tbuckley/cabot-search huggingface dataset:
Abstract 20693: MYBPHL is a Novel Myofilament Protein Implicated in Arrhythmia and Cardiomyopathy
Authors: David Y Barefield, Megan J Puckelwartz, Ellis Y Kim, Lisa D Wilsbacher, Andy H Vo, Emily A Waters, Judy U Earley, Michele Hadhazy, Lisa Dellefave-Castillo, Lorenzo L Pesce, Elizabeth M McNally
Journal: Circulation (2017)

Introduction: Cardiomyopathy is a leading cause of heart failure and is highly heritable. Nearly 100 genes have been associated with inherited cardiomyopathy, which are usually autosomal dominant w...
Long-term outcomes of children with Xp11.2 translocation renal cell carcinoma.
Authors: Hiroshi Asanuma, Ryuichi Mizuno, Aya Masuda, Hiroyuki Satoh, Zenichi Matsui, Hidaka Kono, Kazunobu Shinoda, Eiji Kikuchi, Hirohiko Nagata, Akira Miyajima, Ken Nakagawa, Mototsugu Oya
Journal: Journal of Clinical Oncology (2012)

9569 Background: We aimed to assess the clinico-pathological characteristics and the long-term prognosis of Xp11.2 translocation renal cell carcinoma (Xp-RCC) in children. Methods: A total of 52 Japanese children with renal tumors were presented to our institutions. Of these, 5 (10%) had RCC, and all RCCs were Xp11.2 translocation subtype with positive nuclear transcription factor E3 immunostaining. We retrospectively reviewed the pathological and hospital records of these 5 patients. Results: In the 1 boy and 4 girls with an average age of 9 years 7 months at diagnosis, the most common presenting complains were gross hematuria (60%) and palpable abdominal mass (40%). All patients had unilateral disease and there was no special family or medical history in any children. Computerized tomography revealed characteristic calcification within the tumor in 4 of the 5 patients (80%). In the remaining case, the lesion had high density areas with microcalcification, as confirmed by histopathological study. In 3 patients with regional lymph node metastasis, calcification was also observed in the metastatic lesions. Stage of the disease were stage I in 1 patient, II in 1, IV without and with distant metastasis in 2 and 1, respectively. All patients underwent transabdominal nephrectomy with regional lymphadenectomy. One patient with stage I disease had multiple metastases 15 months after surgery and died of disease in spite of interferon and chemotherapy 4 years postoperatively. Three patients received adjuvant interferon therapy and 2 of them are without evidence of recurrence postoperative 19 and 14 years, respectively. One of them had lymph node and lung metastases 12 years postoperatively. The remaining one patient had multiple lymph node, lung, bone, and dura mater metastases at diagnosis. The latter 2 patients have received targeted therapy (sunitinib, temsirolimus) without their progression for 6 and 12 months, respectively. Conclusions: Calcification within the tumor and/or metastatic lesions is characteristic findings suggestive of Xp-RCC in children. Regional lymphadenectomy or targeted therapy may provide some benefit in selected pediatric patients. Long-term follow-up is essential in pediatric patients with RCC.
Adeno-associated virus in the liver: natural history and consequences in tumour development
Authors: Tiziana La Bella, Sandrine Imbeaud, Camille Peneau, Iadh Mami, Shalini Datta, Quentin Bayard, Stefano Caruso, Theo Z Hirsch, Julien Calderaro, Guillaume Morcrette, Catherine Guettier, Valerie Paradis, Giuliana Amaddeo, Alexis Laurent, Laurent Possenti, Laurence Chiche, Paulette Bioulac-Sage, Jean-Frederic Blanc, Eric Letouze, Jean-Charles Nault, Jessica Zucman-Rossi
Journal: Gut (2019)

Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (35%-80%). Recurrent clonal AAV2 insertions are associated with the pathogenesis of rare human hepatocellular carcinoma (HCC) developed on normal liver. This study aimed to characterise the natural history of AAV infection in the liver and its consequence in tumour development.Viral DNA was quantified in tumour and non-tumour liver tissues of 1461 patients. Presence of episomal form and viral mRNA expression were analysed using a DNAse/TaqMan-based assay and quantitative RT-PCR. In silico analyses using viral capture data explored viral variants and new clonal insertions.AAV DNA was detected in 21% of the patients, including 8% of the tumour tissues, equally distributed in two major viral subtypes: one similar to AAV2, the other hybrid between AAV2 and AAV13 sequences. Episomal viral forms were found in 4% of the non-tumour tissues, frequently associated with viral RNA expression and human herpesvirus type 6, the candidate natural AAV helper virus. In 30 HCC, clonal AAV insertions were recurrently identified in CCNA2, CCNE1, TERT, TNFSF10, KMT2B and GLI1/INHBE. AAV insertion triggered oncogenic overexpression through multiple mechanisms that differ according to the localisation of the integration site.We provided an integrated analysis of the wild-type AAV infection in the liver with the identification of viral genotypes, molecular forms, helper virus relationship and viral integrations. Clonal AAV insertions were positive selected during HCC development on non-cirrhotic liver challenging the notion of AAV as a non-pathogenic virus.
Concurrent chemoradiotherapy of patients with locally advanced squamous cell carcinoma of the oral cavity (stage III, IV)
Authors: D. G. Adilbay, G. B. Adilbaev, D. N. Ahmetov
Journal: Journal of Clinical Oncology (2009)

e17034 Background: Randomized trials have showed a good result of concurrent chemoradiotherapy in advanced SCC of the head and neck. But there are only few trials which evaluates separately the different sites of the head and neck. The aim was to evaluate the toxicity and efficacy of concurrent intra-arterial chemotherapy plus radiotherapy with altered fractionation in SCC of the oral cavity. Methods: 43 patients with previously untreated oral cavity SCC (T 3–4 N 0–2 M 0 ) received concurrent chemoradiotherapy by followed scheme: first day intra-arterial chemotherapy: docetaxel - 80 mg/m 2 , cysplatin - 100 mg/m 2 , from second to 21st day RT (28 Gy by 4 Gy - 3 times week), 22nd day second course of intra-arterial chemotherapy and after RT (total dose- 60 Gy by 2 Gy 5 times week, total equivalent to 70Gy by conventional fractionation), depending on the results salvage surgery if necessary. Results: The clinical effects were pCR in 34 (79.1%) patients, pPR in 9 (20.9%) patients. The following main toxicities of chemoradiotherapy were observed: only 2 cases of grade 3 neutropenia, Non-hemathologic toxicity: 74.4% (32 patients) grade 3 mucosal events. All patients have totally completed the treatment. The 3-year overall survival rate were 83.7%, and 3-year disease free survival were 76.7%. Conclusions: This regimen of concurrent chemoradiotherapy where radiotherapy is used by altered fractionation is feasible, safe and well tolerated. No significant financial relationships to disclose.
Abstract 11501: Dilated Cardiomyopathy Due to Medium-Chain Triglyceride Diet in Mice With a Defect in {beta}-Oxidation
Authors: Ulrich Flogel, Sara Tucci, Jurgen Schrader, Ute Spiekerkotter
Journal: Circulation (2012)

Patients with long-chain fatty acid oxidation disorders are prone to develop cardiac and skeletal myopathy. Therapeutical approaches include fat-modified diets, in which long-chain triglycerides (L...
Black-white disparity in physical performance among older women with breast cancer: The role of physical activity and inflammation.
Authors: Cynthia Owusu, Mark D. Schluchter, Siran M. Koroukian, Kathryn Schmitz, Nathan A. Berger
Journal: Journal of Clinical Oncology (2013)

6525 Background: Compared with non-Hispanic Whites (NHW), African-Americans (AA) experience poorer physical function. However, little is known about the existence of racial disparity in physical performance among older adults with cancer, and clinical factors that might explain such differences. Methods: This is a cross-sectional study of women ≥ 65 years (n=108), with stage I-III breast cancer. Before adjuvant treatment, participants completed the Short Physical Performance Battery (SPPB), an objective measure of lower extremity function on a scale of 0-12, with higher scores denoting higher physical performance. Self-reported physical activity was ascertained with the Minnesota Leisure Time Activity Questionnaire. Serum level of C-reactive protein (CRP) was determined and log transformed for analyses. Results: The median age was 74.0 years (range 65-93 years) and 32% were AA. The mean SPPB score was 8.5 (SD 3.5). Compared to NHW, AA had lower mean SPPB scores (7.0 vs. 9.2, p=0.002), were less physically active (8.2 vs. 19.4 MET-hours/week, p=0.005), and had higher mean serum CRP(log) (-0.43 vs. -0.86, p=0.002). In multivariate linear regression analysis that accounted for age, educational status, comorbidities and geriatric syndromes, AA race relative to NHW was independently associated with decreasing SPPB scores, [beta coefficient = -1.67, SE: 0.57, p=0.004]. When differences in serum CRP and physical activity were accounted for in the model, increasing CRP and decreasing physical activity were independently associated with decreasing SPPB scores, and eliminated the racial difference in physical performance by 23% and 40%, respectively. This suggests sub-clinical inflammation and physical activity mediate the relationship between race and physical performance. Conclusions: Among older women with breast cancer, racial disparity in physical performance may be reduced through increased physical activity and therapeutic strategies that moderate sub-clinical inflammation. Given the clinical importance of functional status in cancer treatment decision-making, interventions directed at attenuating racial disparity in physical performance are warranted.
Multivariate analysis identifies factors that affect survival after stereotactic radiosurgery for brain metastases
Authors: M. L. Diluna, J. T. King, J. P. Knisely, J. E. Bond, A. C. De Lotbiniere, V. L. Chiang
Journal: Journal of Clinical Oncology (2006)

11500 Background: Stereotactic radiosurgery (SRS) has become a standard for the treatment of brain metastases. We attempted to determine if specific tumor- or patient-related factors in our population independently predicted better survival. Methods: Survival data for all 334 patients with brain metastases treated with SRS between Jan 1998 and Dec 2004 were analyzed. Clinical data were abstracted retrospectively from treatment records; survival data were obtained from the Connecticut Tumor Registry. Kaplan-Meier plots and Cox proportional hazard multivariate regression models were used to identify the factors that independently affected survival. Variables analyzed included age, sex, race, histology, number, location and total volume of metastatic lesions, surgical resection, WBXRT, chemotherapy, and systemic disease control. Results: Median age of our patient population was 57.3 years. The median number of lesions treated in a single session was 2 (range 1 to 36). Tumor histologies included non-small cell lung carcinoma (36%), breast (17%), melanoma (16%), small cell lung carcinoma (8%), renal cell (8%), esophageal (2%), and other (16%). Three hundred patients (90%) had confirmed deaths, with a median survival after SRS of 8.1 months. Increased survival was independently associated with systemic control (HR = 0.51, P&lt;0.001), breast cancer (HR = 0.60, P=0.003), and total tumor volume &lt;5cc (HR = 0.68, P=0.003). Decreased survival was independently associated with the presence of four or more cerebral metastases (HR = 1.50, P=0.005) and a trend toward decreased survival was associated with esophageal cancer (HR = 2.24, P=0.055). There was no difference in survival associated with age, race, sex, location of metastases, surgical resection, WBXRT before or after SRS, or chemotherapy. Conclusions: Breast cancer, systemic control, and fewer metastases were all significant independent predictors of improved survival. Of note, histological diagnosis, other than breast or esophageal cancer, did not affect patient survival, and a total tumor burden of 5cc or more was associated with worse survival independent of the number of metastases. These results should assist in survival prognostication in patients with cerebral metastases considering SRS. No significant financial relationships to disclose.
Biologic variations of plasma cells in the bone marrow of smoldering multiple myeloma (SMM) and multiple myeloma (MM) patients: Multiple biopsies in the same patient.
Authors: Elisabet E. Manasanch, Neha Korde, Constance Yuan, Mary Kwok, Nishant Tageja, Manisha Bhutani, Aaron W. Flanders, Adriana Zingone, Rene Costello, Prashant Tembhare, Marcia Mulquin, Diamond Zuchlinski, Irina Maric, Katherine R. Calvo, Seth M. Steinberg, Mark J. Roschewski, Ola Landgren, Raul Braylan, Maryalice Stetler-Stevenson
Journal: Journal of Clinical Oncology (2013)

e19506 Background: The European Myeloma Network has reported that plasma cell (PC) enumeration by flow cytometry (FC) varies depending on quality of aspirate pull and field biopsied. We conducted a prospective study to evaluate PC site variation content in the core biopsy (CB), PC viability (V) and proportion of monoclonal PCs based on immunophenotypic characteristics, anticoagulant use, and aspirate (A) pull sequence in SMM and MM treatment-naïve patients. Methods: Untreated SMM (n=5) and MM (n=5) patients underwent bilateral bone marrow (BM) A and CB. Bilateral first-pull A were anticoagulated with ethylenediaminetetraacetic acid (EDTA). The second-pull A were anticoagulated with heparin. CB were performed after obtaining all A. The first pull A was sent for morphology and FC evaluation, and the second-pull for FC. CB infiltration by PC was assessed by CD138 immunohistochemistry (IHC). Analysis of PC by FC used CD markers: 19, 45, 20, 38, 138, 27, 28, 19, 81, 126, 200 and 117. V was measured by FC using 7-amino-actinomycin D exclusion. We used the two-tailed Wilcoxon signed rank test to determine the significance of the difference between paired values. Results: The mean difference in estimated percentage of PC infiltration between the right and left CB was 0.033 +/- 0.017 (p=0.25). Phenotypic analysis of PCs by FC showed similar expression of CD markers. PC V was significantly lower in samples anticoagulated with EDTA when compared to heparin (p&lt;0.005), suggesting that the latter is superior for PC analysis. Of importance, the fraction of abnormal PCs determined by FC did not differ significantly between the two sides, use of EDTA/heparin or order of A pull (p&gt;0.05). Conclusions: Based on IHC and FC, our results suggest that in untreated patients with SMM or MM there are no major differences in the estimated number or immunophenotypic characteristics and distribution of PC in marrow samples obtained from two distant bone sites. These observations have implications for current diagnostic and treatment of MM and its precursor disease. More advanced molecular profiling may find biological variation in bone marrow tumor PC extracted from different locations.
An anti-CD40 activating antibody induces dendritic cell maturation and promotes autologous anti-tumor T cell responses in an in vitro mixed autologous tumor cell/lymph node cell model
Authors: T. B. Hunter, R. P. Gladue, S. J. Antonia
Journal: Journal of Clinical Oncology (2006)

2537 Background: CD40-mediated interactions play an important role in the response to a variety of diseases, including cancer. Engagement of CD40 on antigen-presenting cells (APC) by CD40L leads to maturation and upregulation of co-stimulatory molecules, B7.1 and B7.2 (CD80 and CD86), which are requisite in the activation of T cells. Clinical trials involving immunologic interventions have shown clinical responses confirming that the immune system can be harnessed for the treatment of cancer. However, the clinical response rate has been low, signifying the need for new immunotherapeutic strategies. To this end, an agonist antibody specific for CD40 has been developed and is being evaluated as a potential anti-cancer agent. Methods: The activation capacity of anti-CD40 antibody CP-870,893 was analyzed by performing flow cytometric analysis of APC maturation markers following incubation of monocyte derived dendritic cells (DC) with the antibody. IL-12 and macrophage inflammatory protein-1α (Mip1 α) secretion were also analyzed. The effect of the antibody on anti-tumor T cell responses was tested in an autologous human model consisting of tumor cells as stimulator cells and tumor-draining lymph node cells as responders from a series of cancer patients. Results: Cultured DC treated with CP-870,893 consistently display a mature phenotype: robust upregulation of CD80, CD83, CD86 and HLA-DR expression, increased Mip1 α secretion, and the loss of antigen presenting capability. IL-12 secretion was not detected. CP-870,893 also promotes the responsiveness of lymph node derived T cells to autologous tumor, indicated by IFNγ and IL-2 ELISpot. Conclusions: These data demonstrate that CP-870,893 binds to and activates DC. A fully autologous mixed lymph node cell/tumor cell model was used to demonstrate that this activation promotes tumor-specific T cell responses. T cells from the tumor draining lymph node are not responsive to autologous tumor cells, however in the presence of CP-870,893 this unresponsiveness is reversed. These data indicate that CP-870,893 warrants further study as an immunotherapeutic agent in the treatment of cancer. No significant financial relationships to disclose.
NUS to lobby UK government over graduate medics’ fee support
Authors: Neil Chanchlani
Journal: BMJ (2013)

The National Union of Students (NUS) has a mandate to lobby the UK government to provide more support for graduate medical and dental students on five year courses.

The motion to increase support and access for graduate students on a five year course passed unanimously in April at the NUS National Conference 2013, which was attended by over 730 delegates composed of representatives from almost every UK university and college.

The conference resolved that student unions under the NUS should lobby the government to …
Instantaneous Amplitude and Frequency Modulations Detect the Footprint of Rotational Activity and Reveal Stable Driver Regions as Targets for Persistent Atrial Fibrillation Ablation
Authors: Jorge G. Quintanilla, José Manuel Alfonso-Almazán, Nicasio Pérez-Castellano, Sandeep V. Pandit, José Jalife, Julián Pérez-Villacastín, David Filgueiras-Rama
Journal: Circulation Research (2019)

Costly proprietary panoramic multielectrode (64-256) acquisition systems are being increasingly used together with conventional electroanatomical mapping systems for persistent atrial fibrillation (PersAF) ablation. However, such approaches target alleged drivers (rotational/focal) regardless of their activation frequency dynamics.To test the hypothesis that stable regions of higher than surrounding instantaneous frequency modulation (iFM) drive PersAF and determine whether rotational activity is specific for such regions.First, novel single-signal algorithms based on instantaneous amplitude modulation (iAM) and iFM to detect rotational-footprints without panoramic multielectrode acquisition systems were tested in 125 optical movies from 5 ex vivo Langendorff-perfused PersAF sheep hearts (sensitivity/specificity, 92.6/97.5%; accuracy, 2.5-mm) and in computer simulations. Then, 16 pigs underwent high-rate atrial pacing to develop PersAF. After a median (interquartile range [IQR]) of 4.4 (IQR, 2.5-9.9) months of high-rate atrial pacing followed by 4.1 (IQR, 2.7-5.4) months of self-sustained PersAF, pigs underwent in vivo high-density electroanatomical atrial mapping (4920 [IQR, 4435-5855] 8-second unipolar signals per map). The first 4 out of 16 pigs were used to adapt ex vivo optical proccessing of iFM/iAM to in vivo electrical signals. In the remaining 12 out of 16 pigs, regions of higher than surrounding average iFM were considered leading-drivers. Two leading-driver + rotational-footprint maps were generated 2.6 (IQR, 2.4-2.9) hours apart to test leading-driver spatiotemporal stability and guide ablation. Leading-driver regions (2.5 [IQR, 2.0-4.0] regions/map) exactly colocalized (95.7%) in the 2 maps, and their ablation terminated PersAF in 92.3% of procedures (radiofrequency until termination, 16.9 [IQR, 9.2-35.8] minutes; until nonsustainability, 20.4 [IQR, 12.8-44.0] minutes). Rotational-footprints were found at every leading-driver region, albeit most (76.8% [IQR, 70.5%-83.6%]) were located outside. Finally, the translational ability of this approach was tested in 3 PersAF redo patients.Both rotational-footprints and spatiotemporally stable leading-driver regions can be located using iFM/iAM algorithms without panoramic multielectrode acquisition systems. In pigs, ablation of leading-driver regions usually terminates PersAF and prevents its sustainability. Rotational activations are sensitive but not specific to such regions. Single-signal iFM/iAM algorithms could be integrated into conventional electroanatomical mapping systems to improve driver detection accuracy and reduce the cost of patient-tailored/mechanistic approaches.
Artificial Intelligence and Training Physicians to Perform Technical Procedures
Authors: George Shorten
Journal: JAMA Network Open (2019)

Alexander Winkler-Schwartz, MD; Recai Yilmaz, MD; Nykan Mirchi, BSc; Vincent Bissonnette, MD; Nicole Ledwos, BA; Samaneh Siyar, MSc; Hamed Azarnoush, PhD; Bekir Karlik, PhD; Rolando Del Maestro, PhD
Changing the norm towards gender equity in surgery: the women in surgery working group of the Association of Surgeons of Great Britain and Ireland’s perspective
Authors: Maria Irene Bellini, Anya Adair, Christina Fotopoulou, Yitka Graham, Alexis Hutson, Scarlett McNally, Helen Mohan, Stella Vig, Rowan Parks, Vassilios Papalois
Journal: Journal of the Royal Society of Medicine (2019)

Competition ratios for surgical specialty applications have declined. To ensure that all individuals attracted to surgery are enabled to flourish and enjoy their surgical careers, we need to change the “surgical norm”. This particularly applies for women, since currently 54% of the foundation trainees in surgery are female (Moberly, 2018), and even if most of the challenges to succeed in a high competitive field are common to both sexes, there are barriers, hidden or evident, peculiar to women. 
We report the Association of Surgeons of Great Britain and Ireland (ASGBI) women in surgery (WiS) working group’ perspective on changing the norm of the surgical environment, so that recruitment and investment in retention of surgical trainees of both genders could flourish.