Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population.

Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials.

Database resources of the National Center for Biotechnology Information in 2025.

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence repository and the PubMed® repository of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 31 distinct repositories and knowledgebases. The E-utilities serve as the programming interface for most of these.

5-Year Outcomes of Anterior Mitral Leaflet Laceration to Prevent Outflow Obstruction.

Background: Left ventricular outflow tract (LVOT) obstruction is a common, often fatal complication of transcatheter mitral valve replacement (TMVR). Laceration of the anterior mitral leaflet to prevent outflow obstruction (LAMPOON) was safe and effective at preventing LVOT obstruction at 30 days in the National Heart, Lung, and Blood Institute LAMPOON trial.

Objectives: The authors report the 5-year outcomes of intentional anterior mitral leaflet laceration before SAPIEN 3 TMVR, in patients at risk of LVOT obstruction.

Interventional cardiovascular magnetic resonance: state-of-the-art.

Transcatheter cardiovascular interventions increasingly rely on advanced imaging. X-ray fluoroscopy provides excellent visualization of catheters and devices, but poor visualization of anatomy. In contrast, magnetic resonance imaging (MRI) provides excellent visualization of anatomy and can generate real-time imaging with frame rates similar to X-ray fluoroscopy.

Transcatheter Mitral Cerclage Ventriculoplasty: From Bench to Bedside.

Background: Transcatheter mitral valve repair is beneficial in patients with mitral regurgitation (MR), left ventricular dysfunction, and persistent symptoms despite maximally tolerated medical therapy.

Objectives: The aim of this study was to evaluate the safety and feasibility of transcatheter mitral cerclage ventriculoplasty in patients with MR and either heart failure with reduced ejection fraction or preserved ejection fraction and in subjects with prior edge-to-edge repair but persistent or recurrent symptomatic MR.

Methods: The National Heart, Lung, and Blood Institute Division of Intramural Research Transcatheter Mitral Cerclage Ventriculoplasty Early Feasibility Study (NCT03929913) was an investigator-initiated prospective multicenter study.

The influence of decision-making in tree ring-based climate reconstructions.

Tree-ring chronologies underpin the majority of annually-resolved reconstructions of Common Era climate. However, they are derived using different datasets and techniques, the ramifications of which have hitherto been little explored. Here, we report the results of a double-blind experiment that yielded 15 Northern Hemisphere summer temperature reconstructions from a common network of regional tree-ring width datasets.

BASILICA Trial: One-Year Outcomes of Transcatheter Electrosurgical Leaflet Laceration to Prevent TAVR Coronary Obstruction.

Background: Coronary artery obstruction is a rare, devastating complication of transcatheter aortic valve replacement. Transcatheter electrosurgical aortic leaflet laceration (Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction [BASILICA]) is a novel technique to prevent coronary artery obstruction. We report the 1-year outcomes of the BASILICA trial.

Curating a comprehensive set of enzymatic reaction rules for efficient novel biosynthetic pathway design.

Enzyme substrate promiscuity has significant implications for metabolic engineering. The ability to predict the space of possible enzymatic side reactions is crucial for elucidating underground metabolic networks in microorganisms, as well as harnessing novel biosynthetic capabilities of enzymes to produce desired chemicals. Reaction rule-based cheminformatics platforms have been implemented to computationally enumerate possible promiscuous reactions, relying on existing knowledge of enzymatic transformations to inform novel reactions.

Dedicated Closure Device for Transcaval Access Closure: From Concept to First-in-Human Testing.

Objectives: This study sought to test safety and exploratory effectiveness of a dedicated transcaval closure device (TCD).

Background: Transcaval access enables delivery of large-caliber devices to the aorta in patients ineligible for transfemoral arterial access. Closure of aortocaval fistulae using off-label nitinol cardiac occluders has been shown to be safe, but persistent aortocaval fistulae at exit from the catheterization lab and bleeding complications were common in a prospective study.

The BASILICA Trial: Prospective Multicenter Investigation of Intentional Leaflet Laceration to Prevent TAVR Coronary Obstruction.

Objectives: The BASILICA (Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction during TAVR) investigational device exemption trial was a prospective, multicenter, single-arm safety and feasibility study.

Background: Coronary artery obstruction is a rare but devastating complication of transcatheter aortic valve replacement (TAVR). Current stent-based preventative strategies are suboptimal.

Anterior Leaflet Laceration to Prevent Ventricular Outflow Tract Obstruction During Transcatheter Mitral Valve Replacement.

Background: Left ventricular outflow tract (LVOT) obstruction is a leading cause of mortality and exclusion from transcatheter mitral valve replacement (TMVR). Intentional laceration of the anterior mitral valve leaflet to prevent LVOT obstruction (LAMPOON) is a transcatheter mimic of surgical chord-sparing leaflet resection.

Objectives: The purpose of this prospective multicenter trial was to study LAMPOON with transseptal (Edwards Lifesciences, Irvine, California) TMVR in annuloplasty rings or native mitral annular calcification (MAC).

The Fate of Transcaval Access Tracts: 12-Month Results of the Prospective NHLBI Transcaval Transcatheter Aortic Valve Replacement Study.

Objectives: The authors investigated 1-year outcomes after transcaval access and closure for transcatheter aortic valve replacement (TAVR), using commercially available nitinol cardiac occluders off-label.

Background: Transcaval access is a fully percutaneous nonfemoral artery route for TAVR. The intermediate-term fate of transcaval access tracts is not known.

Right heart catheterization using metallic guidewires and low SAR cardiovascular magnetic resonance fluoroscopy at 1.5 Tesla: first in human experience.

Background: Cardiovascular magnetic resonance (CMR) fluoroscopy allows for simultaneous measurement of cardiac function, flow and chamber pressure during diagnostic heart catheterization. To date, commercial metallic guidewires were considered contraindicated during CMR fluoroscopy due to concerns over radiofrequency (RF)-induced heating. The inability to use metallic guidewires hampers catheter navigation in patients with challenging anatomy.

Volcanic suppression of Nile summer flooding triggers revolt and constrains interstate conflict in ancient Egypt.

Volcanic eruptions provide tests of human and natural system sensitivity to abrupt shocks because their repeated occurrence allows the identification of systematic relationships in the presence of random variability. Here we show a suppression of Nile summer flooding via the radiative and dynamical impacts of explosive volcanism on the African monsoon, using climate model output, ice-core-based volcanic forcing data, Nilometer measurements, and ancient Egyptian writings. We then examine the response of Ptolemaic Egypt (305-30 BCE), one of the best-documented ancient superpowers, to volcanically induced Nile suppression.

Parental preferences toward genomic sequencing for non-medically actionable conditions in children: a discrete-choice experiment.

PurposeApplication of whole-exome and whole-genome sequencing is likely to increase in clinical practice, public health contexts, and research. We investigated how parental preference for acquiring information from genome-scale testing is influenced by the characteristics of non-medically actionable genetic disorders in children, as well as whether the preferences differed by gender and between African-American and white respondents.MethodsWe conducted a Web-based discrete-choice experiment with 1,289 parents of young children.

CMR fluoroscopy right heart catheterization for cardiac output and pulmonary vascular resistance: results in 102 patients.

Background: Quantification of cardiac output and pulmonary vascular resistance (PVR) are critical components of invasive hemodynamic assessment, and can be measured concurrently with pressures using phase contrast CMR flow during real-time CMR guided cardiac catheterization.

Methods: One hundred two consecutive patients underwent CMR fluoroscopy guided right heart catheterization (RHC) with simultaneous measurement of pressure, cardiac output and pulmonary vascular resistance using CMR flow and the Fick principle for comparison. Procedural success, catheterization time and adverse events were prospectively collected.

Screening for Obstructive Sleep Apnea in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Many adverse health outcomes are associated with obstructive sleep apnea (OSA).

Objective: To review primary care-relevant evidence on screening adults for OSA, test accuracy, and treatment of OSA, to inform the US Preventive Services Task Force.

Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through October 2015, references, and experts, with surveillance of the literature through October 5, 2016.

Physician Response to Contextualized Price-Comparison Claims in Prescription Drug Advertising.

Background: Physician-targeted prescription drug advertisements sometimes include price comparisons between products that may misleadingly imply equivalence of efficacy and safety or misrepresent true savings, suggesting the potential utility of a context statement to explain what the claims do and do not mean.

Methods: We manipulated the presence of a price claim and a context statement in a 1 × 3 (control condition, price-comparison-only, price-comparison-plus-context) between-subjects design. Physicians ( = 1,438), randomly assigned to condition, viewed the prescription drug ad and answered a brief survey.

Transcaval Access and Closure for Transcatheter Aortic Valve Replacement: A Prospective Investigation.

Background: Transcaval access may enable fully percutaneous transcatheter aortic valve replacement (TAVR) without the hazards and discomfort of transthoracic (transapical or transaortic) access.

Objectives: The authors performed a prospective, independently adjudicated, multicenter, single-arm trial of transcaval access for TAVR in patients who were ineligible for femoral artery access and had high or prohibitive risk of complications from transthoracic access.

Methods: A total of 100 patients underwent attempted percutaneous transcaval access to the abdominal aorta by electrifying a caval guidewire and advancing it into a pre-positioned aortic snare.

X-ray Fused With Magnetic Resonance Imaging to Guide Endomyocardial Biopsy of a Right Ventricular Mass.

Background: A patient with a history of cancer in remission and congestive heart failure with no acute symptoms presented for a follow-up echocardiogram. The scan revealed a new echodense mass filling his right ventricular apex. An endomyocardial biopsy guided by x-ray fused with magnetic resonance (MR) imaging (XFM) was performed.

Exploring De Novo metabolic pathways from pyruvate to propionic acid.

Industrial biotechnology provides an efficient, sustainable solution for chemical production. However, designing biochemical pathways based solely on known reactions does not exploit its full potential. Enzymes are known to accept non-native substrates, which may allow novel, advantageous reactions.

Perceptions and plans for prevention of Ebola: results from a national survey.

Background: Literature suggests that Americans may have higher levels of perceived threat to Ebola than are warranted.

Methods: We surveyed 1018 U.S.

Efficient searching and annotation of metabolic networks using chemical similarity.

Motivation: The urgent need for efficient and sustainable biological production of fuels and high-value chemicals has elicited a wave of in silico techniques for identifying promising novel pathways to these compounds in large putative metabolic networks. To date, these approaches have primarily used general graph search algorithms, which are prohibitively slow as putative metabolic networks may exceed 1 million compounds. To alleviate this limitation, we report two methods--SimIndex (SI) and SimZyme--which use chemical similarity of 2D chemical fingerprints to efficiently navigate large metabolic networks and propose enzymatic connections between the constituent nodes.