tbuckley/cabot-search huggingface dataset:
Trifluridine to enhance cytotoxicity by DNA mismatch repair deficiency and subsequent <i>MBD4</i> frameshift mutation in colorectal cancer.
Authors: Satoshi Suzuki, Moriya Iwaizumi, Yasushi Hamaya, Kosuke Takagaki, Satoshi Osawa, Takahisa Furuta, Ken Sugimoto
Journal: Journal of Clinical Oncology (2016)

608 Background: TAS-102 is composed of trifluridine (FTD) and tipiracil hydrochloride and was shown to prolong survival of patients with refractory metastatic colorectal cancer (CRC). FTD is the active antitumor component of TAS102 and its metabolite TF-TTP chemically resembles 5FU-derived metabolite FdUTP in that both of them are misincorporated into DNA and lead to cytotoxicity. Several groups have reported that stage II-III colorectal cancer patients with tumors that lost DNA mismatch repair (MMR) function do not derive a benefit from 5-FU based chemotherapy. Although FTD is reported to be misincorporated into DNA, it is not known if MMR deficient CRC cells have chemoresistance for FTD. Methods: We first utilized human colorectal cancer cell lines HCT-116 (hMLH1-deficient cells) and HCT116+ch3 (hMLH1-retained cells), and compared cytotoxicity for FTD by clonogenic assay. To further analyze if 5FU refractory CRC cells have chemosensitivity for FTD, we established 5FU refractory HCT116 cells by continuous 5FU treatment for 10 month and analyzed cytotoxicity for FTD. Finally we constructed an expression plasmid of truncated DNA grycosylase MBD4, (MBD4tru) by frameshift mutation with MMR deficiency and stably transfected the construct into HCT116 CRC cells and selected HCT116MBD4tru cell clones. The HCT116MBD4tru cells were treated with FTD and analyzed for cytotoxicity by clonogenic assay. Results: In hMLH1-deficient cells, the number of colony was reduced by FTD treatment to a same degree of hMLH1-proficient cells whereas the number of colony by 5FU treatment is higher in hMLH1-deficitent cells than hMLH1-retained cells (p&lt; 0.05). In 5FU refractory cells, treatment of FTD showed cytotoxicity to the same degree of non-5FU refractory cells. Interestingly, HCT116MBD4tru cells led to cytotoxicity with a higher sensitivity than control cells (p&lt; 0.05). Conclusions: FTD induces cytotoxisity independently of MMR status as well as under 5FU refractory condition, and MBD4 frameshift mutation by MMR deficiency enhances FTD sensitivity. These results suggest that FTD may be useful for patients with MSI-H/MBD4 mutant CRC as well as for those with 5FU refractory CRC.
Preliminary data on precision of QuantiFERON-TB Plus performance
Authors: Daniela Maria Cirillo, Lucia Barcellini, Delia Goletti
Journal: European Respiratory Journal (2016)

We agree with D. Gallagher and colleagues on the need to corroborate our recently published preliminary findings with larger and well-designed studies targeting different risk groups and performed in settings with low and high burdens of tuberculosis (TB). Indeed, we do hope that our first assessment of the QuantiFERON-TB Plus (QFT-Plus) (QIAGEN GmbH, Hilden, Germany) performance characteristics, together with the data presented by D. Gallagher and colleagues, may constitute the first body of evidence necessary to guide clinical and programmatic use of QFT-Plus within the context of TB infection management and TB elimination strategy [1]. Variability of QFT-Plus response still needs to be determined with large studies to establish appropriate cut-offs <http://ow.ly/60bP301kLRT>
Transcatheter Edge-to-Edge Treatment of Functional Tricuspid Regurgitation in an Ex Vivo Pulsatile Heart Model
Authors: Riccardo Vismara, Guido Gelpi, Santosh Prabhu, Paolo Romitelli, Lauren G. Troxler, Andrea Mangini, Claudia Romagnoni, Monica Contino, Dylan T. Van Hoven, Federico Lucherini, Michal Jaworek, Alberto Redaelli, Gianfranco B. Fiore, Carlo Antona
Journal: Journal of the American College of Cardiology (2016)

Although associated with left heart pathologies, functional tricuspid regurgitation (FTR) is often left untreated during left heart surgery. Hence, owing to its degenerative character, reoperation is often needed, encompassing an impressive (25% to 35%) mortality rate. Thus transcatheter approaches to FTR are raising great interest. The authors evaluated the post-treatment effectiveness of the edge-to-edge technique using the percutaneous mitral valve repair device in an ex vivo pulsatile model of FTR. The devices were implanted in 11 porcine hearts simulating FTR. In each heart, single-clip treatments involved grasping leaflet pairs in the medial or commissural position (6 combinations). Two-clip treatments were then performed considering all possible 15 combinations of leaflet pairs and medial/commissural grasping. Cardiac output, mean pulmonary pressure, and mean diastolic valve pressure gradient were evaluated in physiological and simulated pathological conditions (FTR), and post-treatments. Grasping the septal and anterior leaflets allowed for the best post-procedural outcome, ensuring a complete re-establishment of physiological-like hemodynamics. Septal and posterior grasping induced a significant recovery from FTR, although less marked. Conversely, grasping the anterior and posterior leaflets did not reduce FTR, and was detrimental in some specific cases. This experimental work demonstrated that the transcatheter edge-to-edge repair technique is a feasible approach for FTR. The study investigated this approach to develop a selective, specific structural intervention methodology for treating FTR, considering the several biomechanical factors that alter proper functionality of valvular substructures. These results can be used to guide the development of edge-to-edge repair techniques in treatment of FTR.
Eradication of Chronic Myelogenous Leukemia By Inactivation of the Polycomb Group Protein EZH2
Authors: Huafeng Xie, Cong Peng, Jun Qi, Giullia Cheloni, Partha Das, Jialiang Huang, Minh Nguyen, Shaoguang Li, James E. Bradner, Stuart H. Orkin
Journal: Blood (2014)
Pneumorrhachis, Pneumothorax, and Subcutaneous Emphysema
Authors: Christoph Straube, Martin Vazan
Journal: New England Journal of Medicine (2016)

A 65-year-old man was admitted for adjuvant radiotherapy after a previous tumor mass reduction and stabilizing spinal surgery for a synovial sarcoma. Ballooning of the left paravertebral area, which increased when the Valsalva maneuver was performed, is shown in a video.
Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation
Authors: Konstantinos Stellos, Aikaterini Gatsiou, Kimon Stamatelopoulos, Ljubica Perisic Matic, David John, Federica Francesca Lunella, Nicolas Jaé, Oliver Rossbach, Carolin Amrhein, Frangiska Sigala, Reinier A Boon, Boris Fürtig, Yosif Manavski, Xintian You, Shizuka Uchida, Till Keller, Jes-Niels Boeckel, Anders Franco-Cereceda, Lars Maegdefessel, Wei Chen, Harald Schwalbe, Albrecht Bindereif, Per Eriksson, Ulf Hedin, Andreas M Zeiher, Stefanie Dimmeler
Journal: Nature Medicine (2016)
Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation
Authors: J Onofre, Y Baert, K Faes, E Goossens
Journal: Human Reproduction Update (2016)

Germ cell depletion caused by chemical or physical toxicity, disease or genetic predisposition can occur at any age. Although semen cryopreservation is the first reflex for preserving male fertility, this cannot help out prepubertal boys. Yet, these boys do have spermatogonial stem cells (SSCs) that able to produce sperm at the start of puberty, which allows them to safeguard their fertility through testicular tissue (TT) cryopreservation. SSC transplantation (SSCT), TT grafting and recent advances in in vitro spermatogenesis have opened new possibilities to restore fertility in humans. However, these techniques are still at a research stage and their efficiency depends on the amount of SSCs available for fertility restoration. Therefore, maintaining the number of SSCs is a critical step in human fertility preservation. Standardizing a successful cryopreservation method for TT and testicular cell suspensions (TCSs) is most important before any clinical application of fertility restoration could be successful. This review gives an overview of existing cryopreservation protocols used in different animal models and humans. Cell recovery, cell viability, tissue integrity and functional assays are taken into account. Additionally, biosafety and current perspectives in male fertility preservation are discussed. An extensive PubMED and MEDline database search was conducted. Relevant studies linked to the topic were identified by the search terms: cryopreservation, male fertility preservation, (immature)testicular tissue, testicular cell suspension, spermatogonial stem cell, gonadotoxicity, radiotherapy and chemotherapy. The feasibility of fertility restoration techniques using frozen-thawed TT and TCS has been proven in animal models. Efficient protocols for cryopreserving human TT exist and are currently applied in the clinic. For TCSs, the highest post-thaw viability reported after vitrification is 55.6 ± 23.8%. Yet, functional proof of fertility restoration in the human is lacking. In addition, few to no data are available on the safety aspects inherent to offspring generation with gametes derived from frozen-thawed TT or TCSs. Moreover, clarification is needed on whether it is better to cryopreserve TT or TCS. Fertility restoration techniques are very promising and expected to be implemented in the clinic in the near future. However, inter-center variability needs to be overcome and the gametes produced for reproduction purposes need to be subjected to safety studies. With the perspective of a future clinical application, there is a dire need to optimize and standardize cryopreservation and safety testing before using frozen-thawed TT of TCSs for fertility restoration.
Computed Tomography Screening for Lung Cancer
Authors: Ambarish Gopal, Matthew J. Budoff
Journal: JAMA (2007)

To the Editor: In their study of computed tomography (CT) screening and lung cancer outcomes, Dr Bach and colleagues concluded that screening for lung cancer with lowdose CT may increase the rate of lung cancer diagnosis and treatment, but may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. The authors also stated that until more conclusive data are available, asymptomatic individuals should not be screened outside of clinical research studies that have a reasonable likelihood of further clarifying the potential benefits and risks. While the intent of cardiac CT angiography is to visualize the coronary, aortic, and cardiac structures, there are portions of lungs visible on the scan. Since cardiac CT is primarily obtained with a small field of view (to maximize coronary visualization with highest spatial resolution), some have argued to reconstruct a small-field-of-view series for coronary arteries to maximize spatial resolution and another series with a larger field of view to include lungs, mediastinum, and bone structures. The suggested benefits of a routine large-field reconstruction to evaluate the extracardiac structures for incidental findings have not been scientifically validated and come from anecdotal experiences. Despite this, routine large-field reconstruction of the lung fields has been suggested as an ethical or medicolegal mandate. Studies of screening lung CT in older smokers have found a prevalence of cancer between 0.3% and 1%. However, when applied to an ambulatory population of patients presenting for an evaluation of coronary artery disease, the prevalence of lung cancer or significant noncardiac findings should be significantly lower in this low-risk predominantly nonsmoker population. Studies such as Bach et al should provide strong evidence that visualization of more (potentially benign) abnormalities cannot be assumed to lead to better outcomes. Large-field-of-view reconstructions on CT angiography should be viewed with even more skepticism than lung cancer screening studies, because the prevalence of disease will be even lower, and the false-positive rate higher. Current evidence suggests it is most prudent not to specifically reconstruct and reread CT angiography scans for lung nodules, given the possibility of doing more harm than good.
Effect of Educational Intervention on the Rate of Rarely Appropriate Outpatient Echocardiograms Ordered by Attending Academic Cardiologists
Authors: David M. Dudzinski, R. Sacha Bhatia, Michael Y. Mi, Eric M. Isselbacher, Michael H. Picard, Rory B. Weiner
Journal: JAMA Cardiology (2016)

Appropriate use criteria-based educational initiatives have been shown to improve transthoracic echocardiography (TTE) ordering practices of physicians in training. Whether such an intervention is successful with attending cardiologists remains unknown.To prospectively investigate the effect of an appropriate use criteria-based educational intervention on ordering of outpatient TTEs by attending academic cardiologists.We conducted a prospective, randomized clinical trial of an educational intervention designed to reduce the number of outpatient TTEs that were deemed to be rarely appropriate by published appropriate use criteria. Investigators classifying TTEs were blinded to participant groupings. The study was conducted within the cardiology division at the Massachusetts General Hospital, an academic quaternary care hospital. Staff members of the cardiology division were included; 66 cardiologists were randomized. The study was conducted from November 19, 2013, to June 1, 2014. An analysis of the evaluable population was performed.The appropriate use criteria-based educational intervention consisted of a review lecture and electronic information card, as well as monthly individual physician feedback via email. The email described the percentage of rarely appropriate TTEs as well as the appropriate use criteria rationale for classifying studies as rarely appropriate.We hypothesized a priori that the educational intervention would reduce the number of rarely appropriate TTEs. The primary outcome was the rate of rarely appropriate TTEs.Of the 66 cardiologists enrolled in the study, 65 were included in the analysis (1 intervention cardiologist retired from practice during the study). The participants' mean (SD) age was 50.6 (10.5) years; 48 (73%) were men. Following intervention, the proportion of rarely appropriate TTEs was significantly lower in the intervention vs control group (143 of 1359 [10.5%] vs 285 of 1728 [16.5%]; odds ratio [OR], 0.59 [95% CI, 0.39-0.88]; P = .01), and there was a nonsignificant increase in the proportion of appropriate TTEs in the intervention vs control group (1054 [77.6%] vs 1244 [72.0%]; OR, 1.38 [95% CI, 0.93-2.05]; P = .11). The most common of the 428 rarely appropriate indications were routine surveillance within 3 years after prosthetic valve insertion (73 [17.1%]), routine surveillance within 1 year for moderate or severe valvular stenosis (64 [15.0%]), and routine surveillance of cardiomyopathy (45 [10.5%]) or ventricular function (36 [8.4%]).An appropriate use criteria-based educational and feedback intervention reduced the number of rarely appropriate TTEs ordered by attending academic cardiologists. This strategy may be feasible to improve TTE utilization among cardiologists, and this type of intervention warrants study in other practice environments.clinicalrials.gov Identifier: NCT01968642.
Australian medical leaders call for urgent action on reports of abuse of immigrant detainees
Authors: Michael Woodhead
Journal: BMJ (2016)

Leaked reports of horrific conditions and widespread abuse of asylum seekers in an Australian immigration detention centre have prompted calls from medical groups to open up the camps to independent oversight.

Michael Gannon, president of the Australian Medical Association (AMA), said that the government needed to respond urgently to the 2000 incident reports compiled by staff of the Nauru offshore processing centre that showed that detainees, including women and children, were experiencing abuse, trauma, self harm, sexual assault, inadequate health services, and deplorable living conditions.

“These disturbing reports echo long held concerns by the AMA about the lack of proper physical and mental healthcare being provided to people in immigration detention,” Gannon said in response to the reports published by the Guardian newspaper.1

Gannon said that there was too much secrecy around immigration detention centres, and he called on the Australian government …
Long-term Survival Following Bariatric Surgery in the VA Health System
Authors: Sameer B. Murali
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mechanistic Studies of Viral Entry: An Overview of Dendrimer-Based Microbicides As Entry Inhibitors Against Both HIV and HSV-2 Overlapped Infections
Authors: Daniel Sepúlveda-Crespo, Rafael Ceña-Díez, José Luis Jiménez, Ma Ángeles Muñoz-Fernández
Journal: Medicinal Research Reviews (2016)

This review provides an overview of the development of different dendrimers, mainly polyanionic, against human immunodeficiency virus (HIV) and genital herpes (HSV-2) as topical microbicides targeting the viral entry process. Vaginal topical microbicides to prevent sexually transmitted infections such as HIV and HSV-2 are urgently needed. To inhibit HIV/HSV-2 entry processes, new preventive targets have been established to maximize the current therapies against wild-type and drug-resistant viruses. The entry of HIV/HSV-2 into target cells is a multistep process that triggers a cascade of molecular interactions between viral envelope proteins and cell surface receptors. Polyanionic dendrimers are highly branched nanocompounds with potent activity against HIV/HSV-2. Inhibitors of each entry step have been identified with regard to generations and surface groups, and possible roles for these agents in anti-HIV/HSV-2 therapies have also been discussed. Four potential binding sites for impeding HIV infection (HSPG, DC-SIGN, GSL, and CD4/gp120 inhibitors) and HSV-2 infection (HS, gB, gD, and gH/gL inhibitors) exist according to their mechanisms of action and structures. This review clarifies that inhibition of HIV/HSV-2 entry continues to be a promising target for drug development because nanotechnology can transform the field of HIV/HSV-2 prevention by improving the efficacy of the currently available antiviral treatments.
The Major Phagocyte Peroxidase-Derived Oxidant HOSCN Stimulates Gene-Specific p38 MAPK- Dependent, NF-κb-Mediated Activation of Tissue Factor, VCAM-1 and ICAM-1 Expression In Endothelium.
Authors: Teena Rehani, Adria Jonas, Arne Slungaard
Journal: Blood (2010)
Monitoring asthma: no matter how?
Authors: Lara S. van den Wijngaart, Jolt Roukema, Peter J.F.M. Merkus
Journal: European Respiratory Journal (2016)

The ultimate goal of asthma care is to obtain and maintain control, and optimise prognosis for patients [1]. Monitoring and treatment adjustments tailored to patients' needs and wishes are essential to achieve controlled asthma and are therefore a fundamental part of comprehensive asthma management. However, the best strategy for asthma monitoring and its frequency are still unknown [2]. In daily practice, healthcare professionals combine scheduled routine clinical visits, lung function tests, repeated targeted education and questionnaires to evaluate asthma control and/or quality of life. Furthermore, adherence to treatment is strongly associated with asthma control [1, 3]. Although proper treatment of asthma could prevent exacerbations, several studies have suggested that the majority of patients do not have adequate control of their disease [4]. For a large part, this may be explained by suboptimal adherence; in patients with asthma adherence varies between 30 and 70% [5–7]. Monitoring asthma: towards personalised e-Health! <http://ow.ly/tkaq301VVu8>
FDA Expanded Access Programs for Experimental Medicines
Authors: Stuart L. Nightingale
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Critical Role Of Interleukin Receptor Signaling In Acute Myeloid Leukemia Identified Using An RNAi Functional Screen
Authors: Anupriya Agarwal, Ryan J. Meckenzie, Alyssa Carey, Monika Davare, Christopher A. Eide, Kevin Watanabe-Smith, Rita M. Braziel, Jeffrey W. Tyner, Grover C. Bagby, Brian J. Druker
Journal: Blood (2013)