tbuckley/cabot-search huggingface dataset:
Programmed death-ligand 1 (PD-L1) expression in small bowel adenocarcinomas (SBA).
Authors: Katrina Pedersen, Thomas C. Smyrk, Susan Harrington, Robert R. McWilliams
Journal: Journal of Clinical Oncology (2015)

3619 Background: SBAs are rare, resulting in a paucity of data on effective treatments. Highly active immune surveillance within all parts of the intestine may explain the rarity. In such an environment, tumor cells may express PD-L1 to inhibit immune-mediated cytotoxicity. We hypothesized that SBAs would have a high prevalence of PD-L1 IHC positive cells, which could be a marker for future immunotherapeutic efficacy. Methods: Forty-five archived SBA primary tumor samples were selected for IHC staining with the PD-L1 (anti-B7-H1 clone 5H1) antibody. Patient records were reviewed for clinical data outcomes including overall survival (OS), gender, primary site, and known microsatellite instability (MSI) status. Results: By site, we examined 25 (56%) duodenal, 14 (31%) jejunal, and five (11%) ileal tumors. 53% of tumors (24/45) demonstrated strong PD-L1 staining, with 4/45 (9%) in a cellular pattern and 21/45 (47%) in the intratumoral stroma, morphologically consisting of a mononuclear cell infiltration. Stratified by disease location, 11/25 (44%) of the duodenal tumors (9/11 stromal pattern, 1/11 cellular pattern, 1/11 positive for both), 9/14 (64%) of the jejunal tumors (8/9 stromal, 1/9 cellular), and 3/5 (60%) of the ileal tumors (2/3 stromal, 1/3 cellular) are PD-L1 positive by IHC. One site-unclassified tumor had positive stromal staining. An unadjusted survival analysis shows that PD-L1 staining within tumor cells is associated with poorer median OS (10 months vs. 5.5 years, p = 0.0009 by Log-Rank). Stromal PD-L1 staining does not exhibit a statistically significant difference in OS (median 66.9 months, vs 34.5 months p = 0.51). Of five tumors known to be MSI-H, 1/5 (20%, stromal pattern) has concomitant PD-L1 expression. Conclusions: To our knowledge, this is the first report of PD-L1 expression in SBA, with 53% staining positive. Given reported activity of anti-PD1 therapy in gastric cancer and MSI-H colon cancer, this indicates a potential role for immunotherapy in SBA. Those expressing PD-L1 intracellularly may have worse outcomes. Further studies to address prognostic and therapeutic implications PD-L1 expression are indicated.
18F-FDOPA PET/CT of Nonfunctioning Paraganglioma of the Gastroepiploic Pedicle
Authors: Benjamin Leroy Freschini, Pietro Addeo, Gerlinde Averous, Bernard Goichot, Philippe Bachellier, Alessio Imperiale
Journal: Clinical Nuclear Medicine (2018)

Abstract We report the case of a 54-year-old woman with a nonfunctioning paraganglioma arising from the gastroepiploic pedicle demonstrated by 18 F-FDOPA PET/CT. Because gastroepiploic arcade can be assimilated to the gastric mesentery, this tumor has been classified as a mesenteric paraganglioma (PGL). Neural crest cells are a multipotent population of cells characterized by effective migratory properties potentially explaining PGL atypical localization as in the mesentery. Mesenteric PGLs are often nonfunctioning and can mimic gastric, colic, or pancreatic primary tumor because of their anatomical boundaries, making more difficult the diagnosis on preoperative imaging.
Dual Vasoconstrictor and Vasodilator Innervation of the Uterine Arterial Supply in the Guinea Pig
Authors: Christopherbell
Journal: Circulation Research (1968)

The innervation of the extrinsic uterine arterial supply of the guinea pig has been studied using an isolated perfused preparation. The preparation was normally at minimal tone and responded to periarterial stimulation by a vaso-constriction which was mimicked by norepinephrine and abolished by bretylium. Constrictor responses both to stimulation and to norepinephrine were similar in both pregnant and non-pregnant states. In pregnant preparations, raising the tone of the vessels with norepinephrine revealed a powerful dilator response to periarterial stimulation. This response was mimicked by acetylcholine, potentiated by anticholinesterases, reduced by hyoscine, and abolished by-local anesthetic treatment. In contrast, virgin preparations showed only a weak dilator response to stimulation, while the response to acetylcholine even at high concentrations was usually negligible. Histochemical examination of the vessels revealed a dense plexus of fine nerve fibers exhibiting high acetylcholinesterase activit...
Congenital sideroblastic anemia in a female
Authors: Sophie Hanina, Barbara J. Bain, Barnaby Clark, D. Mark Layton
Journal: American Journal of Hematology (2018)

A 20-year-old female of Pakistani descent was referred because of a microcytic hypochromic anemia refractory to oral iron that had been present since early childhood. A diagnosis of thalassemia intermedia had previously been suspected but high performance liquid chromatography showed normal hemoglobin A2 and F levels and no mutation of the α- or β-globin genes was detected by DNA sequencing or deletion analysis. Her parents were consanguineous. Neither parent had any hematological abnormality. On physical examination she was of short stature (<4th centile) but exhibited no dysmorphism or other somatic abnormalities. A blood count showed a hemoglobin concentration of 70 g/L with a normal red cell count, MCV of 66.6 fL and MCH of 18.3 pg. The reticulocyte count was 58.6 × 109/L and there were no biochemical markers of hemolysis. Transferrin saturation and serum ferritin were raised at 96% and 349 μg/L, respectively. A blood film was dimorphic with a large proportion of poorly hemoglobinized microcytes (Images); there was anisopoikilocytosis with dacrocytes, elliptocytes, and occasional target cells. Pappenheimer bodies were present, some being very large (bottom right image).The morphological features suggested sideroblastic anemia, most likely congenital in the context. To confirm this, next-generation sequencing of a comprehensive gene panel for inherited red cell disorders was undertaken. This identified a homozygous mutation of the SLC25A38 gene c.401G>A p.(Arg134His). This involves a highly conserved amino acid and has previously been described as a pathogenic variant in autosomal recessive pyridoxine-refractory sideroblastic anemia.1 Both parents were heterozygous for this variant. Congenital sideroblastic anemias are a rare group of inherited disorders characterized by the pathological deposition of iron in mitochondria of erythroid precursors in the bone marrow leading to ineffective erythropoiesis with iron overload, and hypochromic red cells in the peripheral blood. They can be divided into syndromic and nonsyndromic forms and are genetically heterogeneous with nine monogenic forms and others due to mitochondrial DNA deletion. Nonsyndromic forms are either X-linked or autosomal recessive. Their morphological hallmark is the presence of ring sideroblasts in the bone marrow. These represent iron-laden mitochondria which form a ring around the nucleus of erythrocyte precursors. This feature points to a common pathophysiology due to genetic mutations that disrupt heme–iron biosynthesis in the mitochondria. SLC25A38 encodes an erythroid-specific mitochondrial carrier protein that transports glycine into mitochondria for the first step in heme synthesis. In this case molecular diagnosis prompted by characteristic morphological atypia obviated the need for bone marrow examination and enabled genetic counselling and screening to be provided to the patient and her family. The authors declare that they have no conflicts of interest with the contents of this article.
Omega 3 supplements do not reduce risk of heart disease, stroke, or death, finds review
Authors: Jacqui Thornton
Journal: BMJ (2018)

A systematic review of evidence on omega 3 supplements has challenged the belief that they reduce the risk of heart disease, stroke, or death.

The new Cochrane review1 combined the results of 79 randomised trials involving 112 059 people and assessed the effects of consuming additional omega 3 fat, compared with usual or lower omega 3, on diseases of the heart and circulation. Some of the participants were healthy while others had existing conditions.

Twenty five studies were assessed as highly trustworthy because they were well designed and conducted. These covered the three main types of omega 3 fatty acids: alphalinolenic acid (ALA), which is normally found in fats from plant foods, such as nuts and seeds; …
Abstract #4453: DOC2/hDAB2, a candidate tumor suppressor in nasopharyngeal carcinoma
Authors: Joanna Tong, Shuk Chau, David Ng, Patrick Leung, Ken So, Raymond Lung, Kwok Lo, Ka To
Journal: Cancer Research (2009)

Human Disabled-2 (hDAB2), also known as Differentially Expressed in Ovarian Cancer-2 (DOC-2) is a putative tumor suppressor gene discovered in ovarian cancer. It encodes a 96 Kda mitogen responsive phosphoprotein that is one of the two mammalian orthologues of the drosophila disabled protein. Down-regulation of DOC2/hDAB2 is observed in cancers including ovarian, prostate, choriocarcinoma and mammary cancers. In this study, we aimed to investigate the possible tumor suppressor effect of DOC2/hDAB2 in nasopharyngeal carcinoma (NPC). Down-regulation of DOC2/hDAB2 transcript was demonstrated in NPC cell lines, xenografts and primary NPC tumors in comparison to normal nasopharyngeal epithelium by RT-PCR (p=0.001). Lack of DOC2/hDAB2 protein expression was also demonstrated in primary NPC by immunohistochemistry. Aberrant DOC-2/hDAB2 promoter methylation was detected in 63% (n=46) of primary NPC samples by methylation specific PCR. Treatment of the DOC2/hDAB2 negative NPC cell line C666-1 with 5\#8217;-aza-deoxycytidine resulted in DOC2/hDAB2 re-expression. The finding implied that the DOC-2/hDAB2 gene silencing is associated with its promoter hypermethylation. Transfection of DOC-2/hDAB2 expression vector into NPC cell line C666-1 resulted in significantly reduced growth rate, accumulation of cells in G1 phase, and 35% reduction in colony formation comparing to empty vector-transfected controls. Taken together, our data suggested that epigenetic silencing of DOC2/hDAB2 might be important in NPC tumorigenesis.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4453.
Annals Story Slam - Seeing the Body, or Two Sparks
Authors: Kathryn Brouillette
Journal: Annals of Internal Medicine (2018)

Web Exclusives17 July 2018Annals Story Slam - Seeing the Body, or Two SparksFREEKathryn Brouillette, MDKathryn Brouillette, MDMaine Medical Center, Portland, Maine (K.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0015 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Seeing the Body, or Two Sparks "Seeing the Body, or Two Sparks," by Kathryn Brouillette (Duration 6:04)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Maine Medical Center, Portland, Maine (K.B.)Corresponding Author: Kathryn Brouillette, MD; e-mail, Kathryn.[email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 July 2018Volume 169, Issue 2Page: SS1 ePublished: 17 July 2018 Issue Published: 17 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Cytokines Produced by Dendritic Cells Administered Intratumorally Correlate with Clinical Outcome in Patients with Diverse Cancers
Authors: Vivek Subbiah, Ravi Murthy, David S. Hong, Robert M. Prins, Chitra Hosing, Kyle Hendricks, Deepthi Kolli, Lori Noffsinger, Robert Brown, Mary McGuire, Siquing Fu, Sarina Piha-Paul, Aung Naing, Anthony P. Conley, Robert S. Benjamin, Indreshpal Kaur, Marnix L. Bosch
Journal: Clinical Cancer Research (2018)

Purpose: Dendritic cells (DC) initiate adaptive immune responses through the uptake and presentation of antigenic material. In preclinical studies, intratumorally injected activated DCs (aDCs; DCVax-Direct) were superior to immature DCs in rejecting tumors from mice.Experimental Design: This single-arm, open-label phase I clinical trial evaluated the safety and efficacy of aDCs, administered intratumorally, in patients with solid tumors. Three dose levels (2 million, 6 million, and 15 million aDCs per injection) were tested using a standard 3 + 3 dose-escalation trial design. Feasibility, immunogenicity, changes to the tumor microenvironment after direct injection, and survival were evaluated. We also investigated cytokine production of aDCs prior to injection.Results: In total, 39 of the 40 enrolled patients were evaluable. The injections of aDCs were well tolerated with no dose-limiting toxicities. Increased lymphocyte infiltration was observed in 54% of assessed patients. Stable disease (SD; best response) at week 8 was associated with increased overall survival. Increased secretion of interleukin (IL)-8 and IL12p40 by aDCs was significantly associated with survival (P = 0.023 and 0.024, respectively). Increased TNFα levels correlated positively with SD at week 8 (P < 0.01).Conclusions: Intratumoral aDC injections were feasible and safe. Increased production of specific cytokines was correlated with SD and prolonged survival, demonstrating a link between the functional profile of aDCs prior to injection and patient outcomes. Clin Cancer Res; 24(16); 3845-56. ©2018 AACR.
Aspirin Plus Clopidogrel vs Aspirin Alone for Preventing Cardiovascular Events Among Patients at High Risk for Cardiovascular Events
Authors: Marco P. Donadini, Marta Bellesini, Alessandro Squizzato
Journal: JAMA (2018)

Among patients at high risk for or with established cardiovascular disease (ie, history of peripheral artery disease, stroke, or coronary artery disease without a coronary stent), is the addition of clopidogrel to aspirin associated with lower risk of mortality and cardiovascular events compared with aspirin alone?Clopidogrel plus aspirin is associated with a reduced risk for myocardial infarction and ischemic stroke and an increased risk for major bleeding compared with aspirin alone among patients at high risk for or with an established cardiovascular disease but without a coronary stent. However, combined therapy is not associated with lower mortality.
A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects
Authors: Jaber Mohammad, Roberto Scanni, Lukas Bestmann, Henry N. Hulter, Reto Krapf
Journal: Journal of the American Society of Nephrology (2018)

Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption.Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function.Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity.Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity.
Serotonergic antidepressants in COPD: beneficial or harmful?
Authors: Abebaw Mengistu Yohannes
Journal: European Respiratory Journal (2018)

<b>Antidepressants are associated with elevated risk of hospitalisation and mortality. This underscores that the importance of having a collaborative care and patient-centred approach to manage depression in patients with COPD is worthy of consideration.</b>http://ow.ly/BNkT30kGMqq
Boys should be given HPV vaccine, says joint committee
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

The UK government is considering whether to extend the human papilloma virus (HPV) vaccination programme to boys after an expert committee found that it was cost effective.1

In a report released on 18 July the Joint Committee on Vaccination and Immunisation said that deciding whether to recommend the HPV vaccine for boys was complex. It was only after considering the wider issues of health economics—including the benefits of preventing cancer many years into the future—that it found that including boys in …
GIVE: portable genome browsers for personal websites
Authors: Xiaoyi Cao, Zhangming Yan, Qiuyang Wu, Alvin Zheng, Sheng Zhong
Journal: Genome biology (2018)

Growing popularity and diversity of genomic data demand portable and versatile genome browsers. Here, we present an open source programming library called GIVE that facilitates the creation of personalized genome browsers without requiring a system administrator. By inserting HTML tags, one can add to a personal webpage interactive visualization of multiple types of genomics data, including genome annotation, "linear" quantitative data, and genome interaction data. GIVE includes a graphical interface called HUG (HTML Universal Generator) that automatically generates HTML code for displaying user chosen data, which can be copy-pasted into user's personal website or saved and shared with collaborators. GIVE is available at: https://www.givengine.org/ .
68Ga-Labeled Prostate-Specific Membrane Antigen Uptake in Pheochromocytoma
Authors: Deepa Singh, Rajender Kumar, Bhagwant Rai Mittal, Harmandeep Singh, Anish Bhattacharya
Journal: Clinical Nuclear Medicine (2018)

We report a case of adenocarcinoma prostate treated previously with radical prostatectomy and hormonal therapy who underwent Ga-labeled prostate-specific membrane antigen PET/CT for recurrence evaluation. In addition to radiotracer uptake in the prostate bed, unusual intense prostate-specific membrane antigen uptake was also noted in the left adrenal gland. With a clinical suspicion of pheochromocytoma, Ga-DOTANOC PET/CT was done, which revealed tracer-avid left adrenal lesion.
High levels of sewage contamination released from urban areas after storm events: A quantitative survey with sewage specific bacterial indicators
Authors: Hayley T. Olds, Steven R. Corsi, Deborah K. Dila, Katherine M. Halmo, Melinda J. Bootsma, Sandra L. McLellan
Journal: PLoS Medicine (2018)

Past studies have demonstrated an association between waterborne disease and heavy precipitation, and climate change is predicted to increase the frequency of these types of intense storm events in some parts of the United States. In this study, we examined the linkage between rainfall and sewage contamination of urban waterways and quantified the amount of sewage released from a major urban area under different hydrologic conditions to identify conditions that increase human risk of exposure to sewage.Rain events and low-flow periods were intensively sampled to quantify loads of sewage based on two genetic markers for human-associated indicator bacteria (human Bacteroides and Lachnospiraceae). Samples were collected at a Lake Michigan estuary and at three river locations immediately upstream. Concentrations of indicators were analyzed using quantitative polymerase chain reaction (qPCR), and loads were calculated from streamflow data collected at each location. Human-associated indicators were found during periods of low flow, and loads increased one to two orders of magnitude during rain events from stormwater discharges contaminated with sewage. Combined sewer overflow (CSO) events increased concentrations and loads of human-associated indicators an order of magnitude greater than heavy rainfall events without CSO influence. Human-associated indicator yields (load per km2 of land per day) were related to the degree of urbanization in each watershed. Contamination in surface waters were at levels above the acceptable risk for recreational use. Further, evidence of sewage exfiltration from pipes threatens drinking water distribution systems and source water. While this study clearly demonstrates widespread sewage contamination released from urban areas, a limitation of this study is understanding human exposure and illness rates, which are dependent on multiple factors, and gaps in our knowledge of the ultimate health outcomes.With the prediction of more intense rain events in certain regions due to climate change, sewer overflows and contamination from failing sewer infrastructure may increase, resulting in increases in waterborne pathogen burdens in waterways. These findings quantify hazards in exposure pathways from rain events and illustrate the additional stress that climate change may have on urban water systems. This information could be used to prioritize efforts to invest in failing sewer infrastructure and create appropriate goals to address the health concerns posed by sewage contamination from urban areas.
Selective application of fully covered biliary stents and narrow-diameter esophageal stents for proximal esophageal indications
Authors: Maoyin Pang, Michael Bartel, Donnesha Clayton, Bhaumik Brahmbhatt, Timothy Woodward
Journal: Endoscopy (2018)

Abstract Background Proximal esophageal stents are poorly tolerated and have a high risk of complications. We report our experience using fully covered, biliary, self-expandable metal stents (B-SEMS) and narrow-diameter, esophageal, self-expandable metal stents (NDE-SEMS) for this group of patients. Methods 24 patients underwent placement of B-SEMS or NDE-SEMS for proximal esophageal lesions between 1 January 2011 and 31 July 2016. The outcomes included improvement of dysphagia, healing of fistulas, and adverse events. Results 10 patients received B-SEMS and 14 had NDE-SEMS. Median follow-up time was 11.5 months (range 0.5 – 62 months). In both cohorts, stents were left in place for a mean of 6 weeks. The dysphagia score decreased in 7 (70 %) and 10 (71.4 %) patients, and fistulas resolved in 3/5 (60.0 %) and 5/8 (62.5 %) patients with B-SEMS and NDE-SEMS, respectively. Stent migration occurred in three patients (30.0 %) with B-SEMS and five patients (35.7 %) with NDE-SEMS. Conclusions Both stents were well tolerated and resulted in overall improvement of dysphagia in 70.8 % of patients. B-SEMS appeared to be more favorable for cervical esophageal lesions with narrower diameters, while NDE-SEMS may be better for more distal lesions.
Global Trends in the Management of Nonalcoholic Steatohepatitis (NASH) : Treatment Patterns and Outcomes
Authors: Arun J. Sanyal, Amber L. Martin, Sarah M. Cadarette, Karin Henriksson, Bernt Kartman, Mark Berner Hansen
Journal: Hepatology (2016)

Global Trends in the Management of Nonalcoholic Steatohepatitis (NASH) : Treatment Patterns and Outcomes