tbuckley/cabot-search huggingface dataset:
How Similar Are the Disorders Included Under the Umbrella of Obsessive-Compulsive Disorder and Related Disorders?
Authors: Daniel L. C. Costa, Juliana Belo Diniz, Eurípedes Constantino Miguel
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
PD-003 Analysis of single-nucleotide polymorphisms (SNPs) in the phase 3 CORRECT trial of regorafenib vs placebo in patients with metastatic colorectal cancer (mCRC)
Authors: D. Lambrechts, K. Koechert, A. Schulz, R. Vonk, M. Rutstein, S. Kobina, A. Grothey, E. Van Cutsem, M. Teufel
Journal: Annals of Oncology (2016)
Phase I Testing: 60 Years in the Making
Authors: Susan E. Bates
Journal: Clinical Cancer Research (2016)

This CCR Focus had its genesis in a workshop cosponsored by the FDA and the American Association for Cancer Research that was held in May 2015. The participants were inspired by the discussion of new ideas for early-phase drug testing, and hopeful that appropriate dosing for new molecular entities could be better identified. This CCR Focus, with Guest Editors Pasi Jänne and Amy McKee, looks at new approaches for optimizing the dosing of anticancer agents. The need to address the issue of appropriate dosing is underscored by the high rates of discontinuation in several recent registration studies that supported FDA approvals. This meant that for several of the 30 kinase inhibitors approved by the FDA, much work remained to determine the optimal dosing. Thus, the FDA posed the question of how to gain accurate, safe, and effective dosing information as early as possible. The challenge, of course, is how to accomplish this with our current phase I approach, which, although it has served physicians and patients well, is in need of some revamping. The size and complexity of our 60-year-old clinical trial system has made it somewhat less flexible than many would like, which explains why a description of phase I and II trials written by Farber and colleagues (1) 60 years ago still applies:The goals and methods for phase I testing were well codified by the mid-1970s (2, 3). It is notable that many of today's challenges were identifiable even 40 years ago when the FDA sponsored a workshop in 1975 to address clinical trial design (4, 5). Making clinical advances while protecting and helping patients was always going to be complicated. But innovations are possible and that is what this CCR Focus is about: improving methods of dose finding, while preserving that most important goal—patient safety.Susan E. BatesDeputy Editor, CCR FocusColumbia University Medical CenterSee all articles in this CCR Focus section, “New Approaches for Optimizing Dosing of Anticancer Agents.”
Injury surveillance at 23 International Tennis Federation Junior and Pro Circuit tournaments between 2011 and 2015
Authors: José Pedro Correia
Journal: British Journal of Sports Medicine (2016)

International Tennis Federation (ITF) tournaments represent an important step in player development. In 2015, over 400 Junior and 600 Pro Circuit tournaments were played all over the world, involving thousands of players. These players face the challenges of continuous travel and play with little financial return. However, few epidemiological data are available for this playing level.1 We aimed to present a profile of medical injuries reported during ITF Junior and Pro Circuit tournaments in 2015, in keeping with a commitment to injury …
PTH-090 Laboratory experience of anti-tnf drug monitoring in routine practice – perspective from the first uk centre: Abstract PTH-090 Table 1
Authors: Z Arkir, N Unsworth, G Richards, Z Odho, PM Irving
Journal: Gut (2015)

<h3>Introduction</h3> Therapeutic drug monitoring (TDM) of Infliximab (IFX) and Adalimumab (ADAL) has been in use in our centre since 2012. Here we present the TDM experience of our laboratory service at Viapath, St Thomas’ Hospital. <h3>Method</h3> Anti-TNF requests received between June 2012 and January 2015 were reviewed. All assays were performed using LISA-TRACKER Duo kits automated on eRobot (Theradiag, France). These assays measure free drug and anti-drug antibody (ADAb) and therefore inhibition studies were performed on samples with detectable drug levels (&gt;1 ug/ml) and positive ADAb. Results were classified according to drug levels (DL) and ADAb status. <h3>Results</h3> The laboratory analysed 2424 (17% internal) samples for IFX (Median DL 3.8 ug/mL, IQR 1.2–6.3) and 1335 (21% internal) samples for ADAL (Median DL 5.2 ug/mL, IQR 3.4–7.3) from IBD patients. Prevalence of detectable antibodies was higher in IFX (10%) than ADAL (4.1%) samples. External requests originated from &gt;90 different hospitals. Number of requests received for both assays doubled from 2013 to 2014 with batch frequency consequently decreasing from fortnightly to weekly. 40 patients had IFX &gt;1 ug/ml and were antibody positive. 16 of these patients were confirmed to have switched to ADAL due to loss of response to IFX therapy. Detectable DL observed in these cases was due to cross reactivity of ADAL with the IFX assay. 11 patients had false positive drug levels and 4 patients had borderline antibodies due to non specific binding. 1 patient had sample collected around infusion. 4 patients had subtherapeutic ADAL (1.1–1.4 ug/ml) and were antibody positive. 1 of these patients was confirmed to have switched to IFX due to loss of response to ADAL therapy. Detectable DL observed in this case was due to cross reactivity of IFX with the ADAL assay. 3 patients had false positive results for ADAL. From the data, it was evident that some centres monitored patients with serial measurements and made subsequent changes to therapy. 63 patients (IFX) and 52 patients (ADAL) had an average of 7 and 3 repeat measurements taken respectively. <h3>Conclusion</h3> Anti-TNF testing has been embedded in several IBD centres as a way of optimising therapy however variation in TDM practices was observed highlighting the need for national guidance. Significant increase in test requesting suggests assay based treatment strategies combined with clinical assessment is now an accepted practice in IBD. <h3>Disclosure of interest</h3> Z. Arkir: None Declared, N. Unsworth: None Declared, G. Richards: None Declared, Z. Odho: None Declared, P. Irving Speaker Bureau of: MSD, Abbvie and Takeda.
RM-056 Clinic features of gastric neuroendocrine tumors: a single-center analysis
Authors: G. Balli, E. Kamer, K. Atahan, M. Haciyanli, O. Ozsay, H. Kar, E. Durak, F. Cengiz, A. Acar, E. Tarcan
Journal: Annals of Oncology (2016)
Lymphadenopathy Associated With Severe Hypertriglyceridemia-Reply
Authors: David Alexander Leaf
Journal: JAMA (1990)

In Reply.—  The clinical diagnosis of lymphadenopathy is based on the presence of palpable lymph nodes. 1 Our study presents the first reported association between lymphadenopathy and the presence of chylomicronemia in the absence of any of the currently recognized causes of lymphadenopathy. 2 Contrary to Dr Cresson's belief, the histopathologic description provided in the study is taken directly from the report of a pathologist at our institution. The long-standing nature of this patient's lymphadenopathy, the extent of which fluctuated with the degree of hypertriglyceridemia, permitted a repeated biopsy that confirmed these findings.  As is shown on the electron microscopic findings, fat droplets were found within the lymph node cells. Therefore, the example of patients with breast cancer studied by Dr Cresson, as it relates to fatty infiltration that appears to be extracellular, is not relevant to our patient, especially because she did not have breast cancer. Similarly, she
Probing chromatin landscape reveals roles of endocardial TBX20 in septation
Authors: Cornelis J. Boogerd, Ivy Aneas, Noboru Sakabe, Ralph J. Dirschinger, Quen J. Cheng, Bin Zhou, Ju Chen, Marcelo A. Nobrega, Sylvia M. Evans
Journal: Journal of Clinical Investigation (2016)

Mutations in the T-box transcription factor TBX20 are associated with multiple forms of congenital heart defects, including cardiac septal abnormalities, but our understanding of the contributions of endocardial TBX20 to heart development remains incomplete. Here, we investigated how TBX20 interacts with endocardial gene networks to drive the mesenchymal and myocardial movements that are essential for outflow tract and atrioventricular septation. Selective ablation of Tbx20 in murine endocardial lineages reduced the expression of extracellular matrix and cell migration genes that are critical for septation. Using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), we identified accessible chromatin within endocardial lineages and intersected these data with TBX20 ChIP-seq and chromatin loop maps to determine that TBX20 binds a conserved long-range enhancer to regulate versican (Vcan) expression. We also observed reduced Vcan expression in Tbx20-deficient mice, supporting a direct role for TBX20 in Vcan regulation. Further, we show that the Vcan enhancer drove reporter gene expression in endocardial lineages in a TBX20–binding site–dependent manner. This work illuminates gene networks that interact with TBX20 to orchestrate cardiac septation and provides insight into the chromatin landscape of endocardial lineages during septation.
Post-Therapy 18f-Fluorodeoxyglucose Positron Emission Tomography Predicts Outcome In Patients With Peripheral T-Cell Lymphomas
Authors: Naoto Tomita, Yukako Hattori, Shin Fujisawa, Chizuko Hashimoto, Jun Tguchi, Hirotaka Takasaki, Rika Sakai, Ukihide Tateishi, Yoshiaki Ishigatsubo
Journal: Blood (2013)
Polybrominated Diphenyl Ethers in Human Milk and Serum from the U.S. EPA MAMA Study: Modeled Predictions of Infant Exposure and Considerations for Risk Assessment
Authors: Satori A. Marchitti, Suzanne E. Fenton, Pauline Mendola, John F. Kenneke, Erin P. Hines
Journal: Environmental Health Perspectives (2016)

Background:Serum concentrations of polybrominated diphenyl ethers (PBDEs) in U.S. women are believed to be among the world's highest; however, little information exists on the partitioning of PBDEs between serum and breast milk and how this may affect infant exposure.Objectives:Paired milk and serum samples were measured for PBDE concentrations in 34 women who participated in the U.S. EPA MAMA Study. Computational models for predicting milk PBDE concentrations from serum were evaluated.Methods:Samples were analyzed using gas chromatography isotope-dilution high-resolution mass spectrometry. Observed milk PBDE concentrations were compared with model predictions, and models were applied to NHANES serum data to predict milk PBDE concentrations and infant intakes for the U.S. population.Results:Serum and milk samples had detectable concentrations of most PBDEs. BDE-47 was found in the highest concentrations (median serum: 18.6; milk: 31.5 ng/g lipid) and BDE-28 had the highest milk:serum partitioning ratio (2.1 ± 0.2). No evidence of depuration was found. Models demonstrated high reliability and, as of 2007–2008, predicted U.S. milk concentrations of BDE-47, BDE-99, and BDE-100 appear to be declining but BDE-153 may be rising. Predicted infant intakes (ng/kg/day) were below threshold reference doses (RfDs) for BDE-99 and BDE-153 but above the suggested RfD for BDE-47.Conclusions:Concentrations and partitioning ratios of PBDEs in milk and serum from women in the U.S. EPA MAMA Study are presented for the first time; modeled predictions of milk PBDE concentrations using serum concentrations appear to be a valid method for estimating PBDE exposure in U.S. infants.Citation:Marchitti SA, Fenton SE, Mendola P, Kenneke JF, Hines EP. 2017. Polybrominated diphenyl ethers in human milk and serum from the U.S. EPA MAMA Study: modeled predictions of infant exposure and considerations for risk assessment. Environ Health Perspect 125:706–713; http://dx.doi.org/10.1289/EHP332
Pharmacokinetic Behaviors of Intravenously Administered siRNA in Glandular Tissues
Authors: Yuanyu Huang, Qiang Cheng, Jia-Li Ji, Shuquan Zheng, Lili Du, Lingwei Meng, Yidi Wu, Deyao Zhao, Xiaoxia Wang, Li Lai, Huiqing Cao, Kai Xiao, Shan Gao, Zicai Liang
Journal: Theranostics (2016)

The pharmacokinetics of small interfering RNAs (siRNAs) is a pivotal issue for siRNA-based drug development.In this study, we comprehensively investigated the behavior of siRNAs in vivo in various tissues and demonstrated that intravenously-injected naked siRNA accumulated remarkably in the submandibular gland, bulbourethral gland, and pancreas, with a respective half-life of ~22.7, ~45.6, and ~30.3 h.This was further confirmed by gel separation of tissue homogenates and/or supernatants.In vivo imaging and cryosectioning suggested that delivery carriers significantly influence the distribution and elimination profiles of siRNA.Gene-silencing assays revealed that neither naked nor liposome-formulated siRNA resulted in gene knockdown in the submandibular and bulbourethral glands after systemic administration, suggesting that these glands function as drug reservoirs that enable slow siRNA release into the circulation.But robust gene-silencing was achieved by local injection of liposome-encapsulated siRNA into the submandibular gland.Our results enhance understanding of the pharmacokinetic properties of siRNAs and we believe that they will facilitate the development of siRNA therapy, especially for the submandibular gland.
Case 1-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely
Journal: New England Journal of Medicine (1978)

Presentation of Case A 33-year-old man was admitted to the hospital because of painful legs. The patient was known to have the von Hippel-Lindau syndrome. At the age of 14 years a left retinal hemangioma was found. Seven years later a left cerebellar hemangioblastoma was removed at another hospital, and radiation treatment was administered. At the age of 24 years the left eye was enucleated; multiple hemangiomas were observed in the right eye. Repeated photocoagulation procedures were performed, but an irreparable retinal detachment eventually developed. At the age of 27 years a cataract was found, and one year later the . . .
Tampon makers could help reduce violence against women
Authors: S D Shanti
Journal: BMJ (2016)

Preventive strategies and support for a billion victims globally are hugely underfunded

“Physical or sexual violence is a public health problem that affects more than one third of all women globally”—at least a billion—says a 2013 World Health Organization study, conducted with the London School of Hygiene and Tropical Medicine and the South African Medical Research Council.1 Violence against women is a global health problem on a scale bigger than HIV/AIDS and tuberculosis.

Consequences of such violence include physical injuries, psychological trauma, and 43 500 untimely deaths a year worldwide.2 The costs associated with violence against women include healthcare and legal expenses.3 Additionally, lost productivity related to such violence diminishes the world’s gross domestic product by 3.7%.4

We need a public …
Clinical and Histologic Correlation of Melanoma Regression After Intralesional BCG Therapy: A Case Report2
Authors: M. J. Mastrangelo, Y. H. Kim, R. S. Bornstein, D. O. Chee, H. L. Sulit, J. W. Yarbro, R. T. Prehn
Journal: JNCI Journal of the National Cancer Institute (1974)

A 46-year-old white male with dermal and subcutaneous melanoma metastases of the left leg and contralateral inguinal lymph node involvement was treated with intratumoral BCG. Over 9 months, 84 dermal and subcutaneous lesions were inoculated with BCG. It produced an inflammatory response and regression of all treated dermal and most treated subcutaneous metastases. All untreated dermal lesions also regressed. Histologically, melanin-laden macrophages and a chronic granulomatous reaction were noted. While clinical examination revealed no regression of uninoculated subcutaneous metastases, histologic study showed the tissue surrounding the untreated subcutaneous metastases to be heavily laden with lymphocytes which in areas infiltrated the laminated fibrocollagenous capsule surrounding these nodules. This finding was in marked contrast to the virtual absence of lymphocytes surrounding similar lesions before immunotherapy. After immunotherapy, the contralateral inguinal lymph nodes had several subcapsular areas of pigmentation characterized by melaninladen histiocytes but no tumor cells.
Abstract 945: Synthetic lethal screen identifies Aurora A as a selective target in HPV driven cervical cancer
Authors: Brian G. Gabrielli, Fawzi Bokhari, Max Ranall, Zay Yar Oo, Alex Stevenson, Weili Wang, Sara McKee, Graham Leggatt, Paul Leo, Thomas J. Gonda, Nigel AJ McMillan
Journal: Cancer Research (2015)

Abstract HPV has been identified as the definitive agent in cancers of the cervix, penis, vulva, vagina, anus, skin, eye, and head and neck, and is responsible for 5% of the total cancer burden worldwide. HPV oncogenes disable a number of tumour suppressor pathways, including p53 and Rb, contributing to the transformed phenotype. We have performed an siRNA screen using the kinome (779 genes) library to identify genes that when depleted are synthetically lethal with HPV transformation. The primary and validations screens have confirmed Aurora A kinase (AURKA) as a potential synthetic lethal target selective for HPV transformed cells. In vitro research using the investigational selective small molecule AURKA inhibitor alisertib found alisertib to be significantly more potent towards the HPV transformed cells, and selectively promoted apoptosis in the HPV cancers. The drug was shown to target the HPVE7 oncogene, the level of expression of this oncogene possibly influencing sensitivity. Apoptosis was sensitive to Mcl-1 but not Bcl-2 over expression, indicating that the mechanism is associated with the proteolytic destruction of Mcl-1 in the extended mitosis in the alisertib treated HPV cancer lines. Xenograft experiments with cervical cancer cell lines showed alisertib inhibited growth of HPV and non-HPV xenografts during treatment. The non-HPV cancer growth was delayed, but in two separate HPV cancers models, regression and no resumption of growth was detected at even 50 days post-treatment. A second transgenic model of premalignant disease driven solely by HPVE7 similarly demonstrated sensitivity to drug treatment. These findings provide preclinical evidnce that alisertib warrants evaluation as a potential targeted compound with activity in HPV-transformed cervical cancer and premalignant disease that may have application to other HPV driven cancers. Citation Format: Brian G. Gabrielli, Fawzi Bokhari, Max Ranall, Zay Yar Oo, Alex Stevenson, Weili Wang, Sara McKee, Graham Leggatt, Paul Leo, Thomas J. Gonda, Nigel AJ McMillan. Synthetic lethal screen identifies Aurora A as a selective target in HPV driven cervical cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 945. doi:10.1158/1538-7445.AM2015-945
Micro-RNA-21 and micro-RNA-155 as predictors of a malignant phenotype in melanocytic lesions
Authors: G. B. Lesinski, E. T. Raig, J. M. Zimmerer, V. Karpa, G. Nuovo, A. Lehman, S. Peters, J. E. Kacher, C. M. Magro, C. M. Croce, W. E. Carson
Journal: Journal of Clinical Oncology (2008)

9001 Background: Indeterminate melanocytic lesions represent a therapeutic dilemma and improved diagnostic markers are needed. Expression of microRNAs (miRs) is altered in many tumors, however miR expression has not been carefully explored in melanoma. We hypothesized that miR expression in indeterminate melanocytic lesions could serve as a marker of malignant potential. Methods: The miR expression profile of melanocytic lesions including dermal nevi (n=8), malignant melanoma (n=28), and pathologically indeterminate melanocytic tissues (n=51) was evaluated by Real Time PCR in paraffin-embedded samples, and validated by in situ RT-PCR. The small RNA, RNU6B was an internal control. ANOVA and pairwise comparisons (two-sided α=0.05) were used for analyses. Results: Significantly higher miR21 expression was observed in malignant melanoma samples as compared to benign nevi (fold increase = 7.6-fold ± 6.7, p<0.0001). miR155 expression was also significantly higher in melanoma samples versus benign nevi (fold increase = 13.3±16.9, p<0.0001). In contrast, other miRs predicted to be upregulated in melanoma by microarray (of 281 analyzed), including miR30d, miR103, miR146b, were not significantly higher in melanoma versus nevi. Indeterminate lesions with >1 mitosis per 10x high power field had significantly higher miR21 and miR155 compared to lesions with no mitotic activity (p=0.0005 and 0.04, respectively). Also, melanocytic lesions with a depth >1 mm had significantly higher levels of miR155 as compared to lesions with a depth <1 mm (p=0.01). miR21 was also elevated in n=13 human melanoma cell lines as compared to nevi. Sentinel lymph node (SLN) biopsies from patients (n=13) diagnosed with indeterminate lesions of the extremity or trunk were examined for expression of miR21 and miR155. Primary lesions associated with a positive SLN biopsy had higher miR21 and miR155 (fold change vs. nevi = 5.1±3.3 and 7.5±9.7, respectively) as compared to lesions associated with a negative biopsy (fold change vs. nevi = 1.3±0.9 and 2.8±3.2, respectively). Conclusions: miR21 and miR155 are significantly elevated in primary melanomas and indeterminate lesions that possess an aggressive histologic phenotype. Evaluation of miRs may be a useful diagnostic tool in the setting of melanoma. No significant financial relationships to disclose.
Recent advances in crystalline and amorphous particulate protein formulations for controlled delivery
Authors: Sebastian Puhl, Lorenz Meinel, Oliver Germershaus
Journal: Asian Journal of Pharmaceutical Sciences (2016)

The number of particulate delivery systems for biologics is negligible compared to liquid dosage forms, signifying the complications associated with development of solid protein delivery systems. Particulate protein delivery systems can improve stability, reduce viscosity of suspensions at high protein concentration and allow for controlled drug release. This review discusses current advances in controlled delivery of particulate protein formulations. While the focus lies on protein crystals and delivery systems employing protein crystals, amorphous protein particles will also be addressed. Crystallization and precipitations methods and modifications allowing controlled delivery with and without encapsulation are summarized and discussed.