tbuckley/cabot-search huggingface dataset:
Nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in metastatic pancreatic adenocarcinoma (PACT-19): a randomised phase 2 trial
Authors: Michele Reni, Silvia Zanon, Umberto Peretti, Marta Chiaravalli, Diletta Barone, Chiara Pircher, Gianpaolo Balzano, Marina Macchini, Silvia Romi, Elena Gritti, Elena Mazza, Roberto Nicoletti, Claudio Doglioni, Massimo Falconi, Luca Gianni
Journal: The Lancet. Gastroenterology & hepatology (2018)
Artificial corneas
Authors: B. Allan
Journal: BMJ (1999)

Corneal disease is the second commonest cause of world blindness1 and often occurs in the context of a badly damaged ocular surface. Patients with dry eyes and vascularised corneal scarring resulting from, for example, trachoma or chemical injuries have virtually no prospect of retaining a clear corneal allograft.2 Techniques for implanting a synthetic corneal replacement (keratoprosthesis) offer hope to this desperate group of patients, who are often blind for many years. Understandably, press and public imagination is captured by news of possible restoration of sight in these cases. The pioneering spirit of tackling unmet clinical need has been emphasised in recent newspaper reports,3–5 but uncertainty surrounding outcomes is barely mentioned.

Keratoprosthesis techniques reported recently in the British press are not new. Implantation methods and the devices themselves have not materially altered since the 1960s. Devices consist of a porous outer skirt element (Dacron for the Pintucci keratoprosthesis recently implanted in Nottingham and autologous tooth for the Strampelli keratoprosthesis used …
Disección submucosa endoscópica colorrectal (DSE-CR): Riesgo para los pacientes y beneficio basado en el estudio histológico: Estudio multicéntrico
Authors: JC Marín Gabriel, F Ramos Zabala, F Múgica Aguinaga, E Albéniz Urbizu, JG De La Peña, A Sánchez Yagüe, C Dolz Abadía, MG Fernández Esparrach, A Álvarez Delgado, H Cortés Pérez
Journal: Endoscopy (2017)

El beneficio clínico de la DSE-CR radica en obtener una pieza en bloque para incrementar la precisión del estudio anatomopatológico y confirmar una resección R0 sin factores histológicos de riesgo de metástasis linfáticas. Desde un punto de vista teórico, las lesiones sin invasión submucosa, bien diferenciadas y sin invasión linfovascular, son susceptibles de curación mediante resección mucosa, con menor riesgo de complicaciones para el paciente.
<i>TERT</i>promoter mutations are associated with poor prognosis and cell immortalization in meningioma
Authors: Sabine Spiegl-Kreinecker, Daniela Lötsch, Katharina Neumayer, Lucia Kastler, Johannes Gojo, Christine Pirker, Josef Pichler, Serge Weis, Rajiv Kumar, Gerald Webersinke, Andreas Gruber, Walter Berger
Journal: Neuro-Oncology (2018)

Meningiomas are mostly benign tumors tending to progress to higher-grade lesions. Mutations in the telomerase reverse transcriptase (TERT) gene promoter are comparably rare in meningioma, but were recently suggested to predict risk of recurrence and progression. Here we have analyzed a cohort of World Health Organization grades I–III meningiomas regarding the impact of TERT promoter mutations on patient prognosis and in vitro cell propagation feasibility. From 110 meningioma patients, 128 tissue samples were analyzed for the TERT promoter mutations C228T and C250T by direct sequencing. Of the 128 samples, 121 were tested for cell propagation in vitro. Telomerase activity, TERT mRNA expression, and telomere lengths were investigated by telomeric repeat amplification protocol assay, reverse transcription PCR, and quantitative PCR, respectively. Impact of the E-twenty-six (ETS) transcription factor inhibitor YK-4–279 on cell viability and TERT promoter activity was analyzed. TERT promoter mutations were found in 5.5% of all samples analyzed and were associated with a significantly upregulated telomerase activity and TERT mRNA expression (P < 0.0001 both). Regarding telomere lengths, no significant difference between the TERT promoter wild-type and mutated subgroups was detected. Patients with TERT promoter mutated tumors exhibited significantly shorter overall survival (P = 0.0006; 53.8 vs 115.6 mo). The presence of TERT promoter mutations but not telomerase activity or TERT mRNA expression predicted indefinite cell growth in vitro. TERT promoter mutated meningioma cells were hypersensitive against the ETS transcription factor inhibitor YK-4–279, inducing a distinct downregulation of TERT promoter activity. TERT promoter mutations drive meningioma aggressiveness, resulting in reduced patient survival, but might also open novel therapeutic options for progressive disease.
Measles-Rubella Supplementary Immunization Activity Readiness Assessment — India, 2017–2018
Authors: Vandana Gurnani, Pradeep Haldar, Sudhir Khanal, Pankaj Bhatnagar, Balwinder Singh, Danish Ahmed, Mohammad Samiuddin, Arun Kumar, Yashika Negi, Satish Gupta, Pauline Harvey, Sunil Bahl, Alya Dabbagh, James P. Alexander, James L. Goodson
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In 2013, during the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR), the 11 SEAR countries* adopted goals to eliminate measles and control rubella and congenital rubella syndrome by 2020† (1). To accelerate progress in India (2,3), a phased§ nationwide supplementary immunization activity (SIA)¶ using measles-rubella vaccine and targeting approximately 410 million children aged 9 months-14 years commenced in 2017 and will be completed by first quarter of 2019. To ensure a high-quality SIA, planning and preparation were monitored using a readiness assessment tool adapted from the WHO global field guide** (4) by the India Ministry of Health and Family Welfare. This report describes the results and experience gained from conducting SIA readiness assessments in 24 districts of three Indian states (Andhra Pradesh, Kerala, and Telangana) during the second phase of the SIA. In each selected area, assessments were conducted 4-6 weeks and 1-2 weeks before the scheduled SIA. At the first assessment, none of the states and districts were on track with preparations for the SIA. However, at the second assessment, two (67%) states and 21 (88%) districts were on track. The SIA readiness assessment identified several preparedness gaps; early assessment results were immediately communicated to authorities and led to necessary corrective actions to ensure high-quality SIA implementation.
Abstract 510: Regulation of Coronary Vascular Tone via Redox Modulation in the Alpha-Adrenergic-Angiotensin-Endothelin Axis of the Myocardium
Authors: Takashi Kaneshiro, Shuichi Saito, William M Chilian, Yukio Maruyama
Journal: Circulation (2006)

Recently we reported alpha-adrenoceptor stimulation of cardiac myocytes resulted in the production of angiotensin II, which stimulated the coronary vascular production of endothelin (ET) resulting in vasoconstriction. Because signaling induced by these agonists influences the redox state of many cells, we hypothesized that manipulating the redox state of cells may influence the extent of coronary vasoconstriction. To determine the role of the redox state in this pathway, we measured vasoconstriction of isolated, pressurized rat coronary arterioles (74±8μm, diameter) to supernatant collected from enzymatically isolated cardiac myocytes, which were stimulated with an alpha1-adrenoceptor agonist phenylephrine (PH) 50μM. PH increased production of superoxide in cardiac myocytes [dihydroethidium fluorescence (DHE) for oxidative stress 6.2±0.8 fold vs. quiescent myocytes, n=8, p
Abstract 17305: Activation of Soluble Guanylate Cyclase Ameliorates the Progression of Glucose Intolerance and Nephropathy in Obese ZSF1 Rats
Authors: Valdeci da Cunha, Kashmira Shah, Olga Price, Christopher J Sinz, Ronald M Kim
Journal: Circulation (2016)

Introduction: Recent data suggests that activation of the NO-soluble guanylate cyclase (sGC)-cyclic cGMP system has potential metabolic effects, in addition to the regulation of vascular tone. The ...
Exploring the utility of the Chasing Principle: influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension
Authors: ScheylaDaniela Siqueira Jørgensen, Thomas Rades, Huiling Mu, Kirsten Graeser, Anette Müllertz
Journal: Acta Pharmaceutica Sinica B (2018)

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol (CAR), cinnarizine (CIN) or R3040 on drug solubilization in a two-compartment in vitro lipolysis model. Correlation of drug logP or solubility in SNEDDS with drug solubilization during in vitro lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1 (1:1, w/w) and Kolliphor RH40, with ethanol at 10% (w/w) were used. SNEDDS were named F65, F55 and F20 (numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS (F0) were also analyzed. While the ranking order of drug solubilization was F65=F55=F20>F0 for CAR; F65=F55>F20>F0 for CIN and F65=F55=F20>F0 for R3040 - with higher CAR solubilization than for R3040 and CIN - the ranking of Seq of CAR, CIN and R3040 in SNEDDS was F65<F55<F20, F65=F55>F20 and F65>F55>F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high Seq in SNEDDS did not reflect high drug solubilization. As CAR (logP 3.8) showed higher solubilization than CIN (logP 5.8) and R3040 (logP 10.4), a correlation between drug logP and drug solubilization was observed.
Poly(β‐amino ester)‐<i>co</i>‐poly(caprolactone) Terpolymers as Nonviral Vectors for mRNA Delivery In Vitro and In Vivo
Authors: Umberto Capasso Palmiero, James C. Kaczmarek, Owen S. Fenton, Daniel G. Anderson
Journal: Advanced Healthcare Materials (2018)

Abstract The production of new proteins with messenger RNA (mRNA) has gained a broad interest due to its potential for addressing a wide range of diseases. Here, the design and characterization of novel ionizable poly(β‐amino ester)‐ co ‐poly(caprolactone) terpolymers, synthesized via the combination of the ring opening polymerization and the Michael step‐growth polymerization, are reported. The versatility of this method is demonstrated by varying the number of caprolactone units attached to each poly(β‐amino ester) (PBAE) terpolymer. The ability of the novel poly‐caprolactone (PCL)‐based PBAE materials to deliver mRNA is shown to depend on the physiochemical characteristics of the material, such as lipophilicity, as well as the formulation method used to complex the polymer with the oligonucleotide. This latter variable represents a previously unstudied aspect of PBAE library screens that can play an important role in identifying true top candidates for nucleic acid delivery. The most stable terpolymer is injected intravenously (IV) in mice and shows a transfection efficacy several times higher than the polyethylenimine (PEI) which is focused in the spleen, opening the possibility to use these biodegradable carriers in the intravenous delivery of antigen‐encoding mRNA for cancer immunotherapy and vaccination.
ZNF677 Suppresses Akt Phosphorylation and Tumorigenesis in Thyroid Cancer
Authors: Yujun Li, Qi Yang, Haixia Guan, Bingyin Shi, Meiju Ji, Peng Hou
Journal: Cancer Research (2018)

The zinc finger protein 677 (ZNF677) belongs to the zinc finger protein family, which possesses transcription factor activity by binding sequence-specific DNA. Previous studies have reported its downregulated by promoter methylation in non-small cell lung cancer. However, its biological role and exact mechanism in human cancers, including thyroid cancer, remain unknown. In this study, we demonstrate that ZNF677 is frequently downregulated by promoter methylation in primary papillary thyroid cancers (PTC) and show that decreased expression of ZNF677 is significantly associated with poor patient survival. Ectopic expression of ZNF677 in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration, invasion, and tumorigenic potential in nude mice and induced cell-cycle arrest and apoptosis. Conversely, knockdown of ZNF677 promoted thyroid cancer cell proliferation and colony formation. ZNF677 exerted its tumor suppressor functions in thyroid cancer cells through transcriptional repression of two targets CDKN3 and HSPB1 (or HSP27), thereby inhibiting phosphorylation and activation of Akt via distinct mechanisms. Taken together, our data show that ZNF677 functions as a tumor suppressor and is frequently silenced via promoter methylation in thyroid cancer.Significance: These findings report a tumor suppressive role of the zinc-finger protein ZNF677 in primary papillary thyroid cancer through inhibition of Akt phosphorylation. Cancer Res; 78(18); 5216-28. ©2018 AACR.
How Do Resuscitation Teams at Top-Performing Hospitals for In-Hospital Cardiac Arrest Succeed?
Authors: Brahmajee K. Nallamothu, Timothy C. Guetterman, Molly Harrod, Joan E. Kellenberg, Jessica L. Lehrich, Steven L. Kronick, Sarah L. Krein, Theodore J. Iwashyna, Sanjay Saint, Paul S. Chan
Journal: Circulation (2018)

In-hospital cardiac arrest (IHCA) is common, and outcomes vary substantially across US hospitals, but reasons for these differences are largely unknown. We set out to better understand how top-performing hospitals organize their resuscitation teams to achieve high survival rates for IHCA.We calculated risk-standardized IHCA survival to discharge rates across American Heart Association Get With The Guidelines-Resuscitation registry hospitals between 2012 and 2014. We identified geographically and academically diverse hospitals in the top, middle, and bottom quartiles of survival for IHCA and performed a qualitative study that included site visits with in-depth interviews of clinical and administrative staff at 9 hospitals. With the use of thematic analysis, data were analyzed to identify salient themes of perceived performance by informants.Across 9 hospitals, we interviewed 158 individuals from multiple disciplines including physicians (17.1%), nurses (45.6%), other clinical staff (17.1%), and administration (20.3%). We identified 4 broad themes related to resuscitation teams: (1) team design, (2) team composition and roles, (3) communication and leadership during IHCA, and (4) training and education. Resuscitation teams at top-performing hospitals demonstrated the following features: dedicated or designated resuscitation teams; participation of diverse disciplines as team members during IHCA; clear roles and responsibilities of team members; better communication and leadership during IHCA; and in-depth mock codes.Resuscitation teams at hospitals with high IHCA survival differ from non-top-performing hospitals. Our findings suggest core elements of successful resuscitation teams that are associated with better outcomes and form the basis for future work to improve IHCA.
Abstract 14122: Total Artificial Heart Fit Study: Using 3-Dimensional Computer Simulation to Perform Virtual Implantation of the Total Artificial Heart in Adolescents and Young Adults to Ensure Spatial Suitability
Authors: Ryan A Moore, Peace Madueme, Todd Pietila, Angela Lorts, Michael Taylor, David Morales
Journal: Circulation (2013)

Introduction: The Syncardia temporary Total Artificial Heart (TAH-t) replaces a patient’s failing ventricles as a “bridge-to-transplant.” The TAH-t is contraindicated if insufficient space exists i...
Assay to rapidly screen for immunoglobulin light chain glycosylation: a potential path to earlier AL diagnosis for a subset of patients
Authors: Sanjay Kumar, David Murray, Surendra Dasari, Paolo Milani, David Barnidge, Benjamin Madden, Taxiarchis Kourelis, Bonnie Arendt, Giampaolo Merlini, Marina Ramirez-Alvarado, Angela Dispenzieri
Journal: Leukemia (2018)
Tratamiento de la hemorragia digestiva guiado por ecoendoscopia: Resultados y perfil de seguridad
Authors: S López, A Elosua, D Oyón, M Rullán, L Casanova, M Gómez, I Fernández-Urién, E Albéniz, A Pueyo, JJ Vila
Journal: Endoscopy (2017)

El tratamiento guiado por ecoendoscopia en la hemorragia digestiva (HD) constituye una opción de rescate en pacientes seleccionados.
PRIMARY VITREORETINAL LYMPHOMA RECURRENCE AS A CAUSE OF UPPER GASTROINTESTINAL BLEEDING
Authors: AI Ramírez Polo, P Valdez Hernández, LE Zamora Nava, F Valdovinos Andraca, G Grajales-Figueroa
Journal: Endoscopy (2018)

In 2016, an immunocompetent 66-year-old man was diagnosed with diffuse large B cell vitreoretinal lymphoma. In his initial staging, no systemic involvement was found. He received both systemic chemotherapy and intraocular methotrexate with disease control. During follow-up no recurrence was reported. In October 2017, the patient was admitted to ER because of an episode of hematemesis without any other gastrointestinal symptoms. Upper endoscopy revealed an isolated ulcerated lesion, with an exophytic appearance and elevated edges in distal esophagus. In stomach, multiple ulcerated lesions with elevated edges and clean base were found in fundus and body. One of the ulcers had a non-bleeding visible vessel. In order to treat this lesion, haemostasis with double therapy (adrenaline injection and thermal coagulation with bipolar probe) was successfully performed. Tissue sampling of gastric and esophageal ulcers was performed during the procedure. Biopsies with Sydney protocol were also taken. Histopathological diagnosis was diffuse large B cell lymphoma infiltration. A CT revealed multiple retroperitoneal adenopathies and mesenteric implants. A new chemotherapy cycle was started.
ANTIBIOTIC PROPHYLAXIS IN PERCUTANEOUS TRANSHEPATIC CHOLANGIOGRAPHY AND BILIARY DRAINAGE (PTCD), A RETROSPECTIVE MULTICENTER STUDY
Authors: AS Turan, SFM Jenniskens, LJ Schultze Kool, JM Martens, MJCM Rutten, LSF Yo, MJL Van Strijen, PD Siersema, EJM Van Geenen
Journal: Endoscopy (2018)

Yearly, over 2500 percutaneous transhepatic cholangiography (PTC) and biliary drainages (PTCD) are performed in the Netherlands. These interventions are mainly used as a treatment for biliary obstruction in case of failed endoscopic biliary cannulation. The 2010 CIRSE and the SIR guidelines advocate antibiotic prophylaxis (ABp) in PTCD procedures (evidence level 5), because transient bacteremia commonly occurs. In many centers, including ours, no standard protocol for ABp in PTCD is applied. Patients receive ABp at the physician's discretion. The effect of ABp has only been studied in case series with no controls included. Therefore, the crucial question unanswered today is whether ABp indeed reduces the risk of severe infectious complications in patients undergoing PTCD.
Inserción programada de prótesis metálicas autoexpandibles (PMA) en la suboclusión colónica secundaria a cáncer colorrectal (CCR). Resultados preliminares
Authors: R Torres Yuste, AY Carbajo López, P Díez Redondo, H Nuñez Rodríguez, M Pérez-Miranda Castillo
Journal: Endoscopy (2017)

La ESGE no recomienda la colocación de PMAs en individuos sin clínica obstructiva aguda, dados sus riesgos potenciales. Sin embargo, la inserción precoz de PMA en pacientes con CCA estenosante puede resultar beneficiosa al evitar el desarrollo una obstrucción aguda que precise actuación urgente con mayor morbi-mortalidad.
Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018
Authors: David W Eyre, Nicholas D Sanderson, Emily Lord, Natasha Regisford-Reimmer, Kevin Chau, Leanne Barker, Markus Morgan, Robert Newnham, Daniel Golparian, Magnus Unemo, Derrick W Crook, Tim EA Peto, Gwenda Hughes, Michelle J Cole, Helen Fifer, Anne Edwards, Monique I Andersson
Journal: Eurosurveillance (2018)

We describe a gonorrhoea case with combined high-level azithromycin resistance and ceftriaxone resistance. In February 2018, a heterosexual male was diagnosed with gonorrhoea in the United Kingdom following sexual intercourse with a locally resident female in Thailand and failed treatment with ceftriaxone plus doxycycline and subsequently spectinomycin. Resistance arose from two mechanisms combining for the first time in a genetic background similar to a commonly circulating strain. Urgent action is essential to prevent further spread.
Validez diagnóstica de la clasificación NICE para predecir invasión profunda de la submucosa en lesiones del colon evaluadas in vivo
Authors: I Puig Del Castillo, M López-Cerón, Á Ferrández, A Herreros-De-Tejada, Ó Nogales Rincón, L De Castro, J López-Vicente, P Vega, F Vida, M Pellisé
Journal: Endoscopy (2017)

La predicción de invasión submucosa profunda (> 1000 µm) (SM-d) en un pólipo de colon puede ayudar a elegir el tratamiento más adecuado y seguro. La clasificación NICE intenta resolver este problema incluso sin magnificación, pero no ha sido validada in vivo.
Drainage Endoscopique des Faux Kystes Pancréatiques
Authors: O Gharbi, L Hamzaoui, M Medhioub, A Ben Mohamed, K Amal, MM Azouz
Journal: Endoscopy (2018)

Les faux kystes du pancréas (FKP) sont des collections liquidiennes contenant du suc pancréatique elles peuvent survenir dans les suites d'une pancréatite aigüe ou chez les sujets ayant une pancréatite chronique. Ils sont le plus souvent asymptomatiques et régressent spontanément, mais dans certains cas un traitement souvent endoscopique ou chirurgical est indiqué.
FTO-Dependent N <sup>6</sup> -Methyladenosine Regulates Cardiac Function During Remodeling and Repair
Authors: Prabhu Mathiyalagan, Marta Adamiak, Joshua Mayourian, Yassine Sassi, Yaxuan Liang, Neha Agarwal, Divya Jha, Shihong Zhang, Erik Kohlbrenner, Elena Chepurko, Jiqiu Chen, Maria G. Trivieri, Rajvir Singh, Rihab Bouchareb, Kenneth Fish, Kiyotake Ishikawa, Djamel Lebeche, Roger J. Hajjar, Susmita Sahoo
Journal: Circulation (2018)

Background: Despite its functional importance in various fundamental bioprocesses, studies of N 6 -methyladenosine (m6A) in the heart are lacking. Here, we show that the FTO (fat mass and obesity-associated protein), an m6A demethylase, plays a critical role in cardiac contractile function during homeostasis, remodeling, and regeneration. Methods: We used clinical human samples, preclinical pig and mouse models, and primary cardiomyocyte cell cultures to study the functional role of m6A and FTO in the heart and in cardiomyocytes. We modulated expression of FTO by using adeno-associated virus serotype 9 (in vivo), adenovirus (both in vivo and in vitro), and small interfering RNAs (in vitro) to study its function in regulating cardiomyocyte m6A, calcium dynamics and contractility, and cardiac function postischemia. We performed methylated (m6A) RNA immunoprecipitation sequencing to map transcriptome-wide m6A, and methylated (m6A) RNA immunoprecipitation quantitative polymerase chain reaction assays to map and validate m6A in individual transcripts, in healthy and failing hearts, and in myocytes. Results: We discovered that FTO has decreased expression in failing mammalian hearts and hypoxic cardiomyocytes, thereby increasing m6A in RNA and decreasing cardiomyocyte contractile function. Improving expression of FTO in failing mouse hearts attenuated the ischemia-induced increase in m6A and decrease in cardiac contractile function. This is performed by the demethylation activity of FTO, which selectively demethylates cardiac contractile transcripts, thus preventing their degradation and improving their protein expression under ischemia. In addition, we demonstrate that FTO overexpression in mouse models of myocardial infarction decreased fibrosis and enhanced angiogenesis. Conclusions: Collectively, our study demonstrates the functional importance of the FTO-dependent cardiac m6A methylome in cardiac contraction during heart failure and provides a novel mechanistic insight into the therapeutic mechanisms of FTO.