tbuckley/cabot-search huggingface dataset:
Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial
Authors: Celina Jin, Malick M Gibani, Maria Moore, Helene B Juel, Elizabeth Jones, James Meiring, Victoria Harris, Jonathan Gardner, Anna Nebykova, Simon A Kerridge, Jennifer Hill, Helena Thomaides-Brears, Christoph J Blohmke, Ly-Mee Yu, Brian Angus, Andrew J Pollard
Journal: The Lancet (2017)

Salmonella enterica serovar Typhi (S Typhi) is responsible for an estimated 20 million infections and 200 000 deaths each year in resource poor regions of the world. Capsular Vi-polysaccharide-protein conjugate vaccines (Vi-conjugate vaccines) are immunogenic and can be used from infancy but there are no efficacy data for the leading candidate vaccine being considered for widespread use. To address this knowledge gap, we assessed the efficacy of a Vi-tetanus toxoid conjugate vaccine using an established human infection model of S Typhi.
A randomized, controlled, open label phase II study of erlotinib (E) with or without the MET antibody emibetuzumab (Emi) as first-line treatment for <i>EGFR</i>mt non-small cell lung cancer (NSCLC) patients who have disease control after an 8-week lead-in treatment with erlotinib.
Authors: Giorgio V. Scagliotti, Denis Moro-Sibilot, Jens Kollmeier, Adolfo G. Favaretto, Eun Kyung Cho, Heidrun Grosch, Martin Kimmich, Nicolas Girard, Chun-Ming Tsai, Te-Chun Hsia, Matthew Brighenti, Christian Schumann, Xuejing Aimee Wang, Sameera R. Wijayawardana, Aaron M Gruver, Johan Wallin, Kambiz Mansouri, Volker Wacheck, Gee-Chen Chang
Journal: Journal of Clinical Oncology (2017)

9019 Background: MET expression is a mechanism of resistance to EGFR inhibition in EGFRmt NSCLC and correlated with poor prognosis. Emi (LY2875358) is a humanized IgG4 monoclonal bivalent MET antibody that blocks ligand dependent and independent HGF/MET signaling. This Phase 2 study compared the clinical activity of Emi + E versus single agent E in 1 st line EGFRmt metastatic NSCLC. Methods: Stage IV, EGFRmt NSCLC pts with disease control following an 8-week lead-in E (150 mg PO QD) treatment were randomized 1:1 to receive Emi (750 mg IV Q2W) + E or E alone. Pts were stratified by ECOG PS, ethnicity, MET expression status, and response at the end of the lead-in. The primary endpoint was PFS from randomization. Additional endpoints included safety, OS, PK, and exploratory analysis of MET-expressing populations. Results: Out of181 pts enrolled, 141 pts were randomized (Emi+E: 71; E: 70). In the ITT population, median PFS for EMI+E was 9.3 months (m) compared with 9.5 m for E (HR = 0.89: 90% CI 0.64-1.23; p = 0.534). Exploratory analysis of MET-high expressing pts (MET 3+ expression in ≥90% of tumor cells; n = 24 pts) showed a 15.3 m improvement in PFS (EMI+E: 20.7 m; E: 5.4 m [HR: 0.39; 90% CI: 0.17-0.91]). No difference in PFS was observed in the complementary population (HR: 1.1 [90% CI: 0.7-1.7]). Similar frequencies of related AEs were reported for both treatment arms. Drug-related TEAEs that were more frequent ( &gt; 10%) for Emi+E were peripheral edema and fatigue (all grade 1 or 2). Emi serum concentrations were consistent with previously obtained PK results, and no apparent exposure-response was observed. Median OS in the ITT population was not achieved (NA) for either arm. In MET-high expressing pts, median OS was 20.6 m for E (90% CI: 8.87, NA) whereas it was not achieved for Emi+E (90% CI: NA, NA). Conclusions: No statistically significant difference in PFS was noted in the ITT population.Exploratory analysis confirmed that high MET expression is a negative prognostic marker for pts treated with E and indicated that these pts may receive clinically meaningful benefit from Emi+E. Clinical trial information: NCT01897480.
Integrating geometric configuration and appearance information into a unified framework for anatomical landmark localization
Authors: Martin Urschler, Thomas Ebner, Darko Štern
Journal: Medical Image Analysis (2017)

In approaches for automatic localization of multiple anatomical landmarks, disambiguation of locally similar structures as obtained by locally accurate candidate generation is often performed by solely including high level knowledge about geometric landmark configuration. In our novel localization approach, we propose to combine both image appearance information and geometric landmark configuration into a unified random forest framework integrated into an optimization procedure that iteratively refines joint landmark predictions by using the coordinate descent algorithm. Depending on how strong multiple landmarks are correlated in a specific localization task, this integration has the benefit that it remains flexible in deciding whether appearance information or the geometric configuration of multiple landmarks is the stronger cue for solving a localization problem both accurately and robustly. Furthermore, no preliminary choice on how to encode a graphical model describing landmark configuration has to be made. In an extensive evaluation on five challenging datasets involving different 2D and 3D imaging modalities, we show that our proposed method is widely applicable and delivers state-of-the-art results when compared to various other related methods.
Obituary-John V. Glynn
Authors: Michael A. Chirigos
Journal: JNCI Journal of the National Cancer Institute (1971)

Obituary-John V. Glynn Get access Michael A. Chirigos Michael A. Chirigos Viral Biology Branch National Cancer Institute Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 47, Issue 4, October 1971, Pages iii–v, https://doi.org/10.1093/jnci/47.4.V Published: 01 October 1971
Management of germline findings revealed throughout the course of tumor-normal whole genome sequencing in oncology.
Authors: Howard John Lim, Kasmintan A Schrader, Sean Young, Jessica Nelson, Alexandra Fok, Erin Pleasance, Martin Jones, Yaoqing Shen, Linlea Armstrong, Alice Virani, Shahrad Rod Rassekh, Rebecca Deyell, Stephen Yip, Robyn Roscoe, Aly Karsan, Marco Marra, Janessa J. Laskin
Journal: Journal of Clinical Oncology (2017)

e13113 Background: The Personalized OncoGenomics (POG) project at the BC Cancer Agency utilizes tumor-normal whole genome sequencing (WGS) to understand key driver pathways and guide personalized treatment decisions. Analysis of the germline data can reveal variants; these may be presumed pathogenic, presumed benign or of unknown significance (VUS). We have developed a process for evaluating and returning presumed pathogenic variants in known cancer susceptibility genes to patients, for counseling and validation in a clinical-accredited laboratory. Methods: Patients receive germline cancer related information as part of the consent process for participation in the POG program. A sub-committee comprised of medical geneticists, bioinformaticians, pathologists, oncologists and an ethicist review the germline results. Any variants suspicious of being an artifact undergo a technical validation step. Presumed pathogenic findings of known cancer susceptibility genes are returned to the patient by their treating oncologist and patients are referred to the Hereditary Cancer Program (HCP), for genetic counseling and clinical confirmation. Results: From June 2012 - January 2017 – 466 patients have consented to the project. To date, 39 cases (8.4%) had at least one variant that was deemed pathogenic, 86 cases had at least one VUS in a known cancer susceptibility gene. 11 out of 23 cases (47.8%) with high penetrance mutations were already known to HCP. All VUS were reviewed by the sub-committee taking in to consideration the VUS and clinical context. 8 of the subjects with pathogenic results and 3 with VUS were known to HCP before POG data was generated. A VUS in 7 cases (1.5%) was returned after review. Conclusions: The number of pathogenic variants in known cancer susceptibility genes is consistent with published oncology results. We created a process to manage clinically relevant germline findings discovered during the course of genomic research to ensure appropriate care for patients. Genetic counseling within HCP and validation of variants in the clinically accredited Cancer Genetics Laboratory enables seamless return of research generated clinically relevant germline results to affected subjects. Clinical trial information: NCT02155621.
Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study
Authors: Elie Azoulay, Peter Pickkers, Marcio Soares, Anders Perner, Jordi Rello, Philippe R. Bauer, Andry van de Louw, Pleun Hemelaar, Virginie Lemiale, Fabio Silvio Taccone, Ignacio Martin Loeches, Tine Sylvest Meyhoff, Jorge Salluh, Peter Schellongowski, Katerina Rusinova, Nicolas Terzi, Sangeeta Mehta, Massimo Antonelli, Achille Kouatchet, Andreas Barratt-Due, Miia Valkonen, Precious Pearl Landburg, Fabrice Bruneel, Ramin Brandt Bukan, Frédéric Pène, Victoria Metaxa, Anne Sophie Moreau, Virginie Souppart, Gaston Burghi, Christophe Girault, Ulysses V. A. Silva, Luca Montini, François Barbier, Lene B. Nielsen, Benjamin Gaborit, Djamel Mokart, Sylvie Chevret
Journal: Intensive Care Medicine (2017)
Abstract #30: Kalopanaxsaponin A reduces human oral squamous cell carcinoma (OSCC) invasion via inhibition of mRNA stability and trafficking of matrix metalloproteinase-9 (MMP-9)
Authors: Young Sun Hwang, Kwang-Kyun Park, Won-Yoon Chung
Journal: Cancer Research (2009)

An inability to control cancer cell invasion and metastasis is the leading cause of death in patients with cancer. Here we report that kalopanaxsaponin A (KPS-A), isolated from the stem bark of Kalopanax pictus as hederagenin glycosides, potently suppressed PMA-induced matrix metalloproteinases 9 (MMP-9) activity, leading to inhibit cell invasion in human oral squamous cell carcinoma (OSCC). KPS-A had no effects on NF-kB and AP-1 activities, which has been reported as essential transcription factorsinvolved in the induction of the MMP-9 gene by PMA. However, KPS-A suppressed not only the MMP-9 mRNA stability but also proMMP-9 secretion. KPA, at least in part, decreased proMMP-9 trafficking by destabilizing microtuble and reduced PMA-induced Rab1A expression as evidenced by Rab1A gene silencing, resulting in the decreases of proMMP-9 secretion into the media and subsequent invasion activity. These results suggest that KPS-A may reduce OSCC invasion by inhibiting mRNA stability and trafficking of proMMP-9.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 30.
Outcomes of elderly patients with muscle invasive bladder cancer (MIBC) treated with cystectomy or radiation therapy (RT): A surveillance epidemiology and end results (SEER) database analysis.
Authors: Abhishek Tripathi, Jennifer Friderici, Mark A Preston, Quoc-Dien Trinh, Kent Mouw, Clair Beard, Joaquim Bellmunt, James A. Stewart, Adam S. Kibel, Lauren Christine Harshman
Journal: Journal of Clinical Oncology (2017)

e16001 Background: Cystectomy and RT are both utilized in the management of MIBC. Elderly pts are more likely to be treated with non-surgical approaches that include RT. Using the SEER database, we evaluated outcomes in elderly pts with MIBC. Methods: Inclusion required pts ≥75 years with MIBC (T2-4, N0-3, M0). Cohorts were based on treatment received: cystectomy; RT; TURBT or no treatment. A propensity score was developed to address differences in treatment allocation according to age, race, sex, T and N stage, tumor location, and year of diagnosis. Propensity-adjusted competing risks analysis compared cancer specific mortality (CSM) between cohorts. Results: We identified 8506 pts with MIBC treated from 2007-2012. Of the 8423 pts with adequate treatment data, 26% had cystectomy (2196), 21% underwent RT (1752), 49% received TURBT alone (4128), 3% (262) received no treatment, and 1% (85) received both RT and cystectomy. Compared to RT, cystectomy cohort had a significantly higher proportion of pts &lt; 80 yrs (49% vs. 25%) and was surgically staged with a higher degree of node + (22% vs. 4%) and ≥T3 disease (58% vs. 17%; all P &lt; 0.001). At median follow-up of 10 mo (0-71), 48% (1061) of cystectomy pts and 61% (1064) of RT pts had died. MIBC was the leading cause of death (31% cystectomy, 39% RT). On propensity adjusted analysis, RT was associated with significantly worse CSM (HR: 1.62; 95% CI: 1.45-1.82) compared to cystectomy. Patients treated with TURBT or no treatment had the worst outcomes (5 year CSM: 71% each). Conclusions: Even in elderly pts with competing morbidities, MIBC accounted for more deaths than other causes. In this SEER cohort, non-surgical approaches involving RT were associated with significantly worse outcomes compared to cystectomy. However, worse performance status, less concurrent chemotherapy use, discrepancies between pathologic and clinical staging, use of lower dose RT, or lack of completion TURBT could not be examined and could have contributed to worse outcomes in the RT cohort. These results highlight the need for aggressive management of fit elderly patients with cystectomy or multimodality BPT.
Abstract 15529: Correlations Between Estimated Glomerular Filtration Rate, Major Bleeding and Thromboembolic Complications in Patients on Anticoagulation Treatment with Warfarin
Authors: Mattias Wieloch, Karl Jonsson, Peter J Svensson
Journal: Circulation (2011)

Aims: Estimated glomerular filtration rate (eGFR) is an established risk factor for bleeding but has not previously been associated with bleeding risk in patients on anticoagulation treatment with ...
Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhagic Shock
Authors: Todd E. Rasmussen, Curtis J. Franklin, Jonathan L. Eliason
Journal: JAMA Surgery (2017)

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 Surgery 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 Surgery journal
Biomarker findings and mature clinical results from KEYNOTE-052: First-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC).
Authors: Peter H. O'Donnell, Petros Grivas, Arjun Vasant Balar, Joaquim Bellmunt, Jacqueline Vuky, Thomas Powles, Elizabeth R. Plimack, Noah M. Hahn, Ronald De Wit, Lei Pang, Mary J. Savage, Jared K. Lunceford, Stephen Michael Keefe, Dean F. Bajorin, Daniel Castellano
Journal: Journal of Clinical Oncology (2017)

4502 Background: Comorbidities and renal impairment preclude many with advanced UC from receiving chemotherapy. Initial results from the phase 2 KEYNOTE-052 (NCT02335424) trial suggested first-line pembro is active and safe in cisplatin-ineligible advanced UC. We present updated efficacy and safety data (all pts have ≥6 mo follow-up) and evaluate biomarkers correlated with outcomes. Methods: Eligibility criteria included cisplatin-ineligible (ECOG PS 2, CrCl ≥30- &lt; 60 mL/min, grade ≥2 neuropathy/hearing loss, NYHA Class 3 heart failure), advanced UC, and no prior systemic chemotherapy. Pts received pembro 200 mg IV Q3W. Imaging was performed at wk 9, then Q6W for the first year, and Q12W thereafter. Primary end point was confirmed ORR (RECIST v1.1, independent review). Efficacy and safety were assessed in the 370 pts with ≥1 pembro dose. The associations of an 18-gene expression profile (GEP) and IHC PD-L1 combined positive score (CPS) with ORR were evaluated. Results: As of the Dec 19, 2016, data cutoff, ORR was 29% (95% CI, 24-34): 25 (7%) and 81 (22%) pts achieved complete and partial responses. Another 69 pts (19%) had stable disease as best response, for a clinical benefit rate of 47%. Median time to response was 2 mo (range, 1-5). At a median follow-up of 8 mo (range, 0.1-20) across all pts, median duration of response was not reached (range, 1+-18+ mo). 74% of responses were ongoing. Any-grade and grade ≥3 drug-related AEs occurred in 239 (65%) and 68 (18%) pts. Immune-mediated AEs occurred in 76 (21%) pts. Evidence supporting a positive association with response was seen in the first 100 pts for both biomarkers (GEP, n = 72, P = 0.007, ROC AUC 0.69; CPS, n = 96, P= 0.111, ROC AUC 0.58); biomarker data for all pts will be presented. ORR in the 110 pts with CPS ≥10% was 47% (95% CI, 38-57). Conclusions: Results confirm that pembro elicits clinically meaningful, durable responses in cisplatin-ineligible advanced UC. Consistent with PD-1 pathway biology, biomarkers (GEP and CPS) showed the expected trends of positive association with response to pembro. Pembro was well tolerated across cisplatin-ineligible pts, including elderly and pts with poor performance status. Clinical trial information: NCT02335424.
Changes in CpG islands methylation patterns during ductal breast carcinoma progression.
Authors: Maria Prencipe, Mohammad Hoque, Maria Poeta, Antonietta Gallo, Vanna Valori, Evaristo Maiello, Roberto Murgo, Michele Bisceglia, Stefania Tommasi, Angelo Paradiso, David Sidransky, Vito Fazio, Paola Parrella
Journal: Cancer Research (2008)

2646   Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during carcinogenesis and this epigenetic change has been considered as a potential molecular marker for cancer. It would be very important to identify new cancer specific epigenetic alterations in different stages of tumor type to elucidate its tumorigenesis and clinical management.  We examined the changes in methylation patterns of several genes (ESR1, APC, CDH1, CTNNB1, GSTPI, THBS1, MGMT, TMS1 and TIMP3) by candidate gene approach during ductal breast cancer progression from atypical ductal hyperplasia to in situ and invasive carcinoma. Twenty age-matched normal and paired samples of synchronous pre invasive lesions (Atypical Ductal Hyperplasia and/or Ductal Carcinoma in situ) and invasive ductal breast carcinoma from 31 patients were studied. By establishing an empiric cutoff value, we calculated the frequency of methylation in tumors of different types of paired samples and controls and finally for validation of the frequency of methylation we tested additional isolated lesion 8 DCIS AND 16 IDC from 24 samples. Overall, 95 pathological samples and 20 normal breast tissues were analyzed by Quantitative Methylation Specific PCR (QMSP). APC, CDH1, and CTNNB1 promoter regions showed an increase in frequency of methylation and increased methylation levels in pathological samples when compared with normal breast tissues. The analysis of the syncronous paired breast lesions demonstrated an increase in methylation frequency and level for APC, CDH1, and CTNNB1 genes during progression. By establishing a cutoff value, we were able to distinguish among pre-invasive and invasive lesions. Synchronous methylation of APC, CDH1, and CTNNB1 was associated only with invasive lesions, whereas simultaneous methylation of APC and CDH1 or APC and CTNNB1 were more frequent in ductal carcinoma in situ and invasive carcinoma. Our data point to direct involvement of APC, CDH1, and CTNNB1 CpG island promoter methylation in the early stages of breast cancer progression, and suggest that these molecular alterations might be involved in the transition to an invasive phenotype.
Maternal Exposure of BALB/c Mice to Indoor NO2 and Allergic Asthma Syndrome in Offspring at Adulthood with Evaluation of DNA Methylation Associated Th2 Polarization
Authors: Huifeng Yue, Wei Yan, Xiaotong Ji, Rui Gao, Juan Ma, Ziyu Rao, Guangke Li, Nan Sang
Journal: Environmental Health Perspectives (2017)

Background: Fetal stress has been proposed to be associated with diseases in both children and adults. Epidemiological studies suggest that maternal exposure to nitrogen dioxide (NO2) contributes to increased morbidity and mortality of offspring with allergic asthma later in life. Objectives: We aimed to test whether maternal NO2 exposure causes allergic asthma-related consequences in offspring absent any subsequent lung provocation and whether this exposure enhances the likelihood of developing allergic asthma or the intensity of developed allergic airway disease following postnatal allergic sensitization and challenge. In addition, if such consequences and enhancements occurred, we sought to determine the mechanism(s) of these responses. Methods: Pregnant BALB/c mice were exposed to either NO2 (2.5 ppm, 5 h/day) or air daily throughout the gestation period. Offspring were sacrificed on postnatal days (PNDs) 1, 7, 14, 21, and 42, and remaining offspring were sensitized by ovalbumin (OVA) injection followed by OVA aerosol challenge during postnatal wk 7–9. We analyzed the lung histopathology, inflammatory cell infiltration, airway hyper-responsiveness (AHR), immune responses, and gene methylation under different treatment conditions. Results: Maternal exposure to NO2 caused a striking increase in inflammatory cell infiltration and the release of type 2 cytokines in the lungs of offspring at PNDs 1 and 7; however, these alterations were reversed during postnatal development. Following OVA sensitization and challenge, the exposure enhanced the levels of allergic asthma-characterized OVA-immunoglobulin (Ig) E, AHR, and airway inflammation in adult offspring. Importantly, differentiation of T-helper (Th) 2 cells and demethylation of the interleukin-4 (IL4) gene occurred during the process. Conclusions: Maternal exposure to indoor environmental NO2 causes allergic asthma-related consequences in offspring absent any subsequent lung provocation and potentiates the symptoms of allergic asthma in adult offspring following postnatal allergic sensitization and challenge; this response is associated with the Th2-based immune response and DNA methylation of the IL4 gene. https://doi.org/10.1289/EHP685
To Those “Out There”
Authors: Benjamin W. Frush
Journal: JAMA (2017)

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