tbuckley/cabot-search huggingface dataset:
Diplotype analysis of NUDT15 variants and 6-mercaptopurine sensitivity in pediatric lymphoid neoplasms
Authors: Shinichi Tsujimoto, Tomoo Osumi, Meri Uchiyama, Ryota Shirai, Takaya Moriyama, Rina Nishii, Yuji Yamada, Ko Kudo, Masahiro Sekiguchi, Yuki Arakawa, Masanori Yoshida, Toru Uchiyama, Kiminori Terui, Shuichi Ito, Katsuyoshi Koh, Junko Takita, Etsuro Ito, Daisuke Tomizawa, Atsushi Manabe, Nobutaka Kiyokawa, Jun J. Yang, Motohiro Kato
Journal: Leukemia (2018)
First Artificial Iris Ok’d
Authors: Rebecca Voelker
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
Abstract 12311: Increased Repolarization Lability Predicts Sudden Cardiac Death in Asymptomatic Adults
Authors: Larisa G Tereshchenko, Elsayed Z Soliman, Nona Sotoodehnia, Lichy Han, Yiyi Zhang, Ronald D Berger, Gordon F Tomaselli, Dan E Arking, David S Siscovick, Wendy S Post, Josef Coresh, Eliseo Guallar
Journal: Circulation (2012)

Introduction . The overwhelming majority of sudden cardiac deaths (SCDs) occur in asymptomatic adults. Improved strategies are needed to identify those at high risk. Increased repolarization lability characterizes a substrate of life-threatening ventricular arrhythmia. We hypothesized that increased repolarization lability will be an independent predictor of SCD in asymptomatic adults.  Method. We analyzed baseline resting digital 12-lead ECGs of 15574 participants of the prospective community-dwelling Atherosclerosis Risk In Communities (ARIC) cohort. After exclusion of poor quality ECGs and individuals not in sinus rhythm at baseline, 15300 ECGs were analyzed. The inverse Dower transformation was applied to construct orthogonal XYZ leads and vectorcardiograms. The spatial TT’ angle, reflecting repolarization lability, was calculated by custom Matlab software as the angle between two consecutive T vectors using the definition of the inner product.  Results. During a median follow-up of 17 years, 243 cases of SCD and 174 cases of non-sudden cardiac death occurred. Mean spatial TT’ angle was larger in persons with SCD (6.6±5.4 vs. 5.2±3.8 deg, P=0.0003). In univariate Cox regression, the hazard for persons with the highest quartile of mean TT’ angle was about 2 times that of those with the three lower quartiles of mean TT’ angle (hazard ratio (HR): 1.80; 95% CI 1.39-2.34; P  Conclusion. Increased repolarization lability as measured by the mean spatial TT’ angle on the routine resting 12 lead ECG is an independent predictor of SCD in community-dwelling cohort of asymptomatic adults.
Intramuscular Follicular Lymphoma
Authors: Filipe Martins, Gregoire Stalder, Axel Van Der Gucht, Francesco Grandoni, Anne Cairoli
Journal: Clinical Nuclear Medicine (2018)

We present an interesting image of a painless growing mass of the right arm in a 76-year-old man. A musculoskeletal MRI of the right arm showed a 7.5 × 3-cm homogeneous, well-defined mass, elongated along the course of muscle fascias and independent of the adjacent bone. A core-needle biopsy was performed, and the diagnosis of low-grade follicular lymphoma was established. Intramuscular lymphoma should be integrated into the differential diagnosis of tumors surrounding neurovascular structures, alongside peripheral nerve tumors and soft tissue sarcoma. MRI and whole-body F-FDG PET/CT features provided useful information to refine differential diagnosis in this case.
Post-translational modifications of transporters
Authors: Lindsay C. Czuba, Kathleen M. Hillgren, Peter W. Swaan
Journal: Pharmacology & Therapeutics (2018)

Drug transporter proteins are critical to the distribution of a wide range of endogenous compounds and xenobiotics such as hormones, bile acids, peptides, lipids, sugars, and drugs. There are two classes of drug transporters– the solute carrier (SLC) transporters and ATP-binding cassette (ABC) transporters –which predominantly differ in the energy source utilized to transport substrates across a membrane barrier. Despite their hydrophobic nature and residence in the membrane bilayer, drug transporters have dynamic structures and adopt many conformations during the translocation process. Whereas there is significant literature evidence for the substrate specificity and structure-function relationship for clinically relevant drug transporters proteins, there is less of an understanding in the regulatory mechanisms that contribute to the functional expression of these proteins. Post-translational modifications have been shown to modulate drug transporter functional expression via a wide range of molecular mechanisms. These modifications commonly occur through the addition of a functional group (e.g. phosphorylation), a small protein (e.g. ubiquitination), sugar chains (e.g. glycosylation), or lipids (e.g. palmitoylation) on solvent accessible amino acid residues. These covalent additions often occur as a result of a signaling cascade and may be reversible depending on the type of modification and the intended fate of the signaling event. Here, we review the significant role in which post-translational modifications contribute to the dynamic regulation and functional consequences of SLC and ABC drug transporters and highlight recent progress in understanding their roles in transporter structure, function, and regulation.
Gonadotropins and Their Analogs: Current and Potential Clinical Applications
Authors: Ross C Anderson, Claire L Newton, Richard A Anderson, Robert P Millar
Journal: Endocrine Reviews (2018)

The gonadotropin receptors LH receptor and FSH receptor play a central role in governing reproductive competency/fertility. Gonadotropin hormone analogs have been used clinically for decades in assisted reproductive therapies and in the treatment of various infertility disorders. Though these treatments are effective, the clinical protocols demand multiple injections, and the hormone preparations can lack uniformity and stability. The past two decades have seen a drive to develop chimeric and modified peptide analogs with more desirable pharmacokinetic profiles, with some displaying clinical efficacy, such as corifollitropin alfa, which is now in clinical use. More recently, low-molecular-weight, orally active molecules with activity at gonadotropin receptors have been developed. Some have excellent characteristics in animals and in human studies but have not reached the market—largely as a result of acquisitions by large pharma. Nonetheless, such molecules have the potential to mitigate risks currently associated with gonadotropin-based fertility treatments, such as ovarian hyperstimulation syndrome and the demands of injection-based therapies. There is also scope for novel use beyond the current remit of gonadotropin analogs in fertility treatments, including application as novel contraceptives; in the treatment of polycystic ovary syndrome; in the restoration of function to inactivating mutations of gonadotropin receptors; in the treatment of ovarian and prostate cancers; and in the prevention of bone loss and weight gain in postmenopausal women. Here we review the properties and clinical application of current gonadotropin preparations and their analogs, as well as the development of novel orally active, small-molecule nonpeptide analogs.
Transcriptome Characterization of Matched Primary Breast and Brain Metastatic Tumors to Detect Novel Actionable Targets
Authors: Damir Varešlija, Nolan Priedigkeit, Ailís Fagan, Siobhan Purcell, Nicola Cosgrove, Philip J O’Halloran, Elspeth Ward, Sinéad Cocchiglia, Ryan Hartmaier, Carlos A Castro, Li Zhu, George C Tseng, Peter C Lucas, Shannon L Puhalla, Adam M Brufsky, Ronald L Hamilton, Aju Mathew, Jose P Leone, Ahmed Basudan, Lance Hudson, Róisín Dwyer, Sudipto Das, Darran P O’Connor, Patrick G Buckley, Michael Farrell, Arnold D K Hill, Steffi Oesterreich, Adrian V Lee, Leonie S Young
Journal: JNCI Journal of the National Cancer Institute (2018)

Breast cancer brain metastases (BrMs) are defined by complex adaptations to both adjuvant treatment regimens and the brain microenvironment. Consequences of these alterations remain poorly understood, as does their potential for clinical targeting. We utilized genome-wide molecular profiling to identify therapeutic targets acquired in metastatic disease.Gene expression profiling of 21 patient-matched primary breast tumors and their associated brain metastases was performed by TrueSeq RNA-sequencing to determine clinically actionable BrM target genes. Identified targets were functionally validated using small molecule inhibitors in a cohort of resected BrM ex vivo explants (n = 4) and in a patient-derived xenograft (PDX) model of BrM. All statistical tests were two-sided.Considerable shifts in breast cancer cell-specific gene expression profiles were observed (1314 genes upregulated in BrM; 1702 genes downregulated in BrM; DESeq; fold change > 1.5, Padj < .05). Subsequent bioinformatic analysis for readily druggable targets revealed recurrent gains in RET expression and human epidermal growth factor receptor 2 (HER2) signaling. Small molecule inhibition of RET and HER2 in ex vivo patient BrM models (n = 4) resulted in statistically significantly reduced proliferation (P < .001 in four of four models). Furthermore, RET and HER2 inhibition in a PDX model of BrM led to a statistically significant antitumor response vs control (n = 4, % tumor growth inhibition [mean difference; SD], anti-RET = 86.3% [1176; 258.3], P < .001; anti-HER2 = 91.2% [1114; 257.9], P < .01).RNA-seq profiling of longitudinally collected specimens uncovered recurrent gene expression acquisitions in metastatic tumors, distinct from matched primary tumors. Critically, we identify aberrations in key oncogenic pathways and provide functional evidence for their suitability as therapeutic targets. Altogether, this study establishes recurrent, acquired vulnerabilities in BrM that warrant immediate clinical investigation and suggests paired specimen expression profiling as a compelling and underutilized strategy to identify targetable dependencies in advanced cancers.
Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats
Authors: Rikesh M. Rajani, Sophie Quick, Silvie R. Ruigrok, Delyth Graham, Sarah E. Harris, Benjamin F. J. Verhaaren, Myriam Fornage, Sudha Seshadri, Santosh S. Atanur, Anna F. Dominiczak, Colin Smith, Joanna M. Wardlaw, Anna Williams
Journal: Science Translational Medicine (2018)

Endothelial cell–stabilizing drugs reverse white matter pathology in a rat model of cerebral small vessel disease.
Abstract 3012: Insulin-like Growth Factor-1 Deficient Mice Exhibit Resistance to Abdominal Aortic Constriction-induced Cardiac Hypertrophy and Contractile Dysregulation: Role of Microrna-1, Microrna-133a and Microrna-208
Authors: Yinan Hua, Jun Ren
Journal: Circulation (2009)
Association between maternal adherence to healthy lifestyle practices and risk of obesity in offspring: results from two prospective cohort studies of mother-child pairs in the United States
Authors: Klodian Dhana, Jess Haines, Gang Liu, Cuilin Zhang, Xiaobin Wang, Alison E Field, Jorge E Chavarro, Qi Sun
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To examine the association between an overall maternal healthy lifestyle (characterized by a healthy body mass index, high quality diet, regular exercise, no smoking, and light to moderate alcohol intake) and the risk of developing obesity in offspring. <h3>Design</h3> Prospective cohort studies of mother-child pairs. <h3>Setting</h3> Nurses' Health Study II (NHSII) and Growing Up Today Study (GUTS) in the United States. <h3>Participants</h3> 24 289 GUTS participants aged 9-14 years at baseline who were free of obesity and born to 16 945 NHSII women. <h3>Main outcome measure</h3> Obesity in childhood and adolescence, defined by age and sex specific cutoff points from the International Obesity Task Force. Risk of offspring obesity was evaluated by multivariable log-binomial regression models with generalized estimating equations and an exchangeable correlation structure. <h3>Results</h3> 1282 (5.3%) offspring became obese during a median of five years of follow-up. Risk of incident obesity was lower among offspring whose mothers maintained a healthy body mass index of 18.5-24.9 (relative risk 0.44, 95% confidence interval 0.39 to 0.50), engaged in at least 150 min/week of moderate/vigorous physical activities (0.79, 0.69 to 0.91), did not smoke (0.69, 0.56 to 0.86), and consumed alcohol in moderation (1.0-14.9 g/day; 0.88, 0.79 to 0.99), compared with the rest. Maternal high quality diet (top 40% of the Alternate Healthy Eating Index 2010 diet score) was not significantly associated with the risk of obesity in offspring (0.97, 0.83 to 1.12). When all healthy lifestyle factors were considered simultaneously, offspring of women who adhered to all five low risk lifestyle factors had a 75% lower risk of obesity than offspring of mothers who did not adhere to any low risk factor (0.25, 0.14 to 0.47). This association was similar across sex and age groups and persisted in subgroups of children with various risk profiles defined by factors such as pregnancy complications, birth weight, gestational age, and gestational weight gain. Children's lifestyle did not significantly account for the association between maternal lifestyle and offspring obesity risk, but when both mothers and offspring adhered to a healthy lifestyle, the risk of developing obesity fell further (0.18, 0.09 to 0.37). <h3>Conclusion</h3> Our study indicates that adherence to a healthy lifestyle in mothers during their offspring's childhood and adolescence is associated with a substantially reduced risk of obesity in the children. These findings highlight the potential benefits of implementing family or parental based multifactorial interventions to curb the risk of childhood obesity.
Odds Ratios—Current Best Practice and Use
Authors: Edward C. Norton, Bryan E. Dowd, Matthew L. Maciejewski
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
Serotonergic antidepressant use and morbidity and mortality among older adults with COPD
Authors: Nicholas T. Vozoris, Xuesong Wang, Peter C. Austin, Anne L. Stephenson, Denis E. O'Donnell, Andrea S. Gershon, Sudeep S. Gill, Paula A. Rochon
Journal: European Respiratory Journal (2018)

We evaluated the relationship between new selective serotonin reuptake inhibitor (SSRI) or serotonin–noradrenaline reuptake inhibitor (SNRI) drug use and respiratory-related morbidity and mortality among older adults with chronic obstructive pulmonary disease (COPD). This was a retrospective population-based cohort study using heath administrative data from Ontario, Canada. Individuals aged ≥66 years, with validated, physician-diagnosed COPD (n=131 718) were included. New SSRI/SNRI users were propensity score matched 1:1 to controls on 40 relevant covariates to minimise potential confounding. Among propensity score matched community-dwelling individuals, new SSRI/SNRI users compared to non-users had significantly higher rates of hospitalisation for COPD or pneumonia (hazard ratio (HR) 1.15, 95% CI 1.05–1.25), emergency room visits for COPD or pneumonia (HR 1.13, 95% CI 1.03–1.24), COPD or pneumonia-related mortality (HR 1.26, 95% CI 1.03–1.55) and all-cause mortality (HR 1.20, 95% CI 1.11–1.29). In addition, respiratory-specific and all-cause mortality rates were higher among long-term care home residents newly starting SSRI/SNRI drugs versus controls. New use of serotonergic antidepressants was associated with small, but significant, increases in rates of respiratory-related morbidity and mortality among older adults with COPD. Further research is needed to clarify if the observed associations are causal or instead reflect unresolved confounding.
Abstract 17968: Prognostic Value of Right Ventricular Parameters in Patients With Left Ventricular Dysfunction Undergoing Coronary Revascularization. A Longitudinal Study
Authors: Carlo Fino, Diego Cugola, Julien Magne, Attilio Iacovoni, John Pepper, Alice Calabrese, Massimo Caputo, Amedeo Terzi, Lorenzo Galletti, Caterina Simon, Diego Bellavia, Francesco Innocente, Samuele Pentiricci, Maurizio Merlo
Journal: Circulation (2016)

Background:  Data regarding risk stratification in patients with left ventricular (LV) dysfunction undergoing coronary artery bypass grafting (CABG) are scarce. Our objective was to compare echocardiographic, functional and clinical parameters to define independent predictors of long-term outcome.   Methods and Results:  Comprehensive Doppler echocardiographic data, six-minute walking test (6-MWT) and brain natriuretic peptide (BNP) levels were collected pre-operatively, at discharge and at the follow-up in 137 patients (mean age= 68±6 years,) with LV dysfunction (preoperative EF: 35±06%) undergoing CABG. The population was studied in 2 groups: group1: n=84 with EF ≤ 35 %; group 2: n=53 with EF≥35%). The median follow-up was of 7.2 years (range: 0.2-15.7). Early mortality was 7 %. There was no others significant difference between the 2 groups with regard to demographic and clinical data. There was no difference in BNP level and 6MWT distance between groups and according to the period (i.e. preoperative vs. discharge vs. follow-up). The multivariate Cox proportional Hazard model, after adjustment for cofactors, identified advanced age (HR: 1.12, 95%CI: 1.02-1.22, p=0.01), preoperative peak transmitral gradient (HR= 1.88, 95%CI: 1.72-4.13, p=0.001), preoperative mid RV diameter (HR=0.21, 95%CI: 0.04-1.07, p=0.04), preoperative tricuspid annular plane systolic excursion (TAPSE: HR=1.27, 95%CI: 1.01-1.60, p=0.04) and preoperative BNP levels (HR=1.00, 95%CI: 1.00-1.01, p=0.01) as independent predictors of all-causes of death.   Conclusions:  Among all the collected variables, preoperative right ventricular mid-diameter and TAPSE are the main echocardiographic independent predictors of all-causes of death in patients with LV dysfunction undergoing CABG. Our study shows the usefulness of right ventricular parameters for predicting the long-term outcome, and indicates that ventricular interactions may contribute to the outcome. Further studies are warranted to elucidate these findings
HIV-Positive–to–HIV-Positive Liver Transplantation
Authors: Emma Hathorn, Erasmus Smit, Ahmed M Elsharkawy, Simon R Bramhall, Sally A Bufton, Sris Allan, David Mutimer
Journal: New England Journal of Medicine (2016)

There remains a tremendous shortage of transplantable organs. In this report, a liver transplantation is successfully performed from an HIV-infected donor into an HIV-infected recipient, with 5 years of follow-up.
Impact of characteristics of organ failure and infected necrosis on mortality in necrotising pancreatitis
Authors: Nicolien J Schepers, Olaf J Bakker, Marc G Besselink, Usama Ahmed Ali, Thomas L Bollen, Hein G Gooszen, Hjalmar C van Santvoort, Marco J Bruno
Journal: Gut (2018)

Objective In patients with pancreatitis, early persisting organ failure is believed to be the most important cause of mortality. This study investigates the relation between the timing (onset and duration) of organ failure and mortality and its association with infected pancreatic necrosis in patients with necrotising pancreatitis. Design We performed a post hoc analysis of a prospective database of 639 patients with necrotising pancreatitis from 21 hospitals. We evaluated the onset, duration and type of organ failure (ie, respiratory, cardiovascular and renal failure) and its association with mortality and infected pancreatic necrosis. Results In total, 240 of 639 (38%) patients with necrotising pancreatitis developed organ failure. Persistent organ failure (ie, any type or combination) started in the first week in 51% of patients with 42% mortality, in 13% during the second week with 46% mortality and in 36% after the second week with 29% mortality. Mortality in patients with persistent multiple organ failure lasting &lt;1 week, 1–2 weeks, 2–3 weeks or longer than 3 weeks was 43%, 38%, 46% and 52%, respectively (p=0.68). Mortality was higher in patients with organ failure alone than in patients with organ failure and infected pancreatic necrosis (44% vs 29%, p=0.04). However, when excluding patients with very early mortality (within 10 days of admission), patients with organ failure with or without infected pancreatic necrosis had similar mortality rates (28% vs 34%, p=0.33). Conclusion In patients with necrotising pancreatitis, early persistent organ failure is not associated with increased mortality when compared with persistent organ failure which develops further on during the disease course. Furthermore, no association was found between the duration of organ failure and mortality.