tbuckley/cabot-search huggingface dataset:
Modeling cost‐effectiveness and health gains of a “universal” versus “prioritized” hepatitis C virus treatment policy in a real‐life cohort
Authors: Loreta A. Kondili, Federica Romano, Francesca Romana Rolli, Matteo Ruggeri, Stefano Rosato, Maurizia Rossana Brunetto, Anna Linda Zignego, Alessia Ciancio, Alfredo Di Leo, Giovanni Raimondo, Carlo Ferrari, Gloria Taliani, Guglielmo Borgia, Teresa Antonia Santantonio, Pierluigi Blanc, Giovanni Battista Gaeta, Antonio Gasbarrini, Luchino Chessa, Elke Maria Erne, Erica Villa, Donatella Ieluzzi, Francesco Paolo Russo, Pietro Andreone, Maria Vinci, Carmine Coppola, Liliana Chemello, Salvatore Madonia, Gabriella Verucchi, Marcello Persico, Massimo Zuin, Massimo Puoti, Alfredo Alberti, Gerardo Nardone, Marco Massari, Giuseppe Montalto, Giuseppe Foti, Maria Grazia Rumi, Maria Giovanna Quaranta, Americo Cicchetti, Antonio Craxì, Stefano Vella
Journal: Hepatology (2017)

We evaluated the cost‐effectiveness of two alternative direct‐acting antiviral (DAA) treatment policies in a real‐life cohort of hepatitis C virus–infected patients: policy 1, “universal,” treat all patients, regardless of fibrosis stage; policy 2, treat only “prioritized” patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus–infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies’ cost‐effectiveness. The patients’ age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality‐adjusted life‐years (QALY) and incremental cost‐effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country‐specific health states costs and mean treatment cost of €30,000. For the Italian base‐case analysis, the cost‐effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost‐effective in 94%‐97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0‐F3 post–sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost‐saving for the base price (€15,000) discounts of at least 75% applied in patients with F0‐F2 fibrosis. Conclusion : Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost‐effective; cost‐effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (H epatology 2017;66:1814–1825)
Local Modulation of Antigen-Presenting Cell Development after Resolution of Pneumonia Induces Long-Term Susceptibility to Secondary Infections
Authors: Antoine Roquilly, Hamish E.G. McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H. Lahoud, Gabrielle T. Belz, Axel Kallies, Justine D. Mintern, Karim Asehnoune, Jose A. Villadangos
Journal: Immunity (2017)
Gene regulation in adult neural stem cells. Current challenges and possible applications
Authors: Juan Manuel Encinas, Carlos P. Fitzsimons
Journal: Advanced Drug Delivery Reviews (2017)

Adult neural stem and progenitor cells (NSPCs) offer a unique opportunity for neural regeneration and niche modification in physiopathological conditions, harnessing the capability to modify from neuronal circuits to glial scar. Findings exposing the vast plasticity and potential of NSPCs have accumulated over the past years and we currently know that adult NSPCs can naturally give rise not only to neurons but also to astrocytes and reactive astrocytes, and eventually to oligodendrocytes through genetic manipulation. We can consider NSPCs as endogenous flexible tools to fight against neurodegenerative and neurological disorders and aging. In addition, NSPCs can be considered as active agents contributing to chronic brain alterations and as relevant cell populations to be preserved, so that their main function, neurogenesis, is not lost in damage or disease. Altogether we believe that learning to manipulate NSPC is essential to prevent, ameliorate or restore some of the cognitive deficits associated with brain disease and injury, and therefore should be considered as target for future therapeutic strategies. The first step to accomplish this goal is to target them specifically, by unveiling and understanding their unique markers and signaling pathways.
Impact of Point-of-Care Xpert MTB/RIF on Tuberculosis Treatment Initiation. A Cluster-randomized Trial
Authors: Richard J. Lessells, Graham S. Cooke, Nuala McGrath, Mark P. Nicol, Marie-Louise Newell, Peter Godfrey-Faussett
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Point-of-care (POC) diagnostics have the potential to reduce pretreatment loss to follow-up and delays to initiation of appropriate tuberculosis (TB) treatment.To evaluate the effect of a POC diagnostic strategy on initiation of appropriate TB treatment.We conducted a cluster-randomized trial of adults with cough who were HIV positive and/or at high risk of drug-resistant TB. Two-week time blocks were randomized to two strategies: (1) Xpert MTB/RIF test (Cepheid, Sunnyvale, CA) performed at a district hospital laboratory or (2) POC Xpert MTB/RIF test performed at a primary health care clinic. All participants provided two sputum specimens: one for the Xpert test and the other for culture as a reference standard. The primary outcome was the proportion of participants with culture-positive pulmonary tuberculosis (PTB) initiated on appropriate TB treatment within 30 days.Between August 22, 2011, and March 1, 2013, 36 two-week blocks were randomized, and 1,297 individuals were enrolled (646 in the laboratory arm, 651 in the POC arm), 159 (12.4%) of whom had culture-positive PTB. The proportions of participants with culture-positive PTB initiated on appropriate TB treatment within 30 days were 76.5% in the laboratory arm and 79.5% in the POC arm (odds ratio, 1.13; 95% confidence interval, 0.51-2.53; P = 0.76; risk difference, 3.1%; 95% confidence interval, -16.2 to 10.1). The median time to initiation of appropriate treatment was 7 days (laboratory) versus 1 day (POC).POC positioning of the Xpert test led to more rapid initiation of appropriate TB treatment. Achieving one-stop diagnosis and treatment for all people with TB will require simpler, more sensitive diagnostics and broader strengthening of health systems. Clinical trial registered with www.isrctn.com (ISRCTN 18642314) and www.sanctr.gov.za (DOH-27-0711-3568).
Serum neurofilament light chain: a biomarker of neuronal injury in vasculitic neuropathy
Authors: Antje Bischof, Tobias Manigold, Christian Barro, Ingmar Heijnen, Christoph T Berger, Tobias Derfuss, Jens Kuhle, Thomas Daikeler
Journal: Annals of the Rheumatic Diseases (2017)

Peripheral nerve biopsy remains the gold standard for diagnosing vasculitic neuropathy (VN).1 This procedure is invasive, of limited sensitivity and not always feasible.2 A biomarker indicating acute axonal loss in patients with systemic vasculitis would allow rapid screening and adjustments of diagnostic or treatment strategies, potentially improving clinical outcome.3 

Neurofilaments are structural proteins specific to neurons that are released into blood and cerebrospinal fluid following neuronal damage. They have been suggested as a biomarker in various neurological diseases, mainly affecting the central nervous system.4–6 In patients with multiple sclerosis, serum neurofilament light chain (sNfL) levels correlated with MRI and clinical disease activity/severity, were lower in patients under treatment and showed potential to predict future disease activity and disability.5 

In this retrospective study we aimed to test whether sNfL could serve as a marker of vasculitic damage of peripheral nerves and/or disease activity in patients with VN. Patients were recruited from our prospective local ethical board-approved vasculitis …
Alan McCall #FootballScience #aBitWeird
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2017)

Building a professional football team from scratch with a very small team of people (Archie Fraser, Rob Middleby, Han Berger, Jonathan Crisp). Everything from developing the playing philosophy to scouting/recruiting players, hiring coaches/staff and setting up the club’s medical and science department! It hit me most at my ‘farewell’ dinner—looking around at tables full of players and staff, turning to the Football Director and thinking “We helped build this”. A once in a professional-lifetime experience.

Enroll in the dance course at school…. it’s free, you’re young, and you’ll learn much easier! If you wait you’ll have to pay money and it won’t be so easy!

Wake up early(ish), shower, meditate/mindfulness, go for a good walk, drink a nice coffee and plan to take over the world/the rest of the day!

Being lucky enough to be part of the Australia National Team at the Brazil 2014 World Cup. Singing the national anthem while standing in the dugout with arms around Aussie friends/colleagues. Even though I am Scottish, I’m also known as Aussie Al by some, so that was quite a patriotic moment for my Aussie side!

I hope, so far, bringing the field and research closer together. I hope that by giving practitioners a voice I will encourage more meaningful research that …
Gender Confirmation Surgery and Terminology in Transgender Health—Reply
Authors: Jens Urs Berli, Gail Knudson, Loren Schechter
Journal: JAMA Surgery (2017)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Legalization of Same-Sex Marriage and Drop in Adolescent Suicide Rates: Association but Not Causation
Authors: Joseph Kamtchum-Tatuene, Jean Jacques Noubiap, Yannick F. Fogang
Journal: JAMA Pediatrics (2017)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Dimethyl fumarate modulates neutrophil extracellular trap formation in a glutathione‐ and superoxide‐dependent manner
Authors: J.H.O. Hoffmann, K. Schaekel, D. Hartl, A.H. Enk, E.N. Hadaschik
Journal: British Journal of Dermatology (2017)

Neutrophil (polymorphonuclear) granulocytes (PMN) have been shown to contribute to the pathogenesis of psoriasis by releasing interleukin‐17 and LL37‐DNA complexes via neutrophil extracellular traps (NETs), webs of chromatin strands decorated with antimicrobial peptides, in psoriatic skin. Fumaderm®, a fumaric acid ester (FAE) formulation consisting of different FAE salts, has been successfully used to treat psoriasis for decades. Most recently, FAE treatment was reported to inhibit NET formation in murine epidermolysis bullosa acquisita. To elucidate the effect of FAE treatment on human psoriasis and healthy donor NET formation. Among the compounds present in the FAE formulation, dimethyl fumarate (DMF) pretreatment of human psoriasis and healthy donor PMN resulted in a consistent inhibitory effect on NET formation in response to phorbol 12‐myristate 13‐acetate but not to platelet activating factor and ionomycin. This effect was l‐glutathione (GSH) dependent and involved a decrease in reactive oxygen species (ROS) production, a key event in NET formation. In contrast, G‐protein‐coupled signalling and protein synthesis were not involved. Monomethyl fumarate (MMF) was found to slightly reduce ROS production without affecting NET formation. We report DMF as a potent, stimulus‐specific, GSH‐ and ROS‐dependent modulator of NET formation. Our results support the notion that modulation of NET formation contributes to the beneficial effects of FAEs in a variety of inflammatory conditions.
Abstract 170: Mechanism of Cardiotoxicity of Tyrosine Kinase Inhibitors
Authors: Manar F Elmadani, Johanna Ulvila, Suleiman Khan, Tarja Alakoski, Johanna Magga, Tero Aitokallio, Krister Wennerberg, Risto Kerkelä
Journal: Circulation Research (2015)

Aim: It is becoming evident that many of the signaling elements driving cancer cell division, for which kinase inhibitors (KIs) are targeted, are the same as those necessary for cardiomyocyte viability. Adverse cardiac events have been reported for a number of KIs. Aim of this study was to identify KIs that induce toxicity to cardiomyocytes and to elucidate the central molecular mechanisms mediating the toxicity. Methods: 288 anti-cancer agents (123 are KIs) were screened for their ability to induce cardiotoxicity in cultured primary cardiomyocytes. Cell viability assay was done by measuring the ATP levels in cardiomyocytes after exposure of cells to a 3-log concentration range of each compound for 24 hours. Toxicity data was combined with kinase profiling data to identify protein kinases mediating the toxicity of KIs. In parallel, the molecular mechanism mediating the cardiomyocyte toxicity of dasatinib, a second generation Bcr-Abl and Src family tyrosine kinase inhibitor, was investigated. The role of Src kinase in regulation of cardiomyocyte viability was analyzed by siRNA-mediated Src knockdown. Overexpression of wild type Src and dasatinib- resistant Src in cardiomyocytes was performed to investigate the role of Src in regulating the cardiomyocyte toxicity of dasatinib. Western blotting was used to investigate for downstream signaling targets of Src. Results: Of the KIs, 70 compounds decreased the cardiomyocyte viability by 10-80 %. The kinase profiling data showed that IGF1R, MEK/ERK pathway, PI3K and Src kinases are the key kinases regulating cardiomyocyte viability. Dasatinib treatment dose-dependently increased cardiomyocyte death. Depletion of Src by siRNA also reduced cardiomyocyte viability. Dasatinib treatment attenuated FGF induced ERK phosphorylation. Overexpression of dasatinib-resistant mutant of Src, but not wild type Src, protected the cardiomyocyte from dasatinib toxicity and rescued the FGF-induced ERK phosphorylation. Conclusions: Cardiomyocyte toxicity of KIs can be attributed to inhibition of IGF1R, MEK/ERK pathway, PI3Ks and Src family kinases. Cardiomyocyte toxicity of dasatinib is mediated by Src kinase inhibition which in turn attenuates MEK/ERK pathway signalling.
Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with early breast cancer
Authors: A. Shamseddine, F. Jamali, N. El-Saghir, M. Seoud, J. Abbas, M. Khalifeh, A. Tawil, F. Geara, Z. Salem, H. Hatoum
Journal: Journal of Clinical Oncology (2009)

e22084 Background: The status of the axillary lymph nodes (ALN) in early (stage I and II) breast cancer (BC) patients remains the single most important determinant of overall survival (OS). While the absolute number of positive ALN has been demonstrated to have a significant prognostic impact, new emerging data supports the role of axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. Methods: We conducted a single-center retrospective review of 1,255 BC patients and analyzed 930 patients with early BC admitted to American University of Beirut Medical Center between 1983 and 2001. Data included age at diagnosis, type of mastectomy, ALN involvement, use of chemotherapy, hormonal therapy, post-operative radiation therapy, tumor size, histological type and grade, lympho-vascular invasion status, hormonal receptor status, and Her-2/neu overexpression and the calculated ALNR (number of positive ALN / total number of excised ALN). Patients were subdivided into 3 groups according to ALNR value (&lt; 0.25, 0.25–0.49, 0.50–1.00). The status of the axillary lymph nodes was analyzed with respect to 5- and 10-year OS. Results: On univariate analysis both the absolute number of positive ALN and the ALNR were significant predictors of OS .The 5- year OS of patients with ALNRs of &lt; 0.25, 0.25–0.49 and 0.50–1.00 was 88%, 72% and 65 % respectively and the 10-year OS was 83%,54% and 51 % respectively . On multivariate analysis only the ALNR remained an independent predictor of overall survival, with a 2.7- and 3.16-fold risk of dying at ALNRs of 0.25 and 0.5, respectively. Conclusions: Our study demonstrated that the ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes. ALNR may aid in subdividing patients with positive ALN into low and high risk groups, with potential implications on their subsequent adjuvant management. No significant financial relationships to disclose.
EFFICACY AND SAFETY OF LAMIVUDINE PLUS ADEFOVIR DE NOVO COMBINATION THERAPY COMPARED TO ENTECAVIR MONOTHERAPY IN CHRONIC HEPATITIS B: A SINGLE CENTRE CLINICAL PRACTICE EXPERIENCE
Authors: Ivana Carey, Andrea Mendes, Sarah Hughes, Astrid Scalori, Abid Suddle, Kosh Agarwal, Phillip M. Harrison
Journal: Hepatology (2009)
Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes
Authors: Alfonso Blázquez-Moreno, Adriana Pérez-Portilla, Miriam Agúndez-Llaca, Daniela Dukovska, Mar Valés-Gómez, Cigdem Aydogmus, Aydan Ikinciogullari, José R. Regueiro, Hugh T. Reyburn
Journal: Blood (2017)
Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis
Authors: Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G. Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B. Ivashkiv
Journal: Immunity (2017)

Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine-driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F-metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction.
Simultaneous Inhibition of PI3Kδ and PI3Kα Induces ABC-DLBCL Regression Via Attenuation of BCR-Dependent and Independent Activation of NF-Kb and AKT
Authors: Juliane Paul, Maurice Sojoun, Antje M Wengner, Sabine Zitzmann-Kolbe, Andrea Sturz, Katja Haike, Magdalene H-K Koh, Sze-Huey Tan, Lange Martin, Soo-Yong Tan, Soon Thye Lim, Dominik Mumberg, Karl Ziegelbauer, Ningshu Liu
Journal: Blood (2016)