bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hip position and sex differences in motor unit firing patterns of the vastus medialis and vastus medialis oblique in healthy individuals
Authors: Peng Yi-Ling , Tenan Matthew S. , Griffin Lisa 
Published: February 2018

Weakness of the vastus medialis oblique (VMO) has been proposed to explain the high prevalence of knee pain in female subjects. Clinicians commonly use exercises in an attempt to preferentially activate the VMO. Recently, our group found evidence to support clinical theory that the VMO is neurologically distinct from the vastus medialis (VM). However, the ability to voluntarily activate these muscle subsections is still disputed. The aim of this study was to determine if VM and VMO activation varies between sexes and if control of the two muscles is different between rehabilitation exercises. Thirteen men and 13 women performed isometric straight leg raises in two hip positions, neutral hip rotation and 30 degrees lateral hip rotation. Bipolar intramuscular fine-wire electrodes were inserted into the VM and VMO to obtain motor unit recruitment thresholds and initial firing rates at recruitment. Linear mixed models and Tukey post hoc tests were used to assess significant differences in 654 motor units. Women demonstrated faster motor unit firing rate at recruitment, 1.18 ± 0.56 Hz higher than men. Motor units fired 0.47 ± 0.19 Hz faster during neutral hip rotation compared with lateral hip rotation. The VMO motor units were recruited 2.92 ± 1.28% earlier than the VM. All motor units were recruited 3.74 ± 1.27% earlier during neutral hip rotation than lateral hip rotation. Thus the VM and the VMO can be activated differentially, and their motor unit recruitment properties are affected by sex and hip position. NEW & NOTEWORTHY This is the first study to reveal differential activation of the vastus medialis oblique from the vastus medialis in clinical exercise protocols. Our research group used fine-wire electrodes to examine EMG signals of the vastus medialis oblique and vastus medialis to avoid possible cross talk. We also consider the effect of sex on motor unit firing patterns because of higher prevalence of knee pain in women, and yet few studies evaluating the sex differences in neuromuscular control.
Characterizing the Potency and Impact of Carbon Ion Therapy in a Primary Mouse Model of Soft Tissue Sarcoma
Authors: Brownstein Jeremy M. , Wisdom Amy J. , Castle Katherine D. , Mowery Yvonne M. , Guida Peter , Lee Chang-Lung , Tommasino Francesco , Tessa Chiara La , Scifoni Emanuele , Gao Junheng , Luo Lixia , Campos Lorraine Da Silva , Ma Yan , Williams Nerissa , Jung Sin-Ho , Durante Marco , Kirsch David G. 
Published: February 2018

AbstractCarbon ion therapy (CIT) offers several potential advantages for treating cancers compared with X-ray and proton radiotherapy, including increased biological efficacy and more conformal dosimetry. However, CIT potency has not been characterized in primary tumor animal models. Here, we calculate the relative biological effectiveness (RBE) of carbon ions compared with X-rays in an autochthonous mouse model of soft tissue sarcoma. We used Cre/loxP technology to generate primary sarcomas in KrasLSL-G12D/+; p53fl/fl mice. Primary tumors were irradiated with a single fraction of carbon ions (10 Gy), X-rays (20 Gy, 25 Gy, or 30 Gy), or observed as controls. The RBE was calculated by determining the dose of X-rays that resulted in similar time to posttreatment tumor volume quintupling and exponential growth rate as 10 Gy carbon ions. The median tumor volume quintupling time and exponential growth rate of sarcomas treated with 10 Gy carbon ions and 30 Gy X-rays were similar: 27.3 and 28.1 days and 0.060 and 0.059 mm3/day, respectively. Tumors treated with lower doses of X-rays had faster regrowth. Thus, the RBE of carbon ions in this primary tumor model is 3. When isoeffective treatments of carbon ions and X-rays were compared, we observed significant differences in tumor growth kinetics, proliferative indices, and immune infiltrates. We found that carbon ions were three times as potent as X-rays in this aggressive tumor model and identified unanticipated differences in radiation response that may have clinical implications. Mol Cancer Ther; 17(4); 858–68. ©2018 AACR.
MEF2C Phosphorylation Is Required for Chemotherapy Resistance in Acute Myeloid Leukemia
Authors: Brown Fiona C. , Still Eric , Koche Richard P. , Yim Christina Y. , Takao Sumiko , Cifani Paolo , Reed Casie , Gunasekera Shehana , Ficarro Scott B. , Romanienko Peter , Mark Willie , McCarthy Craig , de Stanchina Elisa , Gonen Mithat , Seshan Venkatraman , Bhola Patrick , O'Donnell Conor , Spitzer Barbara , Stutzke Crystal , Lavallée Vincent-Philippe , Hébert Josée , Krivtsov Andrei V. , Melnick Ari , Paietta Elisabeth M. , Tallman Martin S. , Letai Anthony , Sauvageau Guy , Pouliot Gayle , Levine Ross , Marto Jarrod A , Armstrong Scott A. , Kentsis Alex 
Published: February 2018

Abstract
In acute myeloid leukemia (AML), chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that Mef2cS222A/S222A knock-in mutant mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL–AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance and induced by MARK kinases in cells. Treatment with the selective MARK/SIK inhibitor MRT199665 caused apoptosis and conferred chemosensitivity in MEF2C-activated human AML cell lines and primary patient specimens, but not those lacking MEF2C phosphorylation. These findings identify kinase-dependent dysregulation of transcription factor control as a determinant of therapy response in AML, with immediate potential for improved diagnosis and therapy for this disease.
Significance: Functional proteomics identifies phosphorylation of MEF2C in the majority of primary chemotherapy-resistant AML. Kinase-dependent dysregulation of this transcription factor confers susceptibility to MARK/SIK kinase inhibition in preclinical models, substantiating its clinical investigation for improved diagnosis and therapy of AML. Cancer Discov; 8(4); 478–97. ©2018 AACR.
This article is highlighted in the In This Issue feature, p. 371
ERK Inhibition: A New Front in the War against MAPK Pathway–Driven Cancers?
Authors: Smalley Inna , Smalley Keiran S.M. 
Published: February 2018

Abstract
Summary: ERK inhibitors have enormous therapeutic potential against tumors that are BRAF mutant, BRAF–MEK inhibitor resistant, or RAS mutant. In this issue of Cancer Discovery, Sullivan and colleagues report on the first-in-human dose-escalation study of the ERK inhibitor ulixertinib, which they show to be well tolerated with clinical activity against a wide range of tumor types. Cancer Discov; 8(2); 140–2. ©2018 AACR.
See related article by Sullivan et al., p. 184.
What's the FOX Got to Do with the KITten? Regulating the Lineage-Specific Transcriptional Landscape in GIST
Authors: Lee Donna M. , Duensing Anette 
Published: February 2018

Abstract
Summary: Transcriptional regulation of the KIT receptor tyrosine kinase, a master regulator in gastrointestinal stromal tumors (GIST) and their precursors, the interstitial cells of Cajal (ICC), is part of a positive feedback loop involving the transcription factor ETV1. A new study now shows that the forkhead box (FOX) family transcription factor FOXF1 not only is an upstream regulator of ETV1 and hence ICC/GIST lineage-specific gene transcription, but also functions as lineage-specific pioneer factor with an active role in chromatin rearrangement to facilitate ETV1 binding and transcriptional activity. Cancer Discov; 8(2); 146–9. ©2018 AACR.
See related article by Ran et al., p. 234.
ПРОФІЛАКТИКА ВНУТРІШНЬОЛІКАРНЯНИХ ІНФЕКЦІЙ У ВІДДІЛЕННЯХ ХІРУРГІЧНОГО ПРОФІЛЮ
Authors: Romanenko I. I. 
Published: February 2018

У статті розглянуто питання профілактики внутрішньолікарняних інфекцій у відділеннях хірургічного профілю. Висвітлено основні аспекти проведення профілактичних заходів щодо попередження виникнення внутрішньолікарняних інфекцій, а також боротьба з ними.
MiR-146a Regulates Neutrophil Extracellular Trap Formation That Predicts Adverse Cardiovascular Events in Patients With Atrial Fibrillation
Authors: Arroyo Ana B. , de los Reyes-García Ascensión M. , Rivera-Caravaca José M. , Valledor Patricia , García-Barberá Nuria , Roldán Vanessa , Vicente Vicente , Martínez Constantino , González-Conejero Rocío 
Published: February 2018

Objective—
Atrial fibrillation (AF) patients experience adverse cardiovascular events (ACEs) despite anticoagulant therapy. We reported that rs2431697 of miR-146a, a negative regulator of inflammation, predicts ACEs in patients with AF. The relationship between neutrophil extracellular traps and thrombogenesis is known. Thus, our aim was to evaluate the role of neutrophil extracellular trap compounds as prognostic markers of ACEs in AF and to study whether miR-146a affects NETosis.

Approach and Results—

We included 336 steadily anticoagulated AF patients with a median follow-up of 7.9 years (interquartile range, 7.3–8.1) and 127 healthy subjects. The reviewed ACEs included stroke (ischemic/embolic), acute coronary syndrome, acute heart failure, and global or vascular death. We quantified cell-free DNA and NE (neutrophil elastase) at diagnosis. Rs2431697 was genotyped. Neutrophils from human and mice were seeded to analyze shed cell-free DNA and H3cit (citrullinated histone 3) after activation. In human plasmas, higher NE levels (>55.29 ng/mL), but not cell-free DNA, were independently associated with higher risk of all-cause mortality (hazard ratio, 2.24; 95% CI, 1.36–3.68), cardiovascular mortality (hazard ratio, 4.77; 95% CI, 1.11–20.47), and composite cardiovascular events (hazard ratio, 1.84; 95% CI, 1.01–3.76). In patients, NE levels were associated with rs2431697 (TT: 51.82±2.73 versus CC: 40.01±3.05 ng/mL;
P
=0.040). In vitro, both human (TT for rs2431697) and miR-146a
−/−
mice neutrophils yielded higher levels of cell-free DNA and H3cit than CC or wild-type cells, respectively.

Conclusions—
NE activity can provide new ACE prognostic information in AF patients. These findings provide evidence of a potential role of miR-146a in neutrophil extracellular trap generation and cardiovascular risk in AF.
Long-Term Clinical Comparison of Procedural End Points After Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation
Authors: Lee Kwang-No , Roh Seung-Young , Baek Yong-Soo , Park Hee-Soon , Ahn Jinhee , Kim Dong-Hyeok , Lee Dae In , Shim Jaemin , Choi Jong-Il , Park Sang-Weon , Kim Young-Hoon 
Published: February 2018

Background:
Pulmonary vein isolation (PVI) is effective for maintenance of sinus rhythm in 50% to 75% of patients with paroxysmal atrial fibrillation, and it is not uncommon for patients to require additional ablation after PVI. We prospectively evaluated the relative effectiveness of 2 post-PVI ablation strategies in paroxysmal atrial fibrillation.

Methods and Results:

A total of 500 patients (mean age, 55.7±11.0 years; 74.6% male) were randomly assigned to undergo ablation by 2 different strategies after PVI: (1) elimination of non-PV triggers (group A, n=250) or (2) stepwise substrate modification including complex fractionated atrial electrogram or linear ablation until noninducibility of atrial tachyarrhythmia was achieved (group B, n=250). During a median follow-up of 26.0 months, 75 (32.2%) patients experienced at least 1 episode of recurrent atrial tachyarrhythmia after the single procedure in group A compared with 105 (43.8%) patients in group B (
P
value in log-rank test of Kaplan–Meier analysis: 0.012). Competing risk analysis showed that the cumulative incidence of atrial tachycardia was significantly higher in group B compared with group A (
P
=0.007). With the exception of total ablation time, there were no significant differences in fluoroscopic time or procedure-related complications between the 2 groups.

Conclusions:
Elimination of triggers as an end point of ablation in patients with paroxysmal atrial fibrillation decreased long-term recurrence of atrial tachyarrhythmia compared with a noninducibility approach achieved by additional empirical ablation. The post-PVI trigger test is thus a better end point of ablation for paroxysmal atrial fibrillation.
Interaction of Body Mass Index on the Association Between N‐Terminal‐Pro‐b‐Type Natriuretic Peptide and Morbidity and Mortality in Patients With Acute Heart Failure: Findings From ASCEND‐HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure)
Authors: Bhatt Ankeet S. , Cooper Lauren B. , Ambrosy Andrew P. , Clare Robert M. , Coles Adrian , Joyce Emer , Krishnamoorthy Arun , Butler Javed , Felker G. Michael , Ezekowitz Justin A. , Armstrong Paul W. , Hernandez Adrian F. , O'Connor Christopher M. , Mentz Robert J. 
Published: February 2018

Background

Higher body mass index (
BMI
) is associated with lower circulating levels of N‐terminal‐pro‐b‐type natriuretic peptide (
NT
‐pro
BNP
). The Interaction between
BMI
and
NT
‐pro
BNP
with respect to clinical outcomes is not well characterized in patients with acute heart failure.

Methods and Results

A total of 686 patients from the biomarker substudy of the
ASCEND
‐
HF
(Acute Study of Clinical Effectiveness of Nesiritide in Decompensated
HF
) clinical trial with documented
NT
‐pro
BNP
levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese:
BMI
<30 kg/m
2
, Class I obesity:
BMI
30–34.9 kg/m
2
, Class
II
obesity
BMI
35–39.9 kg/m
2
, and Class
III
obesity
BMI
≥40 kg/m
2
). We assessed baseline characteristics and 30‐ and 180‐day outcomes by
BMI
class and explored the interaction between
BMI
and
NT
‐pro
BNP
for these outcomes. Study participants had a median age of 67 years (55, 78) and 71% were female.
NT
‐pro
BNP
levels were inversely correlated with
BMI
(
P
<0.001). Higher
NT
‐pro
BNP
levels were associated with higher 180‐day mortality (adjusted hazard ratio for each doubling of
NT
‐pro
BNP,
1.40; 95% confidence interval, 1.16, 1.71;
P
<0.001), but not 30‐day outcomes. The effect of
NT
‐pro
BNP
on 180‐day death was not modified by
BMI
class (interaction
P
=0.24).

Conclusions

The prognostic value of
NT
‐pro
BNP
was not modified by
BMI
in this acute heart failure population.
NT
‐pro
BNP
remains a useful prognostic indicator of long‐term mortality in acute heart failure even in the obese patient.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00475852.
Programming Cardiac Resynchronization Therapy for Electrical Synchrony: Reaching Beyond Left Bundle Branch Block and Left Ventricular Activation Delay
Authors: Varma Niraj , O'Donnell David , Bassiouny Mohammed , Ritter Philippe , Pappone Carlo , Mangual Jan , Cantillon Daniel , Badie Nima , Thibault Bernard , Wisnoskey Brian 
Published: February 2018

Background

QRS
narrowing following cardiac resynchronization therapy with biventricular (BiV) or left ventricular (LV) pacing is likely affected by patient‐specific conduction characteristics (
PR
, qLV,
LV
‐paced propagation interval), making a universal programming strategy likely ineffective. We tested these factors using a novel, device‐based algorithm (Sync
AV
) that automatically adjusts paced atrioventricular delay (default or programmable offset) according to intrinsic atrioventricular conduction.

Methods and Results

Seventy‐five patients undergoing cardiac resynchronization therapy (age 66±11 years; 65% male; 32% with ischemic cardiomyopathy; LV ejection fraction 28±8%;
QRS
duration 162±16 ms) with intact atrioventricular conduction (PR interval 194±34, range 128–300 ms), left bundle branch block, and optimized
LV
lead position were studied at implant.
QRS
duration (
QRS
d) reduction was compared for the following pacing configurations: nominal simultaneous BiV (Mode I: paced/sensed atrioventricular delay=140/110 ms), BiV+Sync
AV
with 50 ms offset (Mode
II
), BiV+Sync
AV
with offset that minimized
QRS
d (Mode
III
), or
LV
‐only pacing+Sync
AV
with 50 ms offset (Mode
IV
). The intrinsic
QRS
d (162±16 ms) was reduced to 142±17 ms (−11.8%) by Mode I, 136±14 ms (−15.6%) by Mode
IV
, and 132±13 ms (−17.8%) by Mode
II
. Mode
III
yielded the shortest overall
QRS
d (123±12 ms, −23.9% [
P
<0.001 versus all modes]) and was the only configuration without
QRS
d prolongation in any patient.
QRS
narrowing occurred regardless of
QRS
d,
PR
, or
LV
‐paced intervals, or underlying ischemic disease.

Conclusions

Post‐implant electrical optimization in already well‐selected patients with left bundle branch block and optimized
LV
lead position is facilitated by patient‐tailored BiV pacing adjusted to intrinsic atrioventricular timing using an automatic device–based algorithm.
Polygenic Risk for Depression Increases Risk of Ischemic Stroke
Authors: Wassertheil-Smoller Sylvia , Qi Qibin , Dave Tushar , Mitchell Braxton D. , Jackson Rebecca D. , Liu Simin , Park Ki , Salinas Joel , Dunn Erin C. , Leira Enrique C. , Xu Huichun , Ryan Kathleen , Smoller Jordan W. 
Published: February 2018

Background and Purpose—
Although depression is a risk factor for stroke in large prospective studies, it is unknown whether these conditions have a shared genetic basis.

Methods—
We applied a polygenic risk score (PRS) for major depressive disorder derived from European ancestry analyses by the Psychiatric Genomics Consortium to a genome-wide association study of ischemic stroke in the Stroke Genetics Network of National Institute of Neurological Disorders and Stroke. Included in separate analyses were 12 577 stroke cases and 25 643 controls of European ancestry and 1353 cases and 2383 controls of African ancestry. We examined the association between depression PRS and ischemic stroke overall and with pathogenic subtypes using logistic regression analyses.

Results—

The depression PRS was associated with higher risk of ischemic stroke overall in both European (
P
=0.025) and African ancestry (
P
=0.011) samples from the Stroke Genetics Network. Ischemic stroke risk increased by 3.0% (odds ratio, 1.03; 95% confidence interval, 1.00–1.05) for every 1 SD increase in PRS for those of European ancestry and by 8% (odds ratio, 1.08; 95% confidence interval, 1.04–1.13) for those of African ancestry. Among stroke subtypes, elevated risk of small artery occlusion was observed in both European and African ancestry samples. Depression PRS was also associated with higher risk of cardioembolic stroke in European ancestry and large artery atherosclerosis in African ancestry persons.

Conclusions—
Higher polygenic risk for major depressive disorder is associated with increased risk of ischemic stroke overall and with small artery occlusion. Additional associations with ischemic stroke subtypes differed by ancestry.
Reproductive, pathogenic and genotypic characterisation of five Meloidogyne graminicola populations from the Philippines on susceptible and resistant rice varieties
Authors: Cabasan Ma. Teodora Nadong , Kumar Arvind , Bellafiore Stéphane , De Waele Dirk 
Published: February 2018

SummaryFive populations ofMeloidogyne graminicolaisolated from different rice-growing areas in the Philippines were characterised. The populations showed little phenotypic variability of second-stage juveniles and female perineal pattern. Differences in reproduction amongM. graminicolapopulations were not observed on mature resistantOryza glaberrimavarieties ‘TOG5674’, ‘TOG5675’, ‘RAM131’ and ‘CG14’, or on susceptibleO. sativavarieties ‘IR64’ and ‘UPLRi-5’. In all infected rice varieties, plant growth and yield-contributing traits showed no differences among the populations. A search onM. graminicolapopulations from the Philippines for single-nucleotide polymorphism on the sequences of Internal Transcribed Spacer (ITS) of rDNA genes and mtDNA indicated only few points of heteroplasmy. Nematode reproduction and disease induction of the fiveM. graminicolapopulations in the Philippines exerted the same level of aggressiveness and virulence. The absence of resistance-breaking populations ofM. graminicolais important for the maintenance of durability of resistance to this important rice pathogen.
Contributions of Different Time-Scale Variations to Tropical Cyclogenesis over the Western North Pacific
Authors: Cao Xi , Wu Renguang , Bi Mingyu 
Published: February 2018

Abstract
The present study investigates relative contributions of different time-scale variations of environmental factors to the tropical cyclone (TC) genesis over the western North Pacific (WNP) during July–August–September–October (JASO). Distinct from previous studies that are concerned with large-scale spatial patterns during a certain period, the present study focuses on local and instantaneous conditions of the TC genesis. Analysis shows that the contribution of convection and lower-level vorticity to the TC genesis is mainly due to intraseasonal and synoptic variations. The contribution of vertical wind shear is largely related to synoptic variations. The contribution of midlevel specific humidity is almost 2 times more from intraseasonal variations than from synoptic variations. The contribution of sea surface temperature (SST) to the TC genesis is mainly due to interannual and intraseasonal variations. The barotropic energy for synoptic-scale disturbances during the TC genesis comes mainly from climatological mean flows over the southwest quadrant and from intraseasonal wind variations over the northeast quadrant of the WNP, respectively. The contribution of interannual variations to the TC genesis is enhanced over the southeast quadrant of the WNP. More TCs form under weak easterly and westerly vertical shears, respectively, during El Niño developing and decaying JASO. The contribution of interannual variations of SST tends to be larger during El Niño decaying than during developing JASO.
Decadal Variability of Eddy Kinetic Energy in the South Pacific Subtropical Countercurrent in an Ocean General Circulation Model
Authors: Rieck Jan K. , Böning Claus W. , Greatbatch Richard J. 
Published: February 2018

AbstractThe eddy kinetic energy (EKE) associated with the Subtropical Countercurrent (STCC) in the western subtropical South Pacific is known to exhibit substantial seasonal and decadal variability. Using an eddy-permitting ocean general circulation model, which is able to reproduce the observed, salient features of the seasonal cycles of shear, stratification, baroclinic production, and the associated EKE, the authors investigate the decadal changes of EKE. The authors show that the STCC region exhibits, uniquely among the subtropical gyres of the world’s oceans, significant, atmospherically forced, decadal EKE variability. The decadal variations are driven by changing vertical shear between the STCC in the upper 300 m and the South Equatorial Current below, predominantly caused by variations in STCC strength associated with a changing meridional density gradient. In the 1970s, an increased meridional density gradient results in EKE twice as large as in later decades in the model. Utilizing sensitivity experiments, decadal variations in the wind field are shown to be the essential driver. Local wind stress curl anomalies associated with the interdecadal Pacific oscillation (IPO) lead to upwelling and downwelling of the thermocline, inducing strengthening or weakening of the STCC and the associated EKE. Additionally, remote wind stress curl anomalies in the eastern subtropical South Pacific, which are not related to the IPO, generate density anomalies that propagate westward as Rossby waves and can account for up to 30%–40% of the density anomalies in the investigated region.