tbuckley/cabot-search huggingface dataset:
Effect of Expedited Microneedle-Assisted Photodynamic Therapy for Field Treatment of Actinic Keratoses
Authors: Tatyana A. Petukhova, Lauren A. Hassoun, Negar Foolad, Mayanka Barath, Raja K. Sivamani
Journal: JAMA Dermatology (2017)

Photodynamic therapy (PDT) is an effective and cosmetically favorable treatment modality for actinic keratoses (AKs). However, prolonged incubation times and pain associated with treatment are burdensome to the patient and a hindrance to widespread use of PDT as standard field therapy for AK.To evaluate efficacy and pain associated with microneedle expedited PDT.The Microneedle Photodynamic Therapy II (MNPDT-II) study was a randomized, single-blinded, split-face controlled, 2-arm clinical trial. Thirty-three participants with AK on the face were recruited in a university dermatology outpatient clinic from 2015 to 2016, and 32 participants completed the study.Participants were randomized into 2 incubations arms, either 10-minute or 20-minute aminolevulinic acid (ALA) incubation times, after pretreatment with a microneedle roller (200 um) vs a sham roller. They were blinded to the laterality of microneedle and sham roller assignments. After incubation, they were exposed to blue light (Blu-U, Dusa Pharmaceuticals) for 1000 seconds for a total fluence of 10 J/cm2.The primary outcome was to quantitatively measure AK resolution, and the secondary outcome was to assess pain associated with microneedle pretreatment.Thirty-three individuals were recruited and randomized to either the 20-minute or the 10-minute incubation arm. Thirty-two participants completed the study with a mean follow-up time of 34.5 days in the 20-minute group, and 30.2 days in the 10-minute group. For the 20-minute incubation arm, average AK clearance was 76% vs 58% on the sham side (P < .01), including 3 patients with complete clearance, although not statistically significant (P = .25). Pain assessment on the visual analog scale (VAS) during blue light illumination was not significantly different between the microneedle and sham sides (0.7 and 0.4; P = .28), respectively. For the 10-minute incubation arm AK clearance for the microneedle pretreated side was 43% compared with 38% on the sham side (P = .66). Pain during the blue light exposure was not significantly different between the microneedle and sham sides, 4.5 mm and 3.4 mm (P = .21), respectively.Photodynamic therapy with microneedle pretreatment at a 20-minute ALA incubation time significantly improved AK clearance with efficacy similar to that of a conventional 1-hour ALA incubation time. The additional advantage to expedited treatment was that the procedure was virtually painless. However, expedited exposure of a 10-minute ALA incubation time did not reach significantly different AK clearance from the sham control.clinicaltrials.gov Identifier: NCT02594644.
Reduced Fertility among Women Employed as Dental Assistants Exposed to High Levels of Nitrous Oxide
Authors: Andrew S. Rowland, Donna Day Baird, Clarice R. Weinberg, David L. Shore, Carl M. Shy, Allen J. Wilcox
Journal: New England Journal of Medicine (1992)

Fertility is reduced in female rats exposed to levels of nitrous oxide similar to those found in some dental offices. Epidemiologic studies have suggested an association between exposure to mixed anesthetic gases and impaired fertility. We investigated the effects of occupational exposure to nitrous oxide on the fertility of female dental assistants.
Research funders pledge to make trial results publicly available
Authors: Anne Gulland
Journal: BMJ (2017)

Some of the world’s largest funders of medical research have agreed that the results of all the trials they fund or support will be made publicly available.

In a joint statement, 10 international research bodies, including the UK Medical Research Council, the Wellcome Trust, the Indian Council of Medical Research and the Institut Pasteur, agreed that all trials they fund, co-fund, sponsor, or support will be registered in a publicly available registry. They also said that all results would be disclosed within specified time frames, either …
Opportunities and Challenges: Human Papillomavirus and Cancer
Authors: Christina S. Chu, David G. Pfister
Journal: Journal of the National Comprehensive Cancer Network (2017)

Mucosal exposure to human papillomavirus (HPV) can lead to anogenital and head and neck (H&N) cancer. Vaccination at a young age can be almost 100% effective in preventing HPV infection with the viral subtypes in both men and women, at least for disease in the anogenital tract. Therapeutic strategies targeting HPV in cervical dysplasia and cancer are showing promise as well in regressing dysplasia and controlling disease. That HPV-positive H&N cancer is a different disease from HPV-negative disease, with different molecular and clinical features and prognosis, is becoming better appreciated. At this time, however, the NCCN Guidelines for H&N Cancers do not distinguish between the types. This is expected to change.
Abstract #167: Anti-tumor activities of a saponin (Y3) on ovarian cancer cells.
Authors: Pui-Kwong Chan, Kwong-Kwok Wong
Journal: Cancer Research (2009)

Saponins are a class of secondary metabolites found in many plants and are frequently used as herbal medicine. Recently, a novel triterpenoid saponin (Y3) isolated from the plant Xanthoceras sorbifolia Bunge (Sapindaceae) was found to have cytotoxicity toward various human cancer cell lines. Among 12 human cell lines of different tissues origin, an ovarian cancer cell line, OVCAR3, has the lowest IC50 of 2.2µM while other cell lines have an IC50 between 7 to 20 µM. To further investigate the cytotoxicity of the isolated Y3 on ovarian cancer cells, an additional 8 ovarian cancer cell lines were tested. As determined by MTT assay, the IC50 values of Y3 for these ovarian cell lines are: OVCAR3 (2.2 µM), TOV-G21 (2.2 µM), ES2 (4.4 µM), OVCA432 (4.4 µM), Caov3 (7 µM), OVCA 429 (7 µM), RMG2 (8.8 µM), OVCA433 (8.8 µM), and SKOV3 (10.5 µM). To understand the molecular mechanism of the cytotoxic effect of Y3 on ovarian cancer cell, gene expression profiles were generated from ES2 cells treated with Y3 in triplicate experiments. From the expression profiles, angiopoietin-2 (ANGPT2), a naturally occurring inhibitor of angiogenesis, was found to be up-regulated by Y3. Furthermore, several genes: DDIT3, LIF and NFKB1Z, involved in apoptosis were also up-regulated. The up-regulation of these genes was validated by semi-quantitative real-time PCR. The anti-tumor effect of Y3 on ES2 cells was further tested in an orthotopic model. Athymic (nu/nu) mice were inoculated peritoneally with 106 ES2 cells. After 1, 4 and 10 days of inoculation, tumor bearing mice were injected peritoneally at a dosage of 2.5 mg/kg/day of Y3 for 10 days. The survival data from triplicate experiments was shown in table 1. Histological analysis of tumors from both untreated and Y3 treated tumor bearing mice indicated that fewer blood vessels were present in the tumors from treated mice. These results indicate that Y3 has an anti-tumor effect on ovarian cancer cells. The anti-tumor effect may via the activation of apoptotic pathways and the anti-angiogenesis pathway.$$table_{C9A67964-6843-4CDB-B96D-722A73F684F9}$$  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 167.
Novel functional proteomics approach to defining ovarian cancer molecular heterogeneity
Authors: M. S. Carey, B. T. Hennessy, A. M. Gonzalez-Angulo, W. Liu, K. R. Coombes, Y. Guan, W. Kuo, K. Smith-McCune, J. Almeida, G. B. Mills
Journal: Journal of Clinical Oncology (2007)

5502 Background: A number of clinicopathologic risk factors are used for survival prediction and clinical decision-making in epithelial ovarian cancer (EOC). Information from novel technologies such as gene arrays has not had an impact on patient management. We studied EOC protein signaling profiles to determine if their addition to accepted clinicopathologic factors improves their accuracy in predicting individual patient outcomes. Methods: We applied a novel functional proteomics technology, reverse phase protein array (RPPA), to quantify expression and activation of 42 steroid and kinase signaling pathway proteins in 106 high-grade EOCs from patients with stages 1–4 tumors managed with surgery and platinum-based chemotherapy. Cox regression analysis and a novel committee modeling approach were used to study the impact of functional proteomics on patient outcomes. Results: In a Cox model using only clinical variables, stage and residual disease were significantly related to overall survival. By adding the proteins to the clinical Cox model, two proteins that were significantly associated with overall survival on univariate analysis (phosphorylated-MAPK (p-MAPK; log rank p = 0.0047) and progesterone receptor (PR; log rank p = 0.027)) remained significant at the alpha=0.10 level (z-test p-values 0.074 and 0.034, respectively, when treated as binary variables according to martingale residual plots); as a result, these two proteins added to the predictive accuracy of the clinical survival model. However, using the novel committee modeling approach in test and validation EOC sets, a closest neighbor metric was applied to successfully define distinct proteins groups, each composed of nine proteins, that are predictive of specific survival times in patients with EOC. This granular approach to modeling is particularly suited to defining the molecular heterogeneity of EOC. Conclusions: EOC is a complex process with significant individual variability. Using novel approaches to functional proteomic study and statistical modeling, our striking finding is that distinct combinations of steroid and kinase signaling proteins are predictive markers of specific survival times in EOC. No significant financial relationships to disclose.
The impact of gastric acid suppression therapy on tyrosine kinase inhibitors in advanced cancer patients.
Authors: Michael Patvin Chu, Vincent Ha, Margaret Ngo, Sunita Ghosh, Carole Chambers, Michael B. Sawyer
Journal: Journal of Clinical Oncology (2014)

2594 Background: Oral tyrosine kinase inhibitors (TKIs) are used across tumor subtypes. Oral drug absorption is dependent on numerous factors including gastric acidity. Few studies have examined effects of gastric acid suppressants such as proton pump inhibitors (PPIs) on TKI outcomes. This study aims to determine if concurrent PPIs and TKIs impair progression free (PFS) and overall survival (OS) in patients (pts). Methods: Advanced/metastatic non-small cell lung cancer (NSCLC) patients receiving erlotinib from 2007 to 2012 and renal cell cancer (RCC) patients receiving sunitinib from 2007 to 2013 were retrospectively reviewed. The review included the Alberta outpatient/retail pharmacy databases. Pts with ≤ 1 week of therapy were excluded. Aside from demographics, pts were identified as concurrently receiving acid suppression if their pharmacy records included a PPI with prescription dates that overlapped by ≥ 20% of TKI treatment duration. PFS and OS were primary endpoints. Results: Of 545 NSCLC and 383 RCC pts, 507 and 231 were included, respectively. PPIs given concomitantly with erlotinib was detrimental to both PFS (hazard ratio [HR] 1.71, 95% CI: 1.39-2.11, p<0.0001) and OS (HR 1.29, 95% CI: 1.05-1.59, p=0.016). PPIs also affected sunitinib PFS (HR 1.42, 95% CI: 1.00-2.01, p=0.050) and OS (HR 1.27, 95% CI: 0.88-1.82, p=0.202). In pooled analysis, PPIs negatively impacted TKI PFS (HR 1.60, 95% CI: 1.34-1.91, p<0.0001) and OS (HR 1.34, 95% CI: 1.09-1.57, p=0.003). Considering performance status, acid suppression impaired PFS (HR 1.56, 95% CI: 1.31-1.87, p<0.0001) and OS (HR 1.24, 95% CI: 1.04-1.49, p=0.019) in both RCC and NSCLC. Conclusions: Despite limitations of a retrospective study, this large cohort study shows PPIs negatively interact with oral TKIs in NSCLC and RCC pts. Our results lend support that PPIs impair TKI absorption leading to poorer survival. This interaction is not found in electronic drug interaction sources and patients embarking on TKI therapy should be made aware that gastric acid suppressants may limit TKI efficacy. Further investigation as to whether this effect is seen in other TKIs is underway.
Alpha Genotyping in a Heterogeneous Indian Population
Authors: Anita H. Nadkarni, Ajit C. Gorakshakar, Dipika Mohanty, Roshan B. Colah
Journal: American Journal of Hematology (1996)

has prognostic value in lymphoid malignancies such as multiple myeloma and CLL.High P2m values in CLL have been found to correlate mainly with stage of disease and high lymphocyte count 131.Prolymphocytic leukemia is a disease of activated B lymphocytes more differentiated than B-CLL cells.PLL cells express B cell activation antigens CD25, CD38, CD71, FMC7, PCAl, and RABl 141.We found a significantly higher level of p2m in PLL than in CLL patients.Our results indicate that P2m levels may be an additional marker of B-cell activation to further characterize lymphoid diseases arrested in different stages of maturation.
The Consult Guys - Green Urine?!?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2013)

Web ExclusivesOctober 15, 2013The Consult Guys - Green Urine?!?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G13-3003 SectionsSupplemental MaterialAboutVisual AbstractAbstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Bayer, sanofi-aventis; Consultancies: Bristol-Myers Squibb, Bayer, sanofi-aventis. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics October 15, 2013Volume 159, Issue 8Page: CG3KeywordsUrine ePublished: 15 October 2013 Issue Published: October 15, 2013 CopyrightCopyright © 2013 by American College of Physicians. All Rights Reserved.Loading ...
Abstract P044: Activation of Interferon Regulatory Factor-3 Prolongs Stress-Induced Cardiomyocyte Apoptosis and Decreases Survival Post Myocardial Infarction
Authors: Geoffrey de Couto, Fayez Dawood, Mei Sun, Manyin Chen, Scott Heximer, William Stanford, Jeffrey Medin, Peter Liu
Journal: Circulation Research (2011)

Background. The innate immune response is critical in mediating host protection from foreign antigen or stress. It is evident that multiple innate immune pathways also tightly regulate the remodeling process post-myocardial infarction (MI), however it is not clear how this process is mediated. In order to further elucidate the underlying mechanism of this process, we screened both mouse and human post-MI microarray databases and identified a common, significantly upregulated transcription factor of interest, interferon regulatory factor-3 (IRF3). To assess its function in vivo, we tested the hypothesis that activation of IRF3 post-MI coordinates maladaptive repair by promoting cardiomyocyte apoptosis. Methods/Results. We randomly allocated IRF-3 knockout (IRF-3-/-) mice and their wild-type (WT) counterparts to either left anterior descending (LAD) coronary artery ligation or sham operation. Four weeks post-MI, deficiency in IRF3 led to improved survival [88% (44/50) vs. 29% (14/49) in WT, p&lt;0.0001], preserved cardiac function via echocardiography [Fractional Shortening: 37% vs. 22.9% in WT, LVEDD: 5.15mm vs. 5.85mm in WT, LVESD: 4.15mm vs. 5.14mm in WT; p&lt;0.057#x005D;, and attenuated infarct size [27% vs. 44% in WT, p&lt;0.05]. Assessing the stress response 1-week post-MI, we found that NFkB signaling (IKKa, Ikba, p65) as well as pan-ubiquitination of proteins, were both significantly downregulated in the border infarct zone of IRF3-/- mice. These findings were complemented with increased protein and mRNA expression of de-ubiquitinating enzyme A20. Interestingly, in IRF3-/- mice these results were linked with decreased apoptosis (Caspases, TUNEL staining), however with a more specific attenuation of the mitochondrial-specific apoptotic pathway (Bid, Cytochrome C, Caspase9). Conclusions. These data establish a novel link between the innate immune transcription factor IRF3 and maladaptive regulation of cardiomyocyte apoptosis through mitochondrial apoptotic pathway activation. As an acute responder coordinating maladaptive remodeling, IRF3 may prove to be an efficacious therapeutic target to improve outcome following MI.
Margaret McCartney: The NHS needs big, firm IT pants
Authors: Margaret McCartney
Journal: BMJ (2017)

A massive spread of “ransomware” has infected computers around the world, including many in the NHS. Operations have been cancelled, many test results can’t be accessed, and investigations such as x rays have been made near impossible1—all as predicted in The BMJ last week.2

Essentially, hackers infect old computer operating systems, which are still used in much of the NHS. Many similar attacks have occurred before,3 if less well publicised, and many more are likely. Some US hospitals have actually paid ransoms amid great fear, in particular, about litigation resulting from theft of …
“It's a bit more complicated than that”: A broader perspective on determinants of obesity
Authors: Barbara Mullan, Nikos Ntoumanis, Cecilie Thøgersen-Ntoumani, Ottmar V Lipp
Journal: Behavioral and Brain Sciences (2017)

The insurance hypothesis does not address important factors known to contribute to obesity levels in all persons, not just adult women in the industrialized world. These include psychological determinants of eating behaviours, the decline in physical activity leading to a negative energy balance, the dense built environment, pervasive food marketing, and the increased availability of energy-dense, nutrient-poor food.
Abstract 052: Epicardial-derived Adrenomedullin Drives Cardiac Hyperplasia During Embryogenesis
Authors: Sarah E Wetzel-Strong, Manyu Li, Toshio Nishikimi, Kathleen M Caron
Journal: Circulation Research (2013)

The multi-functional peptide adrenomedullin ( Adm = gene, AM = protein) plays important roles in embryonic development and disease. Previous studies demonstrated that Adm knockout mice die at embryonic day 13.5 with small, disorganized hearts and hypoplastic lymphatic vessels, highlighting the importance of this peptide in normal cardiovascular development. Since Adm knockout animals are embryonic lethal, our goal was to generate and characterize a novel model of Adm over-expression to study the role of Adm during development and disease processes. Through gene targeting techniques, we generated a novel mouse model of Adm over-expression, abbreviated as Adm hi/hi . When we assessed gene expression of Adm from 10 different tissues, we found Adm hi/hi mice express 3- to 15-fold more Adm than wildtype littermates. Additionally, peptide levels of AM in lung and kidney, as well as circulating plasma levels of AM were elevated 3-fold over wildtype mice, indicating a functional increase in AM. Our initial analysis revealed that adult Adm hi/hi mice have larger heart weight to body weight ratios than wildtype littermates (4.93±0.23 vs. 5.96±0.29, n = 11-12). We found that compared to wildtype, Adm hi/hi embryos have more proliferating cells during heart development (14.46±1.11 vs. 31.97±2.84, n=4), indicating that hyperplasia drives Adm hi/hi heart enlargement. By crossing the Adm hi/hi line to different tissue-specific Cre lines, we were able to excise the stabilizing bovine growth hormone 3’UTR, thereby returning Adm expression levels back to wildtype in cells with active Cre recombinase. Using this approach, we identified the epicardium as a major source of AM during cardiac development. In conclusion, we found that AM derived primarily from the epicardium drives cardiac hyperplasia during embryonic development resulting in persistent, enlarged hearts of adult Adm hi/hi mice. Since our Adm hi/hi mice recapitulate the 3-fold plasma elevation of AM observed during human disease, this mouse line will be a useful tool for studying the role of elevated AM during disease.
Ulcerative Colitis and Colorectal Cancer
Authors: Anders Ekbom, Charles Helmick, Matthew Zack, Hans-Olov Adami
Journal: New England Journal of Medicine (1990)

The risk of colorectal cancer is increased among patients with ulcerative colitis. The magnitude of this increase in risk and the effects of the length of follow-up, the extent of disease at diagnosis, and age at diagnosis vary substantially in different studies.
Imatinib Generics in Treatment of Chronic Myeloid Leukemia; A Prospective Observation in Large Cohort of Patients from Polish (PALG) Imatinib Generics Registry
Authors: Tomasz Sacha, Joanna Gora-Tybor, Monika Szarejko, Grażyna Bober, Olga Grzybowska-Izydorczyk, Joanna Niesiobędzka-Krężel, Marek Dudziński, Ewa Wasilewska, Krzysztof Myśliwiec, Justyna Gil, Michał Gniot, Iwona Pietkun, Ewa Mędraś, Joanna Wącław, Krzysztof Giannopoulos
Journal: Blood (2016)
Abstract 187: Overexpression of Calpastatin Enhances Cardiotoxicity Induced by Doxorubicin
Authors: Tianqing Peng, Yanpeng Wang, Jian Ma
Journal: Circulation Research (2012)

Background: Doxorubicin causes damage to the heart, which may present as cardiomyopathy. However, the mechanisms by which doxorubicin induces cardiotoxicity remain not fully understood and no effective prevention for doxorubicin cardiomyopathy is available. Calpains, a family of calcium-dependent thiol-proteases, have been implicated in cardiovascular diseases. Their activities are tightly controlled by calpastatin. This study employed transgenic mice over-expressing calpastatin to investigate the role of calpain in doxorubicin-induced cardiotoxicity. Methods and Results: Doxorubicin treatment decreased calpain activities in cultured neonatal mouse cardiomyocytes and in vivo mouse hearts. Over-expression of calpastatin or incubation with pharmacological calpain inhibitors enhanced caspase-3 activity and DNA fragmentation in both neonatal and adult cardiomyocytes induced by doxorubicin. Inhibition of calpain also induced down-regulation of phosphorylated protein kinase B (AKT, Thr308), and a concomitant reduction in glycogen synthase kinase-3beta (GSK-3β) phosphorylation (Ser9) in doxorubicin-treated cardiomyocytes. Blocking AKT further increased doxorubicin-induced cardiac injuries, suggesting the effects of calpain inhibition may be mediated by inactivating the AKT/GSK-3β signaling. In an in vivo model of doxorubicin-induced cardiotoxicity, over-expression of calpastatin decreased calpain activities and exacerbated myocardial dysfunction as assessed by echocardiography and hemodynamic measurement in transgenic mice (C57BL/6) 5 days after doxorubicin injection. The five-day mortality was higher in transgenic mice (29.16%) compared with their wild-type littermates (8%) after doxorubicin treatment. Conclusions: Over-expression of calpastatin enhances doxorubicin-induced cardiac injuries through inhibiting calpain and compromising AKT survival signaling. Thus, calpains may protect cardiomyocytes against doxorubicin-induced cardiotoxicity.