bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying the mechanical and neural properties of the sternocleidomastoid muscles
Authors: Luciani Bhillie D. , Desmet David M. , Alkayyali Amani A. , Leonardis Joshua M. , Lipps David B. 
Published: February 2018

Neck muscles are preferentially activated in specific force directions, but the constraints that the central nervous system considers when programming these preferred directions of muscle activity are unknown. The current study used ultrasound shear wave elastography (SWE) to investigate whether the material properties of the sternocleidomastoid (SCM) muscles exhibit preferred directions similar to their preferred direction of muscle activity during an isometric task. Twenty-four healthy participants matched isometric forces in 16 axial directions. All force targets were scaled to 20% of a maximum voluntary contraction. Muscle activity was recorded with surface electromyography (EMG) from six muscles (the bilateral SCMs, upper trapezius, and splenius capitis muscles), and shear wave velocities (SWVs) were recorded with SWE from both SCM muscles. We observed statistically significant differences between the preferred directions of muscle activity and SWVs for both the left SCM ( P = 0.002) and the right SCM ( P < 0.001), with the SWE data exhibiting a more lateral preferred direction. Significant differences in the spatial focus ( P < 0.001) were also observed, with the dispersion of SWV data covering a greater angular range than the EMG data during isometric tasks. The preferred directions of muscle activity and material properties for the SCM muscles were closer than previous comparisons of muscle activity and moment arms, suggesting muscle mechanics could play a more important role than anatomy in how the central nervous system spatially tunes muscle activation. NEW & NOTEWORTHY Our study used a novel combination of surface electromyography and ultrasound shear wave elastography to investigate the neuromuscular control of the neck. Our work highlights differences in how the activation and material properties of the sternocleidomastoid muscles are modulated as the central nervous system stabilizes the neck during isometric force production. These findings provide normative data for future studies to investigate pathologic changes to both the activation and material properties of the sternocleidomastoid muscles.
Adaptations in muscle oxidative capacity, fiber size, and oxygen supply capacity after repeated-sprint training in hypoxia combined with chronic hypoxic exposure
Authors: van der Zwaard S. , Brocherie F. , Kom B. L. G. , Millet G. P. , Deldicque L. , van der Laarse W. J. , Girard O. , Jaspers R. T. 
Published: February 2018

In this study, we investigate adaptations in muscle oxidative capacity, fiber size and oxygen supply capacity in team-sport athletes after six repeated-sprint sessions in normobaric hypoxia or normoxia combined with 14 days of chronic normobaric hypoxic exposure. Lowland elite field hockey players resided at simulated altitude (≥14 h/day at 2,800–3,000 m) and performed regular training plus six repeated-sprint sessions in normobaric hypoxia (3,000 m; LHTLH; n = 6) or normoxia (0 m; LHTL; n = 6) or lived at sea level with regular training only (LLTL; n = 6). Muscle biopsies were obtained from the m. vastus lateralis before (pre), immediately after (post-1), and 3 wk after the intervention (post-2). Changes over time between groups were compared, including likelihood of the effect size (ES). Succinate dehydrogenase activity in LHTLH largely increased from pre to post-1 (~35%), likely more than LHTL and LLTL (ESs = large-very large), and remained elevated in LHTLH at post-2 (~12%) vs. LHTL (ESs = moderate-large). Fiber cross-sectional area remained fairly similar in LHTLH from pre to post-1 and post-2 but was increased at post-1 and post-2 in LHTL and LLTL (ES = moderate-large). A unique observation was that LHTLH and LHTL, but not LLTL, improved their combination of fiber size and oxidative capacity. Small-to-moderate differences in oxygen supply capacity (i.e., myoglobin and capillarization) were observed between groups. In conclusion, elite team-sport athletes substantially increased their skeletal muscle oxidative capacity, while maintaining fiber size, after only 14 days of chronic hypoxic residence combined with six repeated-sprint training sessions in hypoxia. NEW & NOTEWORTHY Our novel findings show that elite team-sport athletes were able to substantially increase the skeletal muscle oxidative capacity in type I and II fibers (+37 and +32%, respectively), while maintaining fiber size after only 14 days of chronic hypoxic residence combined with six repeated-sprint sessions in hypoxia. This increase in oxidative capacity was superior to groups performing chronic hypoxic residence with repeated sprints in normoxia and residence at sea level with regular training only.
Antisecretory Factor–Mediated Inhibition of Cell Volume Dynamics Produces Antitumor Activity in Glioblastoma
Authors: Ilkhanizadeh Shirin , Sabelström Hanna , Miroshnikova Yekaterina A. , Frantz Aaron , Zhu Wen , Idilli Aurora , Lakins Jon N. , Schmidt Christin , Quigley David A. , Fenster Trenten , Yuan Edith , Trzeciak Jacqueline R. , Saxena Supna , Lindberg Olle R. , Mouw Janna K. , Burdick Jason A. , Magnitsky Sergey , Berger Mitchel S. , Phillips Joanna J. , Arosio Daniele , Sun Dandan , Weaver Valerie M. , Weiss William A. , Persson Anders I. 
Published: February 2018

Abstract
Interstitial fluid pressure (IFP) presents a barrier to drug uptake in solid tumors, including the aggressive primary brain tumor glioblastoma (GBM). It remains unclear how fluid dynamics impacts tumor progression and can be targeted therapeutically. To address this issue, a novel telemetry-based approach was developed to measure changes in IFP during progression of GBM xenografts. Antisecretory factor (AF) is an endogenous protein that displays antisecretory effects in animals and patients. Here, endogenous induction of AF protein or exogenous administration of AF peptide reduced IFP and increased drug uptake in GBM xenografts. AF inhibited cell volume regulation of GBM cells, an effect that was phenocopied in vitro by the sodium-potassium-chloride cotransporter 1 (SLC12A2/NKCC1) inhibitor bumetanide. As a result, AF induced apoptosis and increased survival in GBM models. In vitro, the ability of AF to reduce GBM cell proliferation was phenocopied by bumetanide and NKCC1 knockdown. Next, AF's ability to sensitize GBM cells to the alkylating agent temozolomide, standard of care in GBM patients, was evaluated. Importantly, combination of AF induction and temozolomide treatment blocked regrowth in GBM xenografts. Thus, AF-mediated inhibition of cell volume regulation represents a novel strategy to increase drug uptake and improve outcome in GBM. Mol Cancer Res; 16(5); 777–90. ©2018 AACR.
BET Proteins Exhibit Transcriptional and Functional Opposition in the Epithelial-to-Mesenchymal Transition
Authors: Andrieu Guillaume P. , Denis Gerald V. 
Published: February 2018

Abstract
Transcriptional programs in embryogenesis and cancer, such as the epithelial-to-mesenchymal transition (EMT), ensure cellular plasticity, an essential feature of carcinoma progression. As effectors of signal transduction, the bromodomain and extraterminal (BET) proteins are well suited to support plasticity because they function as co-activators or co-repressors of mammalian transcriptomes. Here, using both hormone-sensitive and triple-negative breast cancer (TNBC) model systems, we systematically altered EMT transcriptional profiles by manipulating individual BET proteins and found that BRD2 positively regulates EMT, whereas BRD3 and BRD4 repress this program. Knockdown of individual BET proteins revealed independent transcriptional networks that differed from each other and from the small-molecule pan-BET inhibitor JQ1, which previously had been misleadingly asserted to be BRD4-selective. Available small-molecule pan-BET inhibitors, proposed as antiproliferative agents in cancer clinical trials, obscure these biological differences. Transcriptional profiling reveals that individual BET proteins, inhibited separately, engage in and control EMT through unique processes.
Implications: The distinct and opposing functions of BET proteins in the EMT process suggests the need for more member-selective epigenetic targeting agents.
Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/4/580/F1.large.jpg. Mol Cancer Res; 16(4); 580–6. ©2018 AACR.
Convergent Therapeutic Strategies to Overcome the Heterogeneity of Acquired Resistance in BRAFV600E Colorectal Cancer
Authors: Hazar-Rethinam Mehlika , Kleyman Marianna , Han G. Celine , Liu David , Ahronian Leanne G. , Shahzade Heather A. , Chen Lifeng , Parikh Aparna R. , Allen Jill N. , Clark Jeffrey W. , Kwak Eunice L. , Faris Jason E. , Murphy Janet E. , Hong Theodore S. , Van Seventer Emily E. , Nadres Brandon , Hong Catriona B. , Gurski Joseph M. , Jessop Nicholas A. , Dias-Santagata Dora , Iafrate A. John , Van Allen Eliezer M. , Corcoran Ryan B. 
Published: February 2018

Abstract
Clonal heterogeneity associated with acquired resistance presents a critical therapeutic challenge. Whole-exome sequencing of paired tumor biopsies and targeted sequencing of cell-free DNA (cfDNA) from patients with BRAFV600E colorectal cancer receiving BRAF inhibitor combinations identified 14 distinct alterations in MAPK pathway components driving acquired resistance, with as many as eight alterations in a single patient. We developed a pooled clone system to study clonal outgrowth during acquired resistance, in vitro and in vivo. In vitro, the dynamics of individual resistant clones could be monitored in real time in cfDNA isolated from culture media during therapy. Outgrowth of multiple resistant clones was observed during therapy with BRAF, EGFR, and MEK inhibitor combinations. However, ERK inhibition, particularly in combination with BRAF and EGFR inhibition, markedly abrogated clonal outgrowth in vitro and in vivo. Thus, convergent, up-front therapy may suppress outgrowth of heterogeneous clones harboring clinically observed resistance alterations, which may improve clinical outcome.
Significance: We observed heterogeneous, recurrent alterations in the MAPK pathway as key drivers of acquired resistance in BRAFV600E colorectal cancer, with multiple concurrent resistance alterations detectable in individual patients. Using a novel pooled clone system, we identify convergent up-front therapeutic strategies capable of intercepting multiple resistance mechanisms as potential approaches to suppress emergence of acquired resistance. Cancer Discov; 8(4); 417–27. ©2018 AACR.
See related commentary by Janku, p. 389.
See related article by Corcoran et al., p. 428.
This article is highlighted in the In This Issue feature, p. 371
A Critical Need for Better Cancer Immunotherapy Models: Are Organotypic Tumor Spheroid Cultures the Answer?
Authors: Balko Justin M. , Sosman Jeffrey A. 
Published: February 2018

Abstract
Summary: Immunotherapy has transformed the therapeutic landscape of cancer, but the preclinical evaluation of combination approaches that will deepen and broaden its clinical benefit has lagged far behind due to the lack of expedient and easily accessible ex vivo human systems. In this issue, Jenkins and colleagues and Deng and colleagues report the use of organotypic cultures of tumors derived from mice and humans containing both tumor cells and cells from their local immune microenvironment to recapitulate the in vivo use of immune checkpoint inhibitors and extend the application of this system to therapeutic combinations of immune checkpoint blockade and molecularly targeted agents. Cancer Discov; 8(2); 143–5. ©2018 AACR.
See related article by Jenkins et al., p. 196.
See related article by Deng et al., p. 216.
Serum Soluble Interleukin 2 Receptor Level as a Marker of Acute Rejection in Pediatric Kidney Transplant Recipients
Authors: Hagras Amal M. , Salah Doaa M. , Ahmed Dina H. , Abd Elaal Omnia K. , Elghobary Hany Ahmed Fouad , Fadel Fatina I. 
Published: February 2018

<b><i>Background:</i></b> Despite advances in immunosuppression, acute allograft rejection remains one of the key factors affecting patient and graft survival in pediatric kidney transplantation. The aim of the study is to evaluate the role of serum soluble IL2 receptor (sIL2R) level as a noninvasive assessment parameter of acute rejection (AR). <b><i>Method:</i></b> Serum sIL2R level was measured (using enzyme-linked immune-sorbent assay technique) in 60 pediatric kidney transplant recipients (30 recipients with AR and 30 transplant recipients with stable graft function). <b><i>Results:</i></b> The mean values of sIL2R level in patients experiencing AR (14.8 ± 6.54) ng/mL were significantly higher than that in patients with stable graft functions (6.44 ±1.95) ng/mL (<i>p</i> = 0.0001). In addition; patients with AR proved by graft biopsy had their mean values of sIL2R level (16.19 ± 7.48) ng/mL significantly higher than that of other recipients in the study population (<i>p</i> = 0.032). <b><i>Conclusion:</i></b> Serum sIL2R level may serve as a noninvasive diagnostic indicator in pediatric kidney transplant recipients experiencing AR.
Does a Ureteral Obstruction Affect the Contralateral Kidney Morphology? A Stereological Analysis in a Rodent Model
Authors: Assumção Rômulo F. , Pereira-Sampaio Marco A. , Sampaio Francisco J.B. , de Souza Diogo B. 
Published: February 2018

<b><i>Objective:</i></b> To investigate, in a rodent model, the influence of an obstructed kidney/ureter on the contralateral organ morphology. <b><i>Methods:</i></b> Thirty-six rats were randomly assigned into the following groups: untreated ureteral obstruction group (UO-U, <i>n</i> = 10), submitted to a ligature of the ureter at day 0; UO group (at day 0) followed by nephrectomy after 24 h (UO-N, <i>n</i> = 8); nephrectomy group (N, <i>n</i> = 9), submitted to nephrectomy at day 0; and sham group (S, <i>n</i> = 9), submitted to simulated surgery at day 0. All these procedures were performed on the left kidney/ureter. All animals were euthanized 30 days after surgery, and the right kidneys were collected for stereological analysis. Data were compared using a one-way analysis of variance with Bonferroni’s post test, considering <i>p</i> &#x3c; 0.05 as significant. <b><i>Results:</i></b> The kidney volume, weight, and cortical volume were augmented in groups UO-N and N, compared to group S. Kidneys from the UO-U group showed only a moderate augmentation in kidney weight, with a reduction in the cortical-medullar ratio, compared to the kidneys in group S. No differences in the glomerular volumetric density, volume-weighted glomerular volume, and number of glomeruli were observed among the right kidneys of the studied groups. <b><i>Conclusion:</i></b> An obstructed kidney/ureter is more prejudicial to the contralateral kidney morphology than an absent kidney.
УПРОВАДЖЕННЯ АЛГОРИТМІЗАЦІЇ В МЕДСЕСТРИНСЬКУ ОСВІТУ
Authors: Popovych N. V. 
Published: February 2018

У статті проаналізовано поняття «алгоритм» і «алгоритмізація навчання», доцільність застосування даної педагогічної технології при підготовці медичної сестри.
Saturated Fatty Acids Undergo Intracellular Crystallization and Activate the NLRP3 Inflammasome in Macrophages
Authors: Karasawa Tadayoshi , Kawashima Akira , Usui-Kawanishi Fumitake , Watanabe Sachiko , Kimura Hiroaki , Kamata Ryo , Shirasuna Koumei , Koyama Yutaro , Sato-Tomita Ayana , Matsuzaka Takashi , Tomoda Hiroshi , Park Sam-Yong , Shibayama Naoya , Shimano Hitoshi , Kasahara Tadashi , Takahashi Masafumi 
Published: February 2018

Objective—
Inflammation provoked by the imbalance of fatty acid composition, such as excess saturated fatty acids (SFAs), is implicated in the development of metabolic diseases. Recent investigations suggest the possible role of the NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3) inflammasome, which regulates IL-1β (interleukin 1β) release and leads to inflammation, in this process. Therefore, we investigated the underlying mechanism by which SFAs trigger NLRP3 inflammasome activation.

Approach and Results—
The treatment with SFAs, such as palmitic acid and stearic acid, promoted IL-1β release in murine primary macrophages while treatment with oleic acid inhibited SFA-induced IL-1β release in a dose-dependent manner. Analyses using polarized light microscopy revealed that intracellular crystallization was provoked in SFA-treated macrophages. As well as IL-1β release, the intracellular crystallization and lysosomal dysfunction were inhibited in the presence of oleic acid. These results suggest that SFAs activate NLRP3 inflammasome through intracellular crystallization. Indeed, SFA-derived crystals activated NLRP3 inflammasome and subsequent IL-1β release via lysosomal dysfunction. Excess SFAs also induced crystallization and IL-1β release in vivo. Furthermore, SFA-derived crystals provoked acute inflammation, which was impaired in IL-1β–deficient mice.

Conclusions—
These findings demonstrate that excess SFAs cause intracellular crystallization and subsequent lysosomal dysfunction, leading to the activation of the NLRP3 inflammasome, and provide novel insights into the pathogenesis of metabolic diseases.
Neighborhood Socioeconomic Status and Outcomes Following the Norwood Procedure: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set
Authors: Bucholz Emily M. , Sleeper Lynn A. , Newburger Jane W. 
Published: February 2018

Background

Children with single ventricle heart disease require frequent interventions and follow‐up. Low socioeconomic status (
SES
) may limit access to high‐quality care and place these children at risk for poor long‐term outcomes.

Methods and Results

Data from the
SVR
(Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use) data set were used to examine the relationship of US neighborhood
SES
with 30‐day and 1‐year mortality or cardiac transplantation and length of stay among neonates undergoing the Norwood procedure (n=525). Crude rates of death or transplantation at 1 year after Norwood were highest for patients living in neighborhoods with low
SES
(lowest tertile 37.0% versus middle tertile 31.0% versus highest tertile 23.6%,
P
=0.024). After adjustment for patient demographics, birth characteristics, and anatomy, patients in the highest
SES
tertile had significantly lower risk of death or transplant than patients in the lowest
SES
tertile (hazard ratio 0.62, 95% confidence interval, 0.40, 0.96). When
SES
was examined continuously, the hazard of 1‐year death or transplant decreased steadily with increasing neighborhood
SES
. Hazard ratios for 30‐day transplant‐free survival and 1‐year transplant‐free survival were similar in magnitude. There were no significant differences in length of stay following the Norwood procedure by
SES
.

Conclusions

Low neighborhood
SES
is associated with worse 1‐year transplant‐free survival after the Norwood procedure, suggesting that socioeconomic and environmental factors may be important determinants of outcome in critical congenital heart disease. Future studies should investigate aspects of
SES
and environment amenable to intervention.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
>
http://www.clinicaltrials.gov
. Unique identifier: NCT00115934.
Neopterin Counters Vascular Inflammation and Atherosclerosis
Authors: Shirai Remina , Sato Kengo , Yamashita Tomoyuki , Yamaguchi Maho , Okano Taisuke , Watanabe‐Kominato Kaho , Watanabe Rena , Matsuyama Taka‐aki , Ishibashi‐Ueda Hatsue , Koba Shinji , Kobayashi Youichi , Hirano Tsutomu , Watanabe Takuya 
Published: February 2018

Background
Neopterin, a metabolite of GTP, is produced by activated macrophages and is abundantly expressed within atherosclerotic lesions in human aorta and carotid and coronary arteries. We aimed to clarify the influence of neopterin on both vascular inflammation and atherosclerosis, as neither effect had been fully assessed.

Methods and Results

We investigated neopterin expression in coronary artery lesions and plasma from patients with coronary artery disease. We assessed the atheroprotective effects of neopterin in vitro using human aortic endothelial cells, human monocyte‐derived macrophages, and human aortic smooth muscle cells. In vivo experiments included a study of aortic lesions in apolipoprotein E–deficient mice. Neopterin expression in coronary artery lesions and plasma was markedly increased in patients with versus without coronary artery disease. In human aortic endothelial cells, neopterin reduced proliferation and
TNF
‐α (tumor necrosis factor α)–induced upregulation of MCP‐1 (monocyte chemotactic protein 1), ICAM‐1 (intercellular adhesion molecule 1), and VCAM‐1 (vascular cell adhesion molecule 1). Neopterin attenuated
TNF
‐α–induced monocyte adhesion to human aortic endothelial cells and the inflammatory macrophage phenotype via NF‐κB (nuclear factor‐κB) downregulation. Neopterin suppressed oxidized low‐density lipoprotein–induced foam cell formation associated with
CD
36 downregulation and upregulation of
ATP
‐binding cassette transporters A1 and G1 in human monocyte‐derived macrophages. In human aortic smooth muscle cells, neopterin suppressed angiotensin
II
–induced migration and proliferation via c‐Src/Raf‐1/
ERK
1/2 downregulation without inducing apoptosis. Exogenous neopterin administration and endogenous neopterin attenuation with its neutralizing antibody for 4 weeks retarded and promoted, respectively, the development of aortic atherosclerotic lesions in apolipoprotein E–deficient mice.

Conclusions
Our results indicate that neopterin prevents both vascular inflammation and atherosclerosis and may be induced to counteract the progression of atherosclerotic lesions. Consequently, neopterin could be of use as a novel therapeutic target for atherosclerotic cardiovascular diseases.
On the morphometric identity of populations of Helicotylenchus pseudorobustus (Steiner, 1914) Golden, 1956 (Tylenchida: Hoplolaimidae)
Authors: Fortuner Renaud , Louis Pierre-Yves , Geniet Dominique 
Published: February 2018

Summary
Helicotylenchus microlobus is considered to be a junior synonym of H. pseudorobustus by several authors while others consider it as valid. To clarify the status of both species, 39 samples collected from various countries were subjected to statistical analyses that showed they could be grouped into six groups. Topotypes of H. pseudorobustus and H. microlobus belong to two different groups. However, samples in the other groups were morphologically intermediate between these two groups. Characters used in the past to uphold the validity of H. microlobus were variable and overlapping from group to group. The 28 samples studied are identified as H. pseudorobustus. Helicotylenchus microlobus, H. bradys and H. phalerus are confirmed as junior synonyms of H. pseudorobustus. There was no complete congruence between the morphological groups and molecular groups proposed by other authors. For these, two MOTU (Molecular Operational Taxonomic Unit) are accepted within H. pseudorobustus.
Studies on the morphology of Macrolaimus arboreus Truskova & Eroshenko, 1977 (Rhabditida: Chambersiellidae) from Iran
Authors: Shokoohi Ebrahim , Panahi Hadi , Fourie Hendrika , Abolafia Joaquín 
Published: February 2018

Summary
A population of Macrolaimus arboreus was collected from the rhizosphere of pine in Iran. This population of M. arboreus is characterised by the body length, 800-1010 μm in females, lip region with six seta-like papillae directed anteriad, stoma nearly as long as wide (9-11 × 7 μm), with cheilostom slightly longer than gymnostom and cheilorhabdia and gymnorhabdia well-developed, pharyngeal corpus 1.8-2.0 times the isthmus length, with slightly swollen metacorpus, excretory pore located at isthmus level, female reproductive system monodelphic-prodelphic reflexed with short post-vulval uterine sac, female tail conical (57-67 μm, c = 13.7-15.0, c′ = 3.5-3.8), ending in an acute tip which is weakly curved dorsad, and phasmids at 54-60% of tail length. Measurements and illustrations, including SEM, are provided.