tbuckley/cabot-search huggingface dataset:
Whole genome sequencing of Salmonella Chester reveals geographically distinct clusters, Norway, 2000 to 2016
Authors: Lotta Siira, Umaer Naseer, Kristian Alfsnes, Nils Olav Hermansen, Heidi Lange, Lin T Brandal
Journal: Eurosurveillance (2019)

Introduction During summer 2016, Norway observed an increase in Salmonella enterica subsp. enterica serovar Chester cases among travellers to Greece. Aim Our aim was to investigate genetic relatedness of S. Chester for surveillance and outbreak detection by core genome multilocus sequence typing (cgMLST) and compare the results to genome mapping. Methods We included S. Chester isolates from 51 cases of salmonellosis between 2000 and 2016. Paired-end sequencing (2 × 250 bp) was performed on Illumina MiSeq. Genetic relatedness by cgMLST for Salmonella enterica subsp. enterica, including 3,002 genes and seven housekeeping genes, was compared by reference genome mapping with CSI Phylogeny version 1.4 and conventional MLST. Results Confirmed travel history was available for 80% of included cases, to Europe (n = 13), Asia (n = 12) and Africa (n = 16). Isolates were distributed into four phylogenetic clusters corresponding to geographical regions. Sequence type (ST) ST411 and a single-locus variant ST5260 (n = 17) were primarily acquired in southern Europe, ST1954 (n = 15) in Africa, ST343 (n = 11) and ST2063 (n = 8) primarily in Asia. Part of the European cluster was further divided into a Greek (n = 10) and a Cypriot (n = 4) cluster. All isolates in the African cluster displayed resistance to ≥ 1 class of antimicrobials, while resistance was rare in the other clusters. Conclusion Whole genome sequencing of S. Chester in Norway showed four geographically distinct clusters, with a possible outbreak occurring during summer 2016 related to Greece. We recommend public health institutes to implement cgMLST-based real-time Salmonella enterica surveillance for early and accurate detection of future outbreaks and further development of cluster cut-offs.
NANT cancer vaccine an orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T cell therapy in patients with third line or greater metastatic pancreatic cancer.
Authors: Tara Elisabeth Seery, John H. Lee, Leonard S. Sender, Frank R. Jones, Arvind Manohar Shinde, Anand Annamalai, Mira Kistler, Omid Jafari, Patrick Soon-Shiong
Journal: Journal of Clinical Oncology (2019)

TPS463 Background: Pancreatic cancer has multiple mechanisms to prevent immune recognition that lead to the creation of an immune suppressive tumor microenvironment. We hypothesize that effective and sustained response against tumors requires a coordinated approach that: 1. reverses the immune-suppressive tumor microenvironment, 2. induces immunogenic tumor cell death and 3. reengages NK and T-cell tumor response against a 4. cascade of tumor antigens. To test this hypothesis, we developed the NANT Cancer Vaccine (NCV), which combines metronomic low-dose chemotherapy, radiotherapy and multifaceted immunotherapy. In proof-of-concept trials, the NCV was tested in 10 patients with 3 rd -line or greater pancreatic cancer. These trials showed that the NCV could be safely administered in an outpatient setting, with AEs that were manageable by dose-reduction, and preliminary survival results that exceed the standard of care in this heavily-treated population. We believe these results warrant further research, and this abstract describes our newly-designed trial. Methods: A phase 1b, single-arm, open-label trial of the NANT Cancer Vaccine in patients with recurrent metastatic pancreatic cancer has been initiated. Treatment will occur in 3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide, oxaliplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy (bevacizumab), SBRT, engineered allogeneic high affinity CD16 NK-92 cells (haNK), IL-15RαFc (N-803), adenoviral vector-based CEA vaccine (Ad-CEA), yeast vector-based RAS vaccine (Ye-RAS), and an IgG1 PD-L1 inhibitor, avelumab. The primary endpoint is incidence of treatment-related adverse events. Secondary endpoints include ORR, DCR, PFS, and OS. A maximum of 24 patients will be enrolled. Clinical trial information: NCT03586869.
Decreased monocytic TNF-a, IL-6 and IL-b after 72 hours of injury lead to positive outcome in severely injured trauma patients
Authors: Nidhi Bhardwaj, Purva Mathur, Surbhi Khurana, Subodh Kumar, Sushma Sagar, Amit Gupta, Kapil Dev Soni, Richa Aggarwal, Rajesh Malhotra
Journal: Journal of Allergy and Clinical Immunology (2019)
Prevention of Cognitive Impairment With Intensive Systolic Blood Pressure Control
Authors: Kristine Yaffe
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A prospective study of robotic rectal surgery for carcinoma rectum assessing the functional and oncological outcomes: Hype or hope?
Authors: S.P. Somashekhar, Rohit Kumar C, Ashwin K Rajgopal, Shabber Zaveri, Amit Rauthan, Ramya Yethadka
Journal: Journal of Clinical Oncology (2019)

661 Background: Robotic surgical systems have dramatically changed minimally invasive surgery as they could potentially address limitations of laparoscopic rectal surgery. This prospective observational study is conducted to evaluate the safety, technique, and outcomes (operative, postoperative,functional and oncological long term) of robotic-assisted rectal surgery for carcinoma rectum in the Indian set up. Methods: This was a prospective observational study conducted between 2010 and 2018, including 135 patients, diagnosed of rectal carcinoma. Patients underwent robotic rectal cancer surgery in form of either low anterior resection (LAR) or abdominoperineal resection (APR). Intraoperative, postoperative data were analysed. Results: Out of 135 patients, 67.5% were male, aged between 34-80 years, 85% had ECOG 0. All patients had adenocarcinoma rectum, with 15% mid rectum and 55% in lower rectum. 85% had stage III disease. 77.5% had received neoadjuvant chemoradiation. 82.5% had LAR and 17.5% APR. Average operative time including docking time and surgery time was 226.32 min (170-300 min), mean blood loss was 146.76 ml (120-200 ml), there were 3 conversion to open surgery. Bowel sounds appeared on average on 3rd day. All margins were negative in all patients, mesorectal grade was complete in 95% and near complete in 5%. Mean number of lymph nodes harvested is 9.5 (2-32). Complete pathological response rate was 39%. 2 patients had anastomotic dehiscence after 1 month. Minor complications were noticed in 10% patients. All had acceptable quality of life and well retained bladder function, with 18% sexual dysfunction. Five year DFS was 85% and OS was 94%. Local recurrence was 2.1%. Conclusions: This is one of the largest single center Indian data available. In conclusion, robotic rectal surgery has several benefits in the treatment and should be part of the armamentarium of the experienced surgeon dealing with rectal cancer. We conclude that the robotic-assisted rectal cancer surgery is safe and an oncologically feasible technique with well retained functional outcomes and has lived up to its hope.
Mesenchymal stem cells in suppression or progression of hematologic malignancy: current status and challenges
Authors: Myoung Woo Lee, Somi Ryu, Dae Seong Kim, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo
Journal: Leukemia (2019)

Abstract Mesenchymal stem cells (MSCs) are known for being multi-potent. However, they also possess anticancer properties, which has prompted efforts to adapt MSCs for anticancer therapies. However, MSCs have also been widely implicated in pathways that contribute to tumor growth. Numerous studies have been conducted to adapt MSCs for further clinical use; however, the results have been inconclusive, possibly due to the heterogeneity of MSC populations. Moreover, the conflicting roles of MSCs in tumor inhibition and tumor growth impede their adaptation for anticancer therapies. Antitumorigenic and protumorigenic properties of MSCs in hematologic malignancies are not as well established as they are for solid malignancies, and data comparing them are still limited. Herein the effect of MSCs on hematologic malignancies, such as leukemia and lymphoma, their mechanisms, sources of MSCs, and their effects on different types of cancer, have been discussed. This review describes how MSCs preserve both antitumorigenic and protumorigenic effects, as they tend to not only inhibit tumor growth by suppressing tumor cell proliferation but also promote tumor growth by suppressing tumor cell apoptosis. Thus clinical studies trying to adapt MSCs for anticancer therapies should consider that MSCs could actually promote hematologic cancer progression. It is necessary to take extreme care while developing MSC-based cell therapies in order to boost anticancer properties while eliminating tumor-favoring effects. This review emphasizes that research on the therapeutic applications of MSCs must consider that they exert both antitumorigenic and protumorigenic effects on hematologic malignancies.
Limitations in the Methodology Assessing Blood Pressure and the Need for Strict Exclusion Criteria
Authors: Vijay Ramadoss, Payal Trupti Kotecha
Journal: JAMA Internal Medicine (2019)

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
Letter to Editor: Role of Pharmacotherapy in Patients With Coexisting Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus
Authors: Sikarin Upala
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest a recent article written by Yan et al.1 The authors conducted a randomized trial in patients with coexisting type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) to receive liraglutide, sitagliptin, or insulin glargine as add‐on to metformin. The authors observed glycemic control and a reduction in body weight, intrahepatic lipid, and visceral adipose tissue in patients who received liraglutide or sitagliptin and then reported these add‐on therapies to be novel pharmacotherapeutic therapies in patients with NAFLD and T2DM. However, the clinical meaningfulness of these pharmacologic treatments has not been conclusively established, especially because histopathology was not used to diagnose and determine the severity of NAFLD in that study. Management of NAFLD consists of treatment of liver disease and its comorbidities, including T2DM. Weight loss with either lifestyle intervention or operation is the mainstay of treatment for patients with NAFLD, as it has been shown to improve histologic features of the liver in these patients.2 Previous studies assessed the efficacy of different pharmacologic treatments for NAFLD.3 These trials enrolled patients with biopsy‐confirmed nonalcoholic steatohepatitis (NASH) and used liver histology to assess improvement in histologic features, such as resolution of steatohepatitis, Kleiner fibrosis stage, and NAFLD activity score. In contrast, the Yan et al. study enrolled patients who were clinically diagnosed with NAFLD but did not disclose how many of their study patients were diagnosed by liver biopsy. This is an important factor given the recommendation that studies in pharmacologic treatments aimed primarily at improving liver disease should include only patients with biopsy‐proven NASH and fibrosis, because NAFLD without steatohepatitis or fibrosis has a better prognosis. In addition, although magnetic resonance imaging–estimated proton density fat fraction could be used to quantify changes in liver fat in clinical trials, its efficacy for detecting other features of NAFLD, such as steatohepatitis and fibrosis, is limited. In conclusion, histopathology should be used to guide the need for pharmacotherapy in NAFLD and monitor disease progression. The risks and benefits of liraglutide and sitagliptin must be carefully considered when using either of these agents in patients at risk for developing severe side effects.
Abstract 17895: Comparison of the Medtronic SelectSecure and Conventional Pacing Leads: Long Term Follow-up In a Multicenter Pediatric and Congenital Cohort
Authors: Jeffrey Moak
Journal: Circulation (2017)

Introduction: The Medtronic SelectSecureTM pacing lead (MSS) has hypothesized advantages compared to conventional transvenous pacing leads (CPL) of similar design (bipolar pacing, thin lead diamete...
Increased Frequency of IDH1/2 Mutations in Extramedullary Acute Myeloid Leukemia
Authors: Todd C. Knepper, Yehuda E. Deutsch, Chirag K Bhagat, Justin M Watts, Terrence J Bradley, Wassim Samra, Mohammad Omar Hussaini, Kendra L. Sweet, Chetasi Talati, Eric Padron, Rami S. Komrokji, Jeffrey E. Lancet, David A Sallman
Journal: Blood (2018)
Abstract 14273: Angioscopic Evaluation of Arterial Repair Following Second Generation Drug-eluting Stent Implantation in Acute Coronary Syndrome: Comparison With Non-Acute Coronary Syndrome
Authors: Koji Yanaka, Takayuki Ishihara, Osamu Iida, Masashi Fujita, Masaharu Masuda, Shin Okamoto, Kiyonori Nanto, Takashi kanda, Takuya Tsujimura, Akihiro Sunaga, Shota Okuno, Yasuhiro Matsuda, Takuya Ohasi, Yosuke Hata, Aki Tsuji, Hiroyuki Kawai, Masaaki Uematsu
Journal: Circulation (2016)

Introduction: Arterial repair following the implantation of a second generation drug-eluting stent (2nd DES) in acute coronary syndrome (ACS) remains to be elucidated. We sought to investigate the ...
Abstract 21266: Valve Oversizing in Transcatheter Aortic Valve Replacement: Impact on Outcome
Authors: Konstantinos Stathogiannis, Konstantinos Toutouzas, Maria Drakopoulou, George Latsios, Andreas Synetos, Archontoula Michelongona, Odysseas Kaitozis, George Trantalis, Vasiliki Penesopoulou, Eleftherios Tsiamis, Dimitrios Tousoulis
Journal: Circulation (2017)

Introduction: In transcatheter aortic valve replacement (TAVR), prosthesis oversizing prevents paravalvular regurgitation. Although the estimated extent of oversizing depends on annular measurements, oversizing strategies are not well established. Hypothesis: The aim of our study was to evaluate the impact of different degrees of valve oversizing based on multislice computed tomography (MSCT) on the outcome of patients. Methods: Patients with severe and symptomatic aortic stenosis scheduled for TAVR with a self-expanding valve, were prospectively enrolled. All patients underwent pre-procedural MSCT. According to the measurements, patients were classified into three groups for the degree of oversizing: normal (10-15%), moderate (15-20%) and severe (&gt;20%) depending on the ratio between valve prosthesis diameter and the perimeter-derived annulus diameter based on MSCT. The main endpoint was mid-term mortality and secondary endpoints were the Valve Academic Research Consortium (VARC-2) end-points. Results: Overall, 177 patients (mean age: 79±7years, mean logEuroscore 24.9±10%, NYHA III-IV: 90%) were consecutively included in the study. Mean annulus area was 23.3±2.5mm 2 and mean perimeter was 74.36±7.27mm. Ninety-one patients (51%) had normal oversizing, 67 patients moderate (38%) and 19 patients (11%) severe oversizing. There were no cases of annular rupture. The primary clinical end-point occurred in 38 patients (21%) during a follow-up period of 24±12 months. While all-cause mortality rates were similar in all groups (24.1% for normal sizing versus 21.9% for moderate oversizing versus 22.9%, for severe oversizing, p=0.93), post-procedural new pacemaker (PPM) implantation rate was significantly higher in severe compared to the moderate and normal oversizing groups respectively (63.2%, versus 38.8%, versus 30.8%, p=0.03). Patients with normal oversizing had a trend of higher rate of significant paravalvular leak (at least moderate) compared to patients with moderate and severe oversizing (18.7%, versus 7.5%, versus 5.3%, p=0.058). Conclusions: Despite a higher rate of pacemaker implantation, a higher extent of valve oversizing in patients undergoing TAVR, seems to reduce the degree of paravalvular leak.
Stratifin Inhibits SCFFBW7 Formation and Blocks Ubiquitination of Oncoproteins during the Course of Lung Adenocarcinogenesis
Authors: Aya Shiba-Ishii, Jeongmin Hong, Takatsugu Hirokawa, Yunjung Kim, Tomoki Nakagawa, Shingo Sakashita, Noriaki Sakamoto, Yukinori Kozuma, Yukio Sato, Masayuki Noguchi
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Aberrant overexpression of SFN (stratifin) plays an oncogenic role in lung adenocarcinoma. We have shown previously that SKP1, an adapter component of E3 ubiquitin ligase forming an SCF complex, is a unique SFN-binding protein in lung adenocarcinoma cells. Experimental Design: In silico simulation and in vitro mutagenesis analysis were performed to identify the SFN-binding domain on SKP1. We examined expression, localization, and stability of SKP1 after knockdown of SFN using lung adenocarcinoma cells including A549. In silico library screening and experimental validation were used for drug screening. Daily oral administration of each candidate drugs to A549-injected tumor-bearing mice was performed to evaluate their in vivo antitumor efficacy. Results: Suppression of SFN upregulated the stability of SKP1 and accelerated its cytoplasm-to-nucleus translocation. Consistently, IHC analysis revealed that cytoplasmic expression of SKP1 was significantly associated with SFN positivity, tumor malignancy, and poorer patient outcome. After SFN suppression, ubiquitination of oncoproteins, including p-cyclin E1, p-c-Myc, p-c-Jun, and cleaved Notch 1, which are target proteins of SCFFBW7, was strongly induced. These results indicate that SFN–SKP1 binding results in SCFFBW7 dysfunction and allows several oncoproteins to evade ubiquitination and subsequent degradation. Because inhibition of SFN-SKP1 binding was expected to have antitumor efficacy, we next searched for candidate SFN inhibitors. Aprepitant and ticagrelor were finally selected as potential SFN inhibitors that dose dependently reduced SFN-SKP1 binding and tumor progression in vivo. Conclusions: As overexpression of SFN is detectable in most adenocarcinoma, we believe that SFN inhibitors would be novel and promising antitumor drugs for lung adenocarcinoma.
Cumulative Risk of End-Stage Renal Disease Among Patients With Type 2 Diabetes: A Nationwide Inception Cohort Study
Authors: Patrik Finne, Per-Henrik Groop, Martti Arffman, Marjo Kervinen, Jaakko Helve, Carola Grönhagen-Riska, Reijo Sund
Journal: Diabetes Care (2019)

OBJECTIVE To estimate long-term cumulative risk of end-stage renal disease (ESRD) after diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS This nationwide population-based inception cohort study included 421,429 patients with type 2 diabetes diagnosed in 1990–2011; patients were followed until the end of 2013. Data linkage between several national health care registers in Finland, covering 100% of the population, enabled the inclusion of almost all inhabitants who started taking diabetes medication or were hospitalized for diabetes. Cumulative risk of ESRD and hazard ratios [HR] for ESRD and death were estimated according to age, sex, and time period of diabetes diagnosis. RESULTS Among 421,429 patients with type 2 diabetes, 1,516 developed ESRD and 150,524 died during 3,458,797 patient-years of follow-up. Cumulative risk of ESRD was 0.29% at 10 years and 0.74% at 20 years from diagnosis of diabetes. Risk was higher among men than among women (HR 1.93 [95% CI 1.72–2.16]), decreased with older age at diagnosis (HR 0.70 [95% CI 0.60–0.81] for age 60–69 vs. 40–49 years), and was lower for those diagnosed in 2000–2011 than in 1990–1994 (HR 0.72 [95% CI 0.63–0.81]). Patients diagnosed with diabetes in 2000–2011 had lower risk of death during follow-up than those diagnosed in 1990–1994 (HR 0.64 [95% CI 0.63–0.65]). CONCLUSIONS Cumulative risk of ESRD is minimal among patients with type 2 diabetes compared with their risk of death. Patients diagnosed with diabetes at an older age have a lower risk of ESRD due to higher competing mortality.
A novel healthy metabolic phenotype developed among a cohort of families enriched for longevity
Authors: Megan M. Marron, Iva Miljkovic, Robert M. Boudreau, Kaare Christensen, Mary F. Feitosa, Joseph H. Lee, Paola Sebastiani, Bharat Thyagarajan, Mary K. Wojczynski, Joseph M. Zmuda, Anne B. Newman
Journal: Metabolism (2019)
Detection of microparticles in nasal lavage fluid that express both integrin β6 and a marker of epithelial-mesenchymal transition (either alpha-smooth muscle actin or Snail) is useful for the identification of severe chronic rhinosinusitis
Authors: Toru Takahashi, Atsushi Kato, Sergejs Berdnikovs, Lydia A. Suh, James E. Norton, Roderick G. Carter, Kathleen E. Harris, Whitney W. Stevens, Anju T. Peters, Leslie C. Grammer, Kevin C. Welch, Stephanie Shintani-Smith, David B. Conley, Robert C. Kern, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2019)
Piggybac CD19 CAR T Cells Eradicate CNS Leukemia By Direct Delivery into Cerebral Ventricle of Xenograft Mice Model
Authors: Kuniaki Tanaka, Itaru Kato, Miyuki Tanaka, Daisuke Morita, Yoshiyuki Takahashi, Tatsutoshi Nakahata, Katsutsugu Umeda, Hidefumi Hiramatsu, Souichi Adachi, Junko Takita, Yozo Nakazawa
Journal: Blood (2018)