bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of Buprenorphine and Methadone among Opioid users who Inject Drugs
Authors: Tsui Judith I. , Burt Richard , Thiede Hanne , Glick Sara N.
Published: August 2017

Background

There has been a rise in opioid abuse and related injection drug use in the United States, and treatment for opioid use disorders may be underutilized. The study aim was to describe utilization of opioid agonist therapy (OAT), and assess factors associated with utilization of OAT, among persons who inject drugs (PWID) in the Seattle metropolitan area.

Methods

Data were obtained from the 2015 National HIV Behavioral Surveillance (NHBS) system among PWID in the Seattle area. Persons aged ≥18 years who injected drugs in the past year were recruited using respondent-driven sampling. Local supplemental questions assessed whether participants had received methadone or buprenorphine treatment in the past year. The analysis was restricted to participants who reported use of any opioids in the past year. Analyses compared the demographic, health insurance status, duration of injection drug use, prior history of overdose, prior receipt of hepatitis C virus/human immunodeficiency virus (HCV/HIV) testing (self-report), and screening positive for HCV/HIV via study testing between methadone- or buprenorphine-treated and untreated PWID. Multivariate logistic models were performed to assess adjusted associations with receipt of any OAT.

Results

The sample included 487 PWID who used opioids in the past year, of whom 27.1% (95% confidence interval [CI]: 23.1–31.1) reported past-year treatment with methadone and 4.7% (95% CI: 2.8–6.6) reported treatment with buprenorphine. There were no significant differences in demographics among participants who did and did not report past-year OAT; however, participants who were treated with methadone were more likely to be insured and have hepatitis C. After adjustment for other covariates, having health insurance was strongly associated with receipt of OAT (adjusted odds ratio [aOR] = 18.6; 95% CI: 2.5–138.7).

Conclusions

OAT, in particular buprenorphine, has been underutilized by opioid-using PWID in the Seattle area. Health insurance is a critical factor for enabling PWID to utilize OAT treatment for opioid use disorders.
PTPN2 regulates T cell lineage commitment and αβ versus γδ specification
Authors: Wiede Florian , Dudakov Jarrod A. , Lu Kun-Hui , Dodd Garron T. , Butt Tariq , Godfrey Dale I. , Strasser Andreas , Boyd Richard L. , Tiganis Tony
Published: August 2017

In the thymus, hematopoietic progenitors commit to the T cell lineage and undergo sequential differentiation to generate diverse T cell subsets, including major histocompatibility complex (MHC)–restricted αβ T cell receptor (TCR) T cells and non–MHC-restricted γδ TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into αβ TCR versus γδ TCR T cells remain unclear. Here, we show that the tyrosine phosphatase PTPN2 attenuates STAT5 (signal transducer and activator of transcription 5) signaling to regulate T cell lineage commitment and SRC family kinase LCK and STAT5 signaling to regulate αβ TCR versus γδ TCR T cell development. Our findings identify PTPN2 as an important regulator of critical checkpoints that dictate the commitment of multipotent precursors to the T cell lineage and their subsequent maturation into αβ TCR or γδ TCR T cells.
Control of cardiac ryanodine receptor by sarcoplasmic reticulum luminal Ca2+
Authors: Jones Peter P. , Guo Wenting , Chen S.R. Wayne
Published: August 2017

Jones et al. propose that SR luminal Ca2+ regulates RyR2 activity via a luminal Ca2+ sensor distinct from the cytosolic Ca2+ sensor.
The role of luminal Ca regulation in Ca signaling refractoriness and cardiac arrhythmogenesis
Authors: Györke Sándor , Belevych Andriy E. , Liu Bin , Kubasov Igor V. , Carnes Cynthia A. , Radwański Przemysław B.
Published: August 2017

Györke et al. discuss the role of sarcoplasmic reticulum Ca2+ in cardiac refractoriness and pathological implications.
Ambiguous interactions between diastolic and SR Ca2+ in the regulation of cardiac Ca2+ release
Authors: Sobie Eric A. , Williams George S.B. , Lederer W.J.
Published: August 2017

Sobie et al. highlight unresolved issues concerning the regulation of sarcoplasmic reticulum calcium release in cardiac myocytes.
Scaling Theory of Polyelectrolyte Nanogels*
Authors: Qu Li-Jian
Published: August 2017

The present paper develops the scaling theory of polyelectrolyte nanogels in dilute and semidilute solutions. The dependencies of the nanogel dimension on branching topology, charge fraction, subchain length, segment number, solution concentration are obtained. For a single polyelectrolyte nanogel in salt free solution, the nanogel may be swelled by the Coulombic repulsion (the so-called polyelectrolyte regime) or the osmotic counterion pressure (the so-called osmotic regime). Characteristics and boundaries between different regimes of a single polyelectrolyte nanogel are summarized. In dilute solution, the nanogels in polyelectrolyte regime will distribute orderly with the increase of concentration. While the nanogels in osmotic regime will always distribute randomly. Different concentration dependencies of the size of a nanogel in polyelectrolyte regime and in osmotic regime are also explored.
A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast
Authors: Clarke Jesse , Dephoure Noah , Horecka Ira , Gygi Steven , Kellogg Douglas
Published: August 2017

In budding yeast, cell cycle progression and ribosome biogenesis are dependent on plasma membrane growth, which ensures that events of cell growth are coordinated with each other and with the cell cycle. However, the signals that link the cell cycle and ribosome biogenesis to membrane growth are poorly understood. Here we used proteome-wide mass spectrometry to systematically discover signals associated with membrane growth. The results suggest that membrane trafficking events required for membrane growth generate sphingolipid-dependent signals. A conserved signaling network appears to play an essential role in signaling by responding to delivery of sphingolipids to the plasma membrane. In addition, sphingolipid-dependent signals control phosphorylation of protein kinase C (Pkc1), which plays an essential role in the pathways that link the cell cycle and ribosome biogenesis to membrane growth. Together these discoveries provide new clues as to how growth-­dependent signals control cell growth and the cell cycle.
The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces
Authors: Wakefield Devin L. , Holowka David , Baird Barbara
Published: August 2017

We examined the spatial targeting of early and downstream signaling mediated by the immunoglobulin E (IgE) receptor (FcεRI) in RBL mast cells using surface-patterned 2,4-dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to FcεRI on cells shows distinctive distributions: uniform for DNP-SLB and edge concentrated for DNP-BSA. These distributions of IgE-FcεRI propagate to the spatial recruitment of early signaling proteins, including spleen tyrosine kinase (Syk), linker for activation of T-cells (LAT), and activated phospholipase C gamma 1 (PLCγ1), which all localize with engaged receptors. We found stimulated polymerization of F-actin is not required for Syk recruitment but is progressively involved in the recruitment of LAT and PLCγ1. We further found β1- and β3-integrins colocalize with IgE-FcεRI at patterned ligand surfaces as cells spread. This recruitment corresponds to directed exocytosis of recycling endosomes (REs) containing these integrins and their fibronectin ligand. Together our results show targeting of signaling components, including integrins, to regions of clustered IgE-FcεRI in processes that depend on stimulated actin polymerization and outward trafficking of REs.
In silico identification of rescue sites by double force scanning
Authors: Tiberti Matteo , Pandini Alessandro , Fraternali Franca , Fornili Arianna
Published: August 2017

Motivation

A deleterious amino acid change in a protein can be compensated by a second-site rescue mutation. These compensatory mechanisms can be mimicked by drugs. In particular, the location of rescue mutations can be used to identify protein regions that can be targeted by small molecules to reactivate a damaged mutant.

Results

We present the first general computational method to detect rescue sites. By mimicking the effect of mutations through the application of forces, the double force scanning (DFS) method identifies the second-site residues that make the protein structure most resilient to the effect of pathogenic mutations. We tested DFS predictions against two datasets containing experimentally validated and putative evolutionary-related rescue sites. A remarkably good agreement was found between predictions and experimental data. Indeed, almost half of the rescue sites in p53 was correctly predicted by DFS, with 65% of remaining sites in contact with DFS predictions. Similar results were found for other proteins in the evolutionary dataset.

Availability and implementation

The DFS code is available under GPL at https://fornililab.github.io/dfs/

Supplementary information

Supplementary data are available at Bioinformatics online.
Decompositions of Grothendieck Polynomials
Authors: Pechenik Oliver , Searles Dominic
Published: August 2017

We investigate the long-standing problem of finding a combinatorial rule for the Schubert structure constants in the $K$-theory of flag varieties (in type $A$). The Grothendieck polynomials of A. Lascoux–M.-P. Schützenberger (1982) serve as polynomial representatives for $K$-theoretic Schubert classes; however no positive rule for their multiplication is known in general. We contribute a new basis for polynomials (in $n$ variables) which we call glide polynomials, and give a positive combinatorial formula for the expansion of a Grothendieck polynomial in this basis. We then provide a positive combinatorial Littlewood–Richardson rule for expanding a product of Grothendieck polynomials in the glide basis. Our techniques easily extend to the $\beta$-Grothendieck polynomials of S. Fomin–A. Kirillov (1994), representing classes in connective $K$-theory, and we state our results in this more general context.
Hyper Suprime-Cam: Camera dewar design
Authors: Komiyama Yutaka , Obuchi Yoshiyuki , Nakaya Hidehiko , Kamata Yukiko , Kawanomoto Satoshi , Utsumi Yousuke , Miyazaki Satoshi , Uraguchi Fumihiro , Furusawa Hisanori , Morokuma Tomoki , Uchida Tomohisa , Miyatake Hironao , Mineo Sogo , Fujimori Hiroki , Aihara Hiroaki , Karoji Hiroshi , Gunn James E , Wang Shiang-Yu
Published: August 2017

This paper describes the detailed design of the CCD dewar and the camera system which is a part of the wide-field imager Hyper Suprime-Cam (HSC) on the 8.2 m Subaru Telescope. On the 1.°5 diameter focal plane (497 mm in physical size), 116 four-side buttable 2 k × 4 k fully depleted CCDs are tiled with 0.3 mm gaps between adjacent chips, which are cooled down to −100°C by two pulse tube coolers with a capability to exhaust 100 W heat at −100°C. The design of the dewar is basically a natural extension of Suprime-Cam, incorporating some improvements such as (1) a detailed CCD positioning strategy to avoid any collision between CCDs while maximizing the filling factor of the focal plane, (2) a spherical washers mechanism adopted for the interface points to avoid any deformation caused by the tilt of the interface surface to be transferred to the focal plane, (3) the employment of a truncated-cone-shaped window, made of synthetic silica, to save the back focal space, and (4) a passive heat transfer mechanism to exhaust efficiently the heat generated from the CCD readout electronics which are accommodated inside the dewar. Extensive simulations using a finite-element analysis (FEA) method are carried out to verify that the design of the dewar is sufficient to satisfy the assigned errors. We also perform verification tests using the actually assembled CCD dewar to supplement the FEA and demonstrate that the design is adequate to ensure an excellent image quality which is key to the HSC. The details of the camera system, including the control computer system, are described as well as the assembling process of the dewar and the process of installation on the telescope.
Exploiting the sequence diversity of TALE-like repeats to vary the strength of dTALE-promoter interactions
Authors: de Lange Orlando , Schandry Niklas , Wunderlich Markus , Berendzen Kenneth Wayne , Lahaye Thomas
Published: August 2017

Designer transcription activator-like effectors (dTALEs) are programmable transcription factors used to regulate user-defined promoters. The TALE DNA-binding domain is a tandem series of amino acid repeats that each bind one DNA base. Each repeat is 33–35 amino acids long. A residue in the center of each repeat is responsible for defining DNA base specificity and is referred to as the base specificying residue (BSR). Other repeat residues are termed non-BSRs and can contribute to TALE DNA affinity in a non-base-specific manner. Previous dTALE engineering efforts have focused on BSRs. Non-BSRs have received less attention, perhaps because there is almost no non-BSR sequence diversity in natural TALEs. However, more sequence diverse, TALE-like proteins are found in diverse bacterial clades. Here, we show that natural non-BSR sequence diversity of TALEs and TALE-likes can be used to modify DNA-binding strength in a new form of dTALE repeat array that we term variable sequence TALEs (VarSeTALEs). We generated VarSeTALE repeat modules through random assembly of repeat sequences from different origins, while holding BSR composition, and thus base preference, constant. We used two different VarSeTALE design approaches combing either whole repeats from different TALE-like sources (inter-repeat VarSeTALEs) or repeat subunits corresponding to secondary structural elements (intra-repeat VarSeTALEs). VarSeTALE proteins were assayed in bacteria, plant protoplasts and leaf tissues. In each case, VarSeTALEs activated or repressed promoters with a range of activities. Our results indicate that natural non-BSR diversity can be used to diversify the binding strengths of dTALE repeat arrays while keeping target sequences constant.
Factors Associated With Health-Related Quality of Life in Patients With Open Fractures
Authors: Sprague Sheila , Petrisor Brad A. , Jeray Kyle J. , McKay Paula , Scott Taryn , Heels-Ansdell Diane , Schemitsch Emil H. , Liew Susan , Guyatt Gordon H. , Walter Stephen D. , Bhandari Mohit ,   on behalf of the FLOW Investigators
Published: August 2017

Objectives:

To analyze FLOW data to identify baseline patient, injury, fracture, and treatment factors associated with lower health-related quality of life (HRQoL) at 12-month postfracture.

Design:

Prognostic study using data from a prospective randomized controlled trial.

Setting:

Thirty-one clinical centers in the United States, Canada, Australia, and India.

Patients/Participants:

One thousand four hundred twenty-seven patients with open fracture from the FLOW trial with complete 12-month Short Form-12 (SF-12) follow-up assessment and no missing data for selected baseline factors.

Intervention:

Not applicable.

Main Outcome Measurement:

Physical Component Score (PCS) and the Mental Component Score (MCS) of the SF-12 at 12-month postfracture.

Results:

One thousand four hundred twenty-seven patients were included in the SF-12 PCS and MCS linear regression models. Smoking, lower preinjury SF-12 PCS and MCS, and work-related injuries were significantly associated with lower SF-12 PCS and MCS at 12-month postfracture. A lower extremity fracture and a wound that was not closed at initial irrigation and debridement were significantly associated with lower 12-month SF-12 PCS but not MCS. Only the adjusted mean difference for lower extremity fractures approached the minimally important difference for the SF-12 PCS.

Conclusions:

We identified a number of statistically significant baseline factors associated with lower HRQoL; however, only the presence of a lower extremity fracture approached clinical significance. More research is needed to quantify the impact of these factors on patients and to determine whether changes to modifiable factors at baseline will lead to clinically significant improvements in HRQoL after open fractures.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Principles of Lower Extremity Deformity Correction in Children
Authors: Mosca Vincent S.
Published: August 2017

Techniques change, but principles are forever. The techniques used to correct lower extremity deformities in children should be based on the principles of assessment and management of those deformities. This writing is a summation of the introductory lecture on deformity correction that highlights some of those principles.
MACROANEURYSMS ASSOCIATED WITH CONGENITAL RETINAL MACROVESSELS
Authors: Sebrow Dov B. , Cunha de Souza Eduardo , Belúcio Neto José , Roizenblatt Marina , Zett Lobos Claudio , Paulo Bonomo Pedro , Modi Yasha , Schuman Joel S. , Freund K. Bailey
Published: August 2017

Purpose:

Congenital retinal macrovessels are large aberrant retinal blood vessels that cross the horizontal raphe and can traverse the central macula. Using multimodal imaging and optical coherence tomography angiography, we describe 2 cases of congenital retinal macrovessel associated with macroaneurysms.

Methods:

Two patients presented for evaluation and were found to have congenital retinal macrovessels associated with macroaneurysms. Color photography, optical coherence tomography, fundus autofluorescence fluorescein angiography, and optical coherence tomography angiography were performed and used to establish the diagnosis and monitor resolution at follow-up visits.

Results:

The first patient presented with central vision loss in the right eye and was noted to have a ruptured macroaneurysm and scattered microaneurysms along the course of a venous macrovessel. After 3 months of observation, the patient's vision improved. The second patient presented for evaluation of a cataract in her left eye and was incidentally found to have an arterial macrovessel in her right eye with an associated macroaneurysm. Both cases demonstrated an intricate capillary network in the central macula best visualized on optical coherence tomography angiography.

Conclusion:

Macroaneurysms can occur on both arterial and venous macrovessels. After rupture of these lesions, hemorrhage and exudation can resolve with observation alone. Macrovessels can also present with microaneurysms. Optical coherence tomography angiography can effectively image the complex capillary network associated with these vascular anomalies.
Outcome of Micropulse Laser Transscleral Cyclophotocoagulation on Pediatric Versus Adult Glaucoma Patients
Authors: Lee Jun Hui , Shi Yuhua , Amoozgar Behzad , Aderman Christopher , De Alba Campomanes Alejandra , Lin Shan , Han Ying
Published: August 2017

Purpose:

To study and compare the outcome of micropulse transscelral cyclophotocoagulation in pediatric glaucoma patients to that in adult glaucoma patients.

Methods:

Consecutive pediatric and adult patients who received micropulse transscelral cyclophotocoagulation between July 2015 and December 2016 at University of California, San Francisco were retrospectively analyzed. All cases had at least 12 months of follow-up.

Results:

Nine eyes from 9 pediatric patients and 27 eyes from 25 adult patients were included. The sample size in pediatric group is small because MP-TCP was not offered to pediatric patients after unsatisfactory results in initial cases. Preoperatively, the mean intraocular pressure (IOP) was 28.41±8.32 mm Hg in adult patients and 34.28±9.92 mm Hg in pediatric patients. Postoperatively, the mean IOP in adult patients significantly decreased at all follow-up points (P<0.001). In pediatric patients, the mean IOP decreased to 20.44±13.41 mm Hg at 1 month (P=0.021), 23.56±10.10 mm Hg at 3 months (P=0.093), 23.00±8.31 mm Hg (P=0.018) at 6 months, and 27.20±15.68 mm Hg (P=0.15) at 12 months. No significant complications were noted in either group. The success rate in adults was 72.22% versus 22.22% in pediatric patients at 12 months (P=0.02). Seven of 9 pediatric patients required reoperation during the 12 months of follow-up.

Conclusions:

Micropulse transscelral cyclophotocoagulation is a safe procedure for pediatric as well as adult glaucoma patients. Its effect seems to be short lived in pediatric patients and the rate of reoperation was high.
Spontaneous Retinal Venous Pulsation in Unilateral Primary Open-angle Glaucoma With Low Intraocular Pressure
Authors: Lee EunJi , Kim Tae-Woo , Kim Jung-Ah , Kim Ji Ah , Kim Hyunjoong
Published: August 2017

Purpose:

The aim of this study was to investigate the presence of spontaneous retinal venous pulsation (SVP) in patients with unilateral primary open-angle glaucoma (POAG) and low intraocular pressure (IOP).

Materials and Methods:

The SVP of 93 POAG patients with unilateral glaucoma and untreated IOP of ≤21 mm Hg was assessed using the movie tool of a confocal scanning laser ophthalmoscope (Spectralis HRA; Heidelberg Engineering). The frequency of SVP was compared between the glaucomatous and fellow eyes. Intereye differences in the frequency of SVP were assessed using McNemar test. A linear mixed-effect model was used to determine the factors associated with glaucomatous eyes, taking into account clustering of eyes within subjects.

Results:

Forty-five patients had SVP in both eyes and 15 had SVP in neither eye. Of the remaining 33 patients who showed SVP only in 1 eye, 31 had SVP only in the fellow eye, and 2 had SVP only in the glaucomatous eye. The SVP was significantly less prevalent in glaucomatous eyes (50.5%) than in fellow control eyes (81.7%) (P<0.001). In the linear mixed-effect model, the presence of SVP (P<0.001) and higher untreated IOP (P=0.001) were the significant predictors for glaucoma.

Conclusions:

SVP was less frequently found in glaucomatous eyes than healthy fellow eyes in unilateral POAG patients with low IOP.
Nurses’ Perceptions of Psychosocial Care and Barriers to Its Provision: A Qualitative Study
Authors: Chen Cassandra Siyun , Chan Sally Wai-Chi , Chan Moon Fai , Yap Suk Foon , Wang Wenru , Kowitlawakul Yanika
Published: August 2017

Background:

Psychosocial care is the culturally sensitive provision of psychological, social, and spiritual care through therapeutic communication. Current evidence suggests that effective psychosocial care improves patients’ health outcomes and quality of life.

Purpose:

The aim of this study was to explore nurses’ perceptions and experiences in providing psychosocial care to patients and to identify the related barriers and challenges.

Methods:

An exploratory qualitative design using semistructured, individual, face-to-face interviews was adopted. A purposive sample of 18 registered nurses was recruited from the geriatric, medical, and surgical wards in an acute general hospital in Singapore. Interviews were audio-recorded, transcribed, and analyzed thematically.

Results:

Four major themes emerged: patient-centered care, communication, interprofessional care, and barriers to psychosocial care. Nurses perceived that psychosocial care consists of providing holistic care, spiritual care, support to the patient and family members, and showing empathy. Furthermore, psychosocial care is composed of communication between nurses and the patient and family members as well as communication among nurses. In addition, psychosocial care involves collaboration between healthcare professionals as well as multidisciplinary care. Barriers that are perceived by nurses include lack of time, language barriers, being task-oriented, excessive documentation, lack of family involvement, and fear of complaints.

Conclusions:

This study highlighted the perceptions of nurses regarding psychosocial care and the challenges in providing this care. Future studies are needed to explore ways to overcome these barriers and to enhance nurses’ competencies in providing psychosocial care. The findings indicate a need to plan future interventions to provide nurses with both skill development and support to improve their ability to integrate psychosocial care, which will improve patient outcomes.
Intention to Receive Breast Cancer Screening and Related Factors of Influence Among Vietnamese Women in Transnational Marriages
Authors: Lee* Fang-Hsin
Published: August 2017

Background:

Breast cancer is a major global health issue. Receiving regular breast cancer screenings aids in the early detection and treatment of breast cancer. Numerous factors influence whether a Vietnamese woman receives breast cancer screening.

Purpose:

The aims of this study were to understand current rates of breast cancer screening and explore the factors that influence intention to undergo breast cancer screening among Vietnamese women in transnational marriages.

Methods:

This was a cross-sectional, community-based study. Data were collected via snowball sampling. We enrolled 250 women aged 18 years and over from September to December 2015.

Results:

The percentage of participants who had received a breast self-examination, breast palpation, or breast ultrasound within the past year were 25.6%, 9.6%, and 21.2%, respectively. Moreover, only 6.8% of participants had received a mammography within the past 2 years. Participants with strong perceptions of breast cancer being a serious illness, who had fewer barriers to obtaining a breast cancer screening, or who had been advised by healthcare personnel to undergo screenings were more likely to report an intention to receive periodic breast self-examinations during the subsequent 1-year period. Participants who had lived in Taiwan for a longer period, had higher levels of perceived susceptibility to breast cancer, had prior experience with breast diseases, or had fewer barriers to obtaining a breast cancer screening were more likely to report an intention to receive a breast ultrasound during the subsequent 1-year period. Finally, participants who were older, perceived greater benefits from receiving breast cancer screening, and had not entered menopause were more likely to report an intention to receive a mammography during the following 2 years.

Conclusions/Implications for Practice:

Medical care personnel should promote breast cancer screening among Vietnamese women in transnational marriages. The results may be useful in promoting greater awareness among medical care personnel of breast cancer issues and efficacy in performing breast cancer screening for Vietnamese women in transnational marriages and provide references for the establishment of breast cancer prevention and control policies.
Rural-Urban Differences in Medicare Quality Outcomes and the Impact of Risk Adjustment
Authors: Henning-Smith Carrie , Kozhimannil Katy , Casey Michelle , Prasad Shailendra , Moscovice Ira
Published: August 2017

Background:

There has been considerable debate in recent years about whether, and how, to risk-adjust quality measures for sociodemographic characteristics. However, geographic location, especially rurality, has been largely absent from the discussion.

Objective:

To examine differences by rurality in quality outcomes, and the impact of adjustment for individual and community-level sociodemographic characteristics on quality outcomes.

Data Sources:

The 2012 Medicare Current Beneficiary Survey, Access to Care module, combined with the 2012 County Health Rankings. All data used were publicly available, secondary data. We merged the 2012 Medicare Current Beneficiary Survey data with the 2012 County Health Rankings data using county of residence.

Research Design:

We compared 6 unadjusted quality of care measures for Medicare beneficiaries (satisfaction with care, blood pressure checked, cholesterol checked, flu shot receipt, change in health status, and all-cause annual readmission) by rurality (rural noncore, micropolitan, and metropolitan). We then ran nested multivariable logistic regression models to assess the impact of adjusting for community and individual-level sociodemographic characteristics to determine whether these mediate the rurality difference in quality of care.

Results:

The relationship between rurality and change in health status was mediated by the inclusion of community-level characteristics; however, adjusting for community and individual-level characteristics caused differences by rurality to emerge in 2 of the measures: blood pressure checked and cholesterol checked. For all quality scores, model fit improved after adding community and individual characteristics.

Conclusions:

Quality is multifaceted and is impacted by individual and community-level socio-demographic characteristics, as well as by geographic location. Current debates about risk-adjustment procedures should take rurality into account.
A National Analysis of Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Stage I Non-small-cell Lung Cancer
Authors: Yang Chi-Fu Jeffrey , Kumar Arvind , Klapper Jacob A. , Hartwig Matthew G. , Tong Betty C. , Harpole David H. , Berry Mark F. , D’Amico Thomas A.
Published: August 2017

Objective:

The objective of this study was to compare the long-term survival of open versus thoracoscopic (VATS) lobectomy for early stage non-small-cell lung cancer (NSCLC).

Background:

Data from national studies on long-term survival for VATS versus open lobectomy are limited.

Methods:

Outcomes of patients who underwent open versus VATS lobectomy for clinical T1–2, N0, M0 NSCLC in the National Cancer Data Base were evaluated using propensity score matching.

Results:

The median follow-up of 7114 lobectomies (5566 open and 1548 VATS) was 52.0 months. The VATS approach was associated with a better 5-year survival when compared to the open approach (66.0% vs. 62.5%, P = 0.026). Propensity score matching resulted in 1464 open and 1464 VATS patients who were well matched by 14 common prognostic covariates including tumor size and comorbidities. After propensity score matching, the VATS approach was associated with a shorter median length of stay (5 vs. 6 days, P < 0.001). The VATS approach was not significantly different compared with the open approach with regard to nodal upstaging (11.6% vs 12.3%, P = 0.53), 30-day mortality (1.7% vs 2.3%, P = 0.50) and 5-year survival (66.3% vs 65.8%, P = 0.92).

Conclusions:

In this national analysis, VATS lobectomy was used in the minority of patients with stage I NSCLC. VATS lobectomy was associated with shorter length of stay and noninferior long-term survival when compared with open lobectomy. These results support previous findings from smaller single- and multi-institutional studies that suggest that VATS does not compromise oncologic outcomes when used for early-stage lung cancer and suggest the need for broader implementation of VATS techniques.
A dual sgRNA approach for functional genomics inArabidopsis thaliana[OPEN]
Authors: Pauwels Laurens , Clercq Rebecca De , Goossens Jonas , Iñigo Sabrina , Williams Clara , Ron Mily , Britt Anne , Goossens Alain
Published: August 2017

Reverse genetics uses loss-of-function alleles to interrogate gene function. The advent of CRISPR/Cas9-based gene editing now allows to generate knock-out alleles for any gene and entire gene families. Even in the model plantArabidopsis thaliana, gene editing is welcomed as T-DNA insertion lines do not always generate null alleles. Here, we show efficient generation of heritable mutations in Arabidopsis using CRISPR/Cas9 with a workload similar to generating overexpression lines. We obtain Cas9 null-segregants with bi-allelic mutations in the T2 generation. Out of seven new mutant alleles we report here, one allele forGRXS17, the ortholog of human GRX3/PICOT, did not phenocopy previously characterized nulls. Notwithstanding, the mutation caused a frameshift and triggered nonsense-mediated decay. We demonstrate that our workflow is also compatible with a dual sgRNA approach in which a gene is targeted by two sgRNAs simultaneously. This paired nuclease method can result in a more reliable loss-of-function alleles that lack a large essential part of the gene. The ease in the CRISPR/Cas9 workflow should help in the eventual generation of true null alleles of every gene in the Arabidopsis genome, which will advance both basic and applied plant research.

One-sentence summary

We present a dual sgRNA approach to delete Arabidopsis gene 34 fragments in order to obtain reliable functional knock-outs.
Systematic analysis ofatx-2 suppressors reveals a novel regulator of PAR-5/14-3-3sigma function during mitosis inCaenorhabditis elegans
Authors: Gnazzo Megan M. , Villarreal Alex R. , Skop Ahna R.
Published: August 2017

RNA regulation plays a critical role in mitosis, yet the mechanisms remain unclear. Our lab recently identified that the conserved RNA-Binding Protein (RBP), ATX-2, regulates cytokinesis by regulating the targeting of ZEN-4 to the spindle midzone through a conserved translation regulator, PAR-5/14-3-3sigma (Gnazzo et al., 2016). While co-depletion of ATX-2 and PAR-5 restored ZEN-4 targeting to the spindle midzone, it did not rescue cell division. To identify factors that may work in concert with ATX-2 to regulate cell division, we conducted a two-part, candidate RNAi suppressor and visual screen to identify factors that are important for cell division and also mediate the targeting of ATX-2 to the centrosomes and the spindle midzone. Using this approach, we identified ten genes that suppress the embryonic lethality defect observed inatx-2mutant embryos. These ten genes, includingact-2,cgh-1,cki-1,hum-6,par-2,rnp-4,vab-3,vhl-1,vps-24, andwve-1, all have some role regulating RNA or the cell cycle. Five of these genes (cgh-1,cki-1,vab-3,vhl-1,vps-24) fail to target ATX-2 to the centrosomes and midzone when depleted. The strongest suppressor of theatx-2phenotype is the DEAD-box RNA helicase CGH-1/DDX6, which has been implicated in cell division, RNA processing and translation, and neuronal function. Loss of CGH-1 rescued the cytokinesis defect and also restored ZEN-4 localization to the spindle midzone. ATX-2 and CGH-1 are mutually required for their localization to centrosomes and the spindle midzone. Our findings provide the first functional evidence that CGH-1/DDX6 regulates ATX-2 function during mitosis to target ZEN-4 to the spindle midzone via PAR-5/14-3-3sigma. We suggest that RNA machinery is necessary for the completion of cytokinesis.
Labeling RNAs in live cells using malachite green aptamer scaffolds as fluorescent probes
Authors: Yerramilli V. Siddartha , Kim Kyung Hyuk
Published: August 2017

RNAs mediate many different processes that are central to cellular function. The ability to quantify or image RNAs in live cells is very useful in elucidating such functions of RNA. RNA aptamerfluorogen systems have been increasingly used in labeling RNAs in live cells. Here, we use the malachite green aptamer (MGA), an RNA aptamer that can specifically bind to malachite green (MG) dye and induces it to emit far-red fluorescence signals. Previous studies on MGA showed a potential for the use of MGA for genetically tagging other RNA molecules in live cells. However, these studies also exhibited low fluorescence signals and high background noise. Here we constructed and tested RNA scaffolds containing multiple tandem repeats of MGA as a strategy to increase the brightness of the MGA aptamer-fluorogen system as well as to make the system fluoresce when tagging various RNA molecules, in live cells. We demonstrate that our MGA scaffolds can induce fluorescence signals by up to ~20 fold compared to the basal level as a genetic tag for other RNA molecules. We also show that our scaffolds function reliably as genetically-encoded fluorescent tags for mRNAs of fluorescent proteins and other RNA aptamers.
A strain-specific multiplex RT-PCR for Australian rabbit haemorrhagic disease viruses uncovers a new recombinant virus variant in rabbits and hares
Authors: Hall Robyn N , Mahar Jackie E. , Read Andrew J. , Mourant R , Piper M , Huang N , Strive Tanja
Published: August 2017

Rabbit haemorrhagic disease virus(RHDV, or GI.1), is a calicivirus in the genusLagovirusthat has been widely utilised in Australia as a biological control agent for the management of overabundant wild European rabbit (Oryctolagus cuniculus) populations since 1996. Recently, two exotic incursions of pathogenic lagoviruses have been reported in Australia; GI.1a-Aus, previously called RHDVa-Aus, is a GI.1a virus detected in January 2014, and the novel lagovirus GI.2 (previously known as RHDV2). Furthermore, an additional GI.1a strain, GI.1a-K5 (also known as 08Q712), was released nationwide in March 2017 as a supplementary tool for wild rabbit management. To discriminate between these lagoviruses, a highly sensitive strain-specific multiplex RT-PCR assay was developed, which allows fast, cost-effective, and sensitive detection of the four pathogenic lagoviruses currently known to be circulating in Australia. In addition, we developed a universal qRT-PCR assay to be used in conjunction with the multiplex assay that broadly detects all four viruses and facilitates quantification of viral RNA load in samples. These assays enable rapid detection, identification, and quantification of pathogenic lagoviruses in the Australian context. Using these assays, a novel recombinant lagovirus was detected in rabbit tissues samples, which contained the non-structural genes of GI.1a-Aus and the structural genes of GI.2. This variant was also recovered from the liver of a European brown hare (Lepus europaeus). The impact of this novel recombinant on Australian wild lagomorph populations and its competitiveness in relation to circulating field strains, particularly GI.2, requires further studies.
Asymmetry of an intracellular scaffold at vertebrate electrical synapses
Authors: Marsh Audrey J , Michel Jennifer Carlisle , Adke Anisha P , Heckman Emily L , Miller Adam C
Published: August 2017

Neuronal synaptic connections are electrical or chemical and together are essential to dynamically defining neural circuit function. While chemical synapses are well known for their biochemical complexity, electrical synapses are often viewed as comprised solely of neuronal gap junction channels that allow direct ionic and metabolic communication. However, associated with the gap junction channels are structures observed by electron microscopy called the Electrical Synapse Density (ESD). The ESD has been suggested to be critical for the formation and function of the electrical synapse, yet the biochemical makeup of these structures is poorly understood. Here we find that electrical synapse formationin vivorequires an intracellular scaffold called Tight Junction Protein 1b (Tjp1b). Tjp1b is localized to electrical synapses where it is required for the stabilization of the gap junction channels and for electrical synapse function. Strikingly, we find that Tjp1b protein localizes and functions asymmetrically, exclusively on the postsynaptic side of the synapse. Our findings support a novel model in which there is molecular asymmetry at the level of the intracellular scaffold that is required for building the electrical synapse. ESD molecular asymmetries may be a fundamental motif of all nervous systems and could support functional asymmetry at the electrical synapse.
Cortical processing of breathing perceptions in the athletic brain
Authors: Faull Olivia K. , Cox Pete J. , Pattinson Kyle T. S.
Published: August 2017

Athletes regularly endure large increases in ventilation, and accompanying perceptions of breathlessness. While breathing perceptions often correlate poorly with objective measures of lung function in both health and clinical populations, we have previously demonstrated closer matching between subjective breathlessness and changes in ventilation in endurance athletes, suggesting that athletes may be more accurate during respiratory interoception. To better understand the link between exercise and breathlessness, we sought to identify the mechanisms by which the brain processing of respiratory perception might be optimised in athletes.

Twenty endurance athletes and 20 sedentary controls underwent 7 Tesla functional magnetic resonance imaging. Inspiratory resistive loading induced conscious breathing perceptions (breathlessness), and a delay-conditioning paradigm was employed to evoke preceding periods of anticipation. Athletes demonstrated anticipatory brain activity that positively correlated with resulting breathing perceptions within key interoceptive areas, such as the thalamus, insula and primary sensorimotor cortices, which was negatively correlated in sedentary controls. Athletes also exhibited greater connectivity between interoceptive attention networks and primary sensorimotor cortex. These functional differences in athletic brains suggest that exercise may optimise processing of respiratory sensations. Future work may probe whether these brain mechanisms are harnessed when exercise is employed to treat breathlessness within chronic respiratory disease.
Efficient parameterization of large-scale mechanistic models enables drug response prediction for cancer cell lines
Authors: Fröhlich Fabian , Kessler Thomas , Weindl Daniel , Shadrin Alexey , Schmiester Leonard , Hache Hendrik , Muradyan Artur , Schütte Moritz , Lim Ji-Hyun , Heinig Matthias , Theis Fabian J. , Lehrach Hans , Wierling Christoph , Lange Bodo , Hasenauer Jan
Published: August 2017

The response of cancer cells to drugs is determined by various factors, including the cells’ mutations and gene expression levels. These factors can be assessed using next-generation sequencing. Their integration with vast prior knowledge on signaling pathways is, however, limited by the availability of mathematical models and scalable computational methods. Here, we present a computational framework for the parameterization of large-scale mechanistic models and its application to the prediction of drug response of cancer cell lines from exome and transcriptome sequencing data. With this framework, we parameterized a mechanistic model describing major cancer-associated signaling pathways (>1200 species and >2600 reactions) using drug response data. For the parameterized mechanistic model, we found a prediction accuracy, which exceeds that of the considered statistical approaches. Our results demonstrate for the first time the massive integration of heterogeneous datasets using large-scale mechanistic models, and how these models facilitate individualized predictions of drug response. We anticipate our parameterized model to be a starting point for the development of more comprehensive, curated models of signaling pathways, accounting for additional pathways and drugs.
Nitric oxide-dependent inflammation underlies Notch and PI3K/Akt oncogene cooperation
Authors: Villegas Santiago Nahuel , Gombos Rita , Pérez Irene Gutiérrez , López Lucia García , García-Castillo Jesús , Vallejos Diana Marcela , Ros Vanina Da , Mihály József , Dominguez Maria
Published: August 2017

Concurrent activating mutations of the Notch and PI3K/Akt signalling pathways cooperate in the induction of aggressive cancers. Unfortunately, direct targeting of any of these aberrant pathways can result in severe side effects due to their broad physiological roles in multiple organs. Here, using an unbiased chemicalin vivoscreen inDrosophilawe identified compounds that suppress the activity of the pro-inflammatory enzymes, nitric oxide synthase (NOS) and lipoxygenase (LOX), capable to block oncogenic Notch-PI3K/Akt cooperation without unwanted side effects. Genetic inactivation of NOS and LOX signalling components mirrors the anti-tumorigenic effect of the hit compounds. We show that NOS activity and immunosuppression associated to inflammation facilitates Notch-mediated tumorigenesis. Our study reveals an unnoticed immune inflammatory process underlying Notch-PI3K/Akt tumours and exposes NOS as a druggable target for anti-cancer therapeutic development.
Divergence estimation in the presence of incomplete lineage sorting and migration
Authors: Jones Graham
Published: August 2017

This paper focuses on the problem of estimating a species tree from multilocus data in the presence of incomplete lineage sorting and migration. We develop a mathematical model similar to IMa2 (Hey 2010) for the relevant evolutionary processes which allows both the the population size parameters and the migration rates between pairs of species tree branches to be integrated out. We then describe a BEAST2 package DENIM which based on this model, and which uses an approximation to sample from the posterior. The approximation is based on the assumption that migrations are rare, and it only samples from certain regions of the posterior which seem likely given this assumption. The method breaks down if there is a lot of migration. Using simulations, Leaché et al 2014 showed migration causes problems for species tree inference using the multispecies coalescent when migration is present but ignored. We re-analyze this simulated data to explore DENIM’s performance, and demonstrate substantial improvements over *BEAST. We also re-analyze an empirical data set. [isolation-with-migration; incomplete lineage sorting; multispecies coalescent; species tree; phylogenetic analysis; Bayesian; Markov chain Monte Carlo]
Population genomics ofWolbachiaand mtDNA inDrosophila simulansfrom California
Authors: Signor Sarah
Published: August 2017

Wolbachia pipientisis an intracellular endosymbiont in fecting many arthropods and filarial nematodes. Little is known about the short-term evolution ofWolbachiaor its interaction with its host.Wolbachiais maternally inherited, resulting in co-inheritance of mitochondrial organelles such as mtDNA. Here I explore the short-term evolution ofWolbachia, and the relationship betweenWolbachiaand mtDNA, using a large inbred panel ofDrosophila simulansinfected with theWolbachiastrainwRi. I find reduced diversity relative to expectation in bothWolbachiaand mtDNA, but only mtDNA shows evidence of a recent selective sweep or population bottleneck. I estimateWolbachiaand mtDNA titre in each genotype, and I find considerable variation in both phenotypes, despite low genetic diversity inWolbachiaand mtDNA. A phylogeny ofWolbachiaand of mtDNA show that both trees are largely unresolved, suggesting a recent origin of the infection and a single origin. Using Wolbachia and mtDNA titre as a phenotype, we perform an association analysis with the nuclear genome and find several regions implicated in the phenotype, including one which contains four CAAX-box protein processing genes. CAAX-box protein processing can be an important part of host-pathogen interactions in other systems, suggesting interesting directions for future research.