tbuckley/cabot-search huggingface dataset:
B cells engineered to express pathogen-specific antibodies protect against infection
Authors: Howell F. Moffett, Carson K. Harms, Kristin S. Fitzpatrick, Marti R. Tooley, Jim Boonyaratanakornkit, Justin J. Taylor
Journal: Science Immunology (2019)

B cells reprogrammed to express pathogen-specific antibodies using CRISPR-Cas9 protect against infection.
A comparative study of voluntary deep inspiration breath hold versus free breathing techniques in adjuvant left breast hypofractionated radiotherapy
Authors: E.A. Elkhouly, N. Abdelbarry, Y. Rashed, A. Alhanafy, N.A. Shabaan
Journal: Annals of Oncology (2019)

Background: Left-sided breast cancer radiation therapy has been associated with an increased risk of major coronary events. There is evidence demonstrating that the increase is proportional to mean heart dose. Deep Inspiration Breath Hold (DIBH) is a radiation therapy technique that has shown significant dose reduction to the heart and lung in hypofractionated radiotherapy of adjuvant left-sided breast cancers. This study explores the potential benefit of utilizing a DIBH technique to reduce heart and ipsilateral lung doses. Methods: This study was done on 65 patients with adjuvant left breast cancer. Patients are coached and asked to voluntarily hold their breath. For each patient, using Computed Tomography simulator machine, two CT scans corresponding to free breathing (FB) and vDIBH were acquired during simulation. Using Monaco treatment planning system FB and vDIBH plans were generated for each patient. All patients were treated on linear accelerator utilizing a vDIBH technique. 40.05 Gy in 15 fractions was prescribed. The evaluating parameters are target coverage; the volume of ipsilateral lung received 20 Gy (V20); mean heart dose (MHD) and volume of heart received 25 Gy (V25). All patients followed an offline portal imaging protocol, where the patients were imaged on day 1-3 and then weekly. Results: The comparing result shows there is a significant reduction in ipsilateral lung and heart dose statistics for vDIBH compared to FB plans without compromising the target coverage. For ipsilateral lung, the V20 was reduced by 15% with vDIBH comparing with FB. The volume of the heart receiving >25 Gy was reduced 20% and MHD was reduced by 18%. These reductions are considered to be statistically significant. The vDIBH mean reproducibility was 2mm (range 1- 4 mm) in antro-posterior direction. Conclusions: Voluntary DIBH technique is successfully implemented and is an important tool for cardiac sparing and has been reproducibly associated with a reduction of mean heart dose. This is a benefit for those patients with left-sided breast irradiation and also has been shown to decrease dose to the lungs. Legal entity responsible for the study: Academic Group. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Impact de l'antibioprophylaxie et des modalités de conditionnement lors de la réalisation d'une myotomie per-orale endoscopique pour troubles moteurs oesophagiens
Authors: A Hastier, R Olivier, I Bentellis, M Pioche, T Piche, T Ponchon, E Coron, M Barthet, G Vanbiervliet
Journal: Endoscopy (2019)

Aucune recommandation concernant l'antibioprophylaxie, les modalités de préparation et le conditionnement sont disponibles chez les patients porteurs de troubles moteurs oesophagiens bénéficiant de myotomie orale per endoscopique (POEM). Le but principal de notre étude était d'évaluer l'impact de l'antibioprophylaxie sur la survenue de complications lors de la réalisation d'un POEM. Les objectifs secondaires étaient: i) d'établir une corrélation entre l'utilisation de l'antibioprophylaxie et l'efficacité du geste; ii) d'établir une corrélation entre le conditionnement pré procédure et la survenue de complications; iii) de rechercher des facteurs prédictifs cliniques et biologiques de complications.
A GIANT ILEAL PSEUDOPOLYP IN CROHN'S DISEASE RESECTED BY DOUBLE-BALLOON ENTEROSCOPY
Authors: JM Rubio Mateos, JF Sánchez Melgarejo, MJ Sánchez Fernandez, A Pérez Fernandez, E Pérez-Cuadrado-Robles, P Esteban Delgado, S Chacón Martínez, JL Rodrigo Agudo, V Sastre Lozano, E Pérez-Cuadrado Martínez
Journal: Endoscopy (2019)

Giant pseudopolyps (> 1.5 cm) are unusual in Crohn's Disease (CD), and oftenly cause intestinal obstruction among other complications that may require surgical management. Endoscopic therapy could be an alternative in such circumstances. We describe a case report of a giant pseudopolyp treated by enteroscopy.
SPLIT-DOSE LACTULOSE WITH ADJUNCTIVE ORAL BISACODYL AND ORAL SODIUM PHOSPHATE: A PILOT STUDY OF A NOVEL BOWEL PREPARATION
Authors: WL Loh, T Tan, O Tan, J Tung, S Ngooi, SS Ngoi
Journal: Endoscopy (2019)

Various colonoscopic bowel preparations are in use clinically. Split-dose preparations are generally recommended for morning colonoscopies. We herein present a novel form of bowel preparation with split-dose lactulose as the backbone with oral bisacodyl and sodium phosphate, in a pilot study assessing its safety and efficacy.
Clinical guidelines on antidepressant withdrawal urgently need updating
Authors: James Davies, John Read, Michael P Hengartner, Fiammetta Cosci, Giovanni Fava, Guy Chouinard, Jim van Os, Antonio Nardi, Peter Gøtzsche, Peter Groot, Emanuela Offidani, Sami Timimi, Joanna Moncrieff, Marcantonio Spada, Anne Guy
Journal: BMJ (2019)

In February 2018 the international debate on antidepressant withdrawal was reignited.In response to a letter published in The Times by Davies et al. on the benefits and harms of antidepressants, the Royal College of Psychiatrists publicly stated that '[for] the vast majority of patients any unpleasant symptoms experienced on
PTC299 Is a Novel DHODH Inhibitor That Modulates VEGFA mRNA Translation and Inhibits Proliferation of a Broad Range of Leukemia Cells
Authors: Liangxian Cao, Arthur Branstrom, John Baird, Christopher Trotta, Joseph Colacino, Marianne T. Santaguida, Diane Heiser, Mark Ma, Kensuke Kojima, Stuart Peltz, Edward O'Mara, Robert Spiegel, Marla Weetall
Journal: Blood (2017)
La coloscopie: quel apport dans le bilan étiologique de la constipation chronique?
Authors: A Hammami, A Bouchareb, N Elleuch, A Ben Slama, H Jaziri, A Braham, S Ajmi, M Ksiaa, A Jmaa
Journal: Endoscopy (2019)

La constipation constitue un symptôme très fréquent, handicapant et bien souvent mal traité avec un impact médico-économique important et sous-évalué. Elle peut être l'expression d'une maladie organique ou fonctionnelle. Les étiologies sont multiples et doivent être éliminées, mais dans plus de 90% des cas ce symptôme restera idiopathique. Un bilan étiologique comportant essentiellement une coloscopie s'impose devant tout patient présentant une constipation chronique, sévère ou avec des signes d'alarmes (Age> 50 ans, apparition récente, rectorragies, anémie, amaigrissement). L'objectif de ce travail est de déterminer l'apport de la coloscopie dans le bilan étiologique de la constipation.
USE OF MOBILE PORTABLE ENDOSCOPY UNIT FOR GASTRO-INTESTINAL DISEASES IN RESOURCE LIMITED RURAL REGION OF INDIA: WHAT WERE THE OUTCOMES?
Authors: H Chaudhari, Y Chaudhari, S Chaudhari, M Chaudhari, S Zagde, S Sawdatkar, A Salok, V Atriwal, A Atriwal, B Atriwal, P Badhe, P Badhe
Journal: Endoscopy (2019)

The aim of this study was to evaluate the role of mobile portable endoscopy unit in patients with gastro-intestinal diseases in resource limited areas of rural India.
EUFOREA consensus on biologics for CRSwNP with or without asthma
Authors: Wytske J. Fokkens, Valerie Lund, Claus Bachert, Joaquim Mullol, Leif Bjermer, Jean Bousquet, Giorgio W. Canonica, Lauren Deneyer, Martin Desrosiers, Zuzana Diamant, Joseph Han, Enrico Heffler, Claire Hopkins, Roger Jankowski, Guy Joos, Andrew Knill, Jivianne Lee, Stella E. Lee, Gert Mariën, Benoit Pugin, Brent Senior, Sven F. Seys, Peter W. Hellings
Journal: Allergy (2019)

Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy. Type 2-targeting biologics such as anti-IgE, anti-IL4Rα, anti-IL5, and anti-IL5Rα have entered the market for selected pheno/endotypes of asthma patients and may soon also become available for CRSwNP patients. Given the high prevalence of chronic respiratory diseases and the high cost associated with biologics, patient selection is crucial in order to implement such therapies into chronic respiratory disease care pathways. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized a multidisciplinary Expert Board Meeting to discuss the positioning of biologics into the care pathways for CRSwNP patients with and without comorbid asthma.
Age and early maternal smoking contribute to epithelial cell IL‐13 responsiveness in a pediatric asthma population
Authors: Jaclyn W. McAlees, Theresa Baker, Davinder Kaur, Christopher McKnight, Andrew Lindsley, Richard T. Strait, Xue Zhang, Jocelyn M. Biagini Myers, Melinda Butsch Kovacic, Ian P. Lewkowich
Journal: Allergy (2019)

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mGlu2 and mGlu3 Negative Allosteric Modulators Divergently Enhance Thalamocortical Transmission and Exert Rapid Antidepressant-like Effects
Authors: Max E. Joffe, Chiaki I. Santiago, Kendra H. Oliver, James Maksymetz, Nicholas A. Harris, Julie L. Engers, Craig W. Lindsley, Danny G. Winder, P. Jeffrey Conn
Journal: Neuron (2019)
Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium thiosulfate at the molecular, cellular and in vivo levels
Authors: D. Thomas Dickey, Y. Jeffrey Wu, Leslie L. Muldoon, Edward A. Neuwelt
Journal: Cancer Research (2005)

5853  Cisplatin (CDDP) is a widely used chemotherapeutic agent that is highly ototoxic and nephrotoxic. This study investigates the potential chemoprotective effects of N-acetylcysteine (NAC) and sodium thiosulfate (STS) on in vitro and in vivo CDDP toxicities. For ototoxicity studies CDDP (6 mg/kg) was administered to Long-Evans rats via a retrograde right external carotid artery infusion to perfuse the vertebral arteries. Auditory brainstem response (ABR) thresholds at 4-20 kHz were tested prior to and 7 days after treatment. NAC (400 mg/kg IV) or STS (8g/m2 IV) were administered at different time points before or after CDDP. For nephrotoxicity studies, rats were treated with CDDP intraperitoneally (10 mg/kg) before or after NAC or STS, and blood urea nitrogen (BUN) and creatinine (CR) concentrations were determined after 3 days. In vitro cytotoxicity and chemoprotection in human tumor cell lines were assessed by cell viability and immunoblotting assays. The otoprotective activity of STS was time dependent. Rats treated with STS 4 h after CDDP exhibited no significant change from baseline ABR thresholds. The STS 8 h group had less otoprotection, while the 12 h rats had marked ototoxicity. CDDP induced abnormally high BUN and creatinine which corresponded to toxic changes in the renal tubules. All NAC-treated animals showed normal BUN and reduced creatinine levels compared to CDDP alone, as well as no histopathological evidence of nephrotoxicity. Delayed treatment with STS at any time point was not consistently protective against nephrotoxicity. STS administration fully protected against the in vitro cytotoxic and apoptotic effects of CDDP if added within 2 h of CDDP, but chemoprotection was reduced if STS administration was delayed to 4 h and was minimal by 6 h after CDDP. Delayed administration of STS provides protection against CDDP-induced ototoxicity when administered 4 and partial protection 8 h after CDDP. Pretreatment with NAC prevented CDDP-induced nephrotoxicity in rats, but delayed administration of STS was not protective. STS blocks the apoptotic pathways induced by CDDP if administered within 2-4 h of CDDP, but not if delayed to 6 h or later. These results show that chemoprotection route and timing of administration can be manipulated to maintain CDDP anti-tumor efficacy while protecting against chemotherapy side effects.
PREVALENCE OF INFLAMMATORY BOWEL DISEASE (IBD) IN A COLORECTAL CANCER POPULATION SCREENING PROGRAM
Authors: C Bezzio, I Arena, G de Nucci, C della Corte, M Devani, D Redaelli, B Omazzi, R Reati, E Domenico Mandelli, G Manes, D Morganti, S Saibeni
Journal: Endoscopy (2019)

iBD are diagnosed in subjects with gastrointestinal symptoms and a diagnostic delay is often observed. IBD may also be present in asymptomatic subjects. In these cases, diagnosis may be further delayed or missed.
OBLITERATION OF GASTRIC VARICES GUIDED BY ECO-ENDOSCOPY WITH COILS INSERTION COATED WITH EXPANDABLE HIDROGEL POLYMERS
Authors: M de Benito, C de la Serna, AY Carbajo, FJ Garcia-Alonso, J Tejedor, S Bazaga, R Sanchez-Ocaña, M Pérez-Miranda
Journal: Endoscopy (2019)

Bleeding from gastric varices is a severe complication of portal hypertension, with few management alternatives, especially when there is a contraindication to TIPS. The usual therapeutic options are the injection of cyanoacrylate, the insertion of coils or both.
A nationwide, multi-institutional retrospective study of efficacy and safety of eribulin in Korean breast cancer patients (REMARK)
Authors: J. Jeong, M.H. Park, S.J. Lee, W.C. Noh, C.W. Jeon, S.W. Lee, G.S. Son, B.I. Moon, J.S. Lee, S.S. Kang
Journal: Annals of Oncology (2019)

Background: This large-scale retrospective study was conducted to evaluate the effectiveness and safety of eribulin for the treatment of metastatic breast cancer in real-world settings in Korea. Methods: Patients who received eribulin between Jun 2014 and December 2016 at 14 hospitals in Korea for treatment of locally advanced or metastatic breast cancer were analyzed in this study. The Primary endpoint was progression-free survival(PFS) rate at 6 months. The Secondary endpoints included PFS, overall survival (OS), time to treatment failure(TTF), overall response rate (ORR) and hematologic adverse events. Results: In total, 398 patients' medical records have been collected and were included in safety analysis set(SAS). Median age was 53 years old and the median number of previous chemotherapy regimens for advanced disease was 3 (range, 0-14). A median of 5 cycles of eribulin (range, 1-34) were administered. Among SAS, 360 patients' records were included in full analysis set(FAS) and have been analyzed for the evaluation of efficacy. The PFS rate at 6 months was 37.78% and the median PFS, OS and TTF was 134, 631, and 120 days, respectively. The best overall response was confirmed as complete response (CR) 0.83%(3/360), partial response (PR) 17.22% (62/360), stable disease (SD) 31.39%(113/360) and progression disease (PD) 50.56%(182/360). We were able to collect only hematologic adverse events and in total, 65.08%(259/398) hematologic adverse events have been reported. The most frequent treatment-emergent adverse events were neutropenia (56.8%) and Anemia (11.3%). Conclusions: The efficacy and safety of eribulin in Korea, in a real world setting, was consistent with previous Asian studies, with no other notable hematologic adverse events observed. Clinical trial identification: NCT03437083. Legal entity responsible for the study: Eisai Korea Company. Funding: Eisai Korea Company. Disclosure: All authors have declared no conflicts of interest.
ENDOSCOPIC MANAGEMENT OF COMPLICATIONS AFTER ESOPHAGECTOMY AND GASTRIC TRASNPOSITION
Authors: A Baptista, C Bravo, J Rodriguez, M Guzman
Journal: Endoscopy (2019)

Esophagectomy with gastric transposition or gastric pulled-up is indicated in some cases of esophageal carcinoma, and severe caustic esophagitis. Serious complications include necrosis, torsion, delayed emptying of the gastric tube and leakage of anastomosis. Surgical reoperation is complex (35% mortality for leaks and 90% in necrosis.). Endosocpic management in selected cases could be an alternative.
Predicting survival in liver abscess: a risk score based on 8,423 patients hospitalized with liver abscess, Thailand.
Authors: K Poovorawan, W Pan-ngum, N Soonthornworasiri, C Kittitrakul, P Wilairatana, S Treeprasertsuk, B Kitsahawong, K Phaosawasdi
Journal: Hepatology (2015)
Toxicology and safety pharmacology of nanoparticle albumin-bound (nab) rapamycin (ABI-009)
Authors: Vuong Trieu, Tapas De, Neil Desai
Journal: Cancer Research (2008)

5732  Background: The mammalian target of rapamycin (mTOR) is involved in the control of cellular growth and proliferation and is an important target in tumor therapy. Rapamycin is currently available in 2 oral forms, and its use as an anticancer agent has been hampered by poor solubility, low oral bioavailability, and dose-limiting intestinal toxicity. Nab-rapamycin (ABI-009) is a nanoparticle albumin-bound injectable form of rapamycin. We have previously shown that ABI-009 exhibited linear PK with respect to dose and was highly effective against different tumor models in mice at 40 mg/kg IV, 3xwkly/4 weeks, which is equivalent to 120 mg/m2 dose in humans. Here, we report on the toxicology and safety pharmacology of nab-rapamycin by IV administration in rats.  Methods: Repeated-dose toxicity of nab-rapamycin was determined in Sprague-Dawley rats with dose levels of 0, 20, 40, 90, 120, and 180 mg/kg (n = 5M/5F per group) on a q4dx3 schedule. A single-dose intravenous central nervous system (CNS) safety pharmacology study was performed using a Functional Observational Battery (FOB) in Sprague Dawley Rats (n = 3M/3F per group) administered nab-rapamycin at 0, 30, 60 and 90 mg/kg.  Results: Repeated IV dosing of nab-rapamycin was well tolerated in rats up to 90 mg/kg/dose on a q4dx3 schedule, with no significant signs of toxicity and no observed hypercholesterolemia and hypertriglyceridemia, whereas repeated doses at 120 and 180 mg/kg resulted in mortality. By the end of the recovery duration on day 37, all surviving animals showed a complete recovery in clinical observations, food consumption, body weight changes, and hematological changes. There were no nab-rapamycin-related changes in any urinalysis or serum chemistry parameters examined. Changes in hematology parameters were limited to slight increases in red cell mass seen on day 16 in both sexes, most notably at 90 mg/kg. In the CNS safety pharmacology study in rats, single intravenous dose of 30, 60, or 90 mg/kg of nab-rapamycin resulted in decreased body weight gain but no significant changes in behavioral parameters.  Conclusion: Nab-rapamycin (ABI-009) was well tolerated at repeated doses up to 90 mg/kg in rats (540 mg/m2) with no remarkable toxicity. Safety pharmacology studies showed nab-rapamycin had no significant CNS toxicity at the highest dose level of 90 mg/kg in rats. These data for nab-rapamycin suggest a several fold safety margin over the expected therapeutic dose of 120 mg/m2.
Antibiotics after assisted childbirth could almost halve maternal infections
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Giving women a single dose of preventive antibiotic after childbirth involving forceps or vacuum extraction could prevent almost half of maternal infections, equivalent to more than 7000 every year in the UK and around 5000 in the US.

The finding came from a randomised trial involving 3420 women from 27 obstetric units in the UK.1 The higher estimated benefit in in the UK than in the US is because of its higher proportion of assisted births: about 12.5% in the UK and 4% in the US.

The study also found that for every additional 100 doses of preventive antibiotic …
FEASIBILITY AND LONG-TERM EFFICACY OF ENDOSCOPIC TREATMENT OF GASTROINTESTINAL STROMAL TUMORS IN UPPER GASTROINTESTINAL TRACT
Authors: JJ Park, JS Koh, MK Joo, BJ Lee, HJ Chun, SW Lee, CH Yang, EY Kim
Journal: Endoscopy (2019)

Endoscopic resection has been introduced for the treatment of subepithelial tumors (SETs) in the upper gastrointestinal tract (UGIT). We aimed in this study to investigate the feasibility and long-term efficacy of endoscopic resection of gastrointestinal stromal tumor (GIST) in UGIT.
ENDOSCOPIC SUBMUCOSAL DISSECTION USING THE SHORT TYPE CLUTCH CUTTER FOR SUPERFICIAL NON-AMPULLARY DUODENAL EPITHELIAL TUMORS
Authors: K Akahoshi, M Kubokawa, M Oya, Y Shiratuchi, J Gibo, K Yodoe, K Akahoshi
Journal: Endoscopy (2019)

Endoscopic submucosal dissection (ESD) using conventional knives for superficial non-ampullary duodenal epithelial tumors (SNADET) is technically demanding and the reported perforation rate was 25%. The aim of this study was to evaluate the efficacy and safety of ESD using the short type CC for SNADET.
LAPAROSCOPY-ASSISTED VS. BALLOON ENTEROSCOPY-ASSISTED ERCP FOR POST BARIATRIC ROUX-EN-Y GASTRIC BYPASS PATIENTS
Authors: TC Julseth, T Glomsaker, T Mala, M Bretthauer, J Young, E Refsum, L Aabakken
Journal: Endoscopy (2019)

Roux-en-Y gastric bypass (RYGB) patients are at increased risk of biliary disease necessitating endoscopic retrograde cholangiopancreaticoscopy (ERCP), which poses a challenge due to the long endoscopic access route to the major papilla. The two most widely utilized treatment strategies are laparoscopy assisted ERCP (LA-ERCP) and balloon enteroscopy assisted ERCP (BEA-ERCP). There are few studies comparing these procedures. The aim of the current study was to compare the performance, benefits and harms of LA-ERCP and BEA-ERCP in a post RYGB patients.
miR-450a Acts as a Tumor Suppressor in Ovarian Cancer by Regulating Energy Metabolism
Authors: Bruna Rodrigues Muys, Josane F. Sousa, Jessica Rodrigues Plaça, Luíza Ferreira de Araújo, Aishe A. Sarshad, Dimitrios G. Anastasakis, Xiantao Wang, Xiao Ling Li, Greice Andreotti de Molfetta, Anelisa Ramão, Ashish Lal, Daniel Onofre Vidal, Markus Hafner, Wilson A. Silva
Journal: Cancer Research (2019)

Abstract Dysregulation of miRNA expression is associated with multiple diseases, including cancers, in which small RNAs can have either oncogenic or tumor suppressive functions. Here we investigated the potential tumor suppressive function of miR-450a, one of the most significantly downregulated miRNAs in ovarian cancer. RNA-seq analysis of the ovarian cancer cell line A2780 revealed that overexpression of miR-450a suppressed multiple genes involved in the epithelial-to-mesenchymal transition (EMT). Overexpression of miR-450a reduced tumor migration and invasion and increased anoikis in A2780 and SKOV-3 cell lines and reduced tumor growth in an ovarian tumor xenographic model. Combined AGO-PAR-CLIP and RNA-seq analysis identified a panel of potential miR-450a targets, of which many, including TIMMDC1, MT-ND2, ACO2, and ATP5B, regulate energetic metabolism. Following glutamine withdrawal, miR-450a overexpression decreased mitochondrial membrane potential but increased glucose uptake and viability, characteristics of less invasive ovarian cancer cell lines. In summary, we propose that miR-450a acts as a tumor suppressor in ovarian cancer cells by modulating targets associated with glutaminolysis, which leads to decreased production of lipids, amino acids, and nucleic acids, as well as inhibition of signaling pathways associated with EMT. Significance: miR-450a limits the metastatic potential of ovarian cancer cells by targeting a set of mitochondrial mRNAs to reduce glycolysis and glutaminolysis.
LARGE NON-PEDUNCULATED COLORECTAL POLYPS REMOVAL AND RESULTS IN A UK DISTRICT HOSPITAL OVER A 12 MONTHS PERIOD
Authors: A Mohamad, S Sabri, H Kroening, A Saleem, M Solkar
Journal: Endoscopy (2019)

To identify results, pit falls to formulate recommendations based on audit of LNPCP removal over a 12 months period and to compare it with BSG (British Society of Gastroenterology Society) guide lines and to see that it meets recommended BSG standards. Data collection was between Aug 2016 till Aug 2017.