bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and synthesis of pleated DNA origami nanotubes with adjustable diameters
Authors: Berengut Jonathan F , Berengut Julian C , Doye Jonathan P K , Prešern Domen , Kawamoto Akihiro , Ruan Juanfang , Wainwright Madeleine J , Lee Lawrence K 
Published: October 2019

Abstract
DNA origami allows for the synthesis of nanoscale structures and machines with nanometre precision and high yields. Tubular DNA origami nanostructures are particularly useful because their geometry facilitates a variety of applications including nanoparticle encapsulation, the construction of artificial membrane pores and as structural scaffolds that can uniquely spatially arrange nanoparticles in circular, linear and helical arrays. Here we report a system of parametrization for the design of radially symmetric DNA origami nanotubes with adjustable diameter, length, crossover density, pleat angle and chirality. The system is implemented into a computational algorithm that provides a practical means to navigate the complex geometry of DNA origami nanotube design. We apply this in the design, synthesis and characterization of novel DNA origami nanotubes. These include structures with pleated walls where the same number of duplexes can form nanotubes with different diameters, and to vary the diameter within the same structure. We also construct nanotubes that can be reconfigured into different chiral shapes. Finally, we explore the effect of strain on the local and global geometry of DNA origami nanotubes and demonstrate how pleated walls can provide a strategy to rigidify nanotubes and to construct closely packed parallel duplexes.
Single molecule analysis of effects of non-canonical guide RNAs and specificity-enhancing mutations on Cas9-induced DNA unwinding
Authors: Okafor Ikenna C , Singh Digvijay , Wang Yanbo , Jung Minhee , Wang Haobo , Mallon John , Bailey Scott , Lee Jungjoon K , Ha Taekjip 
Published: October 2019

Abstract
Cas9 has made a wide range of genomic manipulation possible. However, its specificity continues to be a challenge. Non-canonical gRNAs and new engineered variants of Cas9 have been developed to improve specificity, but at the cost of the on-target activity. DNA unwinding is a checkpoint before cleavage by Cas9, and was shown to be made more sensitive to sequence mismatches by specificity-enhancing mutations in engineered Cas9s. Here we performed single-molecule FRET-based DNA unwinding experiments using various combinations of non-canonical gRNAs and different Cas9s. All engineered Cas9s were less promiscuous than wild type when canonical gRNA was used, but HypaCas9 had much-reduced on-target unwinding. Cas9-HF1 and eCas9 showed the best balance between low promiscuity and high on-target activity with canonical gRNA. When extended gRNAs with one or two non-matching guanines added to the 5′ end were used, Sniper1-Cas9 showed the lowest promiscuity while maintaining high on-target activity. Truncated gRNA generally reduced unwinding and adding a non-matching guanine to the 5′ end of gRNA influenced unwinding in a sequence-context dependent manner. Our results are consistent with cell-based cleavage data and provide a mechanistic understanding of how various Cas9/gRNA combinations perform in genome engineering.
New developments on the Encyclopedia of DNA Elements (ENCODE) data portal
Authors: Luo Yunhai , Hitz Benjamin C , Gabdank Idan , Hilton Jason A , Kagda Meenakshi S , Lam Bonita , Myers Zachary , Sud Paul , Jou Jennifer , Lin Khine , Baymuradov Ulugbek K , Graham Keenan , Litton Casey , Miyasato Stuart R , Strattan J Seth , Jolanki Otto , Lee Jin-Wook , Tanaka Forrest Y , Adenekan Philip , O’Neill Emma , Cherry J Michael 
Published: October 2019

Abstract
The Encyclopedia of DNA Elements (ENCODE) is an ongoing collaborative research project aimed at identifying all the functional elements in the human and mouse genomes. Data generated by the ENCODE consortium are freely accessible at the ENCODE portal (https://www.encodeproject.org/), which is developed and maintained by the ENCODE Data Coordinating Center (DCC). Since the initial portal release in 2013, the ENCODE DCC has updated the portal to make ENCODE data more findable, accessible, interoperable and reusable. Here, we report on recent updates, including new ENCODE data and assays, ENCODE uniform data processing pipelines, new visualization tools, a dataset cart feature, unrestricted public access to ENCODE data on the cloud (Amazon Web Services open data registry, https://registry.opendata.aws/encode-project/) and more comprehensive tutorials and documentation.
Unrestricted Direct Access to Physical Therapist Services Is Associated With Lower Health Care Utilization and Costs in Patients With New-Onset Low Back Pain
Authors: Garrity Brigid M , McDonough Christine M , Ameli Omid , Rothendler James A , Carey Kathleen M , Cabral Howard J , Stein Michael D , Saper Robert B , Kazis Lewis E 
Published: October 2019

Abstract

Background
Low back pain (LBP) is one of the most prevalent conditions for which patients seek physical therapy in the United States. The American Physical Therapy Association categorizes direct access to physical therapist services into 3 levels: limited, provisional, and unrestricted.

Objective
The objective of this study was to evaluate the association of level of access to physical therapist services with LBP-related health care utilization and costs.

Design
This was a retrospective cohort study of patients with new-onset LBP between 2008 and 2013; data were from OptumLabs Data Warehouse.

Methods
We identified 59,670 individuals who were 18 years old or older, who had new-onset LBP, and who had commercial or Medicare Advantage insurance through a private health plan. We examined 2 samples. The first was health care utilization among individuals who saw a physical therapist first in states with either unrestricted access or provisional access. The second was LBP-related costs among individuals who saw either a physical therapist or a primary care physician first.

Results
Individuals who saw a physical therapist first in states with provisional access had significantly higher measures of health care utilization within 30 days, including plain imaging and frequency of physician visits, than individuals who saw a physical therapist first in states with unrestricted access. Compared with individuals who saw a primary care physician first, pooled across provisional-access and unrestricted-access states, those who saw a physical therapist first in provisional-access states had 25% higher relative costs at 30 days and 32% higher relative costs at 90 days, whereas those who saw a physical therapist first in unrestricted-access states had 13% lower costs at 30 days and 32% lower costs at 90 days.

Limitations
This was a claims-based study with limited information on patient characteristics, including severity and duration of pain.

Conclusions
Short-term LBP-related health care utilization and costs were lower for individuals in unrestricted-access states than in provisional-access states.
Diagnosis of giant cell arteritis
Authors: Ponte Cristina , Martins-Martinho Joana , Luqmani Raashid Ahmed 
Published: October 2019

Abstract
GCA is the most common form of primary systemic vasculitis affecting older people. It is considered a clinical emergency because it can lead to irreversible blindness in around 20% of untreated cases. High doses of glucocorticoids should be initiated promptly to prevent disease-related complications; however, glucocorticoids therapy usually results in significant toxicity. Therefore, correct diagnosis is crucial. For many years, temporal artery biopsy has been considered the diagnostic ‘gold standard’ for GCA, but it has many limitations (including low sensitivity). US has proven to be effective for diagnosing GCA and can reliably replace temporal artery biopsy in particular clinical settings. In cases of suspected GCA with large-vessel involvement, other imaging modalities can be used for diagnosis (e.g. CT and PET). Here we review the current evidence for each diagnostic modality and propose an algorithm to diagnose cranial-GCA in a setting with rapid access to high quality US.
Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients
Authors: Roelsgaard Ida K , Ikdahl Eirik , Rollefstad Silvia , Wibetoe Grunde , Esbensen Bente A , Kitas George D , van Riel Piet , Gabriel Sherine , Kvien Tore K , Douglas Karen , Wållberg-Jonsson Solveig , Rantapää Dahlqvist Solbritt , Karpouzas George , Dessein Patrick H , Tsang Linda , El-Gabalawy Hani , Hitchon Carol A , Pascual-Ramos Virginia , Contreras-Yáñez Irazú , Sfikakis Petros P , González-Gay Miguel A , Crowson Cynthia S , Semb Anne Grete 
Published: October 2019

Abstract

Objectives
Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients.

Methods
Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status.

Results
Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5–6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P &lt; 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P &lt; 0.001, respectively]. The CVD event rates for former and never smokers were comparable.

Conclusion
Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.
CONTEMPORARY RADIATION DOSES IN INTERVENTIONAL CARDIOLOGY: A NATIONWIDE STUDY OF PATIENT SKIN DOSES IN FINLAND
Authors: Järvinen Jukka , Sierpowska Joanna , Siiskonen Teemu , Husso Minna , Järvinen Hannu , Kiviniemi Tuomas , Rissanen Tuomas T , Lindholm Carita , Matikka Hanna , Larjava Heli R S , Mäkelä Timo J , Strengell Satu , Eskola Markku , Parviainen Teuvo , Hallinen Elina , Pirinen Markku , Kivelä Antti , Teräs Mika 
Published: October 2019

Abstract
In contemporary interventional cardiology, for typical elderly patients, the most severe radiation-related harm to patients can be considered to come from skin exposures. In this paper, maximum local skin doses in cardiological procedures are explored with Gafchromic film dosimetry. Film and reader calibrations and reading were performed at the Secondary Standards Dosimetry Laboratory of the Radiation and Nuclear Safety Authority (STUK), and data were gathered from seven hospitals in Finland. As alert levels for early transient erythema, 200 Gycm2 kerma area product (KAP) and 2000 mGy air kerma levels for transcatheter aortic valve implantations (TAVI) procedures are proposed. The largest doses were measured in TAVI (4158.8 mGy) and percutaneous coronary interventions (PCI) (941.68 mGy). Accuracies of the GE DoseWatch and Siemens CareMonitor skin dose estimates were reasonable, but more results are needed to reliably assess and validate the tools’ capabilities and reliabilities. Uncertainty of the Gafchromic dosimetry was estimated as 9.1% for a calibration with seven data points and 19.3% for a calibration with five data points.
Diabetes Mellitus
Authors: Kelley Carly E. , Weaver Anne 
Published: October 2019

Abstract:
Diabetes mellitus is a chronic illness with increased morbidity and mortality. The prevalence of diabetes mellitus is increasing among women of all ages. This monograph provides an overview of the pathophysiology, evaluation, and management of diabetes mellitus and comorbidities in women. Management approaches in pediatric, adolescent, reproductive-aged, perimenopausal, and postmenopausal patients are addressed.
Therapeutic Drug Monitoring Can Improve Linezolid Dosing Regimens in Current Clinical Practice: A Review of Linezolid Pharmacokinetics and Pharmacodynamics
Authors: Rao Gauri G. , Konicki Robyn , Cattaneo Dario , Alffenaar Jan-Willem , Marriott Deborah J. E. , Neely Michael ,   On behalf of the IATDMCT Antimicrobial Scientific Committee
Published: October 2019

Abstract:Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistantEnterococcus faecium, multi-drug resistantStreptococcus pneumoniae, and methicillin-resistantStaphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and neuropathy, which are more prevalent with higher exposures and longer treatment durations. Although linezolid is traditionally administered at a standard 600 mg dose every 12 hours, the resulting exposure can vary greatly between patients and can lead to treatment failure or toxicity. The efficacy and toxicity of linezolid are determined by the exposure achieved in the patient; numerous clinical and population pharmacokinetics (popPK) studies have identified threshold measurements for both parameters. Several special populations with an increased need for linezolid dose adjustments have also been identified. Therapeutic Drug Monitoring (TDM) is a clinical strategy that assesses the response of an individual patient and helps adjust the dosing regimen to maximize efficacy while minimizing toxicity. Adaptive feedback control and model-informed precision dosing are additional strategies that use Bayesian algorithms and PK models to predict patient-specific drug exposure. TDM is a very useful tool for patient populations with sparse clinical data or known alterations in pharmacokinetics, including children, patients with renal insufficiency or those receiving renal replacement therapy, and patients taking co-medications known to interact with linezolid. As part of the clinical workflow, clinicians can use TDM with the thresholds summarized from the current literature to improve linezolid dosing for patients and maximize the probability of treatment success.
Immediate Prepectoral Breast Reconstruction in Suboptimal Patients Using an Air-filled Spacer
Authors: Becker Hilton , Mathew Prakash J. 
Published: October 2019

Introduction:
Immediate prepectoral breast reconstruction offers excellent aesthetic results with less pain and elimination of animation deformity due to avoidance of pectoralis dissection and subpectoral implant placement. Concerns about the effects of prostheses on flap perfusion have limited use of the technique to highly selected patients. We present a series of “suboptimal” patients that have undergone immediate prepectoral breast reconstruction utilizing an air-filled “spacer” implant.

Methods:
A single surgeon’s experience with immediate, single-stage prepectoral breast reconstruction using a Spectrum implant was retrospectively reviewed. Patient demographics, adjuvant therapies, risk factors for threatened flaps, and complications, including those that required subsequent intervention, were evaluated.

Results:
Twenty-five patients (39 breasts) underwent immediate prepectoral reconstruction with a Spectrum implant. Ten patients had minor complications, 6 of whom required intervention with successful correction. There was a single case of implant loss in the series; this patient had prior radiation.

Conclusions:
Utilizing the spacer concept, immediate single-stage prepectoral breast reconstruction is a viable alternative to subpectoral implant placement or delay procedures. The technique delivers aesthetic results with less postoperative pain, quicker operative times, and avoidance of animation deformity. It can be considered for any patient, including high-risk patients such as those with radiation exposure, thin/threatened skin flaps, significant ptosis, and obesity.
Dissociation between hypertrophy and fibrosis in the left ventricle early after experimental kidney transplantation
Authors: Krebber Merle M. , Papazova Diana A. , Oosterhuis Nynke R. , Mokry Michal , Cramer Maarten J. , Cheng Caroline , Joles Jaap A. , Verhaar Marianne C. 
Published: October 2019

Objective:
Left ventricular (LV) hypertrophy is the most common cardiac alteration in patients with chronic kidney disease (CKD). Normalization of hypertension in CKD patients receiving a healthy kidney allograft often reverses LV hypertrophy, but effects on LV fibrosis remain unclear. To study causal interactions between graft and environment on LV hypertrophy, fibrosis and inflammation, we applied cross-kidney transplantation

Methods:
Orthotopic transplantation was performed after inducing CKD in rats by two-third bilateral ablation of kidney mass: Healthy kidney (K) donor to healthy heart (H) recipient (healthy-K→healthy-H); CKD-K→healthy-H; healthy-K→CKD-H; CKD-K→CKD-H; N= 6 per group.

Results:
At week 6 after transplantation, mean arterial pressure (MAP) and LV mass index (LVMI) increased in CKD-K versus healthy-K irrespective of recipient. Contrarily, LV fibrosis was more severe in CKD-H versus healthy-H recipients irrespective of graft. Indeed, MAP and plasma creatinine correlated with LVMI but not with LV fibrosis. Increased LVMI in CKD-K→CKD-H not accompanied by cardiomyocyte cross-sectional area gain is consistent with eccentric remodelling. Cardiac RNA sequencing found a strong transcriptional response associated with LV fibrosis but only sparse changes associated with LV hypertrophy. This response was, among others, characterized by changes in extracellular matrix (ECM) and inflammatory gene expression.

Conclusion:
LVMI reversed and MAP and renal function were normalized early after transplantation of a healthy kidney. However, LV fibrosis persisted, dissociating LV hypertrophy from LV fibrosis within 6 weeks. Elucidating cardiac ECM dynamics in CKD patients, although challenging, appears promising.
ASSESSING THE ACTIVITY OF MYOPIC CHOROIDAL NEOVASCULARIZATION
Authors: Li Songshan , Sun Limei , Zhao Xiujuan , Huang Sijian , Luo Xiaoling , Zhang Aiyuan , Chen Chonglin , Wang Zhirong , Liu Chengxi , Ding Xiaoyan 
Published: October 2019

Purpose:
This study aims to suggest a novel strategy for assessing the activity of myopic choroidal neovascularization (mCNV) based on optical coherence tomography angiography (OCTA) and to compare it with traditional fundus fluorescein angiography as the gold standard.

Methods:
Macular OCTA images were obtained using RTVue XR Avanti with AngioVue. Morphologic features of mCNV lesions were analyzed. Characteristics of OCTA in 41 eyes with active mCNV and 41 eyes with inactive mCNV were analyzed. Optical coherence tomography angiography parameters associated with mCNV activity and the clinical significance of their sensitivity and specificity were analyzed using fundus fluorescein angiography as the reference.

Results:
Of the total 108 patients, 82 had OCTA images with good quality which were included in this study. Several anatomical features of the CNV lesions, including overall appearance, branching with tiny vessels, presence of anastomoses/loops, and choroidal dark halo, were considered the possible parameters associated with mCNV activity. The intra- and interobserver agreements were substantial. To evaluate the CNV activity, sensitivity of overall appearance, tiny vascular branching, and presence of anastomoses or loops were 65.9%, 82.9%, and 73.2%, respectively, whereas the specificity was 87.8%, 90.2%, and 92.7%, respectively. However, the choroidal dark halo showed low specificity (46.3%) and failed in terms of evaluating the activity of mCNV. A novel comprehensive procedure integrating branching as a major parameter and overall appearance and presence of anastomoses/loops as minor parameters was developed to evaluate mCNV activity with sensitivity of 95.1% and specificity of 85.4%.

Conclusion:
In mCNV, the acquisition rate of clear OCTA images was 75.9%. A novel comprehensive diagnostic procedure combining mCNV appearance, vascular branching, and anastomoses/loops by OCTA may be a valuable strategy to evaluate neovascular activity in mCNV.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DETECTS SUBCLINICAL RADIAL PERIPAPILLARY CAPILLARY DENSITY REDUCTION AFTER PLAQUE RADIOTHERAPY FOR CHOROIDAL MELANOMA
Authors: Chien Jason L. , Sioufi Kareem , Ferenczy Sandor R. , Say Emil A. T. , Shields Carol L. 
Published: October 2019

Purpose:
To evaluate radial peripapillary capillary density (RPCD) in irradiated eyes without radiation papillopathy clinically.

Methods:
Patients treated with plaque radiotherapy for unilateral choroidal melanoma without radiation papillopathy clinically received optical coherence tomography and optical coherence tomography angiography imaging at ∼12- to 24-month follow-up. Comparison of RPCD globally and meridian closest to plaque and meridian farthest to plaque of irradiated versus nonirradiated eyes was performed.

Results:
Mean age was 55 years (n = 10). Mean largest basal diameter and thickness were 10.1 and 4.4 mm, respectively. Mean radiation dose to the optic nerve head and foveola was 41.7 and 66.2 Gy, respectively. No radiation papillopathy was detected by ophthalmoscopy throughout follow-up (mean:14 months). Radial peripapillary capillary density was significantly reduced globally (all P < 0.02). Meridian closest to plaque RPCD was significantly reduced (P < 0.01), but not meridian farthest to plaque RPCD (P = 0.07). Circumpapillary retinal nerve fiber layer thickness was not significantly reduced (P > 0.26). Radiation dose to the optic nerve head was correlated with meridian closest to plaque RPCD reduction (r = 0.76; P < 0.01). Mean radiation dose to the optic nerve head for <5% and ≥5% RPCD reductions was 35.9 ± 12.2 and 55.2 ± 6.4 Gy, respectively.

Conclusion:
Radial peripapillary capillary density reduction was found in irradiated eyes before clinical evidence of radiation papillopathy and circumpapillary retinal nerve fiber layer thickness reduction. Radial peripapillary capillary density reduction is correlated to plaque location and radiation dose to the optic nerve head.