tbuckley/cabot-search huggingface dataset:
Reply
Authors: Jérôme Boursier, Matthieu Barret, Anna Mae Diehl
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. Reply: We thank Ling and colleagues for their comments about our study. As they stated, there are numerous indexes for the evaluation of gut microbiota structure. In our work, overall structure of the gut microbiota was assessed with richness (chao1 estimator) and phylogenetic diversity (Faith's phylogenetic diversity), and these indexes showed no significant difference according to increasing nonalcoholic fatty liver disease (NAFLD) severity. We agree that nonabundant gut bacteria may act in the pathophysiology of NAFLD. Nevertheless, highlighting a potential role of nonabundant bacteria is difficult in a small subset of patients and requires large samples to produce significant and robust results. For the same reason, we did not intend to evaluate gut dysbiosis as a new biomarker for the noninvasive discrimination of NAFLD severity. Our experience in noninvasive testing of liver lesions demonstrates that large samples of several hundred or thousand patients are crucial to generate data with good external validity.1 Ling and colleagues specified that a control group (i.e., obese patients without liver steatosis) would have been required in our work. This additional group would have only allowed us to assess the association between gut dysbiosis and the presence or the absence of NAFLD. Consequently, as we hypothesized that gut dysbiosis was associated with NAFLD severity, this control group would have added no relevant information for our study goal. At the phylum level, there was no association between the Firmicutes/Bacteroidetes ratio and increasing NAFLD severity (see fig. 1a in the article). At the genus level, the relative abundance of Bacteroides and Ruminococcus was independently linked to liver disease severity. To go beyond the simple description of a statistical association, we used PICRUSt to find some pathophysiological hypotheses. By accurately estimating the whole functional profile rather than the taxonomic composition of the gut microbiota, this approach circumvents the consideration of the ecosystem structure/diversity. Moreover, genes and subsequent functions associated with abundant and nonabundant gut bacteria are taken into account using this method. By showing that gut dysbiosis associated with NAFLD severity is accompanied by a shift in the metabolic functions of the gut microbiota, our study adds new hypotheses about how gut microbiota could promote steatohepatitis or fibrosis in NAFLD.2 Indeed, we can make the hypothesis that gut metabolic pathways could promote liver inflammation or fibrosis by their production of active metabolites, which are then directed to the liver.3 Knowing that gut metabolic pathways and their products are closely linked to nutrition, our study provides a rationale for future work which will need new technologies, such as metagenomics and metabolomics, to decipher the mechanisms linking nutrition, gut microbiota, and NAFLD severity.
Phase I trial of coramsine (SBP002) in patients with advanced solid tumors
Authors: M. Millward, A. Powell, S. Tyson, P. Daly, R. Ferguson, S. Carter
Journal: Journal of Clinical Oncology (2005)

3105 Background: Coramsine (SBP002) is a 1:1 mixture of solasonine and solamargine, plant glycoalkaloids found in the species Solanum linneanum, which have single agent and synergistic combination in vitro and in vivo preclinical efficacy in various tumor models through interaction with rhamnose-containing cell membrane glycoproteins and subsequent internalization. Methods: Coramsine as a 2 hour IV infusion daily x 5 every 2 weeks to define the MTD, recommended Phase II dose, toxicity and pharmacokinetics. Based on preclinical toxicology the infusion was increased to 4 hours at the MTD. Results: 19 previously treated advanced solid tumor pts with PS 0–2 were entered (melanoma 4, renal 4, sarcoma 2, mesothelioma 2, NSCLC 2, other 5). DLT occurred in 2/2 pts at 1.5mg/kg/day (2hr) and 2/2 pts at 3.0mg/kg/day (4hr). Limiting toxicity was grade III/IV transaminitis with grade I-II increases of bilirubin and creatinine. Hepatotoxicity was maximal at days 3–5, resolved over 10–21 days, was clinically asymptomatic apart from grade I-II fatigue, and was not cumulative. Preceding dose levels 1.0mg/kg (2hr) and 1.5mg/kg (4hr) produced DLT in 2/6 pts each with no grade IV toxicity. No myelosuppression or other serious drug-related toxicity was recorded. 3 pts had complications (sepsis, thrombosis) related to venous access devices. Minor responses were documented in 2 pts; renal - mediastinal nodes (prior interferon); unknown primary adenocarcinoma - abdominal nodes (prior platinum based chemotherapy) both at 1.0mg/kg/day over 2 hours and both received 12 cycles. Initial PK results indicate a terminal half-life of >12 hours for both solasonine and solamargine and peak levels of both >2,000ng/ml corresponding to active in vitro levels at doses >0.75mg/kg over 2 hours. Conclusions: On this schedule coramsine produces limiting hepatotoxicity at doses above 1.0mg/kg/day over 2 hours or 1.5mg/kg/day over 4 hours. 1.0mg/kg/day over 2 hours is suitable for Phase II. Some activity has been seen against resistant solid tumors. A continuous infusion schedule will be investigated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Solbec
PTH-045 Effects of an osmotic laxative on the distribution of water between the small and large intestine in humans
Authors: E Placidi, C L Hoad, L Marciani, P A Gowland, R C Spiller
Journal: Gut (2010)

<h3>Introduction/objective</h3> Improving graduate medical trainee involvement with patient safety and incident reporting is an important task in teaching hospitals that has been recognised across the country and led to numerous efforts to address barriers to incident reporting. A variety of studies have started to define the reasons why trainees are not optimally involved and interventions that may be helpful. The present study aims to add to this literature by primarily addressing barriers that can be considered ‘non-technical’ such as fears surrounding potential professional repercussions after submitting a report, perceptions that reporting incidents is not useful, and concerns about anonymity. <h3>Methods</h3> Barriers to incident reporting were previously analysed at our institution. A video was produced to directly target the barriers discovered. A 2-hour educational session was delivered which included the video intervention. The educational session was part of the standard patient safety curriculum at our institution. Paper surveys were used to capture changes in perceived barriers to incident reporting. Baseline and postintervention surveys were analysed for changes using t-tests and a p value of &lt;0.05 to determine significance. Survey development included literature review, patient safety expert discussion and cognitive interviews. <h3>Results</h3> Perceived knowledge about the reporting process significantly improved after the intervention (t=−4.49; p&lt;0.05). Attitudes about reporting also significantly improved with reduction in fear of negative consequences and anonymity. Perceptions of reporting being a futile activity were also diminished after the intervention. <h3>Conclusions</h3> This study demonstrates that targeting non-technical barriers to incident reporting with a video intervention is an effective way to improve perceived knowledge and attitude about incident reporting.
Results of the PERSIST-1 phase III study of pacritinib (PAC) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia-myelofibrosis (PET-MF).
Authors: Ruben A. Mesa, Miklos Egyed, Anita Szoke, Aleksandr Suvorov, Andrew Perkins, Jiri Mayer, Peter Ganly, Eric Jourdan, Harry C. Schouten, Patrizia Tosi, Charles Michael Farber, Pierre Zachee, Christof Scheid, James P. Dean, Paul Cernohous, Jyoti Nangalia, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Adam Mead, Claire N. Harrison
Journal: Journal of Clinical Oncology (2015)

LBA7006 Background: PAC is a potent JAK2 inhibitor without significant JAK1 inhibition with minimal myelosuppression in early-phase studies in MF. Methods: The efficacy and safety of daily oral PAC was compared to BAT (2:1 randomization stratified for risk and platelet count). The 1 0 endpoint was the proportion of ITT patients (pts) achieving ≥ 35% spleen volume reduction (SVR) at week (wk) 24 by centrally reviewed MRI or CT. Secondary endpoints included the proportion achieving ≥ 50% reduction in total symptom score (TSS) at wk 24 using the MPN Symptom Assessment Form. Results: Patients:327 were enrolled (PAC:220, BAT:107), 62% with 1 0 MF. Median time from diagnosis was 1.12 years (PAC 0.99, BAT 1.60): 32% and 15% had a platelet counts &lt; 100,000/µL or &lt;50,000/ µL; 75% were JAK2V617F positive. Efficacy: The median duration of treatment was 16.2 months PAC and 5.9 months BAT. Sixty-two percent of BAT patients received active disease directed therapy. The SVR rates at week 24 were 19.1% for PAC vs. 4.7% for BAT (p=0.0003) in ITT and 25% vs. 5.9% (p=0.0001) in the evaluable population. 79% of BAT patients crossed over to PAC; 21% had achieved a &gt;35% reduction in spleen volume at data cutoff. TSS composite V1 + V2 response rates were 24.5%for PAC vs. 6.5% for BAT (p&lt;0.0001) by ITT, and were 40.9% vs. 9.9% in evaluable pts (p&lt;0.0001). Efficacy with baseline cytopenias: In pts with &lt;100,000 and &lt;50,000 platelets/μ/L, the SVR rates were 16.7% for PAC vs. 0% for BAT (p=0.009), and 22.9% vs. 0% (p=0.045) by ITT and 23.5% vs. 0% (p=0.007) and 33.3% vs. 0% (p=0.037) in evaluable pts. In RBC transfusion dependent pts, 25.7% of PAC pts became RBC independent vs. 0% of BAT pts (p=0.043). Safety: The most common adverse events (AE) for PAC were diarrhea, nausea, and vomiting; (grade 3 were &lt;5%, &lt;1%, &lt;1% respectively). Hematologic AEs were similar between PAC and BAT. Conclusions: This study demonstrated PAC was well tolerated and induced significant and sustained SVR and symptom control even in patients with severe thrombocytopenia. PAC therapy resulted in RBC transfusion independence in a significant proportion of pts. Clinical trial information: NCT01773187.
Impairment of recognition memory with, but not without, conscious recollection in schizophrenia
Authors: C Huron, J M Danion, F Giacomoni, D Grangé, P Robert, L Rizzo
Journal: American Journal of Psychiatry (1995)

To test the hypothesis that there is a link between the memory deficit associated with schizophrenia and an impairment of consciousness, an experiential approach was used to assess recognition memory and awareness in schizophrenic patients and normal subjects.On a recognition memory task with low- and high-frequency words, the schizophrenic (N = 30) and normal (N = 30) subjects gave "remember" responses to recognized items that were accompanied by conscious recollection and "know" responses to items that were recognized on the basis of familiarity without any recollective experience.Schizophrenia selectively impaired recognition based on recollective experience, as measured by "remember" responses, but had no effects on "know" responses. In the comparison group, low-frequency words, relative to high-frequency words, enhanced conscious recollection but not familiarity. The schizophrenic patients did not display the same word-frequency effect.These results indicate that schizophrenia affects differentially two means of access to the personal past: it impairs recognition memory with, but not without, conscious recollection. They suggest that the impairment of conscious recollection observed in schizophrenic patients could be due to a failure of elaborative processing of information.
Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma
Authors: Andreas Willerslev-Olsen, Thorbjørn Krejsgaard, Lise M. Lindahl, Ivan V. Litvinov, Simon Fredholm, David L. Petersen, Claudia Nastasi, Robert Gniadecki, Nigel P. Mongan, Denis Sasseville, Mariusz A. Wasik, Charlotte M. Bonefeld, Carsten Geisler, Anders Woetmann, Lars Iversen, Mogens Kilian, Sergei B. Koralov, Niels Odum
Journal: Blood (2016)
The Pertussis Problem and a Possible Solution
Authors: Mark H. Sawyer
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Final phase II results for sunitinib (SU) in Japanese pts with well-differentiated pancreatic neuroendocrine tumor (NET)
Authors: Tetsuhide Ito, Takuji Okusaka, Masayuki Tori, Satoshi Hashigaki, Nobuyuki Kimura, Emiko Ohki, Akira Sawaki, Toshirou Nishida, Kenji Yamao, Masayuki Imamura
Journal: Annals of Oncology (2015)
Variation in Linked Selection and Recombination Drive Genomic Divergence during Allopatric Speciation of European and American Aspens
Authors: Jing Wang, Nathaniel R. Street, Douglas G. Scofield, Pär K. Ingvarsson
Journal: Molecular Biology and Evolution (2016)

Despite the global economic and ecological importance of forest trees, the genomic basis of differential adaptation and speciation in tree species is still poorly understood. Populus tremula and Populus tremuloides are two of the most widespread tree species in the Northern Hemisphere. Using whole-genome re-sequencing data of 24 P. tremula and 22 P. tremuloides individuals, we find that the two species diverged ∼2.2-3.1 million years ago, coinciding with the severing of the Bering land bridge and the onset of dramatic climatic oscillations during the Pleistocene. Both species have experienced substantial population expansions following long-term declines after species divergence. We detect widespread and heterogeneous genomic differentiation between species, and in accordance with the expectation of allopatric speciation, coalescent simulations suggest that neutral evolutionary processes can account for most of the observed patterns of genetic differentiation. However, there is an excess of regions exhibiting extreme differentiation relative to those expected under demographic simulations, which is indicative of the action of natural selection. Overall genetic differentiation is negatively associated with recombination rate in both species, providing strong support for a role of linked selection in generating the heterogeneous genomic landscape of differentiation between species. Finally, we identify a number of candidate regions and genes that may have been subject to positive and/or balancing selection during the speciation process.
A Time Study of Cancer Genetic Counselors Using a Genetic Counselor-Only Patient Care Model Versus a Traditional Combined Genetic Counselor Plus Medical Geneticist Care Model
Authors: Brandie Heald, Shanna Gustafson, Jessica Mester, Patricia Arscott, Katherine Lynch, Jessica Moline, Charis Eng
Journal: Journal of the National Comprehensive Cancer Network (2013)

Analyses of time-based effort have determined that clinical genetic services are labor-intensive, although these data derive primarily from studying geneticists' efforts in the pediatric model. No studies have investigated the time and patient care activities of cancer genetic counselors (GCs) in traditional clinics with a medical geneticist (GC/MD) compared with genetic counselor-only (GCO) appointments. In this study, 6 GCs prospectively tracked time spent in patient care activities in both clinical settings. The authors found that overall, GCs' time spent per patient was lower for GCO versus GC/MD visits. No differences were seen in time spent on results disclosure, but differences were noted in case preparation, face-to-face, and follow-up times. Furthermore, no differences were seen in number of case preparation activities or topics covered during a session. These data suggest that GCO visits result in better use of GCs' time, without a trade-off in number of patient-related activities.
Female survivors of childhood cancer have good chance of motherhood, study finds
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Modern chemotherapy regimens for childhood cancers have a greater effect on the future fertility of boys than on that of girls, a study published in the Lancet Oncology has found.1

Most women who have survived childhood cancer have a good chance of conceiving, particularly if they try for a child when they are young, the results showed. In contrast, male survivors of childhood cancer are significantly less likely to father children, especially if they were treated with chemotherapy regimens containing high doses of commonly used alkylating drugs (cyclophosphamide, ifosfamide, procarbazine) and cisplatin.

US researchers followed up 10 938 male and female cancer survivors who had been treated with 14 commonly used chemotherapy drugs at 27 institutions across the United States and Canada from …
The Role of Bridge Therapy Prior to Orthotopic Liver Transplantation
Authors: Meena A. Prasad, Laura M. Kulik
Journal: Journal of the National Comprehensive Cancer Network (2014)

Orthotopic liver transplantation (OLT) offers the best chance for cure in the setting of unresectable hepatocellular carcinoma (HCC). A consensus statement recommends locoregional therapy (LRT) be considered in patients with HCC who are expected to wait more than 6 months for OLT to diminish dropout from the waiting list because of tumor progression. This article reviews LRT as a bridge to OLT in patients with HCC.
The incidence of thromboembolism and the hemocoagulative background in patients with rheumatic heart disease.
Authors: Yohichiroh Fukuda, Kazuhiko Nakamura
Journal: Circulation (1984)

We discussed the existence of a thrombotic tendency and the relationship between the high incidence of thromboembolism and the thrombotic tendency in patients with rheumatic heart disease (RHD). The augmentation of platelet function was detected in all kinds of rheumatic valvular disease from the finding of high values of plasma beta-thromboglobulin (72 ng/ml, normal 29 ng/ml). The existence of hypercoagulation was also detected in patients with mitral stenosis by showing low levels of plasma antithrombin III (AT III), while fibrinolytic reaction remained normal. The degree of hypercoagulation became augmented in the order of cases of mitral stenosis (MS) complicated by both atrial fibrillation and chronic congestive heart failure, MS complicated only atrial fibrillation and MS with normal sinus rhythm (AT III: 19.6, 25.0, 26.7 mg/dl, respectively). On the contrary, hypercoagulation, the degree of which was almost the same as that in the respective MS groups, also existed in comparable controls of non-RHD, accompanied by the acceleration of fibrinolytic reaction as shown by the decrease in activity of plasma alpha 2-plasmin inhibitor. Therefore, it was concluded that thrombotic tendency certainly existed in patients with MS compared to those with non RHD and that it was one of the causes of the significantly high incidence of thromboembolism in comparison with non RHD.
Zinc Deficiency and the Development of Esophageal and Forestomach Tumors in Sprague-Dawley Rats Fed Precursors of <italic>N</italic>-Nitroso-<italic>N</italic>-benzylmethylamine<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: L Y Fong, J S Lee, W C Chan, P M Newberne
Journal: JNCI Journal of the National Cancer Institute (1984)

Nine-week-old zinc-sufficient (100 mg zinc/kg feed) and zinc-deficient (7 mg zinc/kg feed) noninbred male Sprague-Dawley rats were given free access 5 days a week to deionized drinking water containing low (0.05%) or high (0.25%) quantities of benzylmethylamine (BMA) and concurrently 0.5% NaNO2. In contrast to the action of the preformed carcinogen N-nitroso-N-benzylmethylamine, which almost invariably produced esophageal tumors, oral administration of its precursors, BMA and NaNO2, resulted in forestomach tumors as well. In both the high-and low-BMA groups given precursors for 16 weeks, the incidence of papillomas in both the esophagus and forestomach was significantly higher in the zinc-deficient than in the zinc-sufficient rats, but zinc deficiency did not significantly increase the yield of forestomach carcinomas. However, when combined high BMA and NaNO2 administration was prolonged to 37 weeks, the yield of forestomach carcinomas was significantly greater in the zinc-deficient than in the zinc-sufficient animals. Because endogenous synthesis of N-nitrosamines from ingested precursors is an important source of human exposure to these carcinogenic compounds and because dietary zinc deficiency might be operating in some areas with a high incidence of esophageal cancer, our data are of more than routine significance.