tbuckley/cabot-search huggingface dataset:
Abstract 85: Cardiac Pathology Is Worsened by Loss of the Cell Junction Protein Claudin-5 and Improved by Claudin-5 Gene Therapy
Authors: Dawn A Delfín, Kevin E Schill, Ying Xu, Sarah Swager, Paul M L Janssen, Jill A Rafael-Fortney
Journal: Circulation Research (2012)

Claudin-5 is a cell-cell adhesion protein that plays established roles in the blood-brain barrier and cancer. We were the first to demonstrate that it plays a role in the heart with implications for heart failure and cardiomyopathy. Several animal models with cardiac pathology show reduced cardiac claudin-5 levels. Importantly, 60% of human heart failure patients show reduced levels of cardiac claudin-5, independent of changes in other cell junction proteins in the heart, supporting that the loss of cardiac claudin-5 has clinical relevance. To test our hypothesis that claudin-5 plays an important role in protecting the heart, we used mouse models to demonstrate whether circumventing reductions in cardiac claudin-5 is able to improve cardiac histology and physiology, and whether ablation of claudin-5 is able to induce cardiac pathology. We now show that maintaining cardiac claudin-5 levels using gene therapy (cldn5 transduction using an adeno-associated virus vector) significantly reduced cardiac pathology in mice which otherwise demonstrate heart failure and cardiomyopathy indicators. We also present preliminary evidence of the effects of knocking out the cldn5 gene specifically in cardiomyocytes using the inducible cre-loxP system.
The homeobox-containing gene Dlx1 is expressed in ovarian cancer tissues, but not serous adenocarcinoma of the ovary
Authors: Kunihiko Nishiwaki, Tsuyoshi Yamashita, Seishiro Tazawa, Hideto Katayama, Yasuhito Kato, Yuko Yokohama, Kazuo Sengoku
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4412 

In the last decade, it has been reported that homeobox-containing genes are important genes not only for embryogenesis but also carcinogenesis. Based on the hypothesis that cancer cells acquirement invasive characterisrics by epithelial-mesenchymal transformation (EMT), we previously reported that two HOX genes, HOXB7 and HOXB13, play an important role in the invasion and/or metastasis of ovarian cancer. To explore other genes similar to HOX genes, we focused our investigation on genes expressed in the mesoderm in early embryogenesis using RT-PCR assay. We found that DLX1, a homeobox-containing gene, shows overexpression in ovarian cancer.    In this study, we first checked the level of DLX1expression in normal ovarian tissue from patients with benign gynecologic diseases such as leiomyoma after obtaining consent. No DLX1 expression was found in any of normal ovarian tissues examined while cells from ovarian carcinoma cell lines, such as caov-3, kuramochi and caov-4 showed relatively high expression of DLX1. However, we found that cells from the skov3 cancer cell line derived from serous adenocarcinoma tissue showed no DLX1 expression. Thus, we then examined tissue samples from patients with serous, mucinous, endometrioid and clear cell adenocarcinoma of the ovary that were retrieved during surgery to investigate whether DLX1 shows histological subtype dependent expression. In the patient samples, DLX1 expression was not observed in serous adenocarcoma but it was observed in mucinous, endometrioid and clear cell carcinoma. Furthermore, immunostaining using DLX1 antibody demonstrated no staining in the serous carcinoma tissue but marked staining in clear cell carcinoma tissue.    It is well known that serous adenocarcinoma of the ovary has different features from other histological subtypes of ovarian carcinoma such as time-course of dissemination (metastasis), response of anticancer drugs and a unique ovarian cancer, called serous surface papillary carcinoma, SSPC, suggesting a different origin from other subtypes. This feature of DLX1 may be useful to distinguish histological subtypes of ovarian epithelial carcinoma at the molecular level and explain the different origin of serous adenocarcinoma from other histological subtypes.
Progress Toward Achieving UNAIDS 90-90-90 in Rural Communities in East Africa
Authors: Carlos del Rio, Wendy S. Armstrong
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production
Authors: Christopher Hine, Hyo-Jeong Kim, Yan Zhu, Eylul Harputlugil, Alban Longchamp, Marina Souza Matos, Preeti Ramadoss, Kevin Bauerle, Lear Brace, John M. Asara, C. Keith Ozaki, Sheue-yann Cheng, Subhankar Singha, Kyo Han Ahn, Alec Kimmelman, Ffolliott M. Fisher, Pavlos Pissios, Dominic J. Withers, Colin Selman, Rui Wang, Kelvin Yen, Valter D. Longo, Pinchas Cohen, Andrzej Bartke, John J. Kopchick, Richard Miller, Anthony N. Hollenberg, James R. Mitchell
Journal: Cell Metabolism (2017)
Consultant is struck off for dishonesty over sildenafil prescription
Authors: Clare Dyer
Journal: BMJ (2017)

A consultant obstetrician and gynaecologist has been struck off for trying to hide her attempts to obtain sildenafil citrate (Viagra) using a prescription pad from a hospital where she had never worked.

Ghazna Siddiqui, who qualified at the University of London in 1996, held locum posts across the UK, the most recent in Scarborough in 2014. She had practised with distinction in the UK and advised on government policy in Pakistan, the tribunal heard.

In February 2014 Siddiqui accompanied a 55 year old man, who was visiting the UK from Pakistan, to a pharmacy in London. She brought an NHS prescription for 50 mg of Viagra, which she had written on a prescription pad from Maidstone Hospital’s women and children’s unit. After she was told that the pharmacy did not have the …
brain-coX: investigating and visualising gene co-expression in seven human brain transcriptomic datasets
Authors: Saskia Freytag, Rosemary Burgess, Karen L. Oliver, Melanie Bahlo
Journal: Genome Medicine (2017)

The pathogenesis of neurological and mental health disorders often involves multiple genes, complex interactions, as well as brain- and development-specific biological mechanisms. These characteristics make identification of disease genes for such disorders challenging, as conventional prioritisation tools are not specifically tailored to deal with the complexity of the human brain. Thus, we developed a novel web-application—brain-coX—that offers gene prioritisation with accompanying visualisations based on seven gene expression datasets in the post-mortem human brain, the largest such resource ever assembled. We tested whether our tool can correctly prioritise known genes from 37 brain-specific KEGG pathways and 17 psychiatric conditions. We achieved average sensitivity of nearly 50%, at the same time reaching a specificity of approximately 75%. We also compared brain-coX's performance to that of its main competitors, Endeavour and ToppGene, focusing on the ability to discover novel associations. Using a subset of the curated SFARI autism gene collection we show that brain-coX's prioritisations are most similar to SFARI's own curated gene classifications. brain-coX is the first prioritisation and visualisation web-tool targeted to the human brain and can be freely accessed via http://shiny.bioinf.wehi.edu.au/freytag.s/ .
Dedicated breast PET to improve clinical diagnosis of breast cancer: Initial evaluation.
Authors: Norio Masumoto, Takayuki Kadoya, Makoto Fujiwara, Chika Murakami, Toru Yoshikawa, Yoshinori Handa, Ai Amioka, Noriko Gohda, Miho Kono, Shinsuke Sasada, Keiko Kajitani, Akiko Emi, Rumi Haruta, Tsuyoshi Kataoka, Morihito Okada
Journal: Journal of Clinical Oncology (2017)

e12097 Background: Unlike whole body (WB) 18F-fluorodeoxyglucose (FDG) PET, dedicated breast PET (DBPET) enables detailed high-resolution images within the breast and quantitative assessment using SUV. We aimed to determine whether DBPET can detect ductal carcinoma in situ (DCIS) and predict the malignancy and neoplastic progress of invasive breast cancer. Methods: We investigated 155 consecutive patients with breast cancer who underwent concurrent DB– and WB– PET (Elmammo®) between January and November 2016. All DB– and WB– PET images were quantified based on standard uptake values (SUV). We also assessed 12 patients with ring-like uptake (RU) without central FDG accumulation in invasive breast cancers on DBPET images. Results: The SUV (means ± SD) determined from DB– and WB– PET images of breast cancer were 8.2 ± 7.7 and 3.1 ± 3.3 respectively. We detected DCIS in DB- and WB– PET images from 22 (84.7%) and 15 (57.6%) of 26 among the 155 patients, respectively (p = 0.003). The SUV on WB– PET images was significantly higher for NG3 than for NG1-2 (p = 0.004), and for high (≥ 20%) than low ( &lt; 20%) Ki67 (p = 0.003), and significantly lower for Luminal A than Luminal B, HER2 and triple-negative cancer (p &lt; 0.05 for all three). The SUV for NG (p = 0.002), Ki67 (p = 0.001) and the luminal (p &lt; 0.05) type also significantly differed in DBPET images. RU without central FDG accumulation was evident in DbPET images of 12 patients, all of whom had Ki67 ≥ 20 (p = 0.0001), two had NG1-2 and 10 had NG3 (p = 0.005), one had clinical T1, 11 had T2 (p = 0.0004), five had clinical N0 and seven had N1 (p = 0.03). RU was associated with high-grade malignancy and neoplastic progress. Conclusions: The detection rate of DBPET was excellent for DCIS. The RU on DBPET offers predictive value for high-grade malignancy and the neoplastic progress of invasive breast cancer. Thus, DBPET might help to determine therapeutic strategies.
Trends in Cardiovascular Health of US Adults by Income, 2005-2014
Authors: Adam L. Beckman, Jeph Herrin, Khurram Nasir, Nihar R. Desai, Erica S. Spatz
Journal: JAMA Cardiology (2017)

This study assesses national trends in cardiovascular risk factors by income level among adults aged 25 years and older using data from the National Health and Nutrition Examination Surveys.
Abstract NTOC-113: TGF–β SIGNALING INHIBITION AS A POTENTIAL APPROACH TO TARGET SUBOPTIMALLY DEBULKED OVARIAN TUMORS
Authors: Wei Wei, Michael J. Birrer
Journal: Clinical Cancer Research (2017)

Abstract The current standard of care for all patients with high-grade, advanced-stage serous ovarian cancer is surgery followed by adjuvant chemotherapy. Resection of all visible residual disease to less than 1 cm is associated with a favorable prognosis, but this optimal debulking can only be achieved in ~70% of patients. Patients with suboptimal cytoreduction are presumed to have lower response rates to subsequent chemotherapy and are known to have a poor prognosis. Recently, we performed a meta-analysis of 1,525 publicly available expression profiling assays and identified a 200-gene expression signature of primary ovarian tumors to predict the outcome of debulking surgery. The signature was validated using two independent sets of tumors. This debulking signature consists of transcripts positively regulated by TGF-β, indicating that hyperactivation of TGF-β signaling may be responsible of the aggressive biological and clinical behavior of suboptimally debulked tumors. In this study, we evaluated the potential anti-tumor effect of TGF-β signaling blockade in ovarian cancer cells in vitro and in vivo. Integrated TGF-β signaling was observed in 8 of 10 ovarian cancer cell lines tested by a SMAD-binding element based luciferase assay. The potential anti-tumor effect of a small molecular TGFBR1 kinase inhibitor LY2157299 was further investigated in SKOV3 cell line, which presents both endogenous and inducible TGF-β signaling and is highly disseminative when inoculated into immunodeficient mice. Although imposing minimal effect on in vitro cellular proliferation, LY2157299 significantly inhibited tumor-dissemination related biological processes in SKOV3 cells including migration, invasion and mesothelial cell adhesion. In an interperitoneal SKOV3 xenograft model, administration of LY2157299 significantly increased cisplatin related cytotoxicity and tumor burden reduction. Taken together, our study has provided evidence for the potential clinical use of LY2157299 to improve the treatment and survival of women with suboptimal surgery. Citation Format: Wei Wei and Michael J. Birrer. TGF–β SIGNALING INHIBITION AS A POTENTIAL APPROACH TO TARGET SUBOPTIMALLY DEBULKED OVARIAN TUMORS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-113.
Treatment and risk of mortality for 58,953 cases of stage 1, ER+/PR+/HER2- breast cancer in four mutually exclusive race/ethnicities.
Authors: Vincent Caggiano, Carol Parise
Journal: Journal of Clinical Oncology (2017)

e12101 Background: The estrogen receptor positive (ER+), progesterone receptor positive (PR+), human epidermal growth factor 2 negative (HER2-) subtype is the most common. Cases of stage 1, ER+/PR+/HER2- are most often treated with hormone therapy alone, although this is not universal. The purpose of this study was to determine if there were differences in mortality for patients with stage 1, ER+/PR+/HER2- breast cancer given no treatment, chemotherapy alone, or both chemotherapy and hormone therapy when compared with hormone therapy alone for four mutually exclusive race/ethnicities. Methods: We identified 58,953cases of Stage 1, ER+/PR+/HER2- first primary female invasive breast cancer from the California Cancer Registry 2000-2014. Cases were stratified into white (n = 41,716), black (n = 2,310), Hispanic (n = 8,186) and Asian/Pacific Islander (API) (n = 6,741). Treatment was categorized as none, hormone therapy alone, chemotherapy alone, or both chemotherapy and hormone therapy. Kaplan Meier survival analysis and Cox Regression were used to assess the risk of mortality associated with treatment using hormone therapy alone as the reference category. Treatment was considered a risk for mortality and hazard ratios (HR) and 95% confidence intervals reported if the Wald χ 2 was statistically significant (p &lt; 0.05). Models were adjusted for age, grade, socioeconomic status, and tumor size. Separate analyses were conducted for each race/ethnicity. Results: White women, having no treatment (HR = 1.33; 1.14-1.54), or chemotherapy alone (HR = 1.49; 1.10-2.00) was associated with an increased risk of mortality. For API women, having the combination of chemotherapy and hormone therapy was associated with increased risk of mortality (HR = 2.47; 1.34-4.56). For black and Hispanic women, there was no difference in risk of morality for any combination of treatment when compared with hormone therapy. Conclusions: The effectiveness of treatment modalities for the Stage 1, ER+/ER+/HER2- subtype varies considerably by race/ethnicity.
Current trend of breast cancer therapeutics from the U.S. clinical trial database
Authors: S. S. Kwok, J. Tsang
Journal: Journal of Clinical Oncology (2009)

e17546 Background: The standard of breast cancer care has been based on clinical trial results. With the International Committee of Medical Journal Editors (ICMJE) requiring all clinical trials registered in a public trial registry as a condition of publication, the US trials registry “ClinicalTrials.gov” has become a global registry of currently available clinical trials. We aim to explore the current clinical trials to study the trend of breast cancer therapeutics development based on analysis of a comprehensive breast cancer trial database. Methods: We performed a systematic review of all breast cancer therapeutic clinical trials. All data were captured from ClinicalTrials.gov for all “industry-sponsored” phase I-IV trials in October, 2007 including trials that were first registered between October 2005 and September 2007. Essential data was extracted by a tailor-made Statistical Analysis System Program developed by Professor JP Karlberg at the University of Hong Kong. The data included register identity, study phase, study compounds and recruitment status etc. Results: Altogether 443 clinical therapeutic interventional trials were identified and classified into 10 modes of action. The latest five mostly studied compounds accounted for 32.73% of all the therapeutic trials (n = 145). Lapatinib, a dual kinase inhibitor is studied most in 31 trials (9 monotherapy). Docetaxel, a mitotic inhibitor is studied in 27 trials (10 monotherapy) while letrozole, an aromatase inhibitor, currently used in adjuvant setting is tested in 18 out of a total 22 trials as monotherapy. Antimetabolites such as gemcitabine being involved in 24 trials (2 monotherapy) with capecitabine studied in 21 trials (11 monotherapy), were followed by bevacizumab, a VEGF monoclonal antibody which is currently studied in 20 trials, and tested as combinations in 75% of the related trials. Conclusions: According to the US trial registry, current most commonly tested compounds for breast cancer include lapatinib, followed by docetaxel, gemcitabine, letrozole, and capecitabine. There is increasing new therapeutics with combination strategy. This supports the trend of personalized medicine in the management of breast cancer which is a heterogeneous disease. No significant financial relationships to disclose.
A Brazilian child with a nodule in the foot
Authors: Khuen Foong Ng, Stephen Owens
Journal: BMJ (2017)

A 2 year old girl from the north coast of Brazil presented on arrival in the UK with a day’s history of a painful and mildly pruritic nodule on the sole of her right foot. Seven days later, the nodule had grown in size and had become more tender (fig 1⇓). What is the diagnosis?



Fig 1  7×7 mm skin nodule on the plantar surface of right foot with central black mark



### Short answer

Tungiasis, a cutaneous ectoparasitic infection caused by female Tunga penetrans , also called jigger, nigua, chica, pico, …
Primary Care–Based Skin Cancer Screening in a Veterans Affairs Health Care System
Authors: Susan M. Swetter, Julia Chang, Amanda R. Shaub, Martin A. Weinstock, Eleanor T. Lewis, Steven M. Asch
Journal: JAMA Dermatology (2017)

<h3>Importance</h3> Skin cancer screening may improve melanoma outcomes and keratinocyte carcinoma morbidity, but little is known about the feasibility of skin cancer training and clinical skin examination (CSE) by primary care practitioners (PCPs) in large health care systems. <h3>Objective</h3> To assess the association of skin cancer training and screening by PCPs with dermatology referral patterns and rates of skin biopsies. <h3>Design, Setting, and Participants</h3> In this pilot interventional study performed at the Veterans Affairs Palo Alto Health Care System, patients 35 years or older scheduled for an annual health habits screen in the PCP general medicine clinics were studied. <h3>Interventions</h3> Six PCPs underwent Internet Curriculum for Melanoma Early Detection (INFORMED) training in May 2015, and 5 screened patients during the following 14 months. <h3>Main Outcomes and Measures</h3> Proportion of dermatology referrals, subsequent skin biopsies, and PCP diagnostic accuracy for skin cancer or precancer compared with dermatologist diagnosis were assessed in screened patients 14 months before the intervention (February 18, 2014, through April 30, 2015) and after the intervention (June 18, 2015, through August 30, 2016). <h3>Results</h3> Among 258 patients offered screening (median age, 70 years; age range, 35-94 years; 255 [98.8%] male), 189 (73.3%) received CSE and 69 (26.7%) declined. A total of 62 of 189 patients (32.8%) were referred to a dermatologist after intervention: 33 (53.2%) for presumptive skin cancers and 15 (24.2%) for precancers. Nine of 50 patients (18.0%) evaluated in dermatology clinic underwent biopsy to exclude skin cancer. Correct diagnoses were made by PCPs in 13 of 38 patients (34.2%; 4 of 27 patients [14.8%] diagnosed with skin cancers and 5 of 11 patients [45.5%] diagnosed with actinic keratoses). Comparison of all outpatient visits for the 5 main participating PCPs before vs after intervention revealed no significant differences in dermatology referrals overall and those for presumptive skin cancer or actinic keratoses, skin biopsies, or PCP diagnostic accuracy with the exception of significantly fewer postintervention dermatology referrals that lacked specific diagnoses (25 [1.0%] vs 10 [0.4%],<i>P</i> = .01). <h3>Conclusions and Relevance</h3> This pilot study suggests that PCP-based skin cancer training and screening are feasible and have the potential to improve PCP diagnostic accuracy without increasing specialty referrals or skin biopsies. Additional studies comparing screening rates, specialty referrals, and patient outcomes in trained vs untrained PCPs are needed before screening is widely implemented in large health care systems in the United States.
Mutation of the angiopoietin-1 gene (ANGPT1) associates with a new type of hereditary angioedema
Authors: Valeria Bafunno, Davide Firinu, Maria D'Apolito, Giorgia Cordisco, Stefania Loffredo, Angelica Leccese, Maria Bova, Maria Pina Barca, Rosa Santacroce, Marco Cicardi, Stefano Del Giacco, Maurizio Margaglione
Journal: Journal of Allergy and Clinical Immunology (2017)