bluuebunny/crossref_metadata_2025_split huggingface dataset:
The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis
Authors: Pung Yuh Fen , Chilian William M. , Bennett Martin R. , Figg Nichola , Kamarulzaman Mohd Hamzah 
Published: December 2016

Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including “cysts,” increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia. NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN.
Altered nuclear dynamics in MDX myofibers
Authors: Iyer Shama R. , Shah Sameer B. , Valencia Ana P. , Schneider Martin F. , Hernández-Ochoa Erick O. , Stains Joseph P. , Blemker Silvia S. , Lovering Richard M. 
Published: December 2016

Duchenne muscular dystrophy (DMD) is a genetic disorder in which the absence of dystrophin leads to progressive muscle degeneration and weakness. Although the genetic basis is known, the pathophysiology of dystrophic skeletal muscle remains unclear. We examined nuclear movement in wild-type (WT) and muscular dystrophy mouse model for DMD (MDX) (dystrophin-null) mouse myofibers. We also examined expression of proteins in the linkers of nucleoskeleton and cytoskeleton (LINC) complex, as well as nuclear transcriptional activity via histone H3 acetylation and polyadenylate-binding nuclear protein-1. Because movement of nuclei is not only LINC dependent but also microtubule dependent, we analyzed microtubule density and organization in WT and MDX myofibers, including the application of a unique 3D tool to assess microtubule core structure. Nuclei in MDX myofibers were more mobile than in WT myofibers for both distance traveled and velocity. MDX muscle shows reduced expression and labeling intensity of nesprin-1, a LINC protein that attaches the nucleus to the microtubule and actin cytoskeleton. MDX nuclei also showed altered transcriptional activity. Previous studies established that microtubule structure at the cortex is disrupted in MDX myofibers; our analyses extend these findings by showing that microtubule structure in the core is also disrupted. In addition, we studied malformed MDX myofibers to better understand the role of altered myofiber morphology vs. microtubule architecture in the underlying susceptibility to injury seen in dystrophic muscles. We incorporated morphological and microtubule architectural concepts into a simplified finite element mathematical model of myofiber mechanics, which suggests a greater contribution of myofiber morphology than microtubule structure to muscle biomechanical performance.NEW & NOTEWORTHY Microtubules provide the means for nuclear movement but show altered organization in the muscular dystrophy mouse model (MDX) (dystrophin-null) muscle. Here, MDX myofibers show increased nuclear movement, altered transcriptional activity, and altered linkers of nucleoskeleton and cytoskeleton complex expression compared with healthy myofibers. Microtubule architecture was incorporated in finite element modeling of passive stretch, revealing a role of fiber malformation, commonly found in MDX muscle. The results suggest that alterations in microtubule architecture in MDX muscle affect nuclear movement, which is essential for muscle function.
New Strategies in Metastatic Hormone Receptor–Positive Breast Cancer: Searching for Biomarkers to Tailor Endocrine and Other Targeted Therapies
Authors: Jankowitz Rachel C. , Oesterreich Steffi , Lee Adrian V. , Davidson Nancy E. 
Published: December 2016

Abstract
Although major advances in our understanding of the molecular underpinnings of hormone receptor–positive (HR+) breast cancer have led to new therapies that have substantially improved patient outcomes, endocrine-resistant disease still remains a leading cause of breast cancer mortality. Comprehensive molecular profiling of breast cancers has highlighted tremendous tumor heterogeneity, and analysis of paired primary and metastatic tumors has shown the evolution that can occur during acquired resistance to systemic therapies. Novel techniques for monitoring tumor load under treatment pressure, including “liquid biopsy” techniques, such as circulating free tumor DNA (cfDNA) and circulating tumor cells, have shown promise as biomarkers to direct treatment without invasive tumor biopsies. However, more research is needed to deepen our understanding of breast cancer alterations under treatment pressure to reveal mechanisms of drug resistance and apply precision medicine in biomarker-driven clinical trials. Clin Cancer Res; 23(5); 1126–31. ©2016 AACR.
Niclosamide Inhibits Oxaliplatin Neurotoxicity while Improving Colorectal Cancer Therapeutic Response
Authors: Cerles Olivier , Benoit Evelyne , Chéreau Christiane , Chouzenoux Sandrine , Morin Florence , Guillaumot Marie-Anne , Coriat Romain , Kavian Niloufar , Loussier Thomas , Santulli Pietro , Marcellin Louis , Saidu Nathaniel E.B. , Weill Bernard , Batteux Frédéric , Nicco Carole 
Published: December 2016

AbstractNeuropathic pain is a limiting factor of platinum-based chemotherapies. We sought to investigate the neuroprotective potential of niclosamide in peripheral neuropathies induced by oxaliplatin. Normal neuron-like and cancer cells were treated in vitro with oxaliplatin associated or not with an inhibitor of STAT3 and NF-κB, niclosamide. Cell production of reactive oxygen species and viability were measured by 2′,7′-dichlorodihydrofluorescein diacetate and crystal violet. Peripheral neuropathies were induced in mice by oxaliplatin with or without niclosamide. Neurologic functions were assessed by behavioral and electrophysiologic tests, intraepidermal innervation, and myelination by immunohistochemical, histologic, and morphologic studies using confocal microscopy. Efficacy on tumor growth was assessed in mice grafted with CT26 colon cancer cells. In neuron-like cells, niclosamide downregulated the production of oxaliplatin-mediated H2O2, thereby preventing cell death. In colon cancer cells, niclosamide enhanced oxaliplatin-mediated cell death through increased H2O2 production. These observations were explained by inherent lower basal levels of GSH in cancer cells compared with normal and neuron-like cells. In neuropathic mice, niclosamide prevented tactile hypoesthesia and thermal hyperalgesia and abrogated membrane hyperexcitability. The teniacide also prevented intraepidermal nerve fiber density reduction and demyelination in oxaliplatin mice in this mixed form of peripheral neuropathy. Niclosamide prevents oxaliplatin-induced increased levels of IL6, TNFα, and advanced oxidized protein products. Niclosamide displayed antitumor effects while not abrogating oxaliplatin efficacy. These results indicate that niclosamide exerts its neuroprotection both in vitro and in vivo by limiting oxaliplatin-induced oxidative stress and neuroinflammation. These findings identify niclosamide as a promising therapeutic adjunct to oxaliplatin chemotherapy. Mol Cancer Ther; 16(2); 300–11. ©2016 AACR.
Evaluation of Nonpeptidic Ligand Conjugates for the Treatment of Hypoxic and Carbonic Anhydrase IX–Expressing Cancers
Authors: Lv Peng-Cheng , Roy Jyoti , Putt Karson S. , Low Philip S. 
Published: December 2016

AbstractThe majority of tumors contain regions of hypoxia, which cause marked phenotypic changes to resident cells. This altered gene expression often leads to increased resistance to anticancer treatments. Therefore, elimination of these resistant hypoxic cells is crucial to prevent disease recurrence. Herein, we describe the selective delivery of imaging and chemotherapeutic agents to cells expressing carbonic anhydrase IX (CA IX), a highly upregulated hypoxia receptor. These agents were conjugated to a potent divalent CA IX ligand through a hydrophilic PEG linker. These conjugates are shown to bind CA IX–expressing cells in a receptor-dependent manner in vitro with mid-nanomolar affinities and in vivo with good tumor selectivity. In a mouse xenograft tumor model using HT-29 cells, a cytotoxic tubulysin B conjugate completely inhibited tumor growth. Overall, the targeting of a hypoxia marker, such as CA IX, to selectively deliver imaging or chemotherapeutic agents may lead to better treatment options for solid, hypoxic tumors. In addition, the combination of standard chemotherapeutics that are most potent in normoxic dividing cells and drugs specifically designed to eliminate hypoxic nondividing cells may elicit a superior clinical outcome. Mol Cancer Ther; 16(3); 453–60. ©2016 AACR.
Follow-Up of a Prospective Surgical Strategy to Prevent Intra-Atrial Reentrant Tachycardia After the Fontan Operation
Authors: Law Ian H. , Alam Osman , Bove Edward L. , Ohye Richard G. , Bradley David J. , Yu Sunkyung , Dick Macdonald 
Published: December 2016

Background—
Intra-atrial reentrant tachycardia (IART) after the Fontan operation had an early reported incidence of 10% to 35% during early and intermediate follow-up and posed substantial management challenges.

Methods and Results—
To reduce the incidence of IART after the Fontan procedure, we performed a randomized, double-blind study to evaluate the impact of an incision in the right atrium joining the lateral tunnel suture line and the tricuspid valve annulus. Between March 1998 and September 2003, 134 subjects (median age: 1.8 years; range: 1.3–5.2 years; 91 men) were randomly assigned to receive the incision. All 134 patients had a form of single ventricle pathological anatomy. The clinical course, electrocardiograms, and Holter monitoring were available for review in 114 subjects at a median of 8.2-year follow-up (range: 0.9–11.9 years). There were 2 late deaths, neither subject had IART. The combined incidence of sustained IART was 3.5% (4/114). There was no difference in the occurrence of sustained IART between those subjects receiving the incision and those who did not (2 in each group) during follow-up. No patients of either group experienced short-term complications.

Conclusions—
Despite the fact that the primary outcome of this trial was not reached, the most significant finding was that with current management, the incidence of IART is considerably lower than the early retrospective, observational studies suggested.
Predictors of Death in Contemporary Adult Patients With Eisenmenger Syndrome
Authors: Kempny Aleksander , Hjortshøj Cristel Sørensen , Gu Hong , Li Wei , Opotowsky Alexander R. , Landzberg Michael J. , Jensen Annette Schophuus , Søndergaard Lars , Estensen Mette-Elise , Thilén Ulf , Budts Werner , Mulder Barbara J. , Blok Ilja , Tomkiewicz-Pająk Lidia , Szostek Kamil , D’Alto Michele , Scognamiglio Giancarlo , Prokšelj Katja , Diller Gerhard-Paul , Dimopoulos Konstantinos , Wort Stephen J. , Gatzoulis Michael A. 
Published: December 2016

Background:
Eisenmenger syndrome is associated with substantial morbidity and mortality. There is no consensus, however, on mortality risk stratification. We aimed to investigate survival and predictors of death in a large, contemporary cohort of Eisenmenger syndrome patients.

Methods:
In a multicenter approach, we identified adults with Eisenmenger syndrome under follow-up between 2000 and 2015. We examined survival and its association with clinical, electrocardiographic, echocardiographic, and laboratory parameters.

Results:

We studied 1098 patients (median age, 34.4 years; range, 16.1–84.4 years; 65.1% female; 31.9% with Down syndrome). The majority had a posttricuspid defect (n=643, 58.6%), followed by patients with a complex (n=315, 28.7%) and pretricuspid lesion (n=140, 12.7%). Over a median follow-up of 3.1 years (interquartile range, 1.4–5.9), allowing for 4361.6 patient-years observation, 278 patients died and 6 underwent transplantation. Twelve parameters emerged as significant predictors of death on univariable analysis. On multivariable Cox regression analysis, only age (hazard ratio [HR], 1.41/10 years; 95% confidence interval [CI], 1.24–1.59;
P
<0.001), pretricuspid shunt (HR, 1.56; 95% CI, 1.02–2.39;
P
=0.041), oxygen saturation at rest (HR, 0.53/10%; 95% CI, 0.43–0.65;
P
<0.001), presence of sinus rhythm (HR, 0.53; 95% CI, 0.32–0.88;
P
=0.013), and presence of pericardial effusion (HR, 2.41; 95% CI, 1.59–3.66;
P
<0.001) remained significant predictors of death.

Conclusions:
There is significant premature mortality among contemporary adults with Eisenmenger syndrome. We report, herewith, a multivariable mortality risk stratification model based on 5 simple, noninvasive predictors of death in this population.
Erythrogene: a database for in-depth analysis of the extensive variation in 36 blood group systems in the 1000 Genomes Project
Authors: Möller Mattias , Jöud Magnus , Storry Jill R. , Olsson Martin L. 
Published: December 2016

Key Points
We extracted 210 412 blood group alleles (∼8.5 × 109 bp) from 1000 Genomes and matched them against official blood group reference lists. Of 1241 nonsynonymous variants found, 241 are known blood group polymorphisms while 1000 may represent undiscovered or altered antigens.
Ugly Data in the Age of Weather Satellites
Authors: Grossman Sara J. 
Published: December 2016

Abstract
Three days before Hurricane Sandy’s East Coast landfall, NASA released its first aerial, time-lapse video of the storm. Roughly 22,000 miles above Earth, NOAA’s GOES-14 satellite scanned the hurricane’s movement across the southern United States. NASA’s video, produced through rapid-scanning technology, captured the enormity of the storm, its dynamic cloud structure, and the sharpening of the storm’s eye as the continent dimmed under the setting sun. But despite the complicated process of data gathering and transmission that is involved in meteorological satellite sensing and imaging, satellite media often pass as uninterpreted weather reality for popular audiences, offering visual and textual narratives of weather crises that abstract the human from environmental disaster. This essay considers the twentieth-century turn toward uninterpreted and visually centered weather media by analyzing the meteorological satellite movement of the 1960s, contemporary GOES-14 experimental satellite technology, and the narratological and ontological ramifications of the visual satellite data and media that constitute a weather “movie” during storm crises.
Field Topography of Defects in Magnetic Non-Destructive Testing
Authors: Покровский  , Pokrovskiy Aleksey , Новиков  , Novikov Ilya , Хвостов  , Khvostov Andrey 
Published: December 2016

The defect parameters can be evaluated by defect induced magnetic field topography using Hall sensor. Investigations were carried out on specially prepared samples with artificial defects. According to calculations and tests tangential component of magnetic field strength extremes were detected values on either side of the defect in the surface layer l only. But this effect can not be detected by Hall sensors or Foerster probes due to their sizes.
The normal component of the magnetic field strength provides a sufficiently accurate determination of the fault location, where this component becomes zero between the two extreme values located quite close to each other.
The results of the study showed that at distances available to Hall transducers one can confine to the experimental research, whereas computational methods shall be used to study the topography of field defects at very small distances from the surface. This could open the prospects for testing at small distances from the surface of the object.
Total Arch versus Hemiarch Replacement for Type A Acute Aortic Dissection: A Single-Center Experience
Authors: Lio Antonio , Nicolò Francesca , Bovio Emanuele , Serrao Andrea , Zeitani Jacob , Scafuri Antonio , Chiariello Luigi , Ruvolo Giovanni 
Published: December 2016

We retrospectively evaluated early and intermediate outcomes of aortic arch surgery in patients with type A acute aortic dissection (AAD), investigating the effect of arch surgery extension on postoperative results.
From January 2006 through July 2013, 201 patients with type A AAD underwent urgent corrective surgery at our institution. Of the 92 patients chosen for this study, 59 underwent hemiarch replacement (hemiarch group), and 33 underwent total arch replacement (total arch group) in conjunction with ascending aorta replacement.
The operative mortality rate was 22%. Total arch replacement was associated with a 33% risk of operative death, versus 15% for hemiarch (P=0.044). Multivariable analysis found these independent predictors of operative death: age (odds ratio [OR]=1.13/yr; 95% confidence interval [CI], 1.04–1.23; P=0.002), body mass index >30 kg/m2 (OR=9.9; 95% CI, 1.28–19; P=0.028), postoperative low cardiac output (OR=10.6; 95% CI, 1.18–25; P=0.035), and total arch replacement (OR=8.8; 95% CI, 1.39–15; P=0.021) The mean overall 5-year survival rate was 59.3% ± 5.5%, and mean 5-year freedom from distal reintervention was 95.4% ± 3.2% (P=NS).
In type A AAD, aortic arch surgery is still associated with high operative mortality rates; hemiarch replacement can be performed more safely than total arch replacement. Rates of distal aortic reoperation were not different between the 2 surgical strategies.
Anesthetic Management in Radiofrequency Catheter Ablation of Ventricular Tachycardia
Authors: Deng Yi , Naeini Payam S. , Razavi Mehdi , Collard Charles D. , Tolpin Daniel A. , Anton James M. 
Published: December 2016

Radiofrequency catheter ablation is increasingly being used to treat patients who have ventricular tachycardia, and anesthesiologists frequently manage their perioperative care. This narrative review is intended to familiarize anesthesiologists with preprocedural, intraprocedural, and postprocedural implications of this ablation.
Ventricular tachycardia typically arises from structural heart disease, most often from scar tissue after myocardial infarction. Many patients thus affected will benefit from radiofrequency catheter ablation in the electrophysiology laboratory to ablate the foci of arrhythmogenesis. The pathophysiology of ventricular tachycardia is complex, as are the technical aspects of mapping and ablating these arrhythmias. Patients often have substantial comorbidities and tenuous hemodynamic status, necessitating pharmacologic and mechanical cardiopulmonary support. General anesthesia and monitored anesthesia care, when used for sedation during ablation, can lead to drug interactions and side effects in the presence of ventricular tachycardia, so anesthesiologists should also be aware of potential perioperative complications. We discuss variables that can help anesthesiologists safely guide patients through the challenges of radiofrequency catheter ablation of ventricular tachycardia.
The Role of Dopamine in Anticipatory Pursuit Eye Movements: Insights from Genetic Polymorphisms in Healthy Adults
Authors: Billino Jutta , Hennig Jürgen , Gegenfurtner Karl R. 
Published: December 2016

AbstractThere is a long history of eye movement research in patients with psychiatric diseases for which dysfunctions of neurotransmission are considered to be the major pathologic mechanism. However, neuromodulation of oculomotor control is still hardly understood. We aimed to investigate in particular the impact of dopamine on smooth pursuit eye movements. Systematic variability in dopaminergic transmission due to genetic polymorphisms in healthy subjects offers a noninvasive opportunity to determine functional associations. We measured smooth pursuit in 110 healthy subjects genotyped for two well-documented polymorphisms, the COMT Val158Met polymorphism and the SLC6A3 3′-UTR-VNTR polymorphism. Pursuit paradigms were chosen to particularly assess the ability of the pursuit system to initiate tracking when target motion onset is blanked, reflecting the impact of extraretinal signals. In contrast, when following a fully visible target sensory, retinal signals are available. Our results highlight the crucial functional role of dopamine for anticipatory, but not for sensory-driven, pursuit processes. We found the COMT Val158Met polymorphism specifically associated with anticipatory pursuit parameters, emphasizing the dominant impact of prefrontal dopamine activity on complex oculomotor control. In contrast, modulation of striatal dopamine activity by the SLC6A3 3′-UTR-VNTR polymorphism had no significant functional effect. Though often neglected so far, individual differences in healthy subjects provide a promising approach to uncovering functional mechanisms and can be used as a bridge to understanding deficits in patients.
Noisy Spiking in Visual Area V2 of Amblyopic Monkeys
Authors: Wang Ye , Zhang Bin , Tao Xiaofeng , Wensveen Janice M. , Smith Earl L. , Chino Yuzo M. 
Published: December 2016

Interocular decorrelation of input signals in developing visual cortex can cause impaired binocular vision and amblyopia. Although increased intrinsic noise is thought to be responsible for a range of perceptual deficits in amblyopic humans, the neural basis for the elevated perceptual noise in amblyopic primates is not known. Here, we tested the idea that perceptual noise is linked to the neuronal spiking noise (variability) resulting from developmental alterations in cortical circuitry. To assess spiking noise, we analyzed the contrast-dependent dynamics of spike counts and spiking irregularity by calculating the square of the coefficient of variation in interspike intervals (CV2) and the trial-to-trial fluctuations in spiking, or mean matched Fano factor (m-FF) in visual area V2 of monkeys reared with chronic monocular defocus. In amblyopic neurons, the contrast versus response functions and the spike count dynamics exhibited significant deviations from comparable data for normal monkeys. The CV2was pronounced in amblyopic neurons for high-contrast stimuli and the m-FF was abnormally high in amblyopic neurons for low-contrast gratings. The spike count, CV2, and m-FF of spontaneous activity were also elevated in amblyopic neurons. These contrast-dependent spiking irregularities were correlated with the level of binocular suppression in these V2 neurons and with the severity of perceptual loss for individual monkeys. Our results suggest that the developmental alterations in normalization mechanisms resulting from early binocular suppression can explain much of these contrast-dependent spiking abnormalities in V2 neurons and the perceptual performance of our amblyopic monkeys.SIGNIFICANCE STATEMENTAmblyopia is a common developmental vision disorder in humans. Despite the extensive animal studies on how amblyopia emerges, we know surprisingly little about the neural basis of amblyopia in humans and nonhuman primates. Although the vision of amblyopic humans is often described as being noisy by perceptual and modeling studies, the exact nature or origin of this elevated perceptual noise is not known. We show that elevated and noisy spontaneous activity and contrast-dependent noisy spiking (spiking irregularity and trial-to-trial fluctuations in spiking) in neurons of visual area V2 could limit the visual performance of amblyopic primates. Moreover, we discovered that the noisy spiking is linked to a high level of binocular suppression in visual cortex during development.