tbuckley/cabot-search huggingface dataset:
Abstract 3618: PELP1 cytoplasmic mislocalization favors estrogen-induced signaling via AIB1 in ER+ breast cancer models
Authors: Thu H. Truong, Julie H. Ostrander, Carol A. Lange
Journal: Cancer Research (2017)

Abstract Luminal breast cancers account for ~75% of cases and express (ER) and frequently contain a range of progesterone receptor (PR) positive cells. ER and PR are steroid hormone receptors (SR) that rapidly and dynamically shuttle between the cytoplasm and the nucleus, a process that allows for essential crosstalk with cytoplasmic signaling pathways that serve as direct inputs to SR transcriptional functions. During disease progression, aberrant hormone signaling often leads to expression of altered SR gene programs and endocrine resistance. An emerging biomarker of increased risk and aggressive cancer behavior is cytoplasmic PELP1. Our lab was the first to show that PELP1 forms a functional signaling and transcriptional complex with ER and PR to regulate novel estrogen-driven SR target genes associated with endocrine resistance. PELP1 is primarily nuclear in normal breast tissue, but cytoplasmic localization of PELP1 (cyto-PELP1) is observed in 40-58% of invasive tumors. To elucidate the impact of PELP1 mislocalization on SR signaling pathways and transcription programs, we have generated SR+ breast cancer cell models expressing vector, wild-type (nuclear) PELP1, and cyto-PELP1. Our studies show that cells expressing cyto-PELP1 exhibit increased mammosphere formation relative to WT-PELP1 or vector control cells in response to estrogen. Moreover, we have identified AIB1 (ER co-activator) as a robust binding partner for cytoplasmic, but not nuclear PELP1, through mass spectrometry. This interaction occurs in a hormone-dependent manner as shown by co-immunoprecipitation assays. AIB1 activation (i.e. phosphorylation levels) is increased in cyto-PELP1 cells relative to WT-PELP1 or control cells. Knockdown of AIB1 reduces cyto-PELP1 protein levels and leads to decreased gene expression of key pro-inflammatory and immune regulatory cyto-PELP1 target genes. Our results reveal novel cytoplasmic actions of AIB1 and highlight the significance of delineating the impact of dynamic PELP1 shuttling/mislocalization with respect to altered hormone/SR-driven target gene expression in luminal breast cancer progression. We conclude direct signaling inputs to SR complexes are profoundly altered in the context of PELP1 mislocalization and interaction with AIB1. Our findings are relevant to mechanisms of endocrine resistance that may be targeted by inhibitors of the PELP1/SR interaction. Citation Format: Thu H. Truong, Julie H. Ostrander, Carol A. Lange. PELP1 cytoplasmic mislocalization favors estrogen-induced signaling via AIB1 in ER+ breast cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3618. doi:10.1158/1538-7445.AM2017-3618
Hereditary angioedema cosegregating with a novel kininogen 1 gene mutation changing the N‐terminal cleavage site of bradykinin
Authors: Konrad Bork, Karin Wulff, Heidi Rossmann, Lars Steinmüller‐Magin, Ingrid Brænne, Günther Witzke, Jochen Hardt
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
RECURRENCE AND CANCER-SPECIFIC MORTALITY DURING FOLLOW UP OF LOW-AND HIGH-RISK ENDOSCOPICALLY RESECTED PT1 COLORECTAL CANCERS: A META-ANALYISIS
Authors: G Antonelli, G Vanella, DG Orlando, S Angeletti, E Di Giulio
Journal: Endoscopy (2019)

Oncological radicality of endoscopic resection of pT1 colorectal cancers (CRCs) is still under debate. Need for subsequent surgery is defined by histopathological factors associated to increased risk of lymph-node metastasis. Data describing this risk are heterogeneous and based on small retrospective surgical series, while follow-up data of non-surgically resected lesions are poorly reported, resulting in a great variability in management of these patients.
Assessing global COPD awareness with Google Trends
Authors: Anna Boehm, Alex Pizzini, Thomas Sonnweber, Judith Loeffler-Ragg, Claudia Lamina, Guenter Weiss, Ivan Tancevski
Journal: European Respiratory Journal (2019)

Although chronic obstructive pulmonary disease (COPD) prevalence and mortality rates rise continuously, patients often remain undiagnosed, probably due to a lack of disease-related awareness. The aim of this study was to quantify public interest in COPD by analysing the frequency of web queries via Google.Data from 2004 to 2018 were collected using the search engine query data analysis tool Google Trends. The relative search volume of the topic "chronic obstructive pulmonary disease" was compared with the relative search volume of nine topics representing the major causes of death in high-income countries according to the World Health Organization.Our analysis showed highest relative search volumes for the topics "diabetes mellitus", followed by "stroke" and "breast cancer". The topic "chronic obstructive pulmonary disease" ranked eighth and its relative search volume clearly displayed a seasonal variation, with peaks in the first and the fourth quarter of the year.This analysis reveals that COPD is highly under-represented in the public interest, while real-world prevalence constantly rises, indicating that there is still an urgent need to raise the levels of awareness for COPD.
Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial
Authors: Yasmin L. Hurd, Sharron Spriggs, Julia Alishayev, Gary Winkel, Kristina Gurgov, Chris Kudrich, Anna M. Oprescu, Edwin Salsitz
Journal: American Journal of Psychiatry (2019)

Despite the staggering consequences of the opioid epidemic, limited nonopioid medication options have been developed to treat this medical and public health crisis. This study investigated the potential of cannabidiol (CBD), a nonintoxicating phytocannabinoid, to reduce cue-induced craving and anxiety, two critical features of addiction that often contribute to relapse and continued drug use, in drug-abstinent individuals with heroin use disorder.This exploratory double-blind randomized placebo-controlled trial assessed the acute (1 hour, 2 hours, and 24 hours), short-term (3 consecutive days), and protracted (7 days after the last of three consecutive daily administrations) effects of CBD administration (400 or 800 mg, once daily for 3 consecutive days) on drug cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder. Secondary measures assessed participants' positive and negative affect, cognition, and physiological status.Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues. CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure. In addition, CBD reduced the drug cue-induced physiological measures of heart rate and salivary cortisol levels. There were no significant effects on cognition, and there were no serious adverse effects.CBD's potential to reduce cue-induced craving and anxiety provides a strong basis for further investigation of this phytocannabinoid as a treatment option for opioid use disorder.
At least 167 healthcare workers were killed in conflict last year
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Over 900 recorded attacks were carried out on healthcare facilities, personnel, and patients in 23 countries in conflict last year, a significant rise on the 701 instances reported in 2017.1

The figures are included the Safeguarding Health in Conflict Coalition 2018 report, which brings together data from bodies such as the World Health Organization and the UN.

The report found that at least 167 health workers died and at least 710 were injured in 2018. Healthcare in the Palestinian occupied territories was the worst affected with a total of 308 attacks, closely followed by Syria (257 attacks). Afghanistan, the Central African Republic, and Libya …
Hanafy Ahmed Mahmoud Youssef
Authors: Zahra Youssef, John Waddington, John Owens
Journal: BMJ (2019)

Hanafy Ahmed Mahmoud Youssef was a strong advocate for community based psychiatry. He set up the first community based service in Ireland. He was able to show that this led to better outcomes for both the patients and their families. On sharing his findings, others followed his lead, and this led to a wholesale change in how psychiatry was practised in Ireland and the UK.

Youssef received his undergraduate education in Alexandria, Egypt, where he was born. Although fully committed to his medical education, he had a thirst for knowledge and for broadening his learning in multiple disciplines. He found university life afforded him the opportunities to explore his other interests, of which there were many, including literature (he authored several published novellas in Arabic), the arts (he was the arts reviewer for the university paper and he won a national poetry award), sport (he played for the university firsts football team), science, politics, and …
Interaction of Alt a 1 with SLC22A17 in the airway mucosa
Authors: María Garrido‐Arandia, Jaime Tome‐Amat, Diego Pazos‐Castro, Vanesa Esteban, Maria M. Escribese, Guadalupe Hernández‐Ramírez, Alma Yuste‐Montalvo, Domingo Barber, Luis F. Pacios, Araceli Díaz‐Perales
Journal: Allergy (2019)

Abstract Background Despite all the efforts made up to now, the reasons that facilitate a protein becoming an allergen have not been elucidated yet. Alt a 1 protein is the major fungal allergen responsible for chronic asthma, but little is known about its immunological activity. Our main purpose was to investigate the ligand‐dependent interactions of Alt a 1 in the human airway epithelium. Methods Alt a 1 with and without its ligand (holo‐ and apo‐ forms) was incubated with the pulmonary epithelial monolayer model, Calu‐3 cells. Allergen transport and cytokine production were measured. Pull‐down and immunofluorescence assays were employed to identify the receptor of Alt a 1 using the epithelial cell model and mouse tissues. Receptor‐allergen‐ligand interactions were analyzed by computational modeling. Results The holo‐form could activate human monocytes, PBMCs, and polarized airway epithelial (Calu‐3) cell lines. The allergen was also transported through the monolayer, without any alteration of the epithelial integrity (TEER). Alt a 1 also induced the production of proinflammatory IL8 and specific epithelial cytokines (IL33 and IL25) by Calu‐3 cells. The interaction between epithelial cells and holo‐Alt a 1 was found to be mediated by the SLC22A17 receptor, and its recognition of Alt a 1 was explained in structural terms. Conclusions Our findings identified the Alt a 1 ligand as a central player in the interaction of the allergen with airway mucosa, shedding light into its potential role in the immunological response, while unveiling its potential as a new target for therapy intervention.
ARTIFICIAL INTELLIGENCE IN EARLY BARRETT'S CANCER: THE SEGMENTATION TASK
Authors: A Ebigbo, R Mendel, A Probst, J Manzeneder, LA de Souza, J Papa, C Palm, H Messmann
Journal: Endoscopy (2019)

The delineation of outer margins of early Barrett's cancer can be challenging even for experienced endoscopists. Artificial intelligence (AI) could assist endoscopists faced with this task. As of date, there is very limited experience in this domain. In this study, we demonstrate the measure of overlap (Dice coefficient = D) between highly experienced Barrett endoscopists and an AI system in the delineation of cancer margins (segmentation task).
Lateral and Vertical Flow Assays for Point‐of‐Care Diagnostics
Authors: Nan Jiang, Rajib Ahmed, Mylon Damayantharan, Barış Ünal, Haider Butt, Ali K. Yetisen
Journal: Advanced Healthcare Materials (2019)

Abstract Lateral flow assays (LFAs) have been the pillar of rapid point‐of‐care (POC) diagnostics due to their simplicity, rapid process, and low cost. Recent advances in sensitivity, selectivity, and chemical stability enhancement have ensured the foothold of LFAs in commercial POC diagnostics. This paper reviews recent developments in labeling strategies and detection methods of LFAs. Moreover, vertical flow assays (VFAs) have emerged as an alternate paper‐based assay due to faster detection time and unique multiplexing capabilities. Smartphones as LFA readers have been transformed into a universal integrated platform for imaging, data processing, and storage, providing quantitative results in low‐resource settings. Commercial LFAs and VFAs products are evaluated with regards to their performance, market trends, and regulatory issues. The future outlook of the flow‐based assays for POC diagnostics is also discussed.
OUTCOMES AND MANAGEMENT STRATEGIES FOR CAPSULE RETENTION: A KOREAN CAPSULE ENDOSCOPY NATIONWIDE DATABASE REGISTRY STUDY
Authors: YJ Lim, HS Lee, SR Jeon, HJ Jang, JJ Park, J Chun, SH Kang, SJ Nam, Y Jung, KO Kim, YJ Lee, SJ Boo, JH Kim, CH Yang
Journal: Endoscopy (2019)

The most concerning complication of capsule endoscopy (CE) is capsule retention (CR) in the gastrointestinal tract although clinical outcome and management of patients with CR are still uncertain. The aim of this study was to investigate clinical outcomes and management of CR.
Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics
Authors: Jasmine Davda, Paul Declerck, Siwen Hu-Lieskovan, Timothy P. Hickling, Ira A. Jacobs, Jeffrey Chou, Shahram Salek-Ardakani, Eugenia Kraynov
Journal: Journal for ImmunoTherapy of Cancer (2019)

The increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment. In this review, we outline the mechanisms of action (MOA) of approved, antibody-based IMD agents, potentially related to their immunogenicity, and discuss the reported incidence of anti-drug antibodies (ADA) as well as their clinical relevance in patients with cancer. In addition, we discuss the impact of the administration route and potential strategies to reduce the incidence of ADA and manage treated patients. Analysis of published reports indicated that the risk of immunogenicity did not appear to correlate with the MOA of anti-programmed death 1 (PD-1)/PD-ligand 1 monoclonal antibodies nor to substantially affect treatment with most of these agents in the majority of patients evaluated to date. Treatment with B-cell depleting agents appears associated with a low risk of immunogenicity. No significant difference in ADA incidence was found between the intravenous and subcutaneous administration routes for a panel of non-oncology IMD antibodies. Additionally, while the data suggest a higher likelihood of immunogenicity for antibodies with T-cell or antigen-presenting cell (APC) targets versus B-cell targets, it is possible to have targets expressed on APCs or T cells and still have a low incidence of immunogenicity.
Abstract 17908: Milrinone Lacks Acute Inotropic And Lusitropic Effects Under Constant Afterload Conditions
Authors: Elizabeth S DeWitt, Katherine Black, Kimberly I Mills, Lauren Ruoss, James A DiNardo, John N Kheir
Journal: Circulation (2015)

Introduction: Phosphodiesterase III inhibitors are known to improve cardiac output in patients with heart failure. Whether this is due to a reduction in afterload, a positive inotropic effect, or an interaction of these factors is uncertain. We compared the inotropic and lusitropic effects of milrinone to those of commonly used catecholamines in a working Langendorff model under constant loading conditions. Methods: Sprague Dawley rats (n=35, 350-400 grams) were anesthetized and heparinized for cardiac explantation. The aorta and left atrium were immediately cannulated by a single experimenter. Left atrial pressure (10 mmHg) and aortic pressure (90 mmHg) were fixed. A conductance catheter (Millar) was inserted into the left ventricle. Following baseline measurements, infusions of milrinone, dopamine, dobutamine, epinephrine, or norephinephrine, alone and in commonly-used combinations, were initiated into the left atrium for 10 minute periods. Changes in cardiac output, contractility (dP/dTmax), diastolic performance (-dP/dT and Tau) relative to baseline were compared between groups by linear regression analysis. Results: Cardiac output increased in linear fashion for each of the catecholamines: Dobutamine&gt;&gt;Dopamine&gt;Norepinephrine&gt;Epinephrine (P&lt;0.001 for each). Dobutamine, Norepinephrine, and Dopamine (P&lt;0.05) significantly increased diastolic function, including negative dP/dT (C) and Tau (D), none of which were changed by Milrinone infusion. Conclusions: When afterload is fixed using a Starling resistor, milrinone at commonly used doses does not acutely change systolic or diastolic performance or cardiac output. It is possible that clinical improvements are due to milrinone’s vasodilatory properties.
Abstract 20669: Structural Basis for the Antiarrhythmic Blockade of a Potassium Channel With a Small Molecule
Authors: Yoshio Takemoto, Diana Slough, Gretchen Meinke, Chris Katnik, Michelle Reiser, Chidipi Bujjibabou, Javier Cuevas, Andrew Bohm, Yu-Shan Lin, Sami Noujaim
Journal: Circulation (2017)

Background: The acetylcholine activated inward rectifier potassium current (IKACh) is constitutively active in persistent atrial fibrillation (AF). We tested the hypothesis that blocking IKACh with...
Clinical assessment of a non-invasive wearable MEMS pressure sensor array for monitoring of arterial pulse waveform, heart rate and detection of atrial fibrillation
Authors: Matti Kaisti, Tuukka Panula, Joni Leppänen, Risto Punkkinen, Mojtaba Jafari Tadi, Tuija Vasankari, Samuli Jaakkola, Tuomas Kiviniemi, Juhani Airaksinen, Pekka Kostiainen, Ulf Meriheinä, Tero Koivisto, Mikko Pänkäälä
Journal: npj Digital Medicine (2019)

There is an unmet clinical need for a low cost and easy to use wearable devices for continuous cardiovascular health monitoring. A flexible and wearable wristband, based on microelectromechanical sensor (MEMS) elements array was developed to support this need. The performance of the device in cardiovascular monitoring was investigated by (i) comparing the arterial pressure waveform recordings to the gold standard, invasive catheter recording (n = 18), (ii) analyzing the ability to detect irregularities of the rhythm (n = 7), and (iii) measuring the heartrate monitoring accuracy (n = 31). Arterial waveforms carry important physiological information and the comparison study revealed that the recordings made with the wearable device and with the gold standard device resulted in almost identical (r = 0.9-0.99) pulse waveforms. The device can measure the heart rhythm and possible irregularities in it. A clustering analysis demonstrates a perfect classification accuracy between atrial fibrillation (AF) and sinus rhythm. The heartrate monitoring study showed near perfect beat-to-beat accuracy (sensitivity = 99.1%, precision = 100%) on healthy subjects. In contrast, beat-to-beat detection from coronary artery disease patients was challenging, but the averaged heartrate was extracted successfully (95% CI: -1.2 to 1.1 bpm). In conclusion, the results indicate that the device could be useful in remote monitoring of cardiovascular diseases and personalized medicine.
Increased Gut Permeability in First-degree Relatives of Children with Irritable Bowel Syndrome or Functional Abdominal Pain
Authors: Mark McOmber, Danny Rafati, Kevin Cain, Sridevi Devaraj, Erica M. Weidler, Margaret Heitkemper, Robert J. Shulman
Journal: Clinical Gastroenterology and Hepatology (2019)
REAL LIFE DATA FOR DYSPLASTIC BARRETT'S ESOPHAGUS MANAGEMENT AND FOLLOW-UP
Authors: S Michopoulos, G Axiaris, P Baxevanis, M Stoupaki, V Gagari, A Karlaftis, E Zampeli, D Theodorou, M Sotiropoulou, K Petraki
Journal: Endoscopy (2019)

Real life data concerning the management and outcome of patients with dysplastic Barrett esophagus (BE) are scarce.
POSITIVE IMPACT OF SWITCHING FROM BSG TO ESGE POST POLYPECTOMY GUIDELINES ON A COLONOSCOPY SURVEILLANCE WAITING LIST
Authors: S Semenov, M Syafiq Ismail, A O'Connor, N Breslin, B Ryan, D McNamara
Journal: Endoscopy (2019)

A consecutive sample of surveillance patients was identified. Indication, surveillance interval, index endoscopy and histology findings were documented. Compliance with BSG and impact of switching to ESGE guidelines was determined.
When to scan? When to treat?
Authors: Fiona Godlee
Journal: BMJ (2019)

We have explored two common clinical dilemmas in The BMJ in recent weeks: whether a child who vomits after a head injury should have undergo computed tomography; and whether an adult with subclinical hypothyroidism should be offered thyroxine.

Head injuries are common in children. Simon Hardman and colleagues say that emergency departments in UK hospitals see nearly 35 000 cases a year, most of which are minor, with no or only mildly impaired consciousness (doi:10.1136/bmj.l1875). They ask to what extent vomiting is predictive of brain injury and what frequency of isolated vomiting should prompt a CT scan. Guidelines differ, as does current …
EUS-GUIDED GALLBLADDER DRAINAGE (EUS-GBD) WITH LUMEN-APPOSING METAL-STENT – BEYOND BILIARY ISSUES. SEDATION AND AIRWAYS MANAGEMENT, ICU ADMISSION AND GENERAL OUTCOMES
Authors: A Lisotti, C Calvanese, A Cominardi, M Serrani, R Linguerri, I Bacchilega, E Jovine, P Fusaroli
Journal: Endoscopy (2019)

EUS-guided gallbladder drainage (EUS-GBD) in high-risk surgical patients with acute cholecystitis is a safe procedure, with a high success rate. Several studies have been published dealing with technical, clinical outcomes, procedural adverse events; moreover, comparison with surgery, percutaneous drainage, trans-papillary endoscopic drainage have been performed.
Preclinical Modeling of Osimertinib for NSCLC With EGFR Exon 20 Insertion Mutations
Authors: Yusoo Lee, Tae Min Kim, Dong-Wan Kim, Soyeon Kim, Miso Kim, Bhumsuk Keam, Ja-Lok Ku, Dae Seog Heo
Journal: Journal of Thoracic Oncology (2019)