tbuckley/cabot-search huggingface dataset:
New awards seek to highlight how “profit mongering” affects US healthcare
Authors: Michael McCarthy
Journal: BMJ (2018)

A new annual top 10 list will highlight the year’s “most egregious examples of profit mongering and lack of empathy” in US healthcare, according to the Lown Institute, a health advocacy group based in Boston (http://lowninstitute.org/news/blog/shkreli-awards).

The list has been named the “Shkreli awards” after Martin Shkreli, the “pharma bro” chief executive of Turing Pharmaceuticals, who raised the price of pyrimethamine, a 60 year old generic drug used to treat toxoplasmosis, by 5000%, from $13.50 (£9; €12) to $750 a tablet.1

Vikas Saini, president of the institute, said the goal …
Pragmatic Psychiatric Epidemiology—If You Can’t Count It, It Won’t Count
Authors: John J. McGrath, Preben Bo Mortensen, Harvey A. Whiteford
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Digoxin-Quinidine Interaction
Authors: W. David Hager, Paul Fenster, Michael Mayersohn, Donald Perrier, Penelope Graves, Frank I. Marcus, Steven Goldman
Journal: New England Journal of Medicine (1979)

Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine. (N Engl J Med 300:1238–1241, 1979)
Abstract 19763: High-Intensity Statin Administration Decreased 6-Month All Cause Death in Asian Population: From Korean Acute Myocardial Infarction Registry-National Institute of Health
Authors: Won-Sik Yoon, Sang-Rok Lee, Ja-yeon Lee, In-Jae Kim, Yi-Shik Kim
Journal: Circulation (2017)

Introduction: There have been conflicting results for the high-intensity statin in reducing major adverse cardiac events (MACE) in asian patients who experienced acute myocardial infarction (AMI). ...
Impact of Next-Generation Flow (NGF) Minimal Residual Disease (MRD) Monitoring in Multiple Myeloma (MM): Results from the Pethema/GEM2012 Trial
Authors: Bruno Paiva, Noemi Puig, Maria Teresa Cedena, Lourdes Cordon, Maria-Belen Vidriales, Leire Burgos, Juan Flores-Montero, Lucía Lopez-Anglada, Norma Gutierrez, Maria Jose Calasanz, Maria Luisa Martin-Ramos, Ramon Garcia-Sanz, Joaquin Martinez-Lopez, Albert Oriol, M Jesús Blanchard, Rafael Rios, Jesús Martín, Rafael Martínez, Josep Sarra, Miguel T Hernández, Javier de la Rubia, Isabel Krsnik, Jose M Moraleda, Luis Palomera, Juan Bargay, Alberto Orfao, Laura Rosinol, Maria-Victoria Mateos, Juan-José Lahuerta, Joan Bladé, Jesus F. San Miguel
Journal: Blood (2017)
Abstract 15125: Non-Invasive Blood Oxygen Saturation Measurement by a Calibration-Free MRI Method
Authors: Juliet Varghese, Rizwan Ahmad, Lee C Potter, Orlando P Simonetti
Journal: Circulation (2016)

Non-invasive oxygen saturation (O2 sat) measurement in the cardiac chambers and blood vessels would be clinically valuable in congenital heart disease, heart failure and pulmonary hypertension. A calibration-free magnetic resonance (MR) technique for accurate, patient-specific O2 sat measurement was developed and compared against the invasive reference method.  The dependence of blood O2 sat on the effective transverse relaxation time (T2) is characterized by the Luz-Meiboom (L-M) model. It includes patient-specific parameters such as hematocrit and O2 sat, and MR-specific parameters such as field strength and inter-echo spacing. Additional unknown parameters characterize physical and magnetic blood properties. We hypothesize that O2 sat can be determined accurately from this complex model by acquiring a set of effective blood T2 values at distinct inter-echo spacings, and jointly fitting the T2 data to the L-M model to estimate all unknown parameters, including O2 sat.  A porcine model (n = 7) was studied with graded hypoxemia across a range of O2 sat levels. To generate a set of effective blood T2 measurements, four distinct blood T2 maps were acquired (~3 minutes) at each hypoxemia stage. O2 sat estimated using two forms of the L-M model with four (Model 1) and six (Model 2) unknown parameters was compared to reference O2 sat measured from invasive catheterization samples.  The linear regression and Bland Altman plots in Figure 1 show O2 sat estimated by the proposed technique against the reference measurement. O2 sat estimation with Model 1 demonstrated a higher correlation (1a, R 2  = 0.90, p = 3.1e-14) with the reference method compared to Model 2 (1c, R 2  = 0.83, p = 3.7e-11). The bias with the reference method was not significant for Model 1 (1b, -0.9 ± 3.7%, p =0.20) and Model 2 (1d, -1.7 ± 6.1%, p = 0.15).  A calibration-free MRI method has been presented for non-invasive measurement of O2 sat. Results from a porcine model show high correlation with invasive blood gas analysis.
The Addition of Chemotherapy to Radiation Therapy Improves Survival in Elderly Patients with Stage III Non–Small Cell Lung Cancer
Authors: Eric D. Miller, James L. Fisher, Karl E. Haglund, John C. Grecula, Meng Xu-Welliver, Erin M. Bertino, Kai He, Peter G. Shields, David P. Carbone, Terence M. Williams, Gregory A. Otterson, Jose G. Bazan
Journal: Journal of Thoracic Oncology (2018)
Transforming the Treatment of Schizophrenia in the United States: The RAISE Initiative
Authors: Lisa B. Dixon, Howard H. Goldman, Vinod H. Srihari, John M. Kane
Journal: Annual Review of Clinical Psychology (2018)

The schizophrenia spectrum disorders are neurodevelopmental illnesses with a lifetime prevalence near 1%, producing extensive functional impairment and low expectations for recovery. Until recently, treatment in the United States has largely attempted to stabilize individuals with chronic schizophrenia. The identification and promotion of evidence-based practices for schizophrenia via the Patient Outcomes Research Team, combined with international studies supporting the value of early intervention, provided the foundation for the Recovery After an Initial Schizophrenia Episode (RAISE) project. The RAISE studies further supported the value of reducing the duration of untreated psychosis and providing a multi-element treatment called coordinated specialty care (CSC) to improve outcomes for patients in usual treatment settings. Although CSC programs have proliferated rapidly in the United States, many challenges remain in the treatment and recovery of individuals with schizophrenia in the aftermath of RAISE.
Erratum to: Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity
Authors: Yohei Sasagawa, Itoshi Nikaido, Tetsutaro Hayashi, Hiroki Danno, Kenichiro D Uno, Takeshi Imai, Hiroki R. Ueda
Journal: Genome biology (2017)
Brain Nat8l Knockdown Suppresses Spongiform Leukodystrophy in an Aspartoacylase-Deficient Canavan Disease Mouse Model
Authors: Peter Bannerman, Fuzheng Guo, Olga Chechneva, Travis Burns, Xiaoqing Zhu, Yan Wang, Bokyung Kim, Naveen K. Singhal, Jennifer A. McDonough, David Pleasure
Journal: Molecular Therapy (2018)

Canavan disease, a leukodystrophy caused by loss-of-function ASPA mutations, is characterized by brain dysmyelination, vacuolation, and astrogliosis ("spongiform leukodystrophy"). ASPA encodes aspartoacylase, an oligodendroglial enzyme that cleaves the abundant brain amino acid N-acetyl-L-aspartate (NAA) to L-aspartate and acetate. Aspartoacylase deficiency results in a 50% or greater elevation in brain NAA concentration ([NAAB]). Prior studies showed that homozygous constitutive knockout of Nat8l, the gene encoding the neuronal NAA synthesizing enzyme N-acetyltransferase 8-like, prevents aspartoacylase-deficient mice from developing spongiform leukodystrophy. We now report that brain Nat8l knockdown elicited by intracerebroventricular/intracisternal administration of an adeno-associated viral vector carrying a short hairpin Nat8l inhibitory RNA to neonatal aspartoacylase-deficient AspaNur7/Nur7 mice lowers [NAAB] and suppresses development of spongiform leukodystrophy.
CT scanning to diagnose CAA: back to the future?
Authors: David J Werring
Journal: The Lancet Neurology (2018)

Most intracerebral haemorrhages are due to cerebral small vessel diseases hypertensive arteriopathy (arteriolosclerosis), which affects deep perforating vessels, and cerebral amyloid angiopathy (CAA), which affects superficial cortical and leptomeningeal vessels. Diagnosis of CAA is important because it has a high recurrence risk (7·4% per year in a pooled analysis of cohort studies)1 and might require specific prevention strategies (eg, modifying the use of antithrombotic drugs) or, in the future, disease-modifying treatments targeting vascular β-amyloid.
Cord Blood NK Cells Engineered to Express a Humanized CD123-Targeted Chimeric Antigen Receptor (CAR) and IL-15 As Off-the-Shelf Therapy for Acute Myeloid Leukemia
Authors: Lucila Nassif Kerbauy, Sonny Ang, Enli Liu, Pinaki P Banerjee, Yewen Wu, Hila Shaim, Francesca Lorraine Wei Inng Lim, Rafet Basar, Li Li, Muharrem Muftuoglu, May Daher, Nobuhiko Imahashi, Mayela Carolina Mendt, Mecit Kaplan, Malini Mukherjee, Jessica Ch Lee, Jordan S. Orange, Marina Konopleva, Michael Andreeff, Richard E Champlin, Elizabeth J Shpall, Katayoun Rezvani
Journal: Blood (2017)
Commercial influence in control of non-communicable diseases
Authors: Kasi Whitaker, Douglas Webb, Natalia Linou
Journal: BMJ (2018)

Policy makers engaging with industry must understand the risks

Non-communicable diseases (NCDs) are a threat to health and development globally, accounting for 72% of all deaths in 2016.1 The UN sustainable development goals (SDGs) include a target to reduce premature mortality from NCDs by one third by 2030.2 To achieve this target and all 17 goals by 2030, the UN encourages public-private and civil society partnerships (see goal 17).

New global partnerships for development are necessary because the ambition, scope, and scale of the SDG agenda require coherent action by all parts of society. Although including diverse stakeholders provides opportunities to pool resources and expertise, it also brings potential risks and questions around legitimacy and accountability.3 This is especially true for public health policy, where involving private sector entities often presents real or perceived conflicts of interest.

We know, for example, that doctors’ behaviours can be influenced by the drugs industry.4 Similarly, efforts by the tobacco industry to undermine tobacco control …
Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity
Authors: Andreas Stahl, Tim U. Krohne, Nicole Eter, Isabel Oberacher-Velten, Rainer Guthoff, Synke Meltendorf, Oliver Ehrt, Sabine Aisenbrey, Johann Roider, Heinrich Gerding, Claudia Jandeck, Lois E. H. Smith, Johanna M. Walz
Journal: JAMA Pediatrics (2018)

Anti-vascular endothelial growth factor (VEGF) therapies are a novel treatment option in retinopathy of prematurity (ROP). Data on dosing, efficacy, and safety are insufficient.To investigate lower doses of anti-VEGF therapy with ranibizumab, a substance with a significantly shorter systemic half-life than the standard treatment, bevacizumab.This randomized, multicenter, double-blind, investigator-initiated trial at 9 academic medical centers in Germany compared ranibizumab doses of 0.12 mg vs 0.20 mg in infants with bilateral aggressive posterior ROP; ROP stage 1 with plus disease, 2 with plus disease, or 3 with or without plus disease in zone I; or ROP stage 3 with plus disease in posterior zone II. Patients were recruited between September 2014 and August 2016. Twenty infants were screened and 19 were randomized.All infants received 1 baseline ranibizumab injection per eye. Reinjections were allowed in case of ROP recurrence after at least 28 days.The primary end point was the number of infants who did not require rescue therapy at 24 weeks. Key secondary end points included time-to-event analyses, progression of physiologic vascularization, and plasma VEGF levels. Stages of ROP were photodocumented and reviewed by an expert committee.Nineteen infants with ROP were enrolled (9 [47.4%] female; median [range] postmenstrual age at first treatment, 36.4 [34.7-39.7] weeks), 3 of whom died during the study (1 in the 0.12-mg group and 2 in the 0.20-mg group). Of the surviving infants, 8 (88.9%) (17 eyes [94.4%]) in the 0.12-mg group and 6 (85.7%) (13 eyes [92.9%]) in the 0.20-mg group did not require rescue therapy. Both ranibizumab doses were equally successful in controlling acute ROP (Cochran-Mantel-Haenszel analysis; odds ratio, 1.88; 95% CI, 0.26-13.49; P = .53). Physiologic intraretinal vascularization was superior in the 0.12-mg group. The VEGF plasma levels were not systematically altered in either group.This pilot study demonstrates that ranibizumab is effective in controlling acute ROP and that 24% of the standard adult dose (0.12 mg) appears equally effective as 40% (0.20 mg). Superior vascularization of the peripheral retina with 0.12 mg of ranibizumab indicates that the lower dose may be favorable. Unchanged plasma VEGF levels point toward a limited systemic drug exposure after ranibizumab.clinicaltrials.gov Identifier: NCT02134457 and clinicaltrialsregister.eu Identifier: 2013-002539-13.
The polycomb group protein EZH2 induces epithelial–mesenchymal transition and pluripotent phenotype of gastric cancer cells by binding to PTEN promoter
Authors: Lu Gan, Midie Xu, Ruixi Hua, Cong Tan, Jieyun Zhang, Yiwei Gong, Zhenhua Wu, Weiwei Weng, Weiqi Sheng, Weijian Guo
Journal: Journal of Hematology & Oncology (2018)

The influences of oncogenic Ezh2 on the progression and prognosis of gastric cancer (GC) and the underlying mechanisms are still poorly understood. Here, we aimed at investigating clinicopathological significance of Ezh2 in GC and the mechanisms underlying its function in GC development. The expression level of Ezh2 was determined by qRT-PCR, immunoblot, and immunohistochemistry analysis in 156 pairs of GC tissues and adjacent normal gastric mucosa tissues. The biological functions of Ezh2 were assessed by in vitro and in vivo functional experiments. Chromatin immunoprecipitation (ChIP), luciferase, and Western blotting analyses were utilized to identify the relationship between Ezh2 and the PTEN/Akt signaling. The expression of Ezh2 was higher in gastric cancer tissues in comparison with para-nontumorous epithelium. High expression of Ezh2 was associated with more aggressive biological behavior and poor prognosis in GC. In vitro studies indicated that Ezh2 promoted GC cells' proliferation and clonogenicity. Besides, Ezh2 led to the acquisition of epithelial–mesenchymal transition (EMT) phenotype of GC cells and enhanced GC cell migration and invasion capacity. In particular, Ezh2 strengthened sphere-forming capacity of GC cells, indicating its role in the enrichment of GC stem cells. Furthermore, we found that PTEN/Akt signaling contributed to the effects of Ezh2 on cancer stem cells (CSC) and EMT phenotype in GC cells, and blocking PTEN signaling significantly rescued the effects of Ezh2. Taken together, Ezh2 has a central role in regulating diverse aspects of the pathogenesis of GC in part by involving PTEN/Akt signaling, indicating that it could be an independent prognostic factor and potential therapeutic target.
Evaluación de la disfagia mediante el cuestionario Eating Assessment Tool (EAT-10) antes y después del tratamiento endoscópico del Divertículo de Zenker
Authors: MF Guerra, G Walsen, MJ González-Mariscal, M Belvis, J Loscertales, FJ Pellicer-Bautista, H Galera-Ruiz, M Congregado, M Rodríguez-Téllez
Journal: Endoscopy (2017)

El Divertículo de Zenker (DZ) es poco prevalente (0 – 01% -0,11%), más frecuente en hombres entre la séptima y octava década de vida. Se diagnostica por endoscopia o esofagograma ante la sospecha clínica, siendo la disfagia su síntoma más frecuente y principal. Se acepta la crico-faringo-miotomía endoscópica como tratamiento eficaz y seguro. Podría ser útil la aplicación de un sencillo cuestionario periódico como el Eating Assessment Tool (EAT-10), tanto para evaluar precozmente la respuesta de la disfagia al tratamiento, como para detectar recidivas e iniciar el estudio pertinente para un retratamiento endoscópico.
Recruitment And Characterization Of The Isle Of Wight 3 rd Generation Birth Cohort
Authors: Frances Mitchell, Wilfried Karmaus, Hongmei Zhang, Susan Ewart, Linda S. Mansfield, John W. Holloway, Stephen Potter, Ramesh Jagath Kurukulaaratchy, Syed H. Arshad
Journal: Journal of Allergy and Clinical Immunology (2018)
Epitranscriptomic m6A Regulation of Axon Regeneration in the Adult Mammalian Nervous System
Authors: Yi-Lan Weng, Xu Wang, Ran An, Jessica Cassin, Caroline Vissers, Yuanyuan Liu, Yajing Liu, Tianlei Xu, Xinyuan Wang, Samuel Zheng Hao Wong, Jessica Joseph, Louis C. Dore, Qiang Dong, Wei Zheng, Peng Jin, Hao Wu, Bin Shen, Xiaoxi Zhuang, Chuan He, Kai Liu, Hongjun Song, Guo-li Ming
Journal: Neuron (2018)
Validation of Dynamic Biomarker-Based Risk Progression Model for Smoldering Multiple Myeloma
Authors: Shebli Atrash, Myra M Robinson, Amanda Aneralla, Taylor Brown, Reed Friend, Chelsea Sprouse, Ami Ndiaye, Qing Zhang, Edward H Lipford, Jared G Block, Elton T Smith, James T Symanowski, Belinda Rene Avalos, Edward A Copelan, Peter M. Voorhees, Saad Z Usmani, Manisha Bhutani
Journal: Blood (2017)
Safety and efficacy of tiotropium in children aged 1–5 years with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial
Authors: Elianne J L E Vrijlandt, Georges El Azzi, Mark Vandewalker, Ned Rupp, Thomas Harper, LeRoy Graham, Stanley J Szefler, Petra Moroni-Zentgraf, Ashish Sharma, Sebastian D Vulcu, Ralf Sigmund, Bo Chawes, Michael Engel, Hans Bisgaard
Journal: The Lancet Respiratory Medicine (2018)
Reimagining Obesity in 2018
Authors: Edward H. Livingston
Journal: JAMA (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 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
Value of Computed Tomography-Defined Sarcopenia: A Prognostic Predictor of Non-Relapse Mortality Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Taiki Ando, Shin Fujisawa, Takayuki Sakuma, Haruka Teshigawara, Ayako Matsumura, Taisei Suzuki, Hiroshi Teranaka, Akiko Negoro, Eriko Ogusa, Jun Aoki, Kazuho Miyashita, Yoshimi Ishii, Hiroyuki Takahashi, Yuki Nakajima, Takuya Miyazaki, Maki Hagihara, Kenji Matsumoto, Etsuko Yamazaki, Hideaki Nakajima
Journal: Blood (2017)
Effect of inhibiting autophagy induced by PTEN loss on intrinsic breast cancer resistance to trastuzumab therapy.
Authors: Ning Liao, Guochun Zhang, Shengli An, XueRui Li, Kun Wang, Jian Zu, Chongyang Ren, Lingzhu Wen, Haitong Lv
Journal: Journal of Clinical Oncology (2015)

e11532 Background: This study determined the effects of the phosphatase and tensin homolog (PTEN) expression level on autophagic status and on breast cancer's de novo resistance to trastuzumab. Methods: The correlation between PTEN and trastuzumab resistance from clinical specimens were detected using immunochemistry and western blot. Estrogen receptor (ER)-expressing breast cancer cell lines were treated with shRNA expression vectors directed against PTEN mRNA and control vectors respectively, effects on autophagy signal transduction pathways and growth of tumors in an orthotopic nude mouse model were determined. The orthotopically implanted model of breast cancer was established using trastuzumab-resistant HER2-expressing breast cancer cells. The expression of autophagy-related proteins (LC3 I/II, p62, LAMP and cathepsin B) was determined by western blot analysis. Cell viability was determined via MTT assay. Results: Down-regulation of PTEN and autophagic proteins LC3-I and -II was observed in non-resistant human breast cancer samples. Knockdown of PTEN with shRNA in SKBR-3, an (ER)-expressing breast cancer cell line, resulted in increased resistance to trastuzumab. Consistent with the in vitro results, tumor size in the PTEN knockdown cells could not be effectively suppressed by trastuzumab treatment in a time-dependent manner. Significant decreases in the levels of autophagic proteins LC3I/II, LAMP, p62, cathepsin B and PI3K-Akt-mTOR and signaling pathway protein Akt were found in PTEN knockdown cells compared to the PTEN normal group after trastuzumab administration, both in vitro and in vivo. Conclusions: In this study, loss of PTEN promotes development of breast cancer primary resistance to trastuzumab via autophagy defects.