low back pain. In this issue, important recommendations to assist clinicians working with rowers is provided by the new consensus statement coauthored by world experts led by Dr Wilson …
Identification of the Nature of Cardiac Resident c-kit(+) Cells
Authors: Chen-Leng Cai, Nishat Sultana, Lu Zhang, Jianyun Yan, Jiqiu Chen, Weibin Cai, Shegufta Razzaque, Dongtak Jeong, Wei Sheng, Lei Bu, Mingjiang Xu, Guo-Ying Huang, Roger Hajjar, Bin Zhou, Anne Moon
Journal: Circulation Research (2016)
FUNDC1 insufficiency sensitizes high fat diet intake-induced cardiac remodeling and contractile anomaly through ACSL4-mediated ferroptosis
Authors: Zhaohui Pei, Yandong Liu, Suqin Liu, Wei Jin, Yuanfei Luo, Mingming Sun, Yu Duan, Amir Ajoolabady, James R Sowers, Yan Fang, Feng Cao, Haixia Xu, Yaguang Bi, Shuyi Wang, Jun Ren
Journal: Metabolism (2021)
Single-Dose Radiotherapy for Prostate Cancer—Lessons Learned From Single-Fraction High-Dose-Rate Brachytherapy
Authors: Bryan S. Squires, Daniel J. Krauss
Journal: JAMA Oncology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Lifestyle Factors and Subsequent Ischemic Heart Disease Risk after Hematopoietic Cell Transplantation
Authors: Kasey J Leger, K. Scott Baker, Kara Cushing-Haugen, Mary E. Flowers, Wendy M. Leisenring, Paul J. Martin, Jason A. Mendoza, Kerryn Reding, Karen L. Syrjala, Stephanie J Lee, Eric J Chow
Journal: Blood (2017)
Neural fragility as an EEG marker of the seizure onset zone
Authors: Adam Li, Chester Huynh, Zachary Fitzgerald, Iahn Cajigas, Damian Brusko, Jonathan Jagid, Angel O. Claudio, Andres M. Kanner, Jennifer Hopp, Stephanie Chen, Jennifer Haagensen, Emily Johnson, William Anderson, Nathan Crone, Sara Inati, Kareem A. Zaghloul, Juan Bulacio, Jorge Gonzalez-Martinez, Sridevi V. Sarma
Journal: Nature Neuroscience (2021)
Predicted Risks of Cardiovascular Disease Following Chemotherapy and Radiotherapy in the UK NCRI RAPID Trial of Positron Emission Tomography–Directed Therapy for Early-Stage Hodgkin Lymphoma
Authors: David J. Cutter, Johanna Ramroth, Patricia Diez, Andy Buckle, Georgios Ntentas, Bilyana Popova, Laura Clifton-Hadley, Peter J. Hoskin, Sarah C. Darby, John Radford, Tim Illidge
Journal: Journal of Clinical Oncology (2021)

The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL.
Self-testing for the detection of SARS-CoV-2 infection with rapid antigen tests for people with suspected COVID-19 in the community
Authors: Joep J.J.M. Stohr, Vivian F. Zwart, Gabriel Goderski, Adam Meijer, Carla R.S. Nagel-Imming, Marjolein F.Q. Kluytmans-van den Bergh, Suzan D. Pas, Femke van den Oetelaar, Marloes Hellwich, Kim H. Gan, Ariene Rietveld, Jaco J. Verweij, Jean-Luc Murk, Wouter van den Bijllaardt, Jan A.J.W. Kluytmans
Journal: Clinical Microbiology and Infection (2021)

To evaluate the performance of nasal mid-turbinate self-testing using rapid antigen detection tests (RDT) for persons with suspected coronavirus disease 2019 (COVID-19) in the community. Self-testing for COVID-19 infection with lateral flow assay severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RDT, provides rapid results and could enable frequent and extensive testing in the community, thereby improving the control of SARS-CoV-2.Participants visiting a municipal SARS-CoV-2 testing centre, received self-testing kits containing either the BD Veritor System (BD-RDT) or Roche SARS-CoV-2 antigen detection test (Roche-RDT). Oro-nasopharyngeal swabs were collected from the participants for quantitative RT-PCR (qRT-PCR) testing. As a proxy for contagiousness, viral culture was performed on a selection of qRT-PCR positive samples to determine the Ct-value at which the chance of a positive culture dropped below 0.5 (Ct-value cut-off). Sensitivity and specificity of self-testing were compared to qRT-PCR with a Ct-value below the Ct value cut-off. Determinants independently associated with a false-negative self-test result were determined.A total of 3201 participants were included (BD-RDT n = 1595; Roche-RDT n = 1606). Sensitivity and specificity of self-testing compared with the qRT-PCR results with a Ct-value below the Ct-value cut-off were 78.4% (95% CI 73.2%-83.5%) and 99.4% (95% CI 99.1%-99.7%), respectively. A higher age was independently associated with a false-negative self-testing result with an odds ratio of 1.024 (95% CI 1.003-1.044).Self-testing using currently available RDT has a high specificity and relatively high sensitivity to identify individuals with a high probability of contagiousness.
P-266 Oncological outcomes of self-expanding metal stent as a bridge to surgery for obstructive left-sided colon cancer
Authors: L. Gomez Fernandez, S. Lamas Moure, Y. Ribas Blasco, J. Bargallo Berzosa, L. Cayetano Paniagua, C. Balaguer del Ojo, E. Dotor Navarro, P. Palma Carazo
Journal: Annals of Oncology (2021)
Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy: A Randomized, Phase 3 Trial
Authors: Hartmut Döhner, Argiris Symeonidis, Dries Deeren, Judit Demeter, Miguel A. Sanz, Achilles Anagnostopoulos, Jordi Esteve, Walter Fiedler, Kimmo Porkka, Hee-Je Kim, Je-Hwan Lee, Kensuke Usuki, Stefano D'Ardia, Chul Won Jung, Olga Salamero, Heinz-August Horst, Christian Recher, Philippe Rousselot, Irwindeep Sandhu, Koen Theunissen, Felicitas Thol, Konstanze Döhner, Veronica Teleanu, Daniel J. DeAngelo, Tomoki Naoe, Mikkael A. Sekeres, Valerie Belsack, Miaomiao Ge, Tillmann Taube, Oliver G. Ottmann
Journal: HemaSphere (2021)

In this phase 3 trial, older patients with acute myeloid leukemia ineligible for intensive chemotherapy were randomized 2:1 to receive the polo-like kinase inhibitor, volasertib (V; 350 mg intravenous on days 1 and 15 in 4-wk cycles), combined with low-dose cytarabine (LDAC; 20 mg subcutaneous, twice daily, days 1–10; n = 444), or LDAC plus placebo (P; n = 222). Primary endpoint was objective response rate (ORR); key secondary endpoint was overall survival (OS). Primary ORR analysis at recruitment completion included patients randomized ≥5 months beforehand; ORR was 25.2% for V+LDAC and 16.8% for P+LDAC (n = 371; odds ratio 1.66 [95% confidence interval (CI), 0.95–2.89]; P = 0.071). At final analysis (≥574 OS events), median OS was 5.6 months for V+LDAC and 6.5 months for P+LDAC (n = 666; hazard ratio 0.97 [95% CI, 0.8–1.2]; P = 0.757). The most common adverse events (AEs) were infections/infestations (grouped term; V+LDAC, 81.3%; P+LDAC, 63.5%) and febrile neutropenia (V+LDAC, 60.4%; P+LDAC, 29.3%). Fatal AEs occurred in 31.2% with V+LDAC versus 18.0% with P+LDAC, most commonly infections/infestations (V+LDAC, 17.1%; P+LDAC, 6.3%). Lack of OS benefit with V+LDAC versus P+LDAC may reflect increased early mortality with V+LDAC from myelosuppression and infections.
Flat-based over-the-scope clip-assisted endoscopic full-thickness resection of a duodenal neuroendocrine tumour: a safe alternative to endoscopic submucosal dissection
Authors: Nikhil Sonthalia, Bhavik Bharat Shah, Mahesh Kumar Goenka
Journal: Endoscopy (2021)

Corrected by: Correction: Flat-based over-the-scope clip-assisted endoscopic full-thickness resection of a duodenal neuroendocrine tumour: a safe alternative to endoscopic submucosal dissectionEndoscopy 2022; 54(07): C9-C9DOI: 10.1055/a-1823-2120
Sepsis
Authors: P. B. Baines, A. P. J. Thomson, J. A. Sills, C. A. Hart, J. Britto, N. Arends, E. Oragui, D. Ajayi-obe, S. Nadel, P. Habibi, M. Levin, P. B. Baines, S. Stanford, D. Bishop-Bailey, A. P. J. Thompson, J. A. Mitchell, C. A. Hart, A. J. Petros, S. Yeung, S. Nadel, M. Levin, G. Turner, R. Taylor, S. Nadel, M. J. Newport, R. Booy, M. Levin, J. E. Fischen, J. C. Fischer, G. Printzen, E. Schmid, D. Nadal, S. Fanconi, M. Widjajanti, None Dhamhur, E. M. Halimun, D. G. Mulyo
Journal: Intensive Care Medicine (1996)
PI3Kα inhibitor CYH33 triggers antitumor immunity in murine breast cancer by activating CD8<sup>+</sup>T cells and promoting fatty acid metabolism
Authors: Pu Sun, Xi Zhang, Rong-Jing Wang, Qing-Yang Ma, Lan Xu, Yi Wang, Hui-Ping Liao, Hai-Long Wang, Lan-Dian Hu, Xiangyin Kong, Jian Ding, Ling-Hua Meng
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The phosphatidylinositol 3-kinase (PI3K) is frequently hyperactivated in cancer and plays important roles in both malignant and immune cells. The effect of PI3Kα inhibitors on the tumor microenvironment (TME) remains largely unknown. Here, we investigated the modulation of the TME by a clinical PI3Kα-specific inhibitor CYH33. Methods The activity of CYH33 against a panel of murine tumors in the immune-competent context or athymic mice was detected. Single-cell RNA sequencing and multi-parameter flow cytometry were performed to determine the immune profiling of TME. The effect of CYH33 on immune cells was conducted with primary murine cells. Results CYH33 exhibited more potent antitumor activity in immune-competent context. CYH33 enhanced the infiltration and activation of CD8 + T and CD4 + T cells, while attenuating M2-like macrophages and regulatory CD4 + T cells. Increase in memory T cells was confirmed by the induction of long-term immune memory on CYH33 treatment. Mechanistically, CYH33 relieved the suppressed expansion of CD8 + T cells via preferential polarization of the macrophages to the M1 phenotype. CYH33 promoted fatty acid (FA) metabolism in the TME, while FA enhanced the activity of CD8 + T cells in vitro. The combination of CYH33 with the FA synthase (FASN) inhibitor C75 synergistically inhibited tumor growth with enhanced host immunity. Conclusions CYH33 induces immune activation and synergizes with FASN inhibitor to further promote the antitumor immunity, which gains novel insights into how PI3K inhibitors exert their activity by modulating TME and provides a rationale for the concurrent targeting of PI3K and FASN in breast cancer treatment.
Review of UKFPO required: unrepresentative, uncommunicative, and uncompassionate
Authors: Amy X Li
Journal: BMJ (2021)

When I submitted my application for the situational judgment test on Oriel an error occurred—my first name was listed as “A” instead of “Amy.”1 I emailed the UK Foundation Programme Office (UKFPO) about this four times. The responses were brief, lacked comprehension of my problem, and concluded that Pearson VUE (the IT service provider) would have received my …
Changes in the hepatitis C cascade of care among individuals attending primary and community health services before and after the introduction of direct-acting antiviral treatment in Australia
Authors: Michael Traeger, Alisa Pedrana, Daniela van Santen, Joseph Doyle, Jess Howell, Alexander Thompson, Carol El-Hayek, Jason Asselin, Victoria Polkinghorne, Dean Membrey, Frances Bramwell, Allison Carter, Rebecca Guy, Mark Stoove, Margaret Hellard
Journal: Journal of Hepatology (2020)
Incidence of Cancer Among Adults With Thrombocytosis in Ontario, Canada
Authors: Vasily Giannakeas, Steven A. Narod
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Individuals with newly diagnosed cancer often have a high platelet count (thrombocytosis). Whether thrombocytosis is associated with the presence of an undiagnosed cancer remains unknown. <h3>Objective</h3> To assess whether a new diagnosis of thrombocytosis is associated with a subsequent risk of cancer among adults. <h3>Design, Setting, and Participants</h3> This population-based retrospective cohort study was conducted using linked laboratory data from Ontario, Canada, from January 1, 2007, to December 31, 2017, with follow-up until December 31, 2018. The study cohort included adults aged 40 to 75 years on the date of a routine complete blood count (CBC) test (index test) who had a normal platelet count in the 2 previous years and no history of cancer. Data analysis was performed in December 2020. <h3>Exposures</h3> Exposed individuals were those with a platelet count greater than 450 × 10<sup>9</sup>/L. Matched unexposed control individuals had a platelet count within the reference range (150 × 10<sup>9</sup>/L to 450 × 10<sup>9</sup>/L) reported within 30 days of the exposure. <h3>Main Outcomes and Measures</h3> Incident cancers within 5 years after diagnosis of thrombocytosis. Absolute and relative risks for cancer associated with thrombocytosis were estimated for all cancers and for cancers at specific sites. <h3>Results</h3> Of the 3 386 716 Ontario residents with a recorded routine CBC test result, 53 339 (1.6%) had thrombocytosis and a prior normal platelet count. Among individuals with thrombocytosis, the median age was 59.7 years (interquartile range, 50.2-67.4 years) and 37 349 (70.0%) were women. Among the 51 624 individuals with thrombocytosis included in the matched analysis, 2844 (5.5%) had received a diagnosis of a solid cancer in the 2-year follow-up period and 3869 (7.5%) had received a diagnosis within 5 years. The relative risk (RR) for developing any solid cancer within 2 years was 2.67 (95% CI, 2.56-2.79). Associations were found between thrombocytosis and cancers of the ovary (RR, 7.11; 95% CI, 5.59-9.03), stomach (RR, 5.53; 95% CI, 4.12-7.41), colon (RR, 5.41; 95% CI, 4.80-6.10), lung (RR, 4.41; 95% CI, 4.02-4.85), kidney (RR, 3.64; 95% CI, 2.94-4.51), and esophagus (RR, 3.64; 95% CI, 2.46-5.40). <h3>Conclusions and Relevance</h3> In this cohort study, an increased platelet count was associated with an increased risk of cancer for at least 2 years. The results suggest that individuals with unexplained thrombocytosis should be offered screening for several cancers.