tbuckley/cabot-search huggingface dataset:
Risk of recurrence when cutting into intramucosal (pT1a) cancer from the cutting-plane side during gastric endoscopic submucosal dissection
Authors: Hiroko Nakahira, Takashi Kanesaka, Noriya Uedo, Masayasu Ohmori, Hiroyoshi Iwagami, Noriko Matsuura, Satoki Shichijo, Akira Maekawa, Sachiko Yamamoto, Yoji Takeuchi, Koji Higashino, Masanori Kitamura, Shinichi Nakatsuka, Ryu Ishihara
Journal: Endoscopy (2020)

Background During endoscopic submucosal dissection (ESD), procedural difficulty and poor visibility of the cutting plane sometimes cause the operator to cut into the lesion from the cutting-plane side, making the vertical margin positive (VM1) or unclear (VMX). In the present study, we evaluated the risk of recurrence of gastric cancer with VM1 /VMX after ESD. Methods In total, 1723 consecutive gastric cancers treated by ESD at Osaka International Cancer Institute from July 2012 to December 2017 were included in this retrospective cohort study. Among them, 231 submucosal or more deeply invasive gastric cancers were excluded because nontechnical factors may contribute to VM1 /VMX in such lesions. To quantify the risk of cutting into cancer from the cutting-plane side during ESD, the proportion of lesions with VM1 /VMX among the pT1a gastric cancers treated by ESD was calculated. The proportion of recurrence among these cases was calculated after exclusion of lesions with positive lymphovascular invasion or a positive horizontal margin in order to eliminate the obvious risk factors for recurrence. Results Among 1492 pT1a gastric cancers treated by ESD, 28 lesions (1.9 %; 95 % confidence interval [CI] 1.3 % – 2.7 %) histologically showed VM1 /VMX. No local recurrence (0.0 %; 95 %CI 0.0 % – 12.2 %) occurred among 23 cases. The median follow-up period was 41 months (range 10 – 84 months). Conclusions No local recurrence was detected in pT1a gastric cancers after VM1 /VMX resection by ESD. Surveillance endoscopy could be adopted for such cases without additional surgery.
Erratum. Changes in Screening Practices for Prediabetes and Diabetes Since the Recommendation for Hemoglobin A<sub>1c</sub> Testing. Diabetes Care 2019;42:576–584
Authors: Joshua M. Evron, William H. Herman, Laura N. McEwen
Journal: Diabetes Care (2020)

Acknowledgment of funding support was inadvertently omitted from the above-mentioned article. The following information is added:

Funding. …
CD200 promotes immunosuppression in the pancreatic tumor microenvironment
Authors: Fouad Choueiry, Molly Torok, Reena Shakya, Kriti Agrawal, Anna Deems, Brooke Benner, Alice Hinton, Jami Shaffer, Bradley W Blaser, Anne M Noonan, Terence M Williams, Mary Dillhoff, Darwin L Conwell, Phil A Hart, Zobeida Cruz-Monserrate, Xue-Feng Bai, William E Carson III, Thomas A Mace
Journal: Journal for ImmunoTherapy of Cancer (2020)

A significant challenge to overcome in pancreatic ductal adenocarcinoma (PDAC) is the profound systemic immunosuppression that renders this disease non-responsive to immunotherapy. Our supporting data provide evidence that CD200, a regulator of myeloid cell activity, is expressed in the PDAC microenvironment. Additionally, myeloid-derived suppressor cells (MDSC) isolated from patients with PDAC express elevated levels of the CD200 receptor (CD200R). Thus, we hypothesize that CD200 expression in the PDAC microenvironment limits responses to immunotherapy by promoting expansion and activity of MDSC.Immunofluorescent staining was used to determine expression of CD200 in murine and human PDAC tissue. Flow cytometry was utilized to test for CD200R expression by immune populations in patient blood samples. In vivo antibody blocking of CD200 was conducted in subcutaneous MT-5 tumor-bearing mice and in a genetically engineered PDAC model (KPC-Brca2 mice). Peripheral blood mononuclear cells (PBMC) from patients with PDAC were analyzed by single-cell RNA sequencing. MDSC expansion assays were completed using healthy donor PBMC stimulated with IL-6/GM-CSF in the presence of recombinant CD200 protein.We found expression of CD200 by human pancreatic cell lines (BxPC3, MiaPaca2, and PANC-1) as well as on primary epithelial pancreatic tumor cells and smooth muscle actin+ stromal cells. CD200R expression was found to be elevated on CD11b+CD33+HLA-DRlo/- MDSC immune populations from patients with PDAC (p=0.0106). Higher expression levels of CD200R were observed in CD15+ MDSC compared with CD14+ MDSC (p<0.001). In vivo studies demonstrated that CD200 antibody blockade limited tumor progression in MT-5 subcutaneous tumor-bearing and in KPC-Brca2 mice (p<0.05). The percentage of intratumoral MDSC was significantly reduced in anti-CD200 treated mice compared with controls. Additionally, in vivo blockade of CD200 can also significantly enhance the efficacy of PD-1 checkpoint antibodies compared with single antibody therapies (p<0.05). Single-cell RNA sequencing of PBMC from patients revealed that CD200R+ MDSC expressed genes involved in cytokine signaling and MDSC expansion. Further, in vitro cytokine-driven expansion and the suppressive activity of human MDSC was enhanced when cocultured with recombinant CD200 protein.These results indicate that CD200 expression in the PDAC microenvironment may regulate MDSC expansion and that targeting CD200 may enhance activity of checkpoint immunotherapy.
Synergistic targeting of <i>FLT3</i> mutations in AML via combined menin-MLL and FLT3 inhibition
Authors: Margarita M. Dzama, Marlene Steiner, Johanna Rausch, Daniel Sasca, Jonas Schönfeld, Kerstin Kunz, Martha C. Taubert, Gerard M. McGeehan, Chun-Wei Chen, Annalisa Mupo, Patricia Hähnel, Matthias Theobald, Thomas Kindler, Richard P. Koche, George S. Vassiliou, Scott A. Armstrong, Michael W. M. Kühn
Journal: Blood (2020)
COVID-19 from the land “Down Under” in an upside-down world: an Australian perspective
Authors: Catherine Rang, Allen Cheng, Paul Kelly, Tom Kotsimbos
Journal: European Respiratory Journal (2020)

<b>Australia9s approach to the current COVID-19 pandemic has resulted in relative containment of the disease. However, it must be remembered that any defence is only as strong as its weakest link.</b>https://bit.ly/2N2hHy1
NHS trust was negligent in failing to recognise child’s serious bacterial infection, says High Court
Authors: Clare Dyer
Journal: BMJ (2020)

A High Court judge has ruled that an NHS trust was negligent in failing to consider early enough that a toddler with fever, lethargy, and vomiting might have had a serious bacterial infection and to give her intramuscular antibiotics.1

Mr Justice Johnson said that doctors from University Hospital Southampton NHS Foundation Trust should have ordered a lumbar puncture on the 15 month old girl on the day she was first seen or the next day.

The girl, referred to in court as SC, was sent by her GP to the hospital by ambulance on 26 January 2006 with a note describing his findings on examination and ending “?meningitis.” The GP, Mark Dennison, had given her intramuscular penicillin.

But the doctors who saw her at the hospital thought …
An all-silk-derived functional nanosphere matrix for sequential biomolecule delivery and in situ osteochondral regeneration
Authors: Wei Zhang, Chen Ling, Aini Zhang, Haoyang Liu, Yujie Jiang, Xiaolong Li, Renwang Sheng, Qingqiang Yao, Jialin Chen
Journal: Bioactive Materials (2020)

Endogenous repair of osteochondral defect is usually limited by the insufficient number of cells in the early stage and incomplete cell differentiation in the later stage. The development of drug delivery systems for sequential release of pro-migratory and pro-chondrogenic molecules to induce endogenous bone marrow-derived mesenchymal stem cells (BMSCs) recruitment and chondrogenic differentiation is highly desirable for in situ osteochondral regeneration. In this study, a novel, all-silk-derived sequential delivery system was fabricated by incorporating the tunable drug-loaded silk fibroin (SF) nanospheres into a SF porous matrix. The loading efficiency and release kinetics of biomolecules depended on the initial SF/polyvinyl alcohol (PVA) concentrations (0.2%, 1% and 5%) of the nanospheres, as well as the hydrophobicity of the loaded molecules, resulting in controllable and programmed delivery profiles. Our findings indicated that the 5% nanosphere-incorporated matrix showed a rapid release of E7 peptide during the first 120 h, whereas the 0.2% nanosphere-incorporated matrix provided a slow and sustained release of Kartogenin (KGN) longer than 30 days. During in vitro culture of BMSCs, this functional SF matrix incorporated with E7/KGN nanospheres showed good biocompatibility, as well as enhanced BMSCs migration and chondrogenic differentiation through the release of E7 and KGN. Furthermore, when implanted into rabbit osteochondral defect, the SF nanosphere matrix with sequential E7/KGN release promoted the regeneration of both cartilage and subchondral bone. This work not only provided a novel all-silk-derived drug delivery system for sequential release of molecules, but also a functional tissue-engineered scaffold for osteochondral regeneration.
Clinical Significance of Circulating Tumor Cells in Hormone Receptor–positive Metastatic Breast Cancer Patients who Received Letrozole with or Without Bevacizumab
Authors: Mark Jesus M. Magbanua, Oleksandr Savenkov, Erik J. Asmus, Karla V. Ballman, Janet H. Scott, John W. Park, Maura Dickler, Ann Partridge, Lisa A. Carey, Eric P. Winer, Hope S. Rugo
Journal: Clinical Cancer Research (2020)

Abstract Purpose: We evaluated the prognostic and predictive value of circulating tumor cells (CTCs) hormone receptor–positive (HR+) metastatic breast cancer (MBC) patients randomized to letrozole alone or letrozole plus bevacizumab in the first-line setting (CALGB 40503). Experimental Design: Blood samples were collected at pretreatment and three additional time points during therapy. The presence of ≥5 CTCs per 7.5 mL of blood was considered CTC positive. Association of CTCs with progression-free survival (PFS) and overall survival (OS) was assessed using Cox regression models. Results: Of 343 patients treated, 294 had CTC data and were included in this analysis. Median follow-up was 39 months. In multivariable analysis, CTC-positive patients at baseline (31%) had significantly reduced PFS [HR, 1.49; 95% confidence interval (CI), 1.12–1.97] and OS (HR, 2.08; 95% CI, 1.49–2.93) compared with CTC negative. Failure to clear CTCs during treatment was associated with significantly increased risk of progression (HR, 2.2; 95% CI, 1.58–3.07) and death (HR, 3.4; 95% CI, 2.36–4.88). CTC-positive patients who received only letrozole had the worse PFS (HR, 2.3; 95% CI, 1.54–3.47) and OS (HR, 2.6; 95% CI, 1.59–4.40). Median PFS in CTC-positive patients was significantly longer (18.0 vs. 7.0 months) in letrozole plus bevacizumab versus letrozole arm (P = 0.0009). Restricted mean survival time analysis further revealed that addition of bevacizumab was associated with PFS benefit in both CTC-positive and CTC-negative patients, but OS benefit was only observed in CTC-positive patients. Conclusions: CTCs were highly prognostic for the addition of bevacizumab to first-line letrozole in patients with HR+ MBC in CALGB 40503. Further research to determine the potential predictive value of CTCs in this setting is warranted.
Preserving Access to the Invaluable Clinical Autopsy
Authors: James W. Salazar, Zian H. Tseng
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine 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 Internal Medicine journal
A global respiratory perspective on the COVID-19 pandemic: commentary and action proposals
Authors: Teresa To, Giovanni Viegi, Alvaro Cruz, Luis Taborda-Barata, Innes Asher, Digambar Behera, Kazi Bennoor, Louis-Philippe Boulet, Jean Bousquet, Paulo Camargos, Claudia Conceiçao, Sandra Gonzalez Diaz, Asma El-Sony, Marina Erhola, Mina Gaga, David Halpin, Letitia Harding, Tamaz Maghlakelidze, Mohammad Reza Masjedi, Yousser Mohammad, Elizabete Nunes, Bernard Pigearias, Talant Sooronbaev, Rafael Stelmach, Ioanna Tsiligianni, Le Thi Tuyet Lan, Arunas Valiulis, Chen Wang, Sian Williams, Arzu Yorgancioglu
Journal: European Respiratory Journal (2020)

<b>This paper offers practical and feasible actions to be implemented at patient, healthcare provider and community level to combat COVID-19 while attending, maintaining and strengthening ongoing health management in people with lung diseases</b>https://bit.ly/30yNyhP
Family history of psoriasis, psychological stressors, and tobacco use are associated with the development of tumor necrosis factor-α inhibitor-induced psoriasis: A case-control study
Authors: Jason Ya, Jeffery Z. Hu, Amy S. Nowacki, Urmi Khanna, Sean Mazloom, Gowri Kabbur, M. Elaine Husni, Anthony P. Fernandez
Journal: Journal of the American Academy of Dermatology (2020)
Ripretinib: First Approval
Authors: Sohita Dhillon
Journal: Drugs (2020)

Abstract Ripretinib (QINLOCK™) is a novel type II tyrosine switch control inhibitor being developed by Deciphera Pharmaceuticals for the treatment of KIT proto-oncogene receptor tyrosine kinase (KIT)-driven and/or platelet derived growth factor receptor A (PDGFRA)-driven cancers, including gastrointestinal stromal tumour (GIST). Ripretinib inhibits KIT and PDGFRA kinase, including wild-type, primary and secondary mutations, as well as other kinases, such as PDGFRB, TIE2, VEGFR2 and BRAF. In May 2020, oral ripretinib received its first approval in the USA for the treatment of adult patients with advanced GIST who have received prior treatment with ≥ 3 kinase inhibitors, including imatinib. The US FDA, Health Canada and the Australian Therapeutic Goods Administration collaborated on the review of the ripretinib new drug application in this indication as part of Project Orbis; regulatory review in Australia and Canada is ongoing. Clinical development for GIST, solid tumours and systemic mastocytosis is underway in several countries worldwide. This article summarizes the milestones in the development of ripretinib leading to this first approval for the treatment of advanced GIST.
COVID-19 Research in Brief: December, 2019 to June, 2020
Authors: Thiago Carvalho
Journal: Nature Medicine (2020)

This week marks our last COVID-19 Research in Brief. COVID-19 research has been progressing at a staggering speed. But a lot still needs to be uncovered to effectively fight this pandemic. We look back at 6 months of biomedical research on COVID-19. In this final roundup of COVID-19 Research in Brief, we look back at 6 months of research
Accuracy and Efficiency of Deep-Learning–Based Automation of Dual Stain Cytology in Cervical Cancer Screening
Authors: Nicolas Wentzensen, Bernd Lahrmann, Megan A Clarke, Walter Kinney, Diane Tokugawa, Nancy Poitras, Alex Locke, Liam Bartels, Alexandra Krauthoff, Joan Walker, Rosemary Zuna, Kiranjit K Grewal, Patricia E Goldhoff, Julie D Kingery, Philip E Castle, Mark Schiffman, Thomas S Lorey, Niels Grabe
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background With the advent of primary human papillomavirus testing followed by cytology for cervical cancer screening, visual interpretation of cytology slides remains the last subjective analysis step and suffers from low sensitivity and reproducibility. Methods We developed a cloud-based whole-slide imaging platform with a deep-learning classifier for p16/Ki-67 dual-stained (DS) slides trained on biopsy-based gold standards. We compared it with conventional Pap and manual DS in 3 epidemiological studies of cervical and anal precancers from Kaiser Permanente Northern California and the University of Oklahoma comprising 4253 patients. All statistical tests were 2-sided. Results In independent validation at Kaiser Permanente Northern California, artificial intelligence (AI)-based DS had lower positivity than cytology (P &amp;lt; .001) and manual DS (P &amp;lt; .001) with equal sensitivity and substantially higher specificity compared with both Pap (P &amp;lt; .001) and manual DS (P &amp;lt; .001), respectively. Compared with Pap, AI-based DS reduced referral to colposcopy by one-third (41.9% vs 60.1%, P &amp;lt; .001). At a higher cutoff, AI-based DS had similar performance to high-grade squamous intraepithelial lesions cytology, indicating a risk high enough to allow for immediate treatment. The classifier was robust, showing comparable performance in 2 cytology systems and in anal cytology. Conclusions Automated DS evaluation removes the remaining subjective component from cervical cancer screening and delivers consistent quality for providers and patients. Moving from Pap to automated DS substantially reduces the number of colposcopies and also achieves excellent performance in a simulated fully vaccinated population. Through cloud-based implementation, this approach is globally accessible. Our results demonstrate that AI not only provides automation and objectivity but also delivers a substantial benefit for women by reduction of unnecessary colposcopies.
Modified Apical Dissection and Lateral Prostatic Fascia Preservation Improves Early Postoperative Functional Recovery in Robotic-assisted Laparoscopic Radical Prostatectomy: Results from a Propensity Score–matched Analysis
Authors: Marcio Covas Moschovas, Seetharam Bhat, Fikret Fatih Onol, Travis Rogers, Shannon Roof, Elio Mazzone, Alexandre Mottrie, Vipul Patel
Journal: European Urology (2020)
The negative impact of comorbidities on the disease course of COVID-19
Authors: Noémi Zádori, Szilárd Váncsa, Nelli Farkas, Péter Hegyi, Bálint Erőss, Lajos Szakó, Nóra Vörhendi, Levente Frim, Zs. Réka Dömötör, Zsolt Szakács, Szabolcs Kiss, Mária Földi, Fanni Dembrovszky, Marcell Imrei, Zsolt Molnár, Zoltán Péterfi, Hussain Alizadeh, László Czopf
Journal: Intensive Care Medicine (2020)
Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia
Authors: Karina A Top, Kristine Macartney, Julie A Bettinger, Ben Tan, Christopher C Blyth, Helen S Marshall, Wendy Vaudry, Scott A Halperin, Peter McIntyre
Journal: Eurosurveillance (2020)

Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases’ surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.
Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation
Authors: Mengyan Xie, Tao Yu, Xinming Jing, Ling Ma, Yu Fan, Fengming Yang, Pei Ma, Huning Jiang, Xi Wu, Yongqian Shu, Tongpeng Xu
Journal: Molecular Cancer (2020)

Abstract Background Circular RNAs (circRNAs) play important regulatory roles in the development of various cancers. However, biological functions and the underlying molecular mechanism of circRNAs in gastric cancer (GC) remain obscure. Methods Differentially expressed circRNAs were identified by RNA sequencing. The biological functions of circSHKBP1 in GC were investigated by a series of in vitro and in vivo experiments. The expression of circSHKBP1 was evaluated using quantitative real-time PCR and RNA in situ hybridization, and the molecular mechanism of circSHKBP1 was demonstrated by western blot, RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. Lastly, mouse xenograft and bioluminescence imaging were used to exam the clinical relevance of circSHKBP1 in vivo. Results Increased expression of circSHKBP1(hsa_circ_0000936) was revealed in GC tissues and serum and was related to advanced TNM stage and poor survival. The level of exosomal circSHKBP1 significantly decreased after gastrectomy. Overexpression of circSHKBP1 promoted GC cell proliferation, migration, invasion and angiogenesis in vitro and in vivo, while suppression of circSHKBP1 plays the opposite role. Exosomes with upregulated circSHKBP1 promoted cocultured cells growth. Mechanistically, circSHKBP1 sponged miR-582-3p to increase HUR expression, enhancing VEGF mRNA stability. Moreover, circSHKBP1 directly bound to HSP90 and obstructed the interaction of STUB1 with HSP90, inhibiting the ubiquitination of HSP90, resulting in accelerated GC development in vitro and in vivo. Conclusion Our findings demonstrate that exosomal circSHKBP1 regulates the miR-582-3p/HUR/VEGF pathway, suppresses HSP90 degradation, and promotes GC progression. circSHKBP1 is a promising circulating biomarker for GC diagnosis and prognosis and an exceptional candidate for further therapeutic exploration.