tbuckley/cabot-search huggingface dataset:
Steps Toward Safe Cell Therapy Using Induced Pluripotent Stem Cells
Authors: HideyukiOkano, MasayaNakamura, KenjiYoshida, YoheiOkada, OsahikoTsuji, SatoshiNori, EijiIkeda, ShinyaYamanaka, KyokoMiura
Journal: Circulation Research (2013)

The enthusiasm for producing patient-specific human embryonic stem cells using somatic nuclear transfer has somewhat abated in recent years because of ethical, technical, and political concerns. However, the interest in generating induced pluripotent stem cells (iPSCs), in which pluripotency can be obtained by transcription factor transduction of various somatic cells, has rapidly increased. Human iPSCs are anticipated to open enormous opportunities in the biomedical sciences in terms of cell therapies for regenerative medicine and stem cell modeling of human disease. On the other hand, recent reports have emphasized the pitfalls of iPSC technology, including the potential for genetic and epigenetic abnormalities, tumorigenicity, and immunogenicity of transplanted cells. These constitute serious safety-related concerns for iPSC-based cell therapy. However, preclinical data supporting the safety and efficacy of iPSCs are also accumulating. In this Review, recent achievements and future tasks for safe iPSC-...
Canadian government ordered to release unpublished Tamiflu data in landmark ruling
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The Canadian government has been instructed to release unpublished clinical trial data relating to Tamiflu, Relenza, and three human papillomavirus vaccines immediately, in a landmark ruling hailed as a “major victory” for transparency.

The case was brought by Peter Doshi, assistant professor at the University of Maryland and associate editor of The BMJ , after Health Canada refused his request to obtain unpublished information relating to Tamiflu, Relenza, Gardasil, Gardasil 9, and Cervarix because he would not sign a confidentiality agreement that would have prevented him from disseminating or publishing anything on it.

A federal court judge said it was “unreasonable” for Health Canada to impose a confidentiality requirement as a condition for the disclosure …
Functional Roles of Cav1.3 (α1D) Calcium Channel in Sinoatrial Nodes
Authors: ZhaoZhang, YanfangXu, HaitaoSong, JenniferRodriguez, DipikaTuteja, YoonNamkung, Hee-SupShin, NipavanChiamvimonvat
Journal: Circulation Research (2002)

We directly examined the role of the Cav1.3 (α1D) Ca2+ channel in the sinoatrial (SA) node by using Cav1.3 Ca2+ channel-deficient mice. A previous report has shown that the null mutant (Cav1.3−/−) mice have sinus bradycardia with a prolonged PR interval. In the present study, we show that spontaneous action potentials recorded from the SA nodes show a significant decrease in the beating frequency and rate of diastolic depolarization in Cav1.3−/− mice compared with their heterozygous (Cav1.3+/−) or wild-type (WT, Cav1.3+/+) littermates, suggesting that the deficit is intrinsic to the SA node. Whole-cell L-type Ca2+ currents (ICa,Ls) recorded in single isolated SA node cells from Cav1.3−/− mice show a significant depolarization shift in the activation threshold. The voltage-dependent activation of Cav1.2 (α1C) versus Cav1.3 Ca2+ channel subunits was directly compared by using a heterologous expression system without β coexpression. Similar to the ICa,L recorded in the SA node of Cav1.3−/− mutant mice, the C...
Experimental microbial dysbiosis does not promote disease progression in SIV-infected macaques
Authors: Alexandra M. Ortiz, Jacob K. Flynn, Sarah R. DiNapoli, Ivan Vujkovic-Cvijin, Carly E. Starke, Stephen H. Lai, MacKenzie E. Long, Ornella Sortino, Carol L. Vinton, Joseph C. Mudd, Leslie Johnston, Kathleen Busman-Sahay, Yasmine Belkaid, Jacob D. Estes, Jason M. Brenchley
Journal: Nature Medicine (2018)
Prehospital Damage-Control Resuscitation
Authors: Jeremy W Cannon
Journal: New England Journal of Medicine (2018)

Severe hemorrhage from injury claims the lives of nearly 50,000 Americans every year. Because many of these deaths occur in young, vital people, this number translates to an astounding loss of almost 2,000,000 years of productive life.1 Recent studies indicate that performing temporizing measures to control bleeding, minimizing factors that exacerbate hemorrhage, and shortening the time to definitive hemostasis may prevent some of these deaths, but more research is needed.2 Because most deaths occur within 2 hours after an injury, severe hemorrhage is the ultimate time-sensitive condition. Many different approaches have been taken to solve this vexing problem. The landmark . . .
Percutaneous absorption and brain distribution facilitation of borneol on tetramethylpyrazine in a microemulsion-based transdermal therapeutic system
Authors: Xiaoge Hu, Ning Cheng, Jihui Zhao, Xianghua Piao, Yulu Yan, Qibo Zhang, Kuan Zhou, Yongtai Zhang, Nianping Feng
Journal: Asian Journal of Pharmaceutical Sciences (2018)

In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine (TMP) is enhanced when combined with borneol (BN) in a microemulsion-based transdermal therapeutic system (ME-TTS). The formulation of the TMP and BN microemulsion (TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher (P < 0.05) Cmax and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group (P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.
The Impact of Liraglutide on Diabetes-Related Foot Ulceration and Associated Complications in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events: Results From the LEADER Trial
Authors: Ketan Dhatariya, Stephen C. Bain, John B. Buse, Richard Simpson, Lise Tarnow, Margit Staum Kaltoft, Michael Stellfeld, Karen Tornøe, Richard E. Pratley
Journal: Diabetes Care (2018)

OBJECTIVE Diabetes-related foot ulcers (DFUs) and their sequelae result in large patient and societal burdens. Long-term data determining the efficacy of individual glucose-lowering agents on DFUs are lacking. Using existing data from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, we conducted post hoc analyses assessing the impact of liraglutide versus placebo in people with type 2 diabetes and at high risk of cardiovascular (CV) events on the incidence of DFUs and their sequelae. RESEARCH DESIGN AND METHODS The LEADER trial (NCT01179048) was a randomized, double-blind, multicenter, CV outcomes trial assessing liraglutide (1.8 mg/day) versus placebo, in addition to standard of care, for up to 5 years. Information on DFUs was collected systematically during the trial, and DFU complications were assessed post hoc through reviewing case narratives. RESULTS During a median of 3.8 years’ follow-up, similar proportions of patients reported at least one episode of DFU in the liraglutide and placebo groups (3.8% [176/4,668] versus 4.1% [191/4,672], respectively; hazard ratio [HR] 0.92 [95% CI 0.75, 1.13; P = 0.41]). Analysis of DFU-related complications demonstrated a significant reduction in amputations with liraglutide versus placebo (HR 0.65 [95% CI 0.45, 0.95; P = 0.03]). However, no differences were found for foot infections, involvement of underlying structures, or peripheral revascularization in the main analysis. CONCLUSIONS Treatment with liraglutide in patients with type 2 diabetes and at high risk of CV events in the LEADER trial did not increase the risk of DFU events and was associated with a significantly lower risk of DFU-related amputations compared with placebo. This association, possibly due to chance, needs further investigation.
Pineal Anaplastic Ependymoma With Multifocal Intradural Extramedullary Metastases on MRI and 18FDG-PET
Authors: Fayçal Ben Bouallègue, Fabien Vauchot, Nicolas Menjot de Champfleur, Denis Mariano-Goulart
Journal: Clinical Nuclear Medicine (2018)

A 49-year-old woman presented to the emergency room with subacute paraparesis associated with bilateral cervicobrachial neuralgia. Brain and spine MRI revealed a heterogeneous hypervascular pineal tumor and a multifocal thoracolumbar intradural-extramedullary infiltrate with signs of medullary compression. C7-T2 laminectomy was performed on the same day for medullary decompression, allowing for partial lesion excision. Histological examination was in favor of a poorly differentiated anaplastic ependymoma. Two weeks later, FDG-PET showed markedly increased uptake in the pineal mass and significant hypermetabolism of the spinal metastases.
Response by Farré and Wellens to Letter Regarding Article, “Unique ECG During Sinus Rhythm in a Patient With a Postmyocardial Infarction-Sustained Ventricular Tachycardia”
Authors: Jerónimo Farré, Hein J. Wellens
Journal: Circulation (2018)

In the case illustrated by Dr Reiffel, it is important to exclude that the notch he identified as a late systolic potential in lead V3 is not an artifact.In our opinion, 2 things would be required to demonstrate the true nature of this deflection: (1) repeated persistence of the notch in subsequently obtained ECGs, which we presume are available in the patient's records; and (2) intracardiac catheter electrode mapping showing late systolic potentials coincidental with the surface ECG deflection in lead V3.
Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo
Authors: Anila K. Madiraju, Yang Qiu, Rachel J. Perry, Yasmeen Rahimi, Xian-Man Zhang, Dongyan Zhang, João-Paulo G. Camporez, Gary W. Cline, Gina M. Butrico, Bruce E. Kemp, Gregori Casals, Gregory R. Steinberg, Daniel F. Vatner, Kitt F. Petersen, Gerald I. Shulman
Journal: Nature Medicine (2018)
Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays
Authors: Christian Rolfo, Luis Raez, Massimo Cristofanilli
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Contrasting Efficacy of Dofetilide in Differing Experimental Models of Atrial Fibrillation
Authors: DanshiLi, AgnesBénardeau, StanleyNattel
Journal: Circulation (2000)

Background—Rapid atrial pacing (RAP) and congestive heart failure (CHF) produce different experimental substrates for atrial fibrillation (AF). We tested the hypothesis that AF maintained by different substrates responds differently to antiarrhythmic-drug therapy. Methods and Results—The class III antiarrhythmic agent dofetilide was given intravenously at doses of 10 (D10) and 80 (D80) μg/kg to dogs with AF induced either (1) after 7 days of RAP at 400 bpm or (2) in the presence of CHF induced by rapid ventricular pacing. Dofetilide terminated AF in all CHF dogs, but D10 failed to terminate AF in any RAP dog, and D80 terminated AF in only 1 of 5 RAP dogs (20%) (P<0.01 for efficacy in CHF versus RAP dogs). Dofetilide was highly effective in preventing AF induction by atrial burst pacing in dogs with CHF but was totally ineffective in dogs with RAP. Dofetilide increased atrial effective refractory period and AF cycle length to a greater extent in CHF dogs. Epicardial mapping with 248 bipolar electrodes show...
SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models
Authors: Carmine Fedele, Hao Ran, Brian Diskin, Wei Wei, Jayu Jen, Mitchell J. Geer, Kiyomi Araki, Ugur Ozerdem, Diane M. Simeone, George Miller, Benjamin G. Neel, Kwan Ho Tang
Journal: Cancer Discovery (2018)

Adaptive resistance to MEK inhibitors (MEKi) typically occurs via induction of genes for different receptor tyrosine kinases (RTK) and/or their ligands, even in tumors of the same histotype, making combination strategies challenging. SHP2 (PTPN11) is required for RAS/ERK pathway activation by most RTKs and might provide a common resistance node. We found that combining the SHP2 inhibitor SHP099 with a MEKi inhibited the proliferation of multiple cancer cell lines in vitroPTPN11 knockdown/MEKi treatment had similar effects, whereas expressing SHP099 binding-defective PTPN11 mutants conferred resistance, demonstrating that SHP099 is on-target. SHP099/trametinib was highly efficacious in xenograft and/or genetically engineered models of KRAS-mutant pancreas, lung, and ovarian cancers and in wild-type RAS-expressing triple-negative breast cancer. SHP099 inhibited activation of KRAS mutants with residual GTPase activity, impeded SOS/RAS/MEK/ERK1/2 reactivation in response to MEKi, and blocked ERK1/2-dependent transcriptional programs. We conclude that SHP099/MEKi combinations could have therapeutic utility in multiple malignancies.Significance: MEK inhibitors show limited efficacy as single agents, in part because of the rapid development of adaptive resistance. We find that SHP2/MEK inhibitor combinations prevent adaptive resistance in multiple cancer models expressing mutant and wild-type KRAS. Cancer Discov; 8(10); 1237-49. ©2018 AACR.See related commentary by Torres-Ayuso and Brognard, p. 1210This article is highlighted in the In This Issue feature, p. 1195.
Intense FDG Uptake in the Muscles Due to Severe Vomiting
Authors: Jie Liu, Wei Wang, Leilei Yuan, Ying Kan, Jigang Yang
Journal: Clinical Nuclear Medicine (2018)

Abstract A 22-year-old woman with acute lymphoblastic leukemia underwent FDG PET/CT to evaluate possible extramedullary disease. The patient experienced severe nausea and vomiting due to ongoing chemotherapy. The image demonstrated increased FDG uptake in multiple muscle groups, including intercostal, bilateral external oblique, internal oblique, transverse abdominal muscles, and psoas major. One week after the patient stopped vomiting, a repeated PET/CT showed much less muscle uptake.
Citrate‐Based Fluorescent Biomaterials
Authors: Dingying Shan, Jer‐Tsong Hsieh, Xiaochun Bai, Jian Yang
Journal: Advanced Healthcare Materials (2018)

Abstract Fluorescence imaging has emerged as a promising technique for monitoring and assessing various biologically relevant species in cells and organisms, driving the demand for effective fluorescent agents with good biocompatibility and high fluorescence performance. However, traditional fluorescent agents, such as quantum dots (QDs) and organic dyes, either suffer from toxicity concerns or poor fluorescence performance (e.g., low photobleaching‐resistance). In this regard, citrate‐based fluorescent biomaterials, which are synthesized from the natural and biocompatible precursor of citric acid (CA), have become competitive alternatives for fluorescence imaging owing to their biocompatibility, cost effectiveness, straightforward synthetic routes, flexible designability, as well as strong fluorescence with adjustable excitation/emission wavelengths. Accordingly, numerous citrate‐based biomaterials, including carbon dots (CDs), biodegradable photoluminescent polymers (BPLPs), and small molecular fluorophores, have been developed and researched in the past few decades. This review discusses recent progress in the research and development of citrate‐based fluorescent materials with emphasis on their design and synthesis considerations, material properties, fluorescence properties and mechanisms, as well as biomedical applications. It is expected that this review will provide an insightful discussion on the citrate‐based fluorescent biomaterials, and lead to innovations for the next generation of fluorescent biomaterials and fluorescence‐based biomedical technology.
Persistent regulatory T-cell response 2 years after 3 years of grass tablet SLIT: Links to reduced eosinophil counts, sIgE levels, and clinical benefit
Authors: Rosa Varona, Tania Ramos, Maria Marta Escribese, Lucia Jimeno, Agustin Galán, Peter A. Würtzen, Francisco Vega, Alicia Marín, Santiago Martín, Ana C. Carrera, Carlos Blanco, Domingo Barber
Journal: Allergy (2018)

In the first 2 years of grass tablet sublingual immunotherapy treatment, we have previously demonstrated a progressive development of a regulatory T-cell response, which was preceded by an early decrease in the frequency of both IL-4+ cells and sIgE levels. A progressive increase in sIgG4 levels and FAB blockage were also found.By monitoring immunological kinetics during 3 years of active treatment + 2 years of follow-up, we aimed to identify key immunological parameters that could explain sustained clinical benefit of grass tablet sublingual immunotherapy.Thirty patients completed the 5-year clinical trial protocol. Although individual responses were heterogeneous, reduction in both sIgE and circulating IL-4+ cells compared to the initial 1- to 4-month peak was maintained throughout the 3-year treatment period and for 2 years after discontinuation. Meanwhile, after a 2-year increase in sIgG4, the levels were stabilized during the third year and decreased post-therapy. FAB inhibition remained significantly inhibited throughout the study compared to preimmunotherapy in 83% of patients. A sustained regulatory T-cell response, after IT cessation, occurs in two-thirds of the patients. There was a statistical association between this regulatory response, the maintenance of lower eosinophil counts during grass pollen seasons, and sIgE titers lower than before immunotherapy treatment, and the latter were significantly associated with clinical response.Our results suggest that the immunological mechanisms underlying the sustained response after 2 years of cessation of immunotherapy (3-year treatment period) are linked to the acquisition and maintenance of a regulatory T-cell response.
PGC-1α driven mitochondrial biogenesis in stromal cells underpins mitochondrial trafficking to leukemic blasts
Authors: Christopher R. Marlein, Lyubov Zaitseva, Rachel E. Piddock, Livia Raso-Barnett, Michael A. Scott, Christopher J. Ingham, Angela Collins, Kristian M. Bowles, Stuart A. Rushworth
Journal: Leukemia (2018)
Regarding the Congruence Between 2 Circulating Tumor DNA Sequencing Assays
Authors: Geoffrey R. Oxnard, Cloud P. Paweletz
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Nonalcoholic fatty liver disease in psoriasis
Authors: R.B. Prussick, L. Miele
Journal: British Journal of Dermatology (2018)

Psoriasis is a chronic, patchy, red, scaly rash affecting around 2% of the population. People with psoriasis, while usually healthy, are more susceptible than others to arthritis, metabolic syndrome (MetS: type 2 diabetes, high blood pressure and obesity) and a liver disorder called non‐alcoholic fatty liver disease (NAFLD). NAFLD starts as excess fat deposits in the liver but can progress to inflammation (non‐alcoholic steatotic hepatosis NASH), cirrhosis and even liver cancer. This paper from researchers in the US and Italy reviews the links between psoriasis and NAFLD, which is more than twice as common, and more severe, in people with psoriasis than in those without. The risk of NAFLD in psoriasis increases with age and with the severity of the psoriasis, even when methotrexate (an effective medicine for psoriasis, known to cause liver damage) is taken out of the equation. Both conditions show increased levels of inflammatory chemicals produced by fat (adipokines), and decreased levels of an anti‐inflammatory adipokine. Adipokines have a role in energy balance, insulin sensitivity, blood pressure, and blood vessel maintenance, as well as inflammation. The liver responds to adipokines by producing hepatokines which can promote MetS and NAFLD. A multistep process involving these and other body chemicals with complicated feedback loops creates an imbalance between liver cell death and regeneration resulting in NAFLD. The inflammatory events in psoriasis feed in to this process. This review emphasises the importance of monitoring general health in psoriasis and raises the possibility that certain anti‐inflammatory medications may alleviate both disorders.
Expression network analysis reveals cord blood vitamin D-associated genes affecting risk of early life wheeze
Authors: Hooman Mirzakhani, Amal A Al-Garawi, Vincent J Carey, Weiliang Qiu, Augusto A Litonjua, Scott T Weiss
Journal: Thorax (2018)

Cord blood 25-hydroxyvitamin D (25OHD) has been reported in association with risk of early life recurrent wheeze. In a subset of infants who participated in the Vitamin D Antenatal Asthma Reduction Trial, we demonstrated that higher cord blood 25OHD at birth (&gt;31 ng/mL) was associated with a reduced risk of recurrent wheeze in the first year of life. We then identified a module of co-expressed genes associated with cord blood 25OHD levels &gt;31 ng/mL. Genes in this module are involved in biological and immune pathways related to development and progression of asthma pathogenesis including the Notch1 and transforming growth factor-beta signalling pathways.
Quebec doctors’ pay rise should be evidence based and transparent
Authors: Claire Godard-Sebillotte, Matthew Hacker Teper, Isabelle Vedel
Journal: BMJ (2018)

As primary care researchers in Quebec, we would like to contextualise the rejected pay rise that was reported in The BMJ .1 This pay rise for physicians is part of a larger rise in remuneration in an era of limited increases in overall health spending and is an attempt to remedy physicians’ compensation discrepancies across …