tbuckley/cabot-search huggingface dataset:
Recommendation of dose banding of cytotoxics according to pharmacokinetic criteria.
Authors: Etienne Chatelut, Melanie White-Koning, Ron H.J. Mathijssen, Sharyn D. Baker, Alex Sparreboom
Journal: Journal of Clinical Oncology (2012)

2549 Background: Dose-banding has been recently suggested in order to optimize chemotherapy preparation. Ranges (or bands) of body surface area (BSA) are predefined. The individual dose of a particular patient is calculated according to a single BSA value per band, usually the mid-point of the BSA band in which the actual BSA of the patient lies. Thanks to this simple procedure, chemotherapy provision can be rationalized and chemotherapies can be prepared in advance for drugs with sufficient long-term drug stability. The primary purpose of dose-banding is to reduce patient waiting time and improve capacity planning of the pharmacy production, but additional benefits can also be found, such as reduced potential for medication errors, reduced drug wastage, and prospective quality control of preparations. The objective of this analysis was to compare dose-banding to individual BSA-dosing (current practice) according to pharmacokinetic (PK) criteria. Methods: Dose-banding was defined according to three bands of BSA: BSA&lt;1.7m², 1.7m²≤BSA&lt;1.9m², and BSA≥1.9m² for which the values of 1.55m², 1.80m², and 2.05m² were allocated, respectively. By using individual actual values of clearance of six drugs (cisplatin, docetaxel, paclitaxel, doxorubicin, topotecan, and irinotecan) from a total of 1,206 adult cancer patients, the AUCs corresponding to the two dosing methods were compared to a target value of AUC for each drug. Results: Over all 6 drugs, by using dose-banding the percent change of individual dose in comparison with BSA dosing ranged between -14% and +22%. In terms of capacity to attain the target AUC, there was no significant difference in precision when using dose-banding as compared to BSA-dosing for all drugs except paclitaxel (precision of 23.2% versus 21.8%, respectively). For all drugs including paclitaxel, distributions of AUC values were very similar with both dosing methods. Conclusions: For these 6 drugs and maybe others, dose-banding may be implemented without any risk of increasing interindividual plasma exposure. Dose-banding would make it possible to anticipate chemotherapy preparation and analytical control without any delay for the patients.
Malária importada no Reino Unido, em 1996
Authors: D J Bradley, D C Warhurst, M Blaze, V Smith, J Williams
Journal: Eurosurveillance (1998)

Virtualmente, todas as infeccoes de malaria identificadas no Reino Unido, nos ultimos anos, foram contraidas noutros continentes e importadas para o Reino Unido, a excepcao de dois casos em 1976, devidos a importacao de mosquitos infectados e casos ocasionais de malaria congenita ou tranfusional.
Dual Targeting of Acute Leukemia and Supporting Niche by CXCR4-Directed Theranostics
Authors: Stefan Habringer, Constantin Lapa, Peter Herhaus, Margret Schottelius, Rouzanna Istvanffy, Katja Steiger, Julia Slotta-Huspenina, Andreas Schirbel, Heribert Hänscheid, Stefan Kircher, Andreas K. Buck, Katharina Götze, Binje Vick, Irmela Jeremias, Markus Schwaiger, Christian Peschel, Robert Oostendorp, Hans-Jürgen Wester, Götz-Ulrich Grigoleit, Ulrich Keller
Journal: Theranostics (2017)

C-X-C chemokine receptor 4 (CXCR4) is a transmembrane receptor with pivotal roles in cell homing and hematopoiesis.CXCR4 is also involved in survival, proliferation and dissemination of cancer, including acute lymphoblastic and myeloid leukemia (ALL, AML).Relapsed/refractory ALL and AML are frequently resistant to conventional therapy and novel highly active strategies are urgently needed to overcome resistance.Methods: We used patient-derived (PDX) and cell line-based xenograft mouse models of ALL and AML to evaluate the efficacy and toxicity of a CXCR4-targeted endoradiotherapy (ERT) theranostic approach.Results: The positron emission tomography (PET) tracer 68 Ga-Pentixafor enabled visualization of CXCR4 positive leukemic burden.In xenografts, CXCR4-directed ERT with 177 Lu-Pentixather distributed to leukemia harboring organs and resulted in efficient reduction of leukemia.Despite a substantial in vivo cross-fire effect to the leukemia microenvironment, mesenchymal stem cells (MSCs) subjected to ERT were viable and capable of supporting the growth and differentiation of non-targeted normal hematopoietic cells ex vivo.Finally, three patients with refractory AML after first allogeneic hematopoietic stem cell transplantation (alloSCT) underwent CXCR4-directed ERT resulting in leukemia clearance, second alloSCT, and successful hematopoietic engraftment.Conclusion: Targeting CXCR4 with ERT is feasible and provides a highly efficient means to reduce refractory acute leukemia for subsequent cellular therapies.Prospective clinical trials testing the incorporation of CXCR4 targeting into conditioning regimens for alloSCT are highly warranted.
Polycystin-1 interacts with TAZ to stimulate osteoblastogenesis and inhibit adipogenesis
Authors: Zhousheng Xiao, Jerome Baudry, Li Cao, Jinsong Huang, Hao Chen, Charles R. Yates, Wei Li, Brittany Dong, Christopher M. Waters, Jeremy C. Smith, L. Darryl Quarles
Journal: Journal of Clinical Investigation (2017)

The molecular mechanisms that transduce the osteoblast response to physical forces in the bone microenvironment are poorly understood. Here, we used genetic and pharmacological experiments to determine whether the polycystins PC1 and PC2 (encoded by Pkd1 and Pkd2) and the transcriptional coactivator TAZ form a mechanosensing complex in osteoblasts. Compound-heterozygous mice lacking 1 copy of Pkd1 and Taz exhibited additive decrements in bone mass, impaired osteoblast-mediated bone formation, and enhanced bone marrow fat accumulation. Bone marrow stromal cells and osteoblasts derived from these mice showed impaired osteoblastogenesis and enhanced adipogenesis. Increased extracellular matrix stiffness and application of mechanical stretch to multipotent mesenchymal cells stimulated the nuclear translocation of the PC1 C-terminal tail/TAZ (PC1-CTT/TAZ) complex, leading to increased runt-related transcription factor 2-mediated (Runx2-mediated) osteogenic and decreased PPARγ-dependent adipogenic gene expression. Using structure-based virtual screening, we identified a compound predicted to bind to PC2 in the PC1:PC2 C-terminal tail region with helix:helix interaction. This molecule stimulated polycystin- and TAZ-dependent osteoblastogenesis and inhibited adipogenesis. Thus, we show that polycystins and TAZ integrate at the molecular level to reciprocally regulate osteoblast and adipocyte differentiation, indicating that the polycystins/TAZ complex may be a potential therapeutic target to increase bone mass.
Tracking and protection of transplanted stem cells using a ferrocenecarboxylic acid-conjugated peptide that mimics hTERT
Authors: Hyun-Hee Park, Kyu-Yong Lee, Dong Woo Park, Na-Young Choi, Young Joo Lee, Jeong-Woo Son, Sangjae Kim, Chanil Moon, Hyun-Wook Kim, Im Joo Rhyu, Seong-Ho Koh
Journal: Biomaterials (2017)
Coronary Computed Tomography–Based Fractional Flow Reserve
Authors: Stefan Baumann, Matthias Renker, U. Joseph Schoepf
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Cortical Structures Associated With Human Blood Pressure Control
Authors: Nuria Lacuey, Johnson P. Hampson, Wanchat Theeranaew, Bilal Zonjy, Ajay Vithala, Norma J. Hupp, Kenneth A. Loparo, Jonathan P. Miller, Samden D. Lhatoo
Journal: JAMA Neurology (2017)

A better understanding of the role of cortical structures in blood pressure control may help us understand cardiovascular collapse that may lead to sudden unexpected death in epilepsy (SUDEP).To identify cortical control sites for human blood pressure regulation.Patients with intractable epilepsy undergoing intracranial electrode implantation as a prelude to epilepsy surgery in the Epilepsy Monitoring Unit at University Hospitals Cleveland Medical Center were potential candidates for this study. Inclusion criteria were patients 18 years or older who had electrodes implanted in one or more of the regions of interest and in whom deep brain electrical stimulation was indicated for mapping of ictal onset or eloquent cortex as a part of the presurgical evaluation. Twelve consecutive patients were included in this prospective case series from June 1, 2015, to February 28, 2017.Changes in continuous, noninvasive, beat-by-beat blood pressure parameter responses from amygdala, hippocampal, insular, orbitofrontal, temporal, cingulate, and subcallosal stimulation. Electrocardiogram, arterial oxygen saturation, end-tidal carbon dioxide, nasal airflow, and abdominal and thoracic plethysmography were monitored.Among 12 patients (7 female; mean [SD] age, 44.25 [12.55] years), 9 electrodes (7 left and 2 right) all in Brodmann area 25 (subcallosal neocortex) in 4 patients produced striking systolic hypotensive changes. Well-maintained diastolic arterial blood pressure and narrowed pulse pressure indicated stimulation-induced reduction in sympathetic drive and consequent probable reduction in cardiac output rather than bradycardia or peripheral vasodilation-induced hypotension. Frequency-domain analysis of heart rate and blood pressure variability showed a mixed picture. No other stimulated structure produced significant blood pressure changes.These findings suggest that Brodmann area 25 has a role in lowering systolic blood pressure in humans. It is a potential symptomatogenic zone for peri-ictal hypotension in patients with epilepsy.
BRAF V600E Targetable Mutation in Relapsed/Refractory Multiple Myeloma (R/R MM) Patients: A High Incidence in R/R MM Detected Using Cell Sorting Screening
Authors: Alina Danu, Sophie Cotteret, Ludovic Lacroix, Véronique Saada, Véronique Vergé, Nathalie Auger, Julien Lazarovici, Edith Carton, Jonathan Farhi, Khalil Saleh, David Ghez, Claude Chahine, Jean-Marie Michot, Vincent Ribrag
Journal: Blood (2016)
Suicide in prisons: an international study of prevalence and contributory factors
Authors: Seena Fazel, Taanvi Ramesh, Keith Hawton
Journal: The Lancet Psychiatry (2017)

Prison suicide rates, rate ratios, and associations with prison-related factors need clarification and updating. We examined prison suicide rates in countries where reliable information was available, associations with a range of prison-service and health-service related factors, how these rates compared with the general population, and changes over the past decade.
Erradicación de la tos ferina: un desafío para la salud pública
Authors: S Salmaso
Journal: Eurosurveillance (1999)

La tos ferina y la vacunacion contra esta enfermedad, en particular los ensayos clinicos llevados a cabo en varias regiones de Europa de forma casi simultanea, han suscitado un controvertido debate en los ultimos diez anos. Sin embargo, todavia quedan por aclarar diversos aspectos importantes para la salud publica. Los tres articulos publicados en este numero de Eurosurveillance son buenos ejemplos de las situaciones a las que se enfrentan algunos paises europeos y aportan algunas lecciones, a saber: la introduccion de la vacunacion disminuye la incidencia (como ha ocurrido en Suecia); la evaluacion de la incidencia de la tos ferina puede ser una tarea dificil si se modifican algunos elementos del sistema de vigilancia (en Suiza, se anadio la reaccion en cadena de polimerasas (polymerase chain reaction; - PCR- ) para mejorar la especificidad del diagnostico y en los Paises Bajos se anadieron criterios serologicos); los brotes pueden surgir incluso con una alta tasa de vacunacion constante (como en los Paises Bajos).
A CD103+ Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis
Authors: Xavier Clemente-Casares, Siyavash Hosseinzadeh, Iulia Barbu, Sarah A. Dick, Jillian A. Macklin, Yiming Wang, Abdul Momen, Crystal Kantores, Laura Aronoff, Maylis Farno, Tiffany M. Lucas, Joan Avery, Dorrin Zarrin-Khat, Heidi J. Elsaesser, Babak Razani, Kory J. Lavine, Mansoor Husain, David G. Brooks, Clinton S. Robbins, Myron Cybulsky, Slava Epelman
Journal: Immunity (2017)
Reply to Joshua A. Linscott, Angela B. Smith, and Jesse D. Sammon's Letter to the Editor re: Woonyoung Choi, Andrea Ochoa, David J. McConkey, et al. Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset. Eur Urol 2017;72:354–65
Authors: Woonyoung Choi, David McConkey
Journal: European Urology (2017)
All stakeholders must commit to improving research integrity, medical editors tell MPs
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Medical journals, researchers, academic institutions, and funders must share responsibility for improving research integrity, senior academic editors have told MPs.

Giving evidence to the House of Commons Science and Technology Committee’s inquiry into research integrity on 21 November, medical editors said that the push for greater research transparency required a commitment from everyone involved in academic publishing.

Among those giving evidence was The BMJ ’s director of academic outreach, Trish Groves, who said that leading journals could help drive improvements by adopting an advocacy role to help “change the culture.”

Catriona Fennell, director of publishing services at Elsevier, representing the Publishers Association, told MPs that the …
Glecaprevir/Pibrentasvir in patients with hepatitis C virus genotype 1 or 4 and past direct‐acting antiviral treatment failure
Authors: Fred Poordad, Stanislas Pol, Armen Asatryan, Maria Buti, David Shaw, Christophe Hézode, Franco Felizarta, Robert W. Reindollar, Stuart C. Gordon, Stephen Pianko, Michael W. Fried, David E. Bernstein, Joel Gallant, Chih‐Wei Lin, Yang Lei, Teresa I. Ng, Preethi Krishnan, Sarah Kopecky‐Bromberg, Jens Kort, Federico J. Mensa
Journal: Hepatology (2017)

Patients with hepatitis C virus (HCV) who have virological failure (VF) after treatment containing a nonstructural protein 5A (NS5A) inhibitor have limited retreatment options. MAGELLAN‐1 Part 2 was a randomized, open‐label, phase 3 study to evaluate the efficacy and safety of ribavirin (RBV)‐free glecaprevir and pibrentasvir (G/P; 300 mg/120 mg) in patients with chronic HCV and past VF on at least one NS3/4A protease and/or NS5A inhibitor‐containing therapy. Patients with compensated liver disease, with or without cirrhosis, and HCV genotype (GT) 1, 4, 5, or 6 were randomized 1:1 to receive 12 or 16 weeks of G/P. The primary endpoint was sustained virological response (SVR) at 12 weeks posttreatment (SVR12). Among 91 patients treated, 87 had GT1 and 4 had GT4 infection. SVR12 was achieved by 89% (39 of 44) and 91% (43 of 47) of patients who received 12 and 16 weeks of G/P, respectively. Virological relapse occurred in 9% (4 of 44) of patients treated with 12 weeks of G/P; there were no relapses with 16 weeks of treatment. Past treatment history with one class of inhibitor (protease or NS5A) had no impact on SVR12, whereas past treatment with both classes of inhibitors was associated with lower SVR12 rate. The most common adverse event (AE) was headache (≥10% of patients), and there were no serious AEs assessed as related to study drugs or AEs leading to discontinuation. Conclusion: Sixteen weeks of G/P treatment achieved a high SVR12 rate in patients with HCV GT1 infection and past failure to regimens containing either NS5A inhibitors or NS3 protease inhibitors. (Hepatology 2018;67:1253‐1260)
The effects of insulin receptor substrate -1 regulation on cell cycle progression in non-small cell lung cancer
Authors: Jeong-Hee Jeon, Yoon Soo Chang, Se Kyu Kim, Hyung Jung Kim, Joon Chang, Chul Min Ahn, Sung Kyu Kim
Journal: Cancer Research (2007)

5205   Purposes : When Insulin receptor substrae-1(IRS-1), major adaptor protein of Insulin growth factor receptor (IGF receptor), was regulated  si RNA and okadaic acid (OA). We investigated the effects of IRS-1 phosphorylation, downstream signaling pathway of IGF-axis. AlsoWe tested effects on cell cycle.  Methods : Using Non-small cell lung cancer 460 and Cos7, we confirmed the effects on cell proliferation with OA treatment by using MTT assay. Anti IRS-1 treatment,  siRNA , repressed IRS-1 protein, and the effects on phosphorylation and expressiom of protein stimulating OA and  siRNA  by using western blotting. Furthermore, the effects on cell cycle progression was studid flow cytometry.  Results :  1. Treatment of NCI-H 460 and Cos7 with OA induced dose-dependent cell proliferation until 5nM. This result exhibited increase about 20% compared control.  2. IRS-1 band intensity did not change but, p ser 307 IRS-1 was phosphorylated 4h after OA treatment, but not p tyr 632 IRS-1. Namely, change in magnitude of phosphorylation of p ser 307 IRS-1 was not due to chages in IRS-1 protein level.  3. OA induced not AKT and GSK3β phosphorylation, but MAP kinase phosphotylation. Phosphorylation level of MAP kinase have no relevance to MAP kinase protein volume.  4. Anti IRS-1,  siRNA , inhibited IRS-1 protein expression.  Because OA treatment and IRS-1 knockdown have influence on cell cycle, treatment of  siRNA  repressed entry from G0-G1 phase to S phase but OA- stimulated cells promoted cell cycle from S phase to G2-M phase, and treatment of them recovered cell cycle repression from S phase to G2-M phase.  Conclusion : OA-stimulated NCI-H460 and Cos7 induced p ser 307 IRS-1. By inducing p ser 307 IRS-1 in OA-stimulated cells, MAP kinase was activated, and induced proteins regulating cell cycle. So we confirmed OA induced entry from S phase to G2-M phase. In addition, regardless of IRS-1, OA prompted cell cycle from S phase to G2-M phase.
Cost-Effectiveness of Publicly Funded Treatment of Opioid Use Disorder in California
Authors: Emanuel Krebs, Benjamin Enns, Elizabeth Evans, Darren Urada, M. Douglas Anglin, Richard A. Rawson, Yih-Ing Hser, Bohdan Nosyk
Journal: Annals of Internal Medicine (2017)

Background: Only 1 in 5 of the nearly 2.4 million Americans with an opioid use disorder received treatment in 2015. Fewer than half of Californians who received treatment in 2014 received opioid agonist treatment (OAT), and regulations for admission to OAT in California are more stringent than federal regulations. Objective: To determine the cost-effectiveness of OAT for all treatment recipients compared with the observed standard of care for patients presenting with opioid use disorder to California's publicly funded treatment facilities. Design: Model-based cost-effectiveness analysis. Data Sources: Linked population-level administrative databases capturing treatment and criminal justice records for California (2006 to 2010); published literature. Target Population: Persons initially presenting for publicly funded treatment of opioid use disorder. Time Horizon: Lifetime. Perspective: Societal. Intervention: Immediate access to OAT with methadone for all treatment recipients compared with the observed standard of care (54.3% initiate opioid use disorder treatment with medically managed withdrawal). Outcome Measures: Discounted quality-adjusted life-years (QALYs) and discounted costs. Results of Base-Case Analysis: Immediate access to OAT for all treatment recipients costs less (by $78 257), with patients accumulating more QALYs (by 0.42) than with the observed standard of care. In a hypothetical scenario where all Californians starting treatment of opioid use disorder in 2014 had immediate access to OAT, total lifetime savings for this cohort could be as high as $3.8 billion. Results of Sensitivity Analysis: 99.6% of the 2000 simulations resulted in lower costs and more QALYs. Limitation: Nonrandomized delivery of OAT or medically managed withdrawal. Conclusion: The value of publicly funded treatment of opioid use disorder in California is maximized when OAT is delivered to all patients presenting for treatment, providing greater health benefits and cost savings than the observed standard of care. Primary Funding Source: National Institute on Drug Abuse.
P2.06-018 Multicenter, Single-Arm Phase II Study of Nab-Paclitaxel/Carboplatin in Untreated PS2 Patients with Advanced NSCLC: TORG1426
Authors: Yasuko Ichikawa, Nobuhiko Seki, Shinobu Hosokawa, Akihiro Bessho, Tsuneo Shimokawa, Hiroaki Okamoto, Sakiko Otani, Yoshiro Nakahara, Makiko Yomota, Yukio Hosomi, Kyoko Murase, Kazuma Kishi, Shunichiro Iwasawa, Takashi Nishimura, Takashi Kasai, Yoichi Nakamura, Koshiro Watanabe
Journal: Journal of Thoracic Oncology (2017)
Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepatitis
Authors: Johannes Hartl, Hanno Ehlken, Marcial Sebode, Moritz Peiseler, Till Krech, Roman Zenouzi, Johann von Felden, Christina Weiler-Normann, Christoph Schramm, Ansgar W. Lohse
Journal: Journal of Hepatology (2017)