tbuckley/cabot-search huggingface dataset:
George A. Bray, MD: Progress in Obesity—Multidisciplinary Research, Multidimensional Man
Authors: Donna H. Ryan, Barbara C. Hansen, William T. Cefalu
Journal: Diabetes Care (2016)

George as a child. Who would have known then the impact he would make on the world of the science of obesity? 





George at the end of his tenure as executive director of Pennington Biomedical Research Center. 





As Mitzi watches, George receives a commemorative plaque from Dr. Claude Bouchard (executive director after George) during a 20th anniversary celebration event for Pennington Biomedical Research Center. 





In gratitude and acknowledgment for his work and contributions, and for always doing things the “George Bray way,” Pennington Biomedical named the walkway between the basic and clinical research buildings Bray’s “Weigh” in his honor on the occasion of his retirement from the center on 10 December 2014. 



George A. Bray was born 25 July 1931 in Winnetka, IL, during the peak of the Depression. He was the first child of George August and Mary H. Bray. His only sibling, Mary Elizabeth (Betsy) Bray, died secondary to rheumatic heart disease. Influenced by his mother, George developed a natural interest in education at a young age, even though one of his teachers at Hubbard Woods School in Winnetka reported that 11-year-old “George is doing good average work in all subjects” (1). Despite this inauspicious assessment, high school marked the emergence of a lifelong interest in and aptitude for science. This is clearly evidenced by his own writing in 1949 in an application for a national college scholarship program when he wrote: “Ever since I took my first science course in high school, I’ve been interested in the infinite possibilities of science.” When it came time to choose a college, George’s choice between Harvard and Brown University was based on the desire to attend one for college and the other for medical school. Choosing Brown University for undergraduate school was to have lifelong implications, as it was at …
Dose-response evaluation of brocolli sprout extract sulforaphane (BSE-SFN) in melanoma patients (Pts) with atypical/dysplastic nevi (A/DN).
Authors: John M. Kirkwood, Shivendra Singh, Yan Lin, Eun-Ryeong Hahm, Jan Hendrik Beumer, Susan M. Christner, Uma N. M. Rao, Cindy Sander, Ahmad A. Tarhini, Hussein Abdul-Hassan Tawbi, Laura Ferris, Melissa Wilson, Mary Petrany, Amy Rose, Jed W Fahey, Sancy Ann Leachman, Pamela Cassidy, Lisa H. Butterfield, Hassane M. Zarour
Journal: Journal of Clinical Oncology (2016)

e21022 Background: Primary & secondary prevention have not reduced the rising melanoma mortality in the US and Europe. We reported STAT3 activation in A/DN and IFNa modulation of STAT3 in A/DN in melanoma pts. BSE-SFN modulates STAT3 in cancer cells, inhibits chemically-induced skin tumors and prevents UV-induced skin cancer in SKH-1 mice. We designed a double-blind trial of BSE-SFN standardized for 50, 100, or 200 µmol SFN in groups of 5-6 pts/dosage for 28 days. Methods: Subjects had history of melanoma & multiple A/DN, normal organ functions,. Endpoints were safety, PK/PD in blood and A/DN skin biopsies and photographic/ pathologic changes in A/DN d1-d28 by IHC for p(Y705)-STAT3/Bcl2/Ki-67 and TUNEL d1, 2, & 28. 17 pts (12 female, 5 male) enrolled. PK in blood by published methods had a dynamic range 10-3000 ng/mL. A/DN were photographed at baseline & d28, and biopsies of A/DN d1, 2, & 28 were measured for SFN, and IHC proliferation and apoptosis markers Ki-67 and TUNEL, respectively. Bcl-2 and p(Y705)-STAT3 were assessed in nevic melanocytes, keratinocytes, lymphocytes, and endothelial cells. Results: No dose-limiting toxicity of BSE-SFN was observed: gr 2 nausea occurred in one pt. All 17 pts completed 28 days at 50, 100, or 200µmol dosages. Plasma SFN d1, 2, & 28 showed increments of 120 ng/mL (-182-208) for 50 µmol, 206 (-356-420) for 100 µmol and 655 (396-1305) for 200 µmol. Pooling d1, 2 & 28 PK demonstrate SFN tissue concentrations 8.2 ng/g at 50 µmol (0-21.9), 9.9 ng/g at 100 µmol and 46 ng/g (0-64) at 200 µmol. IHC for pSTAT3 showed endothelial expression across dosages, but melanocytic expression absent in 100-200 µmol dosage groups. Proteomics demonstrate significant increase in tumor suppressor decorin after BSE-SFN. Wilcoxon signed-rank tests of plasma cytokine changes d1- d28, controlling for false discovery (25%), showed decreased pro-inflammatory levels d28, but sample size precludes dosage correlations. Thioredoxin reductase levels in nevi are in progress. Conclusions: Oral BSE-SFN is well tolerated at 50, 100, and 200 µmol /day attaining blood plasma and skin biopsy levels reasonable for evaluation as a candidate for melanoma chemoprevention at 200µmol in larger numbers. Clinical trial information: NCT01568996.
Phase II trial of single-agent sorafenib in patients with advanced non-small cell lung carcinoma
Authors: U. Gatzemeier, G. Blumenschein, F. Fosella, R. Simantov, J. Elting, D. Bigwood, F. Cihon, M. Reck
Journal: Journal of Clinical Oncology (2006)

7002 Background: Sorafenib, an oral multi-kinase inhibitor, targets the Raf/MEK/ERK pathway at the level of Raf kinase and receptor tyrosine kinases, and has shown efficacy against several tumor types in phase I/II trials. Non-small-cell lung cancer (NSCLC) is associated with mutations in k-ras, upstream of Raf/MEK/ERK. Methods: This multi-center, uncontrolled, phase II trial evaluated efficacy (every 8 weeks using RECIST) and safety of sorafenib (400 mg bid, continuous) in patients with relapsed or refractory advanced NSCLC. Plasma for proteomic biomarker analysis (ELISA [n=44]; mass-spectrometry [n=43]) was taken at screening, Day 21 of Cycle 1, and Day 1 of Cycle 3. Results: Fifty-two of 54 patients enrolled received sorafenib. Most (49/52) patients who received sorafenib had stage IV NSCLC. Thirty patients (59%) out of 51 evaluable for efficacy had SD. Although there were no confirmed PRs, tumor shrinkage was observed in 15 (29%) patients (four had ≥30% shrinkage). Patients with SD had a median progression-free survival (PFS) of 23.7 weeks, while all evaluable patients (n=51) had a median PFS of 11.9 weeks and median overall survival of 29.3 weeks. The most frequent drug-related adverse events observed in 52 patients were diarrhea (21 [40%] patients), hand-foot skin reaction (HFS; 19 [37%]), fatigue (14 [27%]), and nausea (13 [25%]). Frequent drug-related adverse events ≥ grade 3 included HFS (n=5 [10%]) and hypertension (n=2 [4%]). Three patients discontinued due to adverse events (HFS, elevated lipase, and myocardial infarction). There were nine deaths within 30 days of discontinuation of sorafenib (n=5 PD; n=2 cardiopulmonary arrest; n=1 hemoptysis; and n=1 unknown cause). The levels of five proteins measured by ELISA, either at screening or change over treatment duration, correlated significantly with time to progression (TTP) or maximum tumor shrinkage. Levels of five additional proteins, identified by mass-spectrometry, also correlated with TTP. Conclusions: Identified biomarkers may help assess efficacy of sorafenib in NSCLC patients. Sorafenib 400 mg bid is generally well tolerated and shows promising efficacy in patients with advanced, progressive NSCLC, with approximately 60% of pts achieving disease stabilization. [Table: see text]
Validation of the new glioma WHO classification in the french POLA network: Analysis of 1041 cases.
Authors: Emeline Tabouret, Anh Tuan Nguyen, Caroline Dehais, Catherine Carpentier, Laura Lebouil, François Ducray, Ahmed Idbaih, Karima Moktari, Anne Jouvet, Emmanuelle uro-Coste, Jean-Yves Delattre, Dominique Figarella-Branger
Journal: Journal of Clinical Oncology (2016)

2015 Background: The upcoming WHO classification of gliomas will be refined taking into account the robust molecular alterations of gliomagenesis: the 1p19q codeletion and IDH1/2mutations. Methods: All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nation-wide POLA network were reclassified according the upgrading of the 4th WHO classification that integrates pathological features and molecular data. Immunohistochemical expression of IDH1R132H, and ATRX, 1p19q codeletion, chromosome 7p gain and chromosome 10q loss by genomic-array and IDH1/2and histone K27M mutational statuses by sequencing were evaluated. Results: 1041 patients were included with a median age at diagnosis of 50.4 years (range, 17.1-84.4). Based on the new histo-molecular classification, diagnoses were: anaplastic oligodendroglioma with 1p19q codeletion (32.5%), anaplastic astrocytoma IDH mutated (IDHmt) (11.0%), anaplastic astrocytoma IDHwild-type (IDHwt) (5.3%), glioblastoma IDHmt (17.1%) and glioblastoma IDHwt (33.2%). Ten patients presented a midline tumor with the histone H3-K27M mutation. Both new and oldest WHO classifications were predictive for Progression-Free Survival (PFS) and Overall Survival (OS) but the new histo-molecular classification was more discriminant with higher hazard ratio for PFS (1.603, 1.848, 5.025 and 6.135 versus 1.495, 2.705, 2.799 and 4.933) and for OS (3.588, 3.493, 11.020 and 14.708 versus 2.259, 4.340, 4.214 and 7.534). Grading (III versus IV) was not prognostic for IDHmt non 1p19q codeleted gliomas in univariate analyses (PFS, p=0.5; OS, p=0.8) and multivariate analysis (adjusted by age, type of surgery and first line treatment: PFS, p=0.13; OS, p=0.38). Among anaplastic astrocytoma IDHwt, cases presenting with 7p gain and 10q loss (55%) had a worse prognosis that the others for PFS (p=0.027), suggesting that all anaplastic astrocytoma IDHwt should not be considered as glioblastoma IDHwt. Conclusions: WHO histo-molecular classification of gliomas presented with high predictive and discriminative value, allowing the validation of three main molecular subgroups for the future neuro-oncological trials.
Cytogenetic Response Based On Revised IPSS Cytogenetic Risk Stratification and Minimal Residual Disease Monitoringby FISH In MDS Patients Treated By Low-Dose Decitabine
Authors: Xiao Li, Chunkang Chang, Qi He, Feng Xu, Qingxia Zhang, Lingyun Wu, Jiying Su, Xi Zhang, Liyu Zhou, Dong Wu, Zheng Zhang
Journal: Blood (2013)
Acute hepatitis in a teenager
Authors: Sarah Helen Hancox, David C Howlett
Journal: BMJ (2016)

A 19 year old woman presented to the emergency department with worsening pain and distension of the right upper quadrant. She was jaundiced and had ascites. A contrast enhanced portal venous phase computed tomogram of the liver at the level of the caudate lobe was requested. What does this show? (Fig 1⇓)



Fig 1 

The computed tomogram shows hepatomegaly with heterogeneous enhancement of the liver and sparing of the caudate …
Superhydrophilic–Superhydrophobic Patterned Surfaces as High‐Density Cell Microarrays: Optimization of Reverse Transfection
Authors: Erica Ueda, Wenqian Feng, Pavel A. Levkin
Journal: Advanced Healthcare Materials (2016)

High-density microarrays can screen thousands of genetic and chemical probes at once in a miniaturized and parallelized manner, and thus are a cost-effective alternative to microwell plates. Here, high-density cell microarrays are fabricated by creating superhydrophilic-superhydrophobic micropatterns in thin, nanoporous polymer substrates such that the superhydrophobic barriers confine both aqueous solutions and adherent cells within each superhydrophilic microspot. The superhydrophobic barriers confine and prevent the mixing of larger droplet volumes, and also control the spreading of droplets independent of the volume, minimizing the variability that arises due to different liquid and surface properties. Using a novel liposomal transfection reagent, ScreenFect A, the method of reverse cell transfection is optimized on the patterned substrates and several factors that affect transfection efficiency and cytotoxicity are identified. Higher levels of transfection are achieved on HOOC- versus NH2 -functionalized superhydrophilic spots, as well as when gelatin and fibronectin are added to the transfection mixture, while minimizing the amount of transfection reagent improves cell viability. Almost no diffusion of the printed transfection mixtures to the neighboring microspots is detected. Thus, superhydrophilic-superhydrophobic patterned surfaces can be used as cell microarrays and for optimizing reverse cell transfection conditions before performing further cell screenings.
Evidence for Transmission of Zika Virus by Platelet Transfusion
Authors: Iara J F Motta, Bryan R Spencer, Suely G Cordeiro da Silva, Monica B Arruda, Jane A Dobbin, Yung B M Gonzaga, Ingrid P Arcuri, Rita C B S Tavares, Elias H Atta, Regina F M Fernandes, Deise A Costa, Liane J Ribeiro, Fabio Limonte, Luiza M Higa, Carolina M Voloch, Rodrigo M Brindeiro, Amilcar Tanuri, Orlando C Ferreira
Journal: New England Journal of Medicine (2016)

In this report from Brazil, evidence of Zika virus transmission from a platelet donor to two patients is presented.
Association of vorinostat with decrease in gene expression of proliferation-related genes in tumors from women with newly diagnosed breast cancer.
Authors: V. Stearns, L. K. Jacobs, T. N. Tsangaris, Z. Cheng, S. Slater, M. J. Fackler, C. Chao, R. Bugarini, E. Gabrielson, N. E. Davidson
Journal: Journal of Clinical Oncology (2010)

3097 Background: Epigenetic modifications contribute to breast cancer initiation and progression and may be reversible. In preclinical breast cancer models, the histone deacetylase vorinostat induces cell cycle arrest, apoptosis, and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women who received vorinostat and from untreated controls. Methods: Women with a newly diagnosed invasive breast cancer received vorinostat 300 mg PO BID × 6 doses, tlhe last dose 2 hours prior to surgery or biopsy. Pre- and post-vorinostat tumor specimens were analyzed for gene methylation (QM-MSP) and expression (RT-PCR using the Oncotype DX 21-gene assay and IHC for Ki67 and cleaved caspase 3). Tissues were also collected from untreated controls. We performed Wilcoxon nonparametric tests to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated patients, and changes between pre- and post-vorinostat methylation. Results: Samples were collected from 25 vorinostat-treated and from 25 untreated women. Evaluable samples and key results are shown in the Table. For 25 evaluable matched sample sets for both IHC and RT-PCR, 76% had ER+ tumors by both assays (100% concordance). In the vorinostat group, we observed statistically significant decreases in Ki-67 and STK15 by RT-PCR but not in Ki-67 by IHC. Differences between treatments in pre- to post-changes were statistically significant for Ki-67 (p=0.008) and STK15 (p=0.012). No significant changes were observed for ER or in gene methylation. Conclusions: Short-term vorinostat is associated with decreases in expression of proliferation-associated genes. The results will be used to design future studies in which vorinostat will be combined with other therapies. P values associated with change in gene expression and number of patients with paired samples Assay (evaluable: treated/untreated) P value Treated Untreated IHC Ki67 (22,15) 0.51 0.44 Cleaved caspase-3 (19,0) 0.36 - RT-PCR (14,11) STK15 0.004 0.44 Ki-67 0.038 0.85 MYBL2 0.061 0.28 Cyclin B1 0.10 0.74 Survivin 0.12 0.80 ER 0.45 0.80 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wyeth AstraZeneca Abraxis BioScience, Merck, Pfizer
Primary Left Tibial Epithelioid Hemangioendotheliomas With Multiple Metastases Revealed by FDG PET/CT Imaging
Authors: Haimin Zhao, Jiankui Han, Lei Qin, Changming Zhang
Journal: Clinical Nuclear Medicine (2016)

Bone epithelioid angiosarcoma is an extremely rare osseous malignancy with an aggressive and destructive biological behavior. We present FDG PET/CT findings of a 59-year-old woman with left lower limb pain for 1 month. The images revealed abnormal activity in both left fibula and left tibia. In addition, abnormal activity in the sacrum and enlarged retroperitoneal lymph nodes was also noted. Pathological examination demonstrated bone epithelioid angiosarcoma.
Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity
Authors: Luc Pardanaud, Laurence Pibouin-Fragner, Alexandre Dubrac, Thomas Mathivet, Isabel English, Isabelle Brunet, Michael Simons, Anne Eichmann
Journal: Circulation Research (2016)

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood.We set out to identify factors that promote arterial endothelial cell fate in vivo.We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors.These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease.
Using Restriction to Minimize Bias in Observational Studies
Authors: Mintu P. Turakhia, Paul A. Heidenreich
Journal: JAMA (2010)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
The underreporting of hepatocellular carcinoma to the cancer register and a log‐linear model to estimate a more correct incidence
Authors: Anna Törner, Knut Stokkeland, Åke Svensson, Paul W. Dickman, Rolf Hultcrantz, Scott Montgomery, Ann‐Sofi Duberg
Journal: Hepatology (2016)

The Cancer Register (CR) in Sweden has reported that the incidence of primary liver cancer (PLC) has slowly declined over the last decades. Even though all cancers, irrespective of diagnostic method, should be reported to the CR, the PLC incidence may not reflect the true rate. Improved diagnostic tools have enabled diagnosis of hepatocellular carcinoma based on noninvasive methods without histological verification, possibly associated with missed cancer reports or misclassification in the CR. Our objective was to study the completeness and assess the underreporting of PLC to the CR and to produce a more accurate estimate based on three registers. The CR, the Cause of Death Register, and the Patient Register were investigated. Differences and overlap were examined, the incidence was estimated by merging data from the registers, and the number reported to none of the registers was estimated using a log‐linear capture‐recapture model. The results show that 98% of the PLCs reported to the CR were histologically verified; 80% were hepatocellular carcinoma and 20% were intrahepatic cholangiocarcinoma. Unspecified liver cancer decreased over time and constituted &lt;10% of all reported liver cancers. The CR may underestimate the liver cancer incidence by 37%‐45%, primarily due to missed cancer reports. The estimated annual number of liver cancers increased over time, but the standardized incidence was stable around 11 per 100,000. Hepatitis C‐associated liver cancer increased and constituted 20% in 2010. Conclusion : There was an underreporting of PLC diagnosed by noninvasive methods; the incidence was considerably higher than estimated by the CR, with a stable incidence over time; reporting needs to improve and combining registers is recommended when studying incidence. (H epatology 2017;65:885‐892).
All-cause hospitalizations for inflammatory bowel diseases: Can the reason for admission provide information on inpatient resource use? A study from a large veteran affairs hospital
Authors: Ashish Malhotra, K.C. Mandip, Aasma Shaukat, Thomas Rector
Journal: Military Medical Research (2016)

Inflammatory bowel diseases (IBDs) are group of chronic inflammatory illnesses with a remitting and relapsing course that may result in appreciable morbidity and high medical costs secondary to repeated hospitalizations. The study's objectives were to identify the reasons for hospitalization among patients with inflammatory bowel diseases, and compare inpatient courses and readmission rates for IBD-related admissions versus non-IBD-related admissions. A retrospective chart review was performed on all patients with IBD admitted to the Minneapolis VA Medical Center between September 2010 and September 2012. A total of 111 patients with IBD were admitted during the 2-year study period. IBD flares/complications accounted for 36.9 % of the index admissions. Atherothrombotic events comprised the second most common cause of admissions (14.4 %) in IBD patients. Patients with an index admission directly related to IBD were significantly younger and had developed IBD more recently. Unsurprisingly, the IBD admission group had significantly more gastrointestinal endoscopies and abdominal surgeries, and was more likely to be started on medication for IBD during the index stay. The median length of stay (LOS) for the index hospitalization for an IBD flare or complication was 4 (2-8) days compared with 2 (1-4) days for the other patients (P = 0.001). A smaller percentage of the group admitted for an IBD flare/complication had a shorter ICU stay compared with the other patients (9.8 % vs. 15.7 %, respectively); however, their ICU LOSs tended to be longer (4.5 vs. 2.0 days, respectively, P = 0.17). Compared to the other admission types, an insignificantly greater percentage of the group whose index admission was related to an IBD flare or complication had at least one readmission within 6 months of discharge (29 % versus 21 %; P = 0.35). The rate of admission was approximately 80 % greater in the group whose index admission was related to an IBD flare or complication compared to the other types of admission (rate ratio 1.8, 95 % confidence interval 0.96 to 3.4), although this difference did not reach statistical significance (P = 0.07). Identifying the reasons for the patients' index admission, IBD flares versus all other causes, may provide valuable information concerning admission care and the subsequent admission history.
Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation
Authors: Huanjiao Jenny Zhou, Lingfeng Qin, Haifeng Zhang, Wenwen Tang, Weidong Ji, Yun He, Xiaoling Liang, Zongren Wang, Qianying Yuan, Alexander Vortmeyer, Derek Toomre, Germaine Fuh, Minghong Yan, Martin S Kluger, Dianqing Wu, Wang Min
Journal: Nature Medicine (2016)