bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Mutation in
FLNC
(Filamin C) Causes Familial Restrictive Cardiomyopathy
Authors: Tucker Nathan R. , McLellan Micheal A. , Hu Dongjian , Ye Jiangchuan , Parsons Victoria A. , Mills Robert W. , Clauss Sebastian , Dolmatova Elena , Shea Marisa A. , Milan David J. , Scott Nandita S. , Lindsay Mark , Lubitz Steven A. , Domian Ibrahim J. , Stone James R. , Lin Honghuang , Ellinor Patrick T. 
Published: December 2017

Background—
Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy characterized by impaired diastolic ventricular function resulting in a poor clinical prognosis. Rarely, heritable forms of RCM have been reported, and mutations underlying RCM have been identified in genes that govern the contractile function of the cardiomyocytes.

Methods and Results—

We evaluated 8 family members across 4 generations by history, physical examination, electrocardiography, and echocardiography. Affected individuals presented with a pleitropic syndrome of progressive RCM, atrioventricular septal defects, and a high prevalence of atrial fibrillation. Exome sequencing of 5 affected members identified a single novel missense variant in a highly conserved residue of FLNC (filamin C; p.V2297M).
FLNC
encodes filamin C—a protein that acts as both a scaffold for the assembly and organization of the central contractile unit of striated muscle and also as a mechanosensitive signaling molecule during cell migration and shear stress. Immunohistochemical analysis of FLNC localization in cardiac tissue from an affected family member revealed a diminished localization at the z disk, whereas traditional localization at the intercalated disk was preserved. Stem cell-derived cardiomyocytes mutated to carry the effect allele had diminished contractile activity when compared with controls.

Conclusion—

We have identified a novel variant in
FLNC
as pathogenic variant for familial RCM—a finding that further expands on the genetic basis of this rare and morbid cardiomyopathy.
Genome-Wide Gene–Potassium Interaction Analyses on Blood Pressure
Authors: Li Changwei , He Jiang , Chen Jing , Zhao Jinying , Gu Dongfeng , Hixson James E. , Rao Dabeeru C. , Jaquish Cashell E. , Rice Treva K. , Sung Yun Ju , Kelly Tanika N. 
Published: December 2017

Background—

Gene–environmental interaction analysis can identify novel genetic factors for blood pressure (BP). We performed genome-wide analyses to identify genomic loci that interact with potassium to influence BP using single-marker (1 and 2
df
joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity).

Methods and Results—

Among 1876 GenSalt participants, the average of 3 urine samples was used to estimate potassium excretion. Nine BP measurements were taken using a random-zero sphygmomanometer. A total of 2.2 million single nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (
P
<1.00×10
−
4
) from GenSalt were evaluated for replication among 775 Chinese participants of the MESA (Multi-ethnic Study of Atherosclerosis). Single nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1
df
tests identified interactions for
ARL15
rs16882447 on systolic BP (
P
=2.83×10
−9
) and
RANBP3L
rs958929 on pulse pressure (
P
=1.58×10
−8
). The 2
df
tests confirmed the
ARL15
rs16882447 signal for systolic BP (
P
=1.15×10
−9
). Genome-wide gene-based analysis identified
CC2D2A
(
P
=2.59×10
−7
) at 4p15.32 and
BNC2
(
P
=4.49×10
−
10
) at 9p22.2 for systolic BP,
GGNBP1
(
P
=1.18×10
−
8
), and
LINC00336
(
P
=1.36×10
−
8
) at 6p21 for diastolic BP,
DAB1
(
P
=1.05×10
−
13
) at 1p32.2, and
MIR4466
(
P
=5.34×10
−
8
) at 6q25.3 for pulse pressure. The
BNC2
(
P
=3.57×10
−
8
) gene was also significant for mean arterial pressure.

Conclusions—
We identified 2 novel BP loci and 6 genes through the examination of single nucleotide polymorphism- and gene-based interactions with potassium.
Selective NLRP3 (Pyrin Domain–Containing Protein 3) Inflammasome Inhibitor Reduces Brain Injury After Intracerebral Hemorrhage
Authors: Ren Honglei , Kong Ying , Liu Zhijia , Zang Dongyun , Yang Xiaoxia , Wood Kristofer , Li Minshu , Liu Qiang 
Published: December 2017

Background and Purpose—
Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. As a key component of the innate immune system, the NOD-like receptor (NLR) family, NLRP3 (pyrin domain–containing protein 3) inflammasome, when activated after ICH, promotes neuroinflammation and brain edema. MCC950 is a potent, selective, small-molecule NLRP3 inhibitor that blocks NLRP3 activation at nanomolar concentrations. Here, we examined the effect of MCC950 on brain injury and inflammation in 2 models of ICH in mice.

Methods—
In mice with ICH induced by injection of autologous blood or bacterial collagenase, we determined the therapeutic potential of MCC950 and its mechanisms of neuroprotection.

Results—

MCC950 reduced IL-1β (interleukin-1β) production and attenuated neurodeficits and perihematomal brain edema after ICH induction by injection of either autologous blood or collagenase. In mice with autologous blood-induced ICH, the protection of MCC950 was associated with reduced leukocyte infiltration into the brain and microglial production of IL-6. MCC950 improved blood–brain barrier integrity and diminished cell death. Notably, the protective effect of MCC950 was abolished in mice depleted of either microglia or Gr-1
+
myeloid cells.

Conclusions—
These results indicate that the NLRP3 inflammasome inhibitor, MCC950, attenuates brain injury and inflammation after ICH. Hence, NLRP3 inflammasome inhibition is a potential therapy for ICH that warrants further investigation.
IL-23 (Interleukin-23)–Producing Conventional Dendritic Cells Control the Detrimental IL-17 (Interleukin-17) Response in Stroke
Authors: Gelderblom Mathias , Gallizioli Mattia , Ludewig Peter , Thom Vivien , Arunachalam Priyadharshini , Rissiek Björn , Bernreuther Christian , Glatzel Markus , Korn Thomas , Arumugam Thiruma Valavan , Sedlacik Jan , Gerloff Christian , Tolosa Eva , Planas Anna M. , Magnus Tim 
Published: December 2017

Background and Purpose—
Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ and γδ T cells are established mediators of tissue damage in stroke, and the role of dendritic cells (DCs) in inducing the early events of T cell activation and differentiation in stroke is not well understood.

Methods—
In a murine model of experimental stroke, we defined the immune phenotype of infiltrating DC subsets based on flow cytometry of surface markers, the expression of ontogenetic markers, and cytokine levels. We used conditional DC depletion, bone marrow chimeric mice, and IL-23 (interleukin-23) receptor-deficient mice to further explore the functional role of DCs.

Results—

We show that the ischemic brain was rapidly infiltrated by IRF4
+
/CD172a
+
conventional type 2 DCs and that conventional type 2 DCs were the most abundant subset in comparison with all other DC subsets. Twenty-four hours after ischemia onset, conventional type 2 DCs became the major source of IL-23, promoting neutrophil infiltration by induction of IL-17 (interleukin-17) in γδ T cells. Functionally, the depletion of CD11c
+
cells or the genetic disruption of the IL-23 signaling abrogated both IL-17 production in γδ T cells and neutrophil infiltration. Interruption of the IL-23/IL-17 cascade decreased infarct size and improved neurological outcome after stroke.

Conclusions—
Our results suggest a central role for interferon regulatory factor 4-positive IL-23–producing conventional DCs in the IL-17–dependent secondary tissue damage in stroke.
Sphere-Filling Asymptotics of the Barotropic Potential Vorticity Staircase
Authors: Dunkerton Timothy J. 
Published: December 2017

Abstract
For barotropic flow in spherical geometry, the ideal potential vorticity staircase with flat steps and vertical risers exhibits a relationship between prograde jet strength and spacing such that, for regular spacing, the distance between adjacent jets is given by a suitably defined “Rhines scale” multiplied by a positive constant equal to . This result was obtained previously by the author in the equatorial limit of spherical geometry and by others in periodic beta-plane geometry. An improved asymptotic method has been devised to explain the strength–spacing relationship in sphere-filling solutions. This analysis explains the approximate validity of the equatorial asymptotics and yields new insight on minimum energy states and staircase mode transitions simulated in the presence of random, persistent energy inputs at high horizontal wavenumber.
Polar Mesoscale Cyclone Climatology for the Nordic Seas Based on ERA-Interim
Authors: Michel Clio , Terpstra Annick , Spengler Thomas 
Published: December 2017

AbstractPolar mesoscale cyclones (PMCs) are automatically detected and tracked over the Nordic seas using the Melbourne University algorithm applied to ERA-Interim. The novelty of this study lies in the length of the dataset (1979–2014), using PMC tracks to infer relationships to large-scale flow patterns, and elucidating the sensitivity to different selection criteria when defining PMCs and polar lows and their genesis environments. The angle between the ambient mean and thermal wind is used to distinguish two different PMC genesis environments. The forward shear environment (thermal and mean wind have the same direction) features typical baroclinic conditions with a temperature gradient at the surface and a strong jet stream at the tropopause. The reverse shear environment (thermal and mean wind have opposite directions) features an occluded cyclone with a barotropic structure throughout the entire troposphere and a low-level jet. In contrast to previous studies, PMC occurrence features neither a significant trend nor a significant link with the North Atlantic Oscillation and the Scandinavian blocking (SB), though the SB negative pattern seems to promote reverse shear PMC genesis. The sea ice extent in the Nordic seas is not associated with overall changes in PMC occurrence but influences the genesis location. Selected cold air outbreak indices and the temperature difference between the sea surface and 500 hPa (SST − T500) show no robust link with PMC occurrence, but the characteristics of forward shear PMCs and their synoptic environments are sensitive to the choice of the SST − T500 threshold.
Evaluation of RapidScat Ocean Vector Winds for Data Assimilation and Reanalysis
Authors: McCarty Will , Chattopadhyay Mohar , Conaty Austin 
Published: December 2017

Abstract
The Rapid Scatterometer (RapidScat) was built as a low-cost follow-on to the QuikSCAT mission. It flew on the International Space Station (ISS) and provided data from 3 October 2014 to 20 August 2016. These data allowed for the retrieval of surface wind vectors derived from surface roughness estimates measured from multiple coincident azimuth angles. These measurements were unique to the historical scatterometer record in that the ISS flies in a low inclination, non-sun-synchronous orbit. Scatterometry-derived wind vectors have been routinely assimilated in both forward processing and reanalysis systems run at the Global Modeling and Assimilation Office (GMAO). As the RapidScat retrievals were made available in near–real time, they were assimilated in the forward processing system, and the methods to assimilate and evaluate these retrievals are described. Time series of data statistics are presented first for the near-real-time data assimilated in GMAO forward processing. Second, the full data products provided by the RapidScat team are compared passively to the MERRA-2 reanalysis. Both sets of results show that the root-mean-square (RMS) difference of the observations and the GMAO model background fields increased over the course of the data record. Furthermore, the observations and the backgrounds are shown to be biased for both the zonal and meridional wind components. The retrievals are shown to have had a net forecast error reduction via the forecast sensitivity observation impact (FSOI) metric, which is a quantification of 24-h forecast error reduction, though the impact became neutral as the signal-to-noise ratio of the instrument decreased over its lifespan.
Exercise and Implicit Memory: A Brief Systematic Review
Authors: Loprinzi Paul D. , Edwards Meghan K. 
Published: December 2017

Background Emerging work demonstrates that acute exercise may enhance explicit memory function. No published systematic reviews have evaluated the totality of research examining the effects of exercise on implicit memory function, which was the purpose of this systematic review. Methods Databases (PubMed, PsychInfo, and Sports Discus) were searched to evaluate animal and human experimental studies evaluating the effects of exercise on implicit memory function. Results Among the 10 evaluated studies that met inclusionary criteria for this systematic review, 7 were conducted in animal models (rats or mice), with 3 utilizing human samples. Among the seven animal model studies, all employed a fear conditioning paradigm to evaluate implicit memory performance. All six animal studies employing a chronic exercise paradigm demonstrated evidence for associations between chronic exercise and enhanced fear conditioning. The one animal study evaluating a high-intensity acute bout of exercise showed that high-intensity acute exercise worsened implicit memory retrieval. Among the three human studies, one demonstrated a beneficial effect of acute exercise on implicit memory function. Discussion There is consistent evidence in animal models that chronic exercise enhances implicit memory, as assessed by fear conditioning. However, there have been too few human studies investigating this topic to render any meaningful conclusions regarding the relationship between exercise and cognitive-based implicit memory among humans.
Association of the CD11b rs1143679 polymorphism with systemic lupus erythematosus in the Han Chinese population
Authors: Li Chunmei , Tong Fengqing , Ma Yi , Qian Kai , Zhang Junyu , Chen Xingguo 
Published: December 2017

Objective To investigate the association of the CD11b single nucleotide polymorphism (SNP) rs1143679 with systemic lupus erythematosus (SLE) in Han Chinese patients, and to clarify this association with SLE clinical manifestations. Methods PCR–restriction fragment length polymorphism and direct sequencing of CD11b rs1143679 were conducted in 584 patients with SLE and 628 healthy controls in this case–control study to compare genotype and allele frequency distributions. Correlations between CD11b genotypes and clinical manifestations were also determined. Results The frequency of the CD11b rs1143679 GA genotype was 1.89% in Han Chinese patients with SLE, which was much lower than that of European and American populations, but close to the frequency observed in individuals from Hong Kong and Thailand. The CD11b rs1143679 GA genotype was also shown to confer susceptibility to SLE (odds ratio = 4.00, 95% confidence interval = 1.11–14.41). CD11b rs1143679 was found to be significantly associated with nephritis, but not with age of disease onset, arthritis, hematological involvement, or neural lesions. Conclusion CD11b rs1143679 appears to be associated with risk for SLE in the Han Chinese population, and may play an important role in the development of lupus nephritis.
RETRACTED: Pain predicts poorer health-related quality of life in childhood-onset systemic lupus erythematosus: a cohort study
Authors: Li Ji , Jones Jordan T. , Donnelly Catherine , Cunningham Natoshia , Kashikar-Zuck Susmita , Brunner Hermine I. 
Published: December 2017

At the request of the Journal’s Editor, the Publisher and the authors, the following article has been retracted. Li J, Jones JT, Donnelly C, Cunningham N, Kashikar-Zuck S and Brunner HI. Pain predicts poorer health-related quality of life in childhood-onset systemic lupus erythematosus: a cohort study. Journal of International Medical Research. Epub ahead of print 6 December 2017. DOI: 10.1177/0300060517732486. http://journals.sagepub.com/doi/full/10.1177/0300060517732486 The article has been retracted from Journal of International Medical Research because the co-authors of the paper had not consented to the paper’s submission for publication, and because the paper does not present the complete findings of the authors’ research. The corresponding author, Dr Li, submitted the paper with fraudulent contact details for his co-authors and without their consent to submit. Furthermore, the paper made use of an incomplete measurement scale that did not accurately reflect the complete findings of the study, which found other significant variables affected the value of using pain to measure the health-related quality of life of lupus patients. The complete findings of the study are presented in another paper published by the same authors: Donnelly C, Cunningham N, Jones JT, Li J, Brunner HI and Kashikar-Zuck S. Fatigue and depression predict reduced health-related quality of life in childhood-onset lupus. Lupus 2017; 27: 124–133. http://journals.sagepub.com/doi/full/10.1177/0961203317716317
Implementation of a Goal-Directed Mechanical Ventilation Order Set Driven by Respiratory Therapists Improves Compliance With Best Practices for Mechanical Ventilation
Authors: Radosevich Misty A. , Wanta Brendan T. , Meyer Todd J. , Weber Verlin W. , Brown Daniel R. , Smischney Nathan J. , Diedrich Daniel A. 
Published: December 2017

Purpose: Data regarding best practices for ventilator management strategies that improve outcomes in acute respiratory distress syndrome (ARDS) are readily available. However, little is known regarding processes to ensure compliance with these strategies. We developed a goal-directed mechanical ventilation order set that included physician-specified lung-protective ventilation and oxygenation goals to be implemented by respiratory therapists (RTs). We sought as a primary outcome to determine whether an RT-driven order set with predefined oxygenation and ventilation goals could be implemented and associated with improved adherence with best practice. Methods: We evaluated 1302 patients undergoing invasive mechanical ventilation (1693 separate episodes of invasive mechanical ventilation) prior to and after institution of a standardized, goal-directed mechanical ventilation order set using a controlled before-and-after study design. Patient-specific goals for oxygenation partial pressure of oxygen in arterial blood (Pao 2), ARDS Network [Net] positive end-expiratory pressure [PEEP]/fraction of inspired oxygen [Fio 2] table use) and ventilation (pH, partial pressure of carbon dioxide) were selected by prescribers and implemented by RTs. Results: Compliance with the new mechanical ventilation order set was high: 88.2% compliance versus 3.8% before implementation of the order set ( P < .001). Adherence to the PEEP/Fio 2 table after implementation of the order set was significantly greater (86.0% after vs 82.9% before, P = .02). There was no difference in duration of mechanical ventilation, intensive care unit (ICU) length of stay, and in-hospital or ICU mortality. Conclusions: A standardized best practice mechanical ventilation order set can be implemented by a multidisciplinary team and is associated with improved compliance to written orders and adherence to the ARDSNet PEEP/Fio 2 table.
Platelet-Rich Plasma Injection With Percutaneous Needling for Recalcitrant Lateral Epicondylitis: Comparison of Tenotomy and Fenestration Techniques
Authors: Gaspar Michael P. , Motto Michael A. , Lewis Sarah , Jacoby Sidney M. , Culp Randall W. , Lee Osterman A. , Kane Patrick M. 
Published: December 2017

Background: Recalcitrant lateral epicondylitis (LE) is a common debilitating condition, with numerous treatment options of varying success. An injection of platelet-rich plasma (PRP) has been shown to improve LE, although it is unclear whether the method of needling used in conjunction with a PRP injection is of clinical importance. Purpose: To determine whether percutaneous needle tenotomy is superior to percutaneous needle fenestration when each is combined with a PRP injection for the treatment of recalcitrant LE. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 93 patients with recalcitrant LE were treated with a PRP injection and percutaneous needle fenestration (n = 45) or percutaneous needle tenotomy (n = 48) over a 5-year study interval. Preoperative patient data, including visual analog scale for pain (VAS-P), Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Patient-Rated Tennis Elbow Evaluation (PRTEE) scores and grip strength, were obtained from a chart review and compared with postoperative values obtained prospectively. Secondary outcomes included the incidence of complications, need for additional interventions, return to work, and patient satisfaction. Results: At a mean follow-up of 40 months, significant improvements in VAS-P (mean, –6.1; 95% CI, –6.8 to –5.5; P < .0001), QuickDASH (mean, –46; 95% CI, –52 to –40; P < .0001), and PRTEE (mean, –57; 95% CI, –64 to –50; P < .0001) scores and grip strength (mean, +6.1 kg; 95% CI, 4.9 to 7.3; P < .0001) were observed across the entire study cohort, with no significant differences noted between the fenestration and tenotomy groups. Nine of 45 patients (22%) underwent additional procedures to treat recurrent symptoms in the fenestration group compared with 5 of 48 patients (10%) in the tenotomy group ( P = .05). No complications occurred in any patients, and no patients expressed dissatisfaction with their treatment course. Conclusion: A PRP injection with concomitant percutaneous needling is an effective treatment for recalcitrant LE, with sustained improvements in pain, strength, and function demonstrated at a mean follow-up of longer than 3 years. Although the method of concomitant needling does not appear to have a significant effect on treatment outcomes, more aggressive needle tenotomy is less likely to require conversion to open tenotomy than needle fenestration in the short term to midterm.
When can we stop anticoagulation in patients with cancer-associated thrombosis?
Authors: Lee Agnes Y. Y. 
Published: December 2017

Abstract
The optimal duration of anticoagulant therapy in patients with cancer-associated venous thromboembolism (VTE) is unknown. Without well-designed studies evaluating the efficacy, safety, and cost-effectiveness of continuing anticoagulant therapy beyond the acute treatment period of 3 to 6 months, evidence-based recommendations are lacking. Consensus guidelines generally suggest continuing anticoagulation treatment in patients with active cancer or receiving cancer treatment, with periodic reassessment of the risks and benefits. Unfortunately, with very little published data on the epidemiology of cancer-associated VTE beyond the initial 6 months, it is not possible for clinicians and patients to weigh risks and benefits in a quantitatively informed manner. Further research is needed to provide reliable and contemporary estimates on the risk of recurrent VTE off anticoagulant therapy, risk of bleeding on anticoagulant therapy, case fatality or all-cause mortality, and other important consequences of living with cancer-associated VTE. This chapter provides an overview of the published literature on real-world data on anticoagulant therapy use, the risks and risk factors of recurrent VTE and bleeding, and patient preference and values regarding long-term anticoagulation treatment. It will conclude with a pragmatic, experience-informed approach for tailoring anticoagulant therapy in patients with cancer-associated VTE.