tbuckley/cabot-search huggingface dataset:
Abstract 2311: Adenovirus-transduced allogeneic dendritic cells for cancer immunotherapy
Authors: Magnus Essand, Grammatiki Fotaki, Chuan Jin, Mohanraj Ramachandran, Jing Ma, Alex Karlsson-Parra, Di Yu
Journal: Cancer Research (2016)

Abstract Immunotherapy is currently being established as standard treatment for cancer. Immune checkpoint blockade antibodies can cure a large proportion of patients with refractory melanoma and lung cancer, and adoptive transfer of patient-derived CD19 chimeric antigen receptor (CAR) T cells results in complete remission in a majority of patient with refractory leukemia. Cancer vaccines based on patient-derived dendritic cells (DC) modified ex vivo to present tumor antigens are promising for cancer treatment especially when combined with immune checkpoint blockade antibodies. Ex vivo-modified DCs are however poor in migrating to secondary lymphoid organs after re-administration. In reality, it is more likely endogenous DC that endocytos the injected DC, mature and then migrate to lymph nodes where they present peptide fragments of tumor antigen to T cells together with required co-stimulation. Herein, we present a new strategy utilizing adenovirus (Ad)-transduced allogeneic DCs (alloDCs) as immunostimulatory adjuvant to induce both innate and adaptive immune response. Ad/alloDC can be prepared, tested and made ready for release in advance and quickly be prepared for injection in cancer patients upon request, thereby minimizing GMP-processing and handling of cells. Besides encoding tumor antigens, adenovirus also provides stimulatory danger signals for DC activation. We show that Ad/alloDCs secret a panel of proinflammatory cytokines and chemokines including IL-12 and CXCL10 at high levels in a sustainable fashion. We also show that Ad/alloDC recruit and activate neutrophils and NKs to the site of injection. Ad/alloDC can also recruit and interact with allo-reactive T cells to create a proinflammatory milieu, which further recruit and activate endogenous DCs. We verified that endogenous DCs activated in situ by an Ad/alloDC injection migrate to draining lymph node, where they present the engulfed tumor antigen to T cells. We show that these migratory endogenous DCs facilitate T cell activation and proliferation. Moreover, when injected intratumorally, Ad/alloDCs modulate the immunosuppressive environment by reducing the ratio of monocytic to granulocytic myeloid-derived suppressor cells (MDSC). To evaluate the therapeutic efficacy, we use B16 melanoma tumor-bearing C57Bl/6 mice injected with adenovirus-transduced DCs from Balb/c origin to obtain an allogeneic reaction. We show that Ad/alloDC treatment could significantly delay tumor growth and prolong survival of tumor-bearing mice. Citation Format: Magnus Essand, Grammatiki Fotaki, Chuan Jin, Mohanraj Ramachandran, Jing Ma, Alex Karlsson-Parra, Di Yu. Adenovirus-transduced allogeneic dendritic cells for cancer immunotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2311.
Abstract 4441: Non-pathogenic bacteria change host DNA methylation <i>in vivo</i>
Authors: Ang Sun, Jaroslav Jelinek, Shinji Maegawa, Christian Jobin, Jean-Pierre Issa
Journal: Cancer Research (2016)

Abstract Introduction: More than a thousand species of bacteria live in a normal person's gastrointestinal tract. Epigenetic effects on the colon directly caused by the commensal bacteria remain elusive. In the current study, we explore the bacterial effects on DNA methylation of the host colon. Methods: Eight non-pathogenic bacterial species were introduced to the gut of germ-free (GF) mice to make specific-pathogen free (SPF) mice. Our study consisted of the following groups (n = 6 for each): wildtype (WT) GF, WT SPF, IL-10 knockout (KO) GF, IL-10 KO SPF, and IL-10 KO GF or SPF treated with azoxymethane (AOM). We analyzed DNA methylation in genomic DNA extracted from the proximal colon using Digital Restriction Enzyme Analysis of Methylation (DREAM) and compared methylation levels at CpG sites among different groups. Results: 1) Principal component analysis (PCA) performed on methylomes of all the samples separated the mouse samples based on presence or absence of bacteria, IL-10 KO status or AOM treatment into 6 distinct groups. 2) We analyzed CpG sites differentially methylated between GF and SPF mice at p&amp;lt;0.05 significance level. In WT mice, there were 1871 CpG sites (11% out of 17475 analyzed sites), in IL10 KO mice, there were 5986 CpG sites (33% out of 18254 analyzed sites) and in IL10 KO AOM-treated mice there were 6755 CpG sites (31% out of 21697 analyzed sites) differentially methylated. 3) There were 756 common CpG sites differentially methylated in all SPF vs GF comparisons. Interestingly, these sites were enriched 2.6-fold for aging-related CpG sites. 4) WT SPF mice showed increased methylation at CpG sites hypomethylated in WT GF mice and, conversely, decreased methylation at CpG sites hypermethylated in WT GF mice. This pattern of DNA methylation change was also observed by comparing GF with SPF in IL-10 KO mice with or without AOM treatment. 5) Both in GF and SPF mice the DNA methylation changes were more pronounced in IL10 KO while AOM had little additional effect. 6) IL10 KO resulted in genome-wide increase of methylation. However, the introduction of bacteria in SPF mice resulted in the methylation change mainly at CpG islands. Conclusions: Non-pathogenic bacteria introduced in the colon cause methylation gains at CpG sites with low DNA methylation and methylation losses at sites with high DNA methylation in a pattern similar to the changes observed in aging and cancer. Citation Format: Ang Sun, Jaroslav Jelinek, Shinji Maegawa, Christian Jobin, Jean-Pierre Issa. Non-pathogenic bacteria change host DNA methylation in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4441.
Workplace Violence in Health Care
Authors: Ron Wyatt, Kim Anderson-Drevs, Lynn M. Van Male
Journal: JAMA (2016)

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
Effects of sex on naevus body distribution and melanoma risk in two melanoma case-control studies at different latitudes
Authors: S. Ribero, S. Osella-Abate, D. Reyes-Garcia, D. Glass, V. Bataille
Journal: British Journal of Dermatology (2016)

Naevus count is the most predictable phenotypic risk factor for melanoma and is mainly influenced by genetic factors1,2,3. Melanoma disparities according to gender have been reported in many studies in term of body distribution, survival and to a lesser extent incidence1,2. It is well established that women are more likely to get melanoma on the lower limbs, whilst men are more prone to melanoma on the trunk. In this study, we explore the effects of gender on the distribution of naevi on the body in melanoma cases and controls from different latitudes and whether the odds ratios for melanoma associated with naevi at different body sites are affected by gender. Two case control studies are compared, one in the UK and the other in Australia using the same protocol for naevus counts and the same examiner1,2.

This article is protected by copyright. All rights reserved.
The Pathophysiologic Role of Disrupted Circadian and Neuroendocrine Rhythms in Breast Carcinogenesis
Authors: Lonnele J. Ball, Oxana Palesh, Lance J. Kriegsfeld
Journal: Endocrine Reviews (2016)

Most physiological processes in the brain and body exhibit daily (circadian) rhythms coordinated by an endogenous master clock located in the suprachiasmatic nucleus of the hypothalamus that are essential for normal health and functioning. Exposure to sunlight during the day and darkness at night optimally entrains biological rhythms to promote homeostasis and human health. Unfortunately, a major consequence of the modern lifestyle is increased exposure to sun-free environments during the day and artificial lighting at night. Additionally, behavioral disruptions to circadian rhythms (ie, repeated transmeridian flights, night or rotating shift work, or sleep disturbances) have a profound influence on health and have been linked to a number of pathological conditions, including endocrine-dependent cancers. Specifically, night shift work has been identified as a significant risk factor for breast cancer in industrialized countries. Several mechanisms have been proposed by which shift work-induced circadian disruptions promote cancer. In this review, we examine the importance of the brain-body link through which circadian disruptions contribute to endocrine-dependent diseases, including breast carcinogenesis, by negatively impacting neuroendocrine and neuroimmune cells, and we consider preventive measures directed at maximizing circadian health.
Intelligent pain management system (IPMS): An effective approach to control pain and improve quality of life in cancer patients in China.
Authors: Gang Ding, Jing Li, WeiWei Hu, Juan J Gu, Feng Jiang
Journal: Journal of Clinical Oncology (2015)

e20544 Background: More than one-third of cancer patients experienced cancer pain in China, which is one the major reasons to negatively impact on the effective treatment and quality of life. Prompt and effective pain control is an urgent need in cancer patients. To achieve this aim, we investigated clinical intervention of cancer pain using intelligent pain management system (IPMS) developed by Shanghai Xinhua Translational Institute for Cancer Pain. Methods: 140 patients with cancer pain symptom from our hospital were randomized into two groups (trial group and control groups). After 90 days, cancer pain assessment data was collected by IPMS in trial group, whereas data of control group was collected by conventional methods such as telephone or door to door visit. Based on the real-time data, clinicians adopt adequate anti-pain medicine in time. Results: Pain controlled days in IPMS trial group were significantly longer compared to those of control group, 48.64 ±3.83 vs 39.49 ± 3.76 respectively, p < 0.001. The frequency of daily breakthrough pain of the trial group was significantly lower than that of the control group, p < 0.05. Before clinical intervention, the average KPS score was no statistical difference between two groups. In the trail group the average KPS score after the follow-up 76.57±8.66 is 11.57±5.81 higher than that at the beginning of the study 65.57±8.95, while in the control group the average KPS score after the follow-up 65.57±8.95 is 9.43±5.62 higher than that before the follow-up 75.00±8.47.These two group had statistical significance, P < 0.001. Conclusions: IPMS can serve as a reliable and effective approach to control cancer pain and improve quality of life in cancer pain patients.
Pressured general practices get £16m support fund
Authors: Gareth Iacobucci
Journal: BMJ (2016)

NHS England has released the first instalment of its £40m (€47.3m; $52.9m) rescue package to help struggling general practices across the country.

An initial £16m released last week will be targeted at practices that have been under most pressure and those with workforce issues. It will fund practical support in areas such as staffing, practice management, human resources, and information technology.

The funding follows a commitment in the General Practice Forward View to offer support to general practices that have been worst affected by rising patient demand.1 It will be …
Serial circulating tumor DNA (ctDNA) and recurrence risk in patients (pts) with resectable colorectal liver metastasis (CLM).
Authors: Jeanne Tie, Yuxuan Wang, Simeon Springer, Isaac Kinde, Hui-Li Wong, Suzanne Kosmider, Ben Tran, Michael Christie, Benjamin N Thomson, Rachel Wong, Matthew E. Burge, Jenny Shannon, Dusan Kotasek, Kathryn Maree Field, Robert Strausberg, Luis A. Diaz, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Peter Gibbs
Journal: Journal of Clinical Oncology (2016)

e15131 Background: In pts with metastatic colorectal cancer (mCRC), the resection of isolated CLM is potentially curative. Previous studies have shown that ctDNA can be detected in a high proportion of pts with mCRC. ctDNA detection after resection of CLM may be a marker of residual micrometastatic disease. If so, serial analysis of ctDNA after CLM resection could inform adjuvant chemotherapy decision making and pt follow-up. Methods: We prospectively collected serial (pre-op, post-op and 3 to 6 monthly during adjuvant chemotherapy and follow-up) plasma in pts with resectable CLM. Chemotherapy use was at clinician discretion, blinded to ctDNA result. With targeted sequencing of 15 genes commonly mutated in CRC, we identified somatic mutations in each pt's tumor, and then designed a personalised assay to quantify a selected mutant DNA in plasma samples (ctDNA) using the Safe-SeqS digital genomic assay. Results: From July 2011 to March 2014, 37 pts were recruited, 25 male, median age 64 years (range 31-82). 19 had a single liver metastasis, 11 had 2-3, and seven had ≥ 4 lesions. Available plasma samples were analyzed. Prior to any treatment, ctDNA was positive in 31/35 (89%) pts. 36 pts (97%) underwent R0 resection, 26 pts (70%) received chemotherapy after surgery. At a median follow-up of 27 months, 14 of 37 pts (38%) have recurred. Ten of 10 pts (100%) with positive post-treatment (surgery and chemotherapy) ctDNA experienced recurrence vs 4 of 27 (15%) with negative post-treatment ctDNA (HR 13.16, p < 0.0001). Of 9 pts with positive ctDNA after surgery, one had negative ctDNA after adjuvant chemotherapy and remains disease free. All 6 pts where ctDNA remained positive after chemotherapy and all 2 who did not have chemotherapy have recurred. At recurrence, ctDNA was positive in 12/13 (92%), while 6/13 (46%) had an elevated CEA (p = 0.03). ctDNA was detectable at a median of 3 months (range 0 - 14) prior to clinical recurrence. Conclusions: ctDNA is detectable in the majority of pts with CLM. In our series, all pts where ctDNA remained positive following treatment experienced recurrence. Serial ctDNA after chemotherapy and during follow-up may be a marker of adjuvant chemotherapy impact and an early marker of recurrence. Clinical trial information: ACTRN12612000345886.
Les infections à hantavirus Puumala en Finlande
Authors: Angie Rose, O Vapalahti, O Lyytikäinen, P Nuorti
Journal: Eurosurveillance (2003)

Les infections a Hantavirus sont prevalentes en Europe et, dans les zones endemiques, elles peuvent etre la cause la plus frequente d’insuffisance renale. Afin d’evaluer l’evolution des infections a virus Puumala en Finlande, nous avons analyse les donnees nationales de surveillance, collectees sur des periodes de 12 mois de mars 1995 a fevrier 2002. Sur cette periode, 8184 cas confirmes ont ete notifies au registre national des maladies infectieuses. Trois periodes epidemiques ont ete identifiees, avec un nombre de cas depassant 1400 (compares a 600–900 cas approximativement en periodes non epidemiques). L’incidence des infections a hantavirus Puumala variait selon les regions durant la periode etudiee et le nombre global de cas semblerait en augmentation.
The impact of insurance status on performance of retroperitoneal lymph node dissection and cancer specific death in patients with non seminomatous germ cell tumors.
Authors: Shaheen Riadh Alanee, Atif Cheema, Whitney Zahnd, Danuta Dynda
Journal: Journal of Clinical Oncology (2016)

e16062 Background: The objective of this study was to evaluate the impact of insurance status on disease stage on diagnosis, receiving retroperitoneal lymph node dissection (RPLND), and cancer specific death in patients diagnosed with testicular non seminomatous germ cell tumors (NSGCT). Methods: We identified 5,071 patients younger than 65 years with NSGCT in the 2007–2011 SEER database. Fisher’s exact tests were performed to assess categorical variables and independent t-tests were performed to assess continuous variables. Multivariable logistic regression was used to examine the analysis the relationship between insurance status and the end points of diagnosis with advanced stage and receiving RPLND.Cox proportional hazard analysis was used to examine the association between variables of interest and cancer specific death (CSD). All multivariate analyses controlled for the confounder of age, race, education, marital status, year of diagnosis, rural residence, and density of healthcare providers Results: 70.28% of NSGCT cases were insured, 18.26% had Medicaid, and 11.6% were uninsured. 58.63% had localized disease, 21.86% had regional disease, and 19.51% distant NSGCT. Of the entire cohort, 20.27% underwent RPLND. At multivariable analysis, insurance status was the strongest predictor of presentation with advanced disease stage. Compared to insured patients, patients on Medicaid had 2.06 times the odds, and those with no insurance had 1.34 times the odds of being diagnosed with advanced disease stage (p < 0.05). Insurance had no association with the patient’s odds of undergoing RPLND controlling for other confounders (p > 0.05). However, being on Medicaid and not having insurance were strong predictors of NSGCT cancer specific death controlling for confounder (Medicaid vs. insured Hazard ratio (HR): 2.21, CI: 1.57-3.12; uninsured vs. Medicaid HR: 2.41, CI: 1.59-3.67). Conclusions: Medicaid beneficiaries and uninsured patients are diagnosed with advanced disease stage and are at a higher risk of CSD. Just expanding Medicaid coverage may not be enough to remedy the healthcare disparities in patients with NSGCT.
Global cost of physical inactivity is estimated at $67.5bn a year
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The worldwide economic burden of physical inactivity was at least $67.5bn (£51.5bn; €61.5bn) in 2013—equivalent to the gross domestic product of Costa Rica that year—researchers have estimated.

Their analysis, published in the Lancet , found that the worldwide cost of physical inactivity to healthcare systems was $53.8bn in 2013, of which $31.2bn was paid by the public sector, $12.9bn by the private sector, and $9.7bn by households.1 Physical inactivity related deaths were responsible …
Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol
Authors: B O Wolthers, T L Frandsen, J Abrahamsson, B K Albertsen, L R Helt, M Heyman, Ó G Jónsson, L T Kõrgvee, B Lund, R A Raja, K K Rasmussen, M Taskinen, M Tulstrup, G E Vaitkevičienė, R Yadav, R Gupta, K Schmiegelow
Journal: Leukemia (2016)
Hypercoagulability Promotes Atrial Fibrosis and Fibrillation
Authors: Henri M.H. Spronk, Anne-Margreet de Jong, Hetty C. de Boer, Alexander Maas, Sander Verheule, Michiel Rienstra, Pieter W. Kamphuisen, Hugo ten Cate, Harry J Crijns, Isabelle van Gelder, Anton Jan van Zonneveld, Ullrich Schotten
Journal: Blood (2014)
Incidence of testosterone escape with LHRH agonists in patients receiving radiotherapy for prostate cancer.
Authors: Derek R Wilke, Nikhilesh Gajanan Patil, Helmut Hollenhorst, David Bowes, Robert Rutledge
Journal: Journal of Clinical Oncology (2016)

24 Background: LHRH agonists (LHRHa) are commonly combined with radiotherapy in the neoadjuvant, concurrent, and adjuvant setting. Testosterone escape (TTE) (&gt;1.74 nmol/L or &gt;50 ng/dL) during therapy with LHRHa has been described, but the incidence and impact of TTE on outcome in this patient group needs to be characterized further. Methods: We performed a retrospective review of a database used for clinical outcomes and research ethics board approved studies, including chart audit of select patients (pts) where information was missing. To be included in the study, there had to be information on: 1) type of LHRHa, date of initiation, date of cessation, or duration of therapy and 2) radiotherapy information, with at least 6 months of follow-up after radiotherapy, 3) had to have radiotherapy to the prostate or prostate bed, and 4) had to have a least one testosterone- (TT) and prostatic-specific antigen (PSA) measurement. Results: 670 pts had a start date for androgen deprivation therapy (ADT) in the database. 630 pts had received an LHRHa, 560 pts had a start date for radiotherapy. 375 pts had sufficient information on ADT, radiotherapy, TT, and PSA levels, and 361 of these patients had information regarding their LHRHa. Median follow-up of patients still alive is 4.7 years. The median duration of LHRHa was 2.02 years. The median number of testosterone measurements per patient was 6. The incidence of TTE per patient course of treatment was: buserelin 9.3%; goserelin 10.5%; leuprolide IM 11.5%; leuprolide sc 23.9%; triptorelin 6.7% (p=0.02). Biochemical failure was defined as per the "nadir +2" definition, or at a value &gt; 0.2 in those patients having had previous radical prostatectomy. There was no significant difference in either biochemical failure-free survival or overall survival in patients who experienced TTE versus those who did not. The most common PSA level during a TTE was an undetectable PSA. Conclusions: Even though there appears to be no impact of TTE on either biochemical relapse-free survival or overall survival, this study demonstrates that a rising PSA does not rule out TTE. Longer-term follow-up is planned.