tbuckley/cabot-search huggingface dataset:
Abstract 17298: Association of Left Atrial Size and Incident Heart Failure and All-cause Death: The Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Payman Zamani, Jesse Y Hsu, Martin G Keane, Nisha Bansal, Patrice Delafontaine, Alan S Go, Jiang He, Steven M Kawut, Bonnie Ky, Claudia M Lora, Stephen L Seliger, Tariq Sharif, Michael Shlipak, Kelvin Tao, Raymond R Townsend, Harold I Feldman, Rajat Deo
Journal: Circulation (2015)

Introduction: Chronic kidney disease (CKD) increases the risk for adverse cardiovascular events including heart failure (HF) and death. Left atrial size is an easily quantified metric that provides prognostic information in non-CKD populations. Hypothesis: We hypothesized that left atrial size would be an independent risk marker for incident HF and death in individuals with CKD. Methods: The Chronic Renal Insufficiency Cohort (CRIC) is a large, multicenter, multiracial cohort study established to understand the progression of cardiovascular and renal disease among individuals with CKD. We evaluated echocardiograms among participants without a history of heart failure. The left atrial area was measured in the apical 4-chamber view and indexed to body surface area (LAAI). Cox proportional hazards models were constructed to assess the risk between left atrial size and incident HF and death. Results: Among the 2960 CKD participants without known heart failure, higher tertiles of LAAI were associated with older age, Hispanic ethnicity, a history of stroke, myocardial infarction, atrial fibrillation, higher systolic blood pressure, hypertension, diabetes, and lower eGFR (P&lt;0.005 for all). The median left ventricular ejection fraction was 55% across LAAI tertiles. Over a median [IQR] follow-up of 6.6 [5.7-7.6] years, 344 participants developed HF and 472 died. An increase in LAAI was a strong risk marker for the development of heart failure after multivariable adjustment (Table 1). LAAI was modestly associated with all-cause death after controlling for demographics and clinical variables; however, additional adjustment for echocardiographic variables and cardiac biomarkers rendered the association non-significant. There was no significant interaction between LAAI and sex or race for either outcome. Conclusion: Among adults with CKD, LAAI is a stronger marker of risk for incident HF than death.
Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort
Authors: Carmine Rossi, Zahid A. Butt, Stanley Wong, Jane A. Buxton, Nazrul Islam, Amanda Yu, Maryam Darvishian, Mark Gilbert, Jason Wong, Nuria Chapinal, Mawuena Binka, Maria Alvarez, Mark W. Tyndall, Mel Krajden, Naveed Z. Janjua
Journal: Journal of Hepatology (2018)
Tracking Fenestrae Dynamics in Live Murine Liver Sinusoidal Endothelial Cells
Authors: Bartlomiej Zapotoczny, Karolina Szafranska, Edyta Kus, Filip Braet, Eddie Wisse, Stefan Chlopicki, Marek Szymonski
Journal: Hepatology (2018)

The fenestrae of liver sinusoidal endothelial cells (LSECs) allow passive transport of solutes, macromolecules, and particulate material between the sinusoidal lumen and the liver parenchymal cells. Until recently, fenestrae and fenestrae‐associated structures were mainly investigated using electron microscopy on chemically fixed LSECs. Hence, the knowledge about their dynamic properties has remained to date largely elusive. Recent progress in atomic force microscopy (AFM) has allowed the study of live cells in three dimensions (X, Y, and Z) over a prolonged time ( t ) and this at unprecedented speeds and resolving power. Hence, we employed the latest advances in AFM imaging on living LSECs. As a result, we were able to monitor the position, size, and number of fenestrae and sieve plates using four‐dimensional AFM (X, Y, Z, and t ) on intact LSECs in vitro . During these time‐lapse experiments, dynamic data were collected on the origin and morphofunctional properties of the filtration apparatus of LSECs. We present structural evidence on single laying and grouped fenestrae, thereby elucidating their dynamic nature from formation to disappearance. We also collected data on the life span of fenestrae. More especially, the formation and closing of entire sieve plates were observed, and how the continuous rearrangement of sieve plates affects the structure of fenestrae within them was recorded. We observed also the dawn and rise of fenestrae‐forming centers and defenestration centers in LSECs under different experimental conditions. Conclusion: Utilizing a multimodal biomedical high‐resolution imaging technique we collected fine structural information on the life span, formation, and disappearance of LSEC fenestrae; by doing so, we also gathered evidence on three different pathways implemented in the loss of fenestrae that result in defenestrated LSECs.
Interventions for Postsurgical Opioid Prescribing
Authors: Martha Wetzel, Jason Hockenberry, Mehul V. Raval
Journal: JAMA Surgery (2018)

Over the past 20 years, opioid misuse and opioid addiction have risen to epidemic proportions in the United States. One-third of adults receiving long-term opioid therapy report that their first opioid prescription came from a surgeon, indicating that postsurgical prescribing is an important point of intervention in the opioid epidemic. Such interventions differ from historical interventions on prescribing in that they must be closely monitored to ensure pain continues to be adequately controlled after surgical procedures. As evidence on nonopioid-based pain control grows, a key question is how to implement practice change in postsurgical discharge prescribing.To examine interventions associated with changing opioid prescription practices on surgical discharge.Studies published after 2000 that included interventions that aimed at postsurgical opiate stewardship and evaluated outcomes were included. PubMed and Embase were searched through March 2018 for relevant articles, with additional articles retrieved based on citations in articles retrieved in the initial search. Quality was assessed by 2 independent reviewers using the Quality Assessment Tool for Quantitative Studies, and quality scores were reconciled through discussion and mutual agreement.Eight studies met inclusion criteria, of which 3 were preintervention and postintervention comparison studies, 3 were controlled clinical studies, 1 was a time-series study, and 1 compared postintervention results with a predetermined baseline. Interventions done at the organization level, including changes to electronic health records order sets and workflow, showed clear positive results. Additionally, 2 studies that centered on developing guidelines based on actual patient opioid use and disseminating these guidelines to clinicians reported reductions up to 53% in the quantity prescribed. No increases in emergency department visits or refill requests were reported in studies measuring these outcomes. However, 1 study focused on reducing the number of children who were prescribed codeine found via check-in telephone calls that 13 of 240 patients (5.4%) had inadequately controlled pain.The studies reviewed provide evidence that clinician-mediated and organizational-level interventions are powerful tools in creating change in postsurgical opioid prescribing. This summary highlights paucity of high-quality studies that provide clear evidence on the most effective intervention at reducing postoperative opioid prescribing.
Meropenem/Vaborbactam: A Review in Complicated Urinary Tract Infections
Authors: Sohita Dhillon
Journal: Drugs (2018)

The global threat of the spread of carbapenem resistance in Enterobacteriaceae has led to the search for new antibacterials. Intravenous meropenem/vaborbactam (Vabomere™) is the first carbapenem/β-lactamase inhibitor combination approved in the USA for use in patients with complicated urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a potent inhibitor of class A serine carbapenemases, which, when combined with the antibacterial meropenem, restores the activity of meropenem against β-lactamase producing Enterobacteriaceae, particularly Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Meropenem/vaborbactam demonstrated excellent in vitro activity against Gram-negative clinical isolates, including KPC- and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. In the phase 3, noninferiority TANGO I trial in patients with cUTIs, intravenous meropenem/vaborbactam was noninferior to intravenous piperacillin/tazobactam for overall success (composite of clinical cure and microbial eradication; FDA primary endpoint) and microbial eradication (EMA primary endpoint). In subsequent superiority testing, meropenem/vaborbactam was superior to piperacillin/tazobactam for overall success. Meropenem/vaborbactam was generally well tolerated, with a tolerability profile generally similar to that of piperacillin/tazobactam. TANGO I did not assess the efficacy of meropenem/vaborbactam for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae and meropenem/vaborbactam is currently not indicated for these patients. Available evidence indicates that meropenem/vaborbactam is a useful treatment option for patients with cUTIs.
Sodium Excretion in Population Subgroups
Authors: Gesche Jürgens
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
Child Deaths From Pneumococcus and Hib Plummet
Authors: M.J. Friedrich
Journal: JAMA (2018)

The deaths of children in developing countries from the leading bacterial causes of pneumonia and meningitis—Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib)—declined between 2000 and 2015, according to a recent report in the Lancet Global Health.
Improving on Tail-of-the-Curve Evaluation With the American Society of Clinical Oncology Value Framework
Authors: Alexandre Vivot, Perrine Créquit, Raphaël Porcher
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
Combatting implant-associated biofilms through localized drug synthesis
Authors: Raoul Walther, Signe Maria Nielsen, Rikke Christiansen, Rikke L. Meyer, Alexander N. Zelikin
Journal: Journal of Controlled Release (2018)

Bacterial contamination of implantable biomaterials is a significant socioeconomic and healthcare burden. Indeed, bacterial colonization of implants after surgery has a high rate of incidence whereas concurrent prophylaxis using systemic antibiotics has limited clinical success. In this work, we develop enzyme-prodrug therapy (EPT) to prevent and to treat bacteria at interfaces. Towards the overall goal, novel prodrugs for fluoroquinolone antibiotics were developed on a privileged glucuronide scaffold. Whereas carbamoyl prodrugs were not stable and not suitable for EPT, glucuronides containing self-immolative linker between glucuronic acid masking group and the antibiotic were stable in solution and readily underwent bioconversion in the presence of β-glucuronidase. Surface coatings for model biomaterials were engineered using sequential polymer deposition technique. Resulting coatings afforded fast prodrug conversion and mediated antibacterial measures against planktonic species as evidenced by pronounced zone of bacterial growth inhibition around the biomaterial surface. These biomaterials coupled with the glucuronide prodrugs also effectively combatted bacteria within established biofilms and also successfully prevented bacterial colonization of the surface. To our knowledge, this is the first report of EPT engineered to the surface of biomaterials to mediate antibacterial measures.
Molecular Basis and Clinical Overview of McLeod Syndrome Compared With Other Neuroacanthocytosis Syndromes
Authors: Eileen Roulis, Catherine Hyland, Robert Flower, Christoph Gassner, Hans H. Jung, Beat M. Frey
Journal: JAMA Neurology (2018)

<h3>Importance</h3> McLeod syndrome, encoded by the gene<i>XK</i>, is a rare and progressive disease that shares important similarities with Huntington disease but has widely varied neurologic, neuromuscular, and cardiologic manifestations. Patients with McLeod syndrome have a distinct hematologic presentation with specific transfusion requirements. Because of its X-linked location, loss of the<i>XK</i>gene or pathogenic variants in this gene are principally associated with the McLeod blood group phenotype in male patients. The clinical manifestation of McLeod syndrome results from allelic variants of the<i>XK</i>gene or as part of a contiguous gene deletion syndrome involving<i>XK</i>and adjacent genes, including those for chronic granulomatous disease, Duchenne muscular dystrophy, and retinitis pigmentosa. McLeod syndrome typically manifests as neurologic and cardiologic symptoms that evolve in individuals beginning at approximately 40 years of age. <h3>Observations</h3> Diagnosis of McLeod syndrome encompasses a number of specialties, including neurology and transfusion medicine. However, information regarding the molecular basis of the syndrome is incomplete, and clinical information is difficult to find. The International Society of Blood Transfusion has recently compiled and curated a listing of<i>XK</i>alleles associated with the McLeod phenotype. Of note, McLeod syndrome caused by structural variants as well as those cases diagnosed as part of a contiguous gene deletion syndrome were previously classified under a singular allele designation. <h3>Conclusions and Relevance</h3> This review discusses the clinical manifestations and molecular basis of McLeod syndrome and provides a comprehensive listing of alleles with involvement in the syndrome published to date. This review highlights the clinical diversity of McLeod syndrome and discusses the development of molecular tools to elucidate genetic causes of disease. A more precise and systematic genetic classification is the first step toward correlating and understanding the diverse phenotypic manifestations of McLeod syndrome and may guide clinical treatment of patients and support for affected and carrier family members. This review provides a knowledge base for neurologists, hematologists, and clinical geneticists on this rare and debilitating disease.
Abstract 13129: Acute Inhibition of Sodium Channel Beta Subunit (β1) -mediated Adhesion is Highly Proarrhythmic
Authors: Rengasayee Veeraraghavan, Gregory S Hoeker, Steven Poelzing, Robert G Gourdie
Journal: Circulation (2016)

Introduction: The sodium channel auxiliary subunit and cell adhesion molecule β1 (SCN1b) is enriched at cardiomyocyte intercalated disks (ID) along with the pore-forming subunit Na V 1.5. We recently demonstrated that the perinexus, an Na V 1.5-rich ID nanodomain located near connexin43 (Cx43) gap junctions (GJ), is important for cell-to-cell electrical coupling. Disrupting close membrane apposition within the perinexus was highly proarrhythmic. Hypothesis: β1-mediated adhesion is key to close membrane apposition within the perinexus; therefore, inhibiting β1-mediated adhesion may disrupt perinexal structure, impair conduction and precipitate arrhythmias. Methods and Results: Na V 1.5 and β1 localization within ID nanodomains was quantitatively assessed from super-resolution STochastic Optical Reconstruction Microscopy (STORM) images of en face IDs from adult guinea pig ventricles. Na V 1.5 and β1 were located 63±15 and 75±25 nm from Cx43 GJ; 31% of both Na V 1.5 and β1 localized to GJ perinexi. β1-mediated adhesion was acutely inhibited by βadp1, a novel peptide mimetic of β1’s putative extracellular adhesion domain. βadp1 decreased cellular adhesion as assessed by Electric Cell-Substrate Impedance Spectroscopy (ECIS) in β1-overexpressing 1610 cells in a dose-dependent manner but not in native 1610 cells. Perinexal intermembrane spacing as measured by Transmission Electron Microscopy (TEM) increased 3-fold from 17±1 nm in vehicle controls (0.25% DMSO) to 49±5 nm (p&lt;0.05) in 100 μM βadp1-treated hearts; however, intermembrane spacing at other ID locations was unaltered (22±1 vs. 24±1 nm). Optical mapping revealed preferential slowing of transverse conduction (8.0±0.7 vs. 16.5±1.2 cm/s, p&lt;0.05) and increased anisotropy (3.9±0.2 vs. 2.6±0.2, p&lt;0.05) in βadp1-treated hearts relative to vehicle controls. Further, 3 of 4 βadp1-treated hearts exhibited spontaneous ventricular tachycardias. Conclusions: These data support a role for β1-mediated adhesion in maintaining close apposition between Na V 1.5-rich perinexal membranes. Importantly, acute inhibition of β1-mediated adhesion resulted in disruption of close membrane apposition within the GJ perinexus and precipitated severe conduction slowing and spontaneous arrhythmias.
Long-read sequencing across the C9orf72 ‘GGGGCC’ repeat expansion: implications for clinical use and genetic discovery efforts in human disease
Authors: Mark T. W. Ebbert, Stefan L. Farrugia, Jonathon P. Sens, Karen Jansen-West, Tania F. Gendron, Mercedes Prudencio, Ian J. McLaughlin, Brett Bowman, Matthew Seetin, Mariely DeJesus-Hernandez, Jazmyne Jackson, Patricia H. Brown, Dennis W. Dickson, Marka van Blitterswijk, Rosa Rademakers, Leonard Petrucelli, John D. Fryer
Journal: Molecular Neurodegeneration (2018)

Many neurodegenerative diseases are caused by nucleotide repeat expansions, but most expansions, like the C9orf72 'GGGGCC' (G4C2) repeat that causes approximately 5-7% of all amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases, are too long to sequence using short-read sequencing technologies. It is unclear whether long-read sequencing technologies can traverse these long, challenging repeat expansions. Here, we demonstrate that two long-read sequencing technologies, Pacific Biosciences' (PacBio) and Oxford Nanopore Technologies' (ONT), can sequence through disease-causing repeats cloned into plasmids, including the FTD/ALS-causing G4C2 repeat expansion. We also report the first long-read sequencing data characterizing the C9orf72 G4C2 repeat expansion at the nucleotide level in two symptomatic expansion carriers using PacBio whole-genome sequencing and a no-amplification (No-Amp) targeted approach based on CRISPR/Cas9.Both the PacBio and ONT platforms successfully sequenced through the repeat expansions in plasmids. Throughput on the MinION was a challenge for whole-genome sequencing; we were unable to attain reads covering the human C9orf72 repeat expansion using 15 flow cells. We obtained 8× coverage across the C9orf72 locus using the PacBio Sequel, accurately reporting the unexpanded allele at eight repeats, and reading through the entire expansion with 1324 repeats (7941 nucleotides). Using the No-Amp targeted approach, we attained > 800× coverage and were able to identify the unexpanded allele, closely estimate expansion size, and assess nucleotide content in a single experiment. We estimate the individual's repeat region was > 99% G4C2 content, though we cannot rule out small interruptions.Our findings indicate that long-read sequencing is well suited to characterizing known repeat expansions, and for discovering new disease-causing, disease-modifying, or risk-modifying repeat expansions that have gone undetected with conventional short-read sequencing. The PacBio No-Amp targeted approach may have future potential in clinical and genetic counseling environments. Larger and deeper long-read sequencing studies in C9orf72 expansion carriers will be important to determine heterogeneity and whether the repeats are interrupted by non-G4C2 content, potentially mitigating or modifying disease course or age of onset, as interruptions are known to do in other repeat-expansion disorders. These results have broad implications across all diseases where the genetic etiology remains unclear.