bluuebunny/crossref_metadata_2025_split huggingface dataset:
Care-limiting decisions in acute stroke and association with survival: analyses of UK national quality register data
Authors: Parry-Jones Adrian R , Paley Lizz , Bray Benjamin D , Hoffman Alex M , James Martin , Cloud Geoffrey C , Tyrrell Pippa J , Rudd Anthony G ,   on behalf of the SSNAP Collaborative Group
Published: January 2016

Background Prognosis after intracerebral hemorrhage (ICH) is poor and care-limiting decisions may worsen outcomes. Aims To determine whether in current UK stroke practice, key acute care decisions are associated with stroke subtype (ICH/ischemic) and whether these decisions are independently associated with survival. Methods We extracted data describing all stroke patients included in a UK quality register between 1 April 2013 and 31 March 2014. Key care decisions in our analyses were transfer to higher level care on admission and palliation in the first 72 h. We used multivariable regression models to test for associations between stroke subtype (ICH/ischemic), key care decisions, and survival. Results A total of 65,818 patients were included in the final analysis. After ICH ( n = 7020/65,818, 10.7%), 10.5% were palliated on the day of admission and 19.3% by 72 h (vs. 0.7% and 3.3% for ischemic stroke). Although a greater proportion were admitted directly to higher level care after ICH (3.7% vs. 1.5% for ischemic stroke), ICH was not independently associated with the decision to admit to higher level care (adjusted odds ratio (OR): 1.12, 95% confidence interval (95%CI): 0.95–1.31, p = 0.183). However, ICH was strongly associated with the decision to commence palliative care on the day of admission (OR: 7.27, 95%CI: 6.31–8.37, p < 0.001). Palliative care was independently associated with risk of death by 30 days regardless of stroke subtype. Conclusions When compared to ischemic stroke, patients with ICH are much more likely to commence palliative care during the first 72 h of their care, independent of level of consciousness, age, and premorbid health.
Comparative impact of implementing the 2013 or 2014 cholesterol guideline on vascular events in a quality improvement network
Authors: Egan Brent M. , Sutherland Susan E. , Childers William F. , Dahlheimer Ruthanne M. , Helmrich George A. , Lapeyrolerie Daryl A. , Markle Nancy , Murphy Dennis W. , Simmons Locke , Davis Robert A. , Tilkemeier Peter , Sinopoli Angelo 
Published: January 2016

Objectives: The Quality and Care Model Committee for a clinically integrated network requested a comparative analysis on the projected cardiovascular benefits of implementing either the 2013 and 2014 cholesterol guideline in a South Carolina patient population. A secondary request was to assess the relative risk of the two guidelines based on the literature. Methods: Electronic health data were obtained on 1,580,860 adults aged 21–80 years who had had one or more visits from January 2013 to June 2015; 566,688 had data to calculate 10-year atherosclerotic cardiovascular disease (ASCVD10) risk. Adults with end-stage renal disease ( n = 7852), congestive heart failure ( n = 19,818), alcohol or drug abuse ( n = 68,547), or currently on statins ( n = 154,964) were excluded leaving 315,508 for analysis. Estimated reduction in ASCVD10 assumed that: (a) moderate-intensity statins lowered low-density lipoprotein cholesterol (LDL-C) by 35% and high-intensity statins by 50%; (b) ASCVD events declined 22% for each 1 mmol/l fall in LDL-C. Results: Among the 315,508 adults in the analysis, 131,289 (41.6%) were eligible for statins according to the 2013 guideline and 137,375 (43.5%) to the 2014 guideline. The 2013 and 2014 guidelines were estimated to prevent 6780 and 5915 ASCVD events over 10 years with: (a) relative risk reductions of 29.0% and 21.8%; (b) absolute risk reductions of 5.2% and 4.3%; (c) number needed-to-treat (NNT) of 19 and 23, respectively. The greater projected cardiovascular protection with the 2013 guideline was largely related to greater use of high-dose statins, which carry a greater risk for adverse events. The literature indicates that the NNT for benefit with high-intensity versus moderate-intensity statins is 31 in high-risk patients with a number needed-to-harm of 47. Conclusions: The 2013 guideline is projected to prevent more clinical ASCVD events and with lower NNTs than the 2014 guideline, yet both have substantial benefit. The 2013 guideline is also expected to generate more adverse events, but the risk-benefit profile appears favor .
High Prevalence of Superior Labral Tears Diagnosed by MRI in Middle-Aged Patients With Asymptomatic Shoulders
Authors: Schwartzberg Randy , Reuss Bryan L. , Burkhart Bradd G. , Butterfield Matt , Wu James Y. , McLean Kevin W. 
Published: January 2016

Background: The incidence of superior labral surgery has increased in the past decade in the United States, and a contributing factor could be an increased rate of superior labral tears diagnosed with magnetic resonance imaging (MRI). Prior MRI studies of the asymptomatic shoulder have focused on rotator cuff pathology or pathology in a narrow and specific group of athletes. Labral abnormalities have not previously been thoroughly evaluated in asymptomatic middle-aged individuals. Purpose: To evaluate the prevalence of superior labral tears diagnosed by MRI in the asymptomatic shoulders of middle-aged people (age range, 45-60 years). Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 53 asymptomatic adults (age range, 45-60 years) with no history of surgery or injury to either shoulder were included in the study. Physical examinations of all shoulders were performed. Noncontrast MRI (1.5 T) was performed in 1 randomly determined shoulder of each subject. Two fellowship-trained musculoskeletal radiologists who were blinded to the purpose of the study and ages of the subjects evaluated each MRI. Results: Radiologists interpreted the MRIs as consistent with superior labral tears in 55% and 72% of the cohort. Comparison of the radiological evaluations of the superior labra were moderate (κ = 0.410, P = .033). There were no differences in readings for superior labral tear regarding age ( P = .87), sex ( P = .41), whether the dominant shoulder underwent MRI ( P = .99), whether the subject worked a physical job ( P = .08), or whether the subject participated in overhead sports for a period of 1 year ( P = .62). Conclusion: Superior labral tears are diagnosed with high frequency using MRI in 45- to 60-year-old individuals with asymptomatic shoulders. These shoulder MRI findings in middle-aged populations emphasize the need for supporting clinical judgment when making treatment decisions for this patient population. Clinical Relevance: To avoid overtreatment, physicians should realize that superior labral tears diagnosed by MRI in individuals between the ages of 45 and 60 years may be normal age-related findings.
Evangelization from the Inside: Reflections from a Prison Cell
Authors: Arias Mortimer 
Published: January 2016

The military coup in Bolivia on July 17, 1980 initiated a bloody and repressive situation in that country. It brought about the arrest and imprisonment in late August of former Methodist Bishop Mortimer Arias in Cochabamba, Bolivia—along with many other Protestant and Roman Catholic leaders, as well as countless lesser-known individuals. After thirty-seven days—during which time little was known by his family, friends, and church of his whereabouts and condition—Dr. Arias was suddenly released by the Bolivian authorities on condition that he leave the country immediately. Born in Uruguay, Mortimer Arias served as bishop of the Evangelical Methodist Church in Bolivia, and as executive secretary of the Council of Methodist Churches in Latin America, with offices in La Paz, Bolivia. Widely respected for his leadership in the ecumenical movement, Dr. Arias gave a memorable plenary address at the Fifth Assembly of the World Council of Churches (Nairobi, 1975) in which he called for a renewed recognition of evangelism as “an essential priority.” Renewal of the church, he said on that occasion, “does not come before mission but in mission.” He has served on previous occasions as visiting professor of evangelism both at Bostom University School of Theology and at Perkins School of Theology, Southern Methodist University, Dallas, Texas. In January 1981 Dr. Arias was appointed Professor of Mission and Evangelism at the School of Theology in Claremont, California. Upon his arrival in the United States, the International Bulletin invited Dr. Arias to share with our readers an account of his experience while in prison.
Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation
Authors: Machlus Kellie R. , Wu Stephen K. , Stumpo Deborah J. , Soussou Thomas S. , Paul David S. , Campbell Robert A. , Kalwa Hermann , Michel Thomas , Bergmeier Wolfgang , Weyrich Andrew S. , Blackshear Perry J. , Hartwig John H. , Italiano Joseph E. 
Published: January 2016

Key PointsProteomic analyses and polysome profiling of developing MKs identified a striking increase in the levels of a novel protein, MARCKS, during proplatelet formation. MARCKS deletion, inhibition, or phosphorylation inhibits proplatelet formation associated with activation of the actin-binding protein Arp2/3.
Optimization of a hybrid tower for onshore wind turbines by Building Information Modeling and prefabrication techniques
Authors: Alvarez-Anton Laura , Koob Manuel , Diaz Joaquin , Minnert Jens 
Published: January 2016

Abstract
Background
Nowadays wind energy is becoming increasingly significant in the planning, development and growth of new electricity supply systems. Special attention has been given to land-based turbines for ensuring the efficient economical operation of massive hubs rising 100m above the ground, based on the idea that the bigger the turbine, the more complicated are the transportation and assembly processes.

Methods
A new design of a wind turbine has several advantages compared to conventional designs; one of these advantages lies in the use of prefabricated elements, which increases efficiency. The implementation of information technology as a complement to prefabrication techniques is a further aim of this research, which seeks to improve the overall performance of the project. Consequently, Building Information Modelling is suggested as the most suitable methodology for complementing off-site techniques and reaching higher efficiency by improving design, manufacture, transportation and assembly processes.

Results
This paper will present the research project “hybrid² tower for wind turbines” funded by the State of Hesse, Germany, which focuses on a new, efficient and economical design for high wind turbine towers. The new hybrid² tower is composed of a concrete tower containing prefabricated concrete quarter-circle elements, steel beams and a steel tube tower on the top. The combination of concrete and steel beams improves the static and dynamic performance of the main supporting structure. With this new design, the weight of the concrete tower is estimated to decrease by 40 % compared to a traditional full-concrete tower and, as a positive consequence, the cost of assembly (including assembly on site) is reduced.

Conclusions
Due to the energy revolution, a special focus is put on the development of renewable energies, especially wind power. The steadily increasing hub heights of wind turbines means that tower structures have to be more massive. The development of the hybrid² tower by using Building Information Modeling and prefabrication techniques leads to an optimized performance and reduces transport and assembly costs.
Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue-Selective Estrogen Complex
Authors: Andersson Annica , Bernardi Angelina I. , Nurkkala-Karlsson Merja , Stubelius Alexandra , Grahnemo Louise , Ohlsson Claes , Carlsten Hans , Islander Ulrika 
Published: January 2016

AbstractIn addition to the systemic inflammation present in rheumatoid arthritis (RA), decreased estradiol levels in postmenopausal RA patients further accelerate bone loss in these patients. The tissue-selective estrogen complex (TSEC), an estrogen combined with a selective estrogen receptor modulator, is a new hormone replacement therapy option. The first approved TSEC, containing conjugated estrogens and bazedoxifene (BZA), reduces menopausal symptoms and prevents osteoporosis with an improved safety profile compared with conventional hormone replacement therapy. Previous studies have shown that estrogens strongly inhibit experimental arthritis whereas BZA is mildly suppressive. In this study the antiarthritic potential of combined BZA and estradiol is explored for the first time. Female ovariectomized DBA/1 mice were subjected to collagen-induced arthritis, an experimental postmenopausal RA model, and treated with BZA, 17β-estradiol (E2), combined BZA and E2 (BZA/E2), or vehicle. BZA/E2 suppressed arthritis severity and frequency, synovitis, and joint destruction, equally efficient as E2 alone. Unwanted estrogenic proliferative effects on the endometrium were blocked by the addition of BZA, determined by collecting uterine weights. Bone mineral density was measured by peripheral quantitative computed tomography, and all treatments protected collagen-induced arthritis mice from both trabecular and cortical bone loss. Moreover, BZA/E2, but not E2 alone, inhibited preosteoclast formation and reduced serum anticollagen type II antibodies. In conclusion, a TSEC, herein combined BZA/E2, suppresses experimental arthritis and prevents associated bone loss as efficiently as E2 alone but with minimal uterine effects, highlighting the need for clinical trials that evaluate the addition of a TSEC to conventional postmenopausal RA treatment.
SNaPP: Simplified Nanoproteomics Platform for Reproducible Global Proteomic Analysis of Nanogram Protein Quantities
Authors: Huang Eric L. , Piehowski Paul D. , Orton Daniel J. , Moore Ronald J. , Qian Wei-Jun , Casey Cameron P. , Sun Xiaofei , Dey Sudhansu K. , Burnum-Johnson Kristin E. , Smith Richard D. 
Published: January 2016

AbstractGlobal proteomic analyses of complex protein samples in nanogram quantities require a fastidious approach to achieve in-depth protein coverage and quantitative reproducibility. Biological samples are often severely mass limited and can preclude the application of more robust bulk sample processing workflows. In this study, we present a system that minimizes sample handling by using online immobilized trypsin digestion and solid phase extraction to create a simple, sensitive, robust, and reproducible platform for the analysis of nanogram-size proteomic samples. To demonstrate the effectiveness of our simplified nanoproteomics platform, we used the system to analyze preimplantation blastocysts collected on day 4 of pregnancy by flushing the uterine horns with saline. For each of our three sample groups, blastocysts were pooled from three mice resulting in 22, 22, and 25 blastocysts, respectively. The resulting proteomic data provide novel insight into mouse blastocyst protein expression on day 4 of normal pregnancy because we characterized 348 proteins that were identified in at least two sample groups, including 59 enzymes and blastocyst specific proteins (eg, zona pellucida proteins). This technology represents an important advance in which future studies could perform global proteomic analyses of blastocysts obtained from an individual mouse, thereby enabling researchers to investigate interindividual variation as well as increase the statistical power without increasing animal numbers. This approach is also easily adaptable to other mass-limited sample types.
Young Sexual Minority Males in the United States: Sociodemographic Characteristics And Sexual Attraction, Identity and Behavior
Authors: Fasula Amy M. , Oraka Emeka , Jeffries William L. , Carry Monique , Bañez Ocfemia M. Cheryl , Balaji Alexandra B. , Rose Charles E. , Jayne Paula E. ,   for the Workgroup on Adolescent Sexual and Reproductive Health
Published: January 2016

CONTEXTHIV incidence is increasing among 13–24‐year‐old U.S. men who have sex with men, yet limited research is available to guide HIV prevention efforts for this population.METHODSNational Survey of Family Growth data collected in 2002, in 2006–2010 and in 2011–2013 from 8,068 males aged 15–24 were analyzed to describe the population of U.S. young sexual minority males (i.e., males reporting same‐sex attraction, identity or behavior). Correlates of sexual minority classification were assessed in logistic regression models.RESULTSAn estimated 10% of young males, representing a population of 2.1 million, were sexual minorities. Males had an elevated likelihood of being sexual minorities if they were aged 18–19 or 20–24, rather than 15–17 (prevalence ratio, 1.7 for each); belonged to nonblack, non‐Hispanic racial or ethnic minority groups (1.6); had no religious affiliation, rather than considering religion very important (1.9); or lived below the federal poverty level (1.3). They had a reduced likelihood of being sexual minorities if they lived in metropolitan areas outside of central cities (0.7). Among young sexual minority males, 44% were 15–19 years old, 29% were poor and 59% resided outside central cities. Forty‐seven percent had engaged in same‐sex behavior. Of those with data on all measured dimensions of sexuality, 24% reported same‐sex attraction, identity and behavior; 22% considered themselves heterosexual, yet had had a male sex partner.CONCLUSIONFuture investigations can further explore subpopulations of young sexual minority males and assess sexual trajectories, resilience and HIV risk.
Cochlear Implant Stimulation of a Hearing Ear Generates Separate Electrophonic and Electroneural Responses
Authors: Sato Mika , Baumhoff Peter , Kral Andrej 
Published: January 2016

Electroacoustic stimulation in subjects with residual hearing is becoming more widely used in clinical practice. However, little is known about the properties of electrically induced responses in the hearing cochlea. In the present study, normal-hearing guinea pig cochleae underwent cochlear implantation through a cochleostomy without significant loss of hearing. Using recordings of unit activity in the midbrain, we were able to investigate the excitation patterns throughout the tonotopic field determined by acoustic stimulation. With the cochlear implant and the midbrain multielectrode arrays left in place, the ears were pharmacologically deafened and electrical stimulation was repeated in the deafened condition. The results demonstrate that, in addition to direct neuronal (electroneuronal) stimulation, in the hearing cochlea excitation of the hair cells occurs (“electrophonic responses”) at the cochlear site corresponding to the dominant temporal frequency components of the electrical stimulus, provided these are < 12 kHz. The slope of the rate–level functions of the neurons in the deafened condition was steeper and the firing rate was higher than in the hearing condition at those sites that were activated in the two conditions. Finally, in a monopolar stimulation configuration, the differences between hearing status conditions were smaller than in the narrower (bipolar) configurations.SIGNIFICANCE STATEMENTStimulation with cochlear implants and hearing aids is becoming more widely clinically used in subjects with residual hearing. The neurophysiological characteristics underlying electroacoustic stimulation and the mechanism of its benefit remain unclear. The present study directly demonstrates that cochlear implantation does not interfere with the normal mechanical and physiological function of the cochlea. For the first time, it double-dissociates the electrical responses of hair cells (electrophonic responses) from responses of the auditory nerve fibers (electroneural responses), with separate excited cochlear locations in the same animals. We describe the condition in which these two responses spatially overlap. Finally, the study implicates that using the clinical characteristics of stimulation makes electrophonic responses unlikely in implanted subjects.
Direct Evidence for Daily Plasticity of Electrical Coupling between Rod Photoreceptors in the Mammalian Retina
Authors: Jin Nan Ge , Ribelayga Christophe P. 
Published: January 2016

Rod photoreceptors are electrically coupled through gap junctions. Coupling is a key determinant of their light response properties, but whether rod electrical coupling is dynamically regulated remains elusive and controversial. Here, we have obtained direct measurements of the conductance between adjacent rods in mouse retina and present evidence that rod electrical coupling strength is dependent on the time of day, the lighting conditions, and the mouse strain. Specifically, we show in CBA/Ca mice that under circadian conditions, the rod junctional conductance has a median value of 98 pS during the subjective day and of 493 pS during the subjective night. In C57BL/6 mice, the median junctional conductance between dark-adapted rods is ∼140 pS, regardless of the time in the circadian cycle. Adaptation to bright light decreases the rod junctional conductance to ∼0 pS, regardless of the time of day or the mouse strain. Together, these results establish the high degree of plasticity of rod electrical coupling over the course of the day. Estimates of the rod coupling strength will provide a foundation for further investigations of rod interactions and the role of rod coupling in the ability of the visual system to anticipate, assimilate, and respond to the daily changes in ambient light intensity.SIGNIFICANCE STATEMENTMany cells in the CNS communicate via gap junctions, or electrical synapses, the regulation of which remains largely unknown. Here, we show that the strength of electrical coupling between rod photoreceptors of the retina is regulated by the time of day and the lighting conditions. This mechanism may help us understand some key aspects of day and night vision as well as some visual malfunctions.
Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2α‐mediated stress signaling
Authors: Santos Celio XC , Hafstad Anne D , Beretta Matteo , Zhang Min , Molenaar Chris , Kopec Jola , Fotinou Dina , Murray Thomas V , Cobb Andrew M , Martin Daniel , Zeh Silva Maira , Anilkumar Narayana , Schröder Katrin , Shanahan Catherine M , Brewer Alison C , Brandes Ralf P , Blanc Eric , Parsons Maddy , Belousov Vsevelod , Cammack Richard , Hider Robert C , Steiner Roberto A , Shah Ajay M 
Published: January 2016

AbstractPhosphorylation of translation initiation factor 2α (eIF2α) attenuates global protein synthesis but enhances translation of activating transcription factor 4 (ATF4) and is a crucial evolutionarily conserved adaptive pathway during cellular stresses. The serine–threonine protein phosphatase 1 (PP1) deactivates this pathway whereas prolonging eIF2α phosphorylation enhances cell survival. Here, we show that the reactive oxygen species‐generating NADPH oxidase‐4 (Nox4) is induced downstream of ATF4, binds to a PP1‐targeting subunit GADD34 at the endoplasmic reticulum, and inhibits PP1 activity to increase eIF2α phosphorylation and ATF4 levels. Other PP1 targets distant from the endoplasmic reticulum are unaffected, indicating a spatially confined inhibition of the phosphatase. PP1 inhibition involves metal center oxidation rather than the thiol oxidation that underlies redox inhibition of protein tyrosine phosphatases. We show that this Nox4‐regulated pathway robustly enhances cell survival and has a physiologic role in heart ischemia–reperfusion and acute kidney injury. This work uncovers a novel redox signaling pathway, involving Nox4–GADD34 interaction and a targeted oxidative inactivation of the PP1 metal center, that sustains eIF2α phosphorylation to protect tissues under stress.