tbuckley/cabot-search huggingface dataset:
Brainstem processing of peripheral punctate stimuli in patients with and without chemotherapy-induced peripheral neuropathy: a prospective cohort functional MRI study
Authors: Marta Seretny, Liana Romaniuk, Heather Whalley, Catherine Warnaby, Jonathan Murnane, Neil Roberts, Stephen M Lawrie, Lesley Colvin, Irene Tracey, Marie Fallon
Journal: The Lancet (2016)
Abstract 352: Pulmonary Vein Thrombosis can make Pulmonary Vein Acidic States, which may be Associated with Atrial Fibrillation.
Authors: Hidekazu Takeuchi
Journal: Circulation Research (2014)

Atrial fibrillation can cause ischemic stroke. To prevent atrial fibrillation (AF) is crucial to prevent ischemic stroke. The pulmonary vein has a myocardial layer that can generate spontaneous or triggered action potentials. The myocardial layer is extended from the left atrial myocardium. Pulmonary vein myocardium sleeve is known to be associated with generating and maintaining AF. Pulmonary vein myocardium can be classified into two types. One is short and thin myocardium sleeve, which has no potential to cause atrial fibrillation (AF). And the other is long and thick myocardium sleeve, which has potential to cause AF. The mechanisms of such myocardium sleeve changes are not understood well. Pulmonary vein thrombosis (PVT) is believed to be rare, which was reported as a rare complication of chest surgeries such as lobectomy or lung cancers. But since 2012, I reported seven cases of PVT in elderly patients without such conditions, which suggests that PVT is not uncommon. That is a novel notion. PVT prevents arterial blood flow, which inhibits oxygen and nourishment supply and carbon dioxide excretion. Hypoxia activates hypoxia inducible factors (HIFs), and HIFs can modulate epigenetic changes, reprogramming and ES cells. Undernourishments may activate nuclear respiratory factor-1 (NRF-1) and the aryl hydrocarbon receptor (AhR). PVT can make pulmonary vein acidic states by inhibiting excretion of carbon dioxide and may modulate pulmonary vein myocardium. Under acidic states, pulmonary vein cells such as pulmonary vein myocardium cells may obtain some kinds of multipotency. After obtaining multipotency, the cells may turn into new cells to adapt changed surroundings. The changes of myocardium sleeve may be caused by acidic state conditions and HIFs, AhR and NRF-1, which seemed to modulate pulmonary vein myocardium functions. To clear these, more studies are needed.
Multiple Molecular Data Sets and the Classification of Adult Diffuse Gliomas
Authors: David W. Ellison
Journal: New England Journal of Medicine (2015)

In these days of individualized precision medicine and "big data" generated by means of next-generation sequencing, there are expectations that new therapeutic strategies for cancer will be quickly conceived and then realized in the clinic. Next-generation sequencing has certainly provided new insights into some cancers, stimulating the study of underlying biologic mechanisms and the development of targeted treatments. But even when whole-genome sequencing reveals that the genetic landscape of a cancer consists largely of known recurrent mutations, the power of data sets from multiple complementary molecular platforms — exome, transcriptome, and microRNA sequencing alongside DNA methylation, DNA copy number, and . . .
Divergence of Antiangiogenic Activity and Hepatotoxicity of Different Stereoisomers of Itraconazole
Authors: Joong Sup Shim, Ruo-Jing Li, Namandje N. Bumpus, Sarah A. Head, Kalyan Kumar Pasunooti, Eun Ju Yang, Junfang Lv, Wei Shi, Jun O. Liu
Journal: Clinical Cancer Research (2016)

Itraconazole is a triazole antifungal drug that has recently been found to inhibit angiogenesis. Itraconazole is a relatively well-tolerated drug but shows hepatotoxicity in a small subset of patients. Itraconazole contains three chiral centers and the commercial itraconazole is composed of four cis-stereoisomers (named IT-A, IT-B, IT-C, and IT-D). We sought to determine whether the stereoisomers of itraconazole might differ in their antiangiogenic activity and hepatotoxicity.We assessed in vitro antiangiogenic activity of itraconazole and each stereoisomer using human umbilical vein endothelial cell (HUVEC) proliferation and tube formation assays. We also determined their hepatotoxicity using primary human hepatocytes in vitro and a mouse model in vivo Mouse Matrigel plug and tumor xenograft models were used to evaluate in vivo antiangiogenic and antitumor activities of the stereoisomers.Of the four stereoisomers contained in commercial itraconazole, we found that IT-A (2S,4R,2'R) and IT-C (2S,4R,2'S) were more potent for inhibition of angiogenesis than IT-B (2R,4S,2'R) and IT-D (2R,4S,2'S). Interestingly, IT-A and IT-B were more hepatotoxic than IT-C and IT-D. In mouse models, IT-C showed more potent antiangiogenic/antitumor activity with lower hepatotoxicity compared with itraconazole and IT-A.These results demonstrate the segregation of influence of stereochemistry at different positions of itraconazole on its antiangiogenic activity and hepatotoxicity, with the 2 and 4 positions affecting the former and the 2' position affecting the latter. They also suggest that IT-C may be superior to the racemic mixture of itraconazole as an anticancer drug candidate due to its lower hepatotoxicity and improved antiangiogenic activity. Clin Cancer Res; 22(11); 2709-20. ©2016 AACR.
GPs lack awareness of non-steroidal anti-inflammatory drugs available over the counter
Authors: B Pal
Journal: BMJ (1996)

on which over the counter drug they had recom- mended and the reason for the recommendation.Table 1 gives the number and proportion of consultations at which information on prior use of an over the counter drug was elicited and at which a prescription was issued or an over the counter drug was recommended, or both.Over the counter drugs were recommended during 444 consultations, but the actual drug was stated in only 413.The six general practitioners varied considerably in their rates of recommending over the counter drugs (from 2.3% to 37.5%) and issuing prescriptions (from 30.6% to 78.2%).Recommending an over the counter drug seems to be a management option that is used in addition to, rather than instead of, issuing a prescription.Most recommendations (305/413) were for simple analgesics, especially paracetamol preparations (184/413).Medicines that have changed since 1990 from being available only on prescription to being available in pharmacies hardly featured (8/413).The main reason doctors gave for recommending over the counter drugs was that they were cheaper for some patients.Increasing patient autonomy or capacity for self care and potential savings in the practice's prescribing budget did not emerge as major reasons for recommending over the counter drugs.
Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer
Authors: V.M. Villaflor, J.M. Melotek, T.G. Karrison, R.J. Brisson, E.A. Blair, L. Portugal, J.A. De Souza, D.T. Ginat, K.M. Stenson, A. Langerman, M. Kocherginsky, M.T. Spiotto, N. Hannigan, T.Y. Seiwert, E.E.W. Cohen, E.E. Vokes, D.J. Haraf
Journal: Annals of Oncology (2016)
PTH-264 Preoperative chemoradiotherapy does not appear to have short-term effects on human rectal neuromuscular functions: Abstract PTH-264 Table 1
Authors: V Kung, J Broad, M Machesney, M Thaha, C Knowles, G Sanger
Journal: Gut (2015)

<h3>Introduction</h3> Preoperative chemoradiotherapy may impair anorectal functions. Its effect on neuromuscular functions was investigated in human rectum <i>ex-vivo</i>. <h3>Method</h3> Following informed consent, 3 groups of patients undergoing surgery for anorectal cancer were studied: 13 patients treated by surgery alone (Group I); 13 with long course neoadjuvant chemoradiotherapy (capecitabine) (Group II); and 4 with prior platinum-based chemoradiotherapy (oxaliplatin/capecitabine n = 2, FOLFOX/capecitabine n = 1, carboplatin/paclitaxel n = 1) (Group III). Age and gender were similar between Group I and II. Group III [55 (range=51–60)] were younger than Group I [72 (range=50–87)]. Postoperatively, macroscopically-normal rectum (without taenia) was obtained 5–10cm away from tumour. Mucosa-free circular muscle strips were suspended in tissue baths for isometric recording and electrical field stimulation (EFS, 1–20Hz, 50V, 0.5ms, for 10s) applied.<sup>1</sup>Data are expressed as median (inter-quartile range) and analysed using ANOVA with multiple comparison post-tests. <h3>Results</h3> EFS usually caused contraction (or relaxation at low frequencies), often followed by an ‘after-contraction’ on termination. Amplitudes of contractions during and after EFS, and area under curve (AUC) of the full muscle movement increased with frequency (see table). Contractions were abolished by atropine 1 µM and tachykinin (NK<sub>1–3</sub>) receptor antagonists (n = 4) and greatly reduced by the neurotoxin tetrodotoxin 1 µM (n = 2). All parameters of the movements evoked by EFS at all frequencies [AUC, amplitude of responses during EFS and after EFS] were similar amongst the 3 groups. There were no significant differences in tension generated by carbachol 10 µM (maximally-effective concentration) between groups (see Table 1, <i>P &gt; 0</i>.05 for all measurements). <h3>Conclusion</h3> In this pilot study, preoperative chemoradiotherapy with capecitabine or platinum-based agents does not appear to have short-term effects on human rectal neuromuscular function. Reported impairment of anorectal function may be due to its long term effects or via other mechanisms. <h3>Disclosure of interest</h3> V. Kung Grant/ Research Support from: AgeUK PhD studentship, Barts and the London Charity, J. Broad: None Declared, M. Machesney: None Declared, M. Thaha: None Declared, C. Knowles: None Declared, G. Sanger Grant/ Research Support from: Takeda. <h3>Reference</h3> Broad <i>et al</i>. Br J Pharmacol. 2013;179:1253–61
A pilot study of operational tolerance with a regulatory T‐cell‐based cell therapy in living donor liver transplantation
Authors: Satoru Todo, Kenichiro Yamashita, Ryoichi Goto, Masaaki Zaitsu, Akihisa Nagatsu, Tetsu Oura, Masaaki Watanabe, Takeshi Aoyagi, Tomomi Suzuki, Tsuyoshi Shimamura, Toshiya Kamiyama, Norihiro Sato, Junichi Sugita, Kanako Hatanaka, Hisashi Bashuda, Sonoko Habu, Anthony J. Demetris, Ko Okumura
Journal: Hepatology (2016)

Potent immunosuppressive drugs have significantly improved early patient survival after liver transplantation (LT). However, long‐term results remain unsatisfactory because of adverse events that are largely associated with lifelong immunosuppression. To solve this problem, different strategies have been undertaken to induce operational tolerance, for example, maintenance of normal graft function and histology without immunosuppressive therapy, but have achieved limited success. In this pilot study, we aimed to induce tolerance using a novel regulatory T‐cell‐based cell therapy in living donor LT. Adoptive transfer of an ex vivo ‐generated regulatory T‐cell‐enriched cell product was conducted in 10 consecutive adult patients early post‐LT. Cells were generated using a 2‐week coculture of recipient lymphocytes with irradiated donor cells in the presence of anti‐CD80/86 monoclonal antibodies. Immunosuppressive agents were tapered from 6 months, reduced every 3 months, and completely discontinued by 18 months. After the culture, the generated cells displayed cell‐number‐dependent donor‐specific inhibition in the mixed lymphocyte reaction. Infusion of these cells caused no significant adverse events. Currently, all patients are well with normal graft function and histology. Seven patients have completed successful weaning and cessation of immunosuppressive agents. At present, they have been drug free for 16‐33 months; 4 patients have been drug free for more than 24 months. The other 3 recipients with autoimmune liver diseases developed mild rejection during weaning and then resumed conventional low‐dose immunotherapy. Conclusions: A cell therapy using an ex vivo ‐generated regulatory T‐cell‐enriched cell product is safe and effective for drug minimization and operational tolerance induction in living donor liver recipients with nonimmunological liver diseases. (H epatology 2016;64:632‐643)
18F-FDG Dynamic PET/CT in Patients with Multiple Myeloma
Authors: Christos Sachpekidis, Elias K Mai, Hartmut Goldschmidt, Jens Hillengass, Dirk Hose, Leyun Pan, Uwe Haberkorn, Antonia Dimitrakopoulou-Strauss
Journal: Clinical Nuclear Medicine (2015)

The value of F-FDG PET in the diagnostic approach of multiple myeloma (MM) remains incompletely elicited. Little is known about the kinetics of F-FDG in the bone marrow and extramedullary sites in MM. This study aimed to evaluate quantitative data on kinetics and distribution patterns of F-FDG in MM patients with regard to pelvic bone marrow plasma cell infiltration.The study included 40 patients with primary MM. Dynamic PET/CT scanning of the lower lumbar spine and pelvis was performed after the administration of F-FDG. Whole-body PET/CT studies were performed. Sites of focal increased tracer uptake were considered as highly suggestive of myelomatous involvement after taking into account the patient history and CT findings. Bone marrow of the os ilium without pathologic tracer accumulation served as reference. The evaluation of dynamic PET/CT studies was based in addition to the conventional visual (qualitative) assessment, on semiquantitative (SUV) calculations, as well as on absolute quantitative estimations after application of a 2-tissue compartment model and a noncompartmental approach. F-FDG quantitative information and corresponding distribution patterns were correlated with pelvic bone marrow plasma cell infiltration.Fifty-two myelomatous lesions were detected in the pelvis. All parameters in suspected MM lesions ranged in significantly higher levels than in reference tissue (P < 0.01). Correlative analyses revealed that bone marrow plasma cell infiltration rate correlated significantly with SUVaverage, SUVmax, and the parameters K1, influx, and fractal dimension of F-FDG in reference bone marrow (P < 0.01). In addition, whole-body static PET/CT imaging demonstrated 4 patterns of tracer uptake; these are as follows: negative, focal, diffuse, and mixed (focal/diffuse) tracer uptake. Patients with a mixed pattern of radiotracer uptake had the highest mean plasma cell infiltration rate in their bone marrow, whereas those with negative PET/CT scans demonstrated the lowest bone marrow plasma cell infiltration. In total, 265 focal myeloma-indicative F-FDG-avid lesions were detected, 129 of which correlated with low-dose CT osteolytic findings. No significant correlation between the number of focal lesions detected in PET/CT and bone marrow infiltration was detected.The F-FDG kinetic parameters K1, influx, and fractal dimension as well as SUVaverage from reference tissue correlated significantly with bone marrow malignant plasma cell infiltration rate. Patients with negative PET/CT demonstrated the lowest bone marrow infiltration by malignant plasma cells, whereas those with a mixed pattern of tracer uptake had the highest infiltration.
Effect of understaging of early oesophageal tumors on treatment
Authors: A. Rohatgi, S. Naji, A. Hamouda, P. J. Ross, R. C. Mason
Journal: Journal of Clinical Oncology (2009)

e15572 Background: Early and node negative oesophageal cancers do not undergo chemotherapy as it is felt that as the risk of lymph node metastasis is small, early operative intervention is considered the best option. We analysed a prospective database in a tertiary referral centre to see, with current preoperative staging modalities, if a significant number of patients were under staged and hence under treated preoperatively. Methods: Four hundred and fifteen patients underwent esophagectomies for cancer in our unit between March 2000 and December 2006. 117 were preoperatively staged as either T1/T2 N0. Pre-operative staging was by gastroscopy, endoscopic ultrasound (EUS), CT scan and PET-CT. These were discussed in a multi-disciplinary meeting and as per current evidence did not undergo preoperative chemotherapy. Results: 115 patients were analysed as two were excluded. Preoperatively there were 35 T0N0, 30 T1N0, and 50 T2N0. There were 42 (36.5%) patients who were under staged utilising the standard preoperative staging protocol. These were preoperatively staged as T0N0 –2, T1N0 –6, T2N0 –34. 6 did not have EUS, only 4 had a PET- CT and 1 had a staging laparoscopy. Gastroscopy, CT scan and EUS was the staging protocol in 87%. Post op staging was T1N1–7, T2N1–12, T2N2–1, T3N0–10, T3N1–11, T3N2–1. Conclusions: Utilising current preoperative staging methods one third of patients were under staged. Looking specifically at T2N0 68% were under staged. We feel that early oesophageal cancer especially T2N0 disease may benefit from neoadjuvant chemotherapy based on the current staging protocols. No significant financial relationships to disclose.
Comparative Risk of Hospitalized Infection Associated With Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare
Authors: Huifeng Yun, Fenglong Xie, Elizabeth Delzell, Emily B. Levitan, Lang Chen, James D. Lewis, Kenneth G. Saag, Timothy Beukelman, Kevin L. Winthrop, John W. Baddley, Jeffrey R. Curtis
Journal: Arthritis & Rheumatology (2015)

Objective The risks of hospitalized infection associated with biologic agents used to treat rheumatoid arthritis (RA) are unclear. The aim of this study was to determine whether the associated risk of hospitalized infections differed between specific biologic agents used to treat RA. Methods In a retrospective cohort study using Medicare data from 2006–2011 for all enrolled patients with RA, new episodes of treatment with etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab, and tocilizumab were identified. Patients were required to have received another biologic agent previously and to have been continuously enrolled in Medicare medical and pharmacy plans during the baseline period and throughout followup. Followup started on the date of initiation of treatment with the new biologic agent (after previous treatment with a different biologic agent) and ended on the date of the earliest hospitalized infection, at 12 months, after an exposure gap of &gt;30 days, or at the time of death or loss of Medicare coverage. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) for hospitalized infection, adjusting for an infection risk score and other confounders. Results Of 31,801 new biologic treatment episodes in patients who had previously received another biologic agent, 12.0% were with etanercept, 15.2% with adalimumab, 5.9% with certolizumab, 4.4% with golimumab, 12.4% with infliximab, 28.9% with abatacept, 14.8% with rituximab, and 6.3% with tocilizumab. During followup, we identified 2,530 hospitalized infections; incidence rates ranged from 13.1 per 100 person‐years (abatacept) to 18.7 per 100 person‐years (rituximab). After adjustment, etanercept (HR 1.24, 95% confidence interval [95% CI] 1.07–1.45), infliximab (HR 1.39, 95% CI 1.21–1.60), and rituximab (HR 1.36, 95% CI 1.21–1.53) had significantly higher HRs for hospitalized infection compared with abatacept. Conclusion In RA patients with prior exposure to a biologic agent, exposure to etanercept, infliximab, or rituximab was associated with a greater 1‐year risk of hospitalized infection compared with the risk associated with exposure to abatacept.
Hypoxanthine:guanine phosphoribosyltransferase activity in primary human osteosarcomas. A rationale for therapy with methotrexate-thymidine rescue?
Authors: W H Meyer, J A Houghton, P J Houghton
Journal: Journal of Clinical Oncology (1987)

Hypoxanthine:guanine phosphoribosyltransferase (HPRT) activity was measured in 14 human osteosarcomas to test whether a subset of these tumors was deficient in the purine salvage pathway enzyme and thus provide a rationale for therapy with methotrexate-thymidine rescue. All tumors contained HPRT activity within the range previously reported for xenografts of human osteosarcoma. Three patients received methotrexate (3.375 g/m2/24 hours) as a 72-hour continuous infusion with thymidine rescue (2.0 g/m2/24 hours) beginning 24 hours after the start of the methotrexate infusion. The methotrexate-thymidine infusion was well tolerated by all patients with no significant toxicity; however, there were no responses. We conclude that osteosarcomas are not deficient in HPRT activity. Therefore, the previously reported rationale for therapy of osteosarcoma with methotrexate-thymidine based on lack of activity of this enzyme is not valid. This combination, although well tolerated, is inconvenient and requires prolonged hospitalization. Therefore, without a valid rationale it cannot be recommended for therapy of patients with osteosarcoma.
Abstract 17508: Defective SR-mitochondria Calcium Transfer and Increased Mitochondrial Oxidative State in Aged Myocardium
Authors: Celia Fernandez-Sanz, Marisol Ruiz-Meana, Elisabet Miro-Casas, Ignasi Barba, Estefania Nunez, Jesus Vazquez, David Garcia-Dorado
Journal: Circulation (2013)

Mitochondrial alterations have been proposed as critical players of impaired myocardial function during aging by mechanisms not fully elucidated. We investigate the role of altered sarcoplasmic ret...
A Novel Diagnostic Method For AITL By Detecting RHOA G17V Hotspot Mutation Using Allele-Specific Real-Time PCR
Authors: Rie Nakamoto-Matsubara, Mamiko Sakata-Yanagimoto, Terukazu Enami, Kenichi Yoshida, Yuichi Shiraishi, Hideharu Muto, Yuhei Kamada, Naoshi Obara, Naoki Kurita, Masanori Seki, Yasuhisa Yokoyama, Emiko Noguchi, Koji Izutsu, Yasunori Ota, Masashi Sanada, Kenichi Chiba, Hiroko Tanaka, Seiichi Shimizu, Takuya Komeno, Yuji Satou, Takayoshi Itoh, Kazumi Suzukawa, Yuichi Hasegawa, Kengo Takeuchi, Satoru Miyano, Naoya Nakamura, Seishi Ogawa, Shigeru Chiba
Journal: Blood (2013)
Long Term Follow up on Patients with Ph-Abnormal Clones Emerged during Imatinib Therapy.
Authors: Elisabetta Abruzzese, Alessandro Gozzetti, Nicoletta Testoni, Alfonso Zaccaria, Franca Radaelli, Sara Galimberti, Malgorzata M. Trawinska, Marco Mancini, Dario Ferrero, Michela Salvio, Federica Sora’, Monica Crugnola, Michele Cedrone, Gianantonio Rosti, Sergio Amadori, Paolo de Fabritiis, Michele Baccarani
Journal: Blood (2006)
Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers
Authors: Yu-An Zhang, Xiaotu Ma, Adwait Sathe, Junya Fujimoto, Ignacio I. Wistuba, Stephen Lam, Yasushi Yatabe, Yi-Wei Wang, Victor Stastny, Boning Gao, Jill E. Larsen, Luc Girard, Xiaoyun Liu, Kai Song, Carmen Behrens, Neda Kalhor, Yang Xie, Michael Q. Zhang, John D. Minna, Adi F. Gazdar
Journal: Journal of Thoracic Oncology (2015)