bluuebunny/crossref_metadata_2025_split huggingface dataset:
Periostin (POSTN) Regulates Tumor Resistance to Antiangiogenic Therapy in Glioma Models
Authors: Park Soon Young , Piao Yuji , Jeong Kang Jin , Dong Jianwen , de Groot John F. 
Published: June 2016

Abstract
Periostin (POSTN) interacts with multiple integrins to coordinate a variety of cellular processes, including epithelial-to-mesenchymal transition (EMT) and cell migration. In our previous study, anti-VEGF-A therapy was associated with resistance and EMT. This study sought to determine the role of POSTN in the resistance of glioma stem cells (GSC) to antiangiogenic therapy. In mouse xenograft models of human glioma, POSTN expression was associated with acquired resistance to anti-VEGF-A therapy and had a synergistic effect with bevacizumab in prolonging survival and decreasing tumor volume. Resistance to anti-VEGF-A therapy regulated by POSTN was associated with increased expression of TGFβ1 and hypoxia-inducible factor-1α (HIF1α) in GSCs. At the molecular level, POSTN regulated invasion and expression of EMT (caveolin-1) and angiogenesis-related genes (HIF1α and VEGF-A) through activation of STAT3. Moreover, recombinant POSTN increased GSC invasion. Collectively, our findings suggest that POSTN plays an important role in glioma invasion and resistance to antiangiogenic therapy. Mol Cancer Ther; 15(9); 2187–97. ©2016 AACR.
High-Resolution Mapping of Ventricular Scar
Authors: Tschabrunn Cory M. , Roujol Sebastien , Dorman Nicole C. , Nezafat Reza , Josephson Mark E. , Anter Elad 
Published: June 2016

Background—
Mapping resolution is influenced by electrode size and interelectrode spacing. The aims of this study were to establish normal electrogram criteria for 1-mm multielectrode-mapping catheters (Pentaray) in the ventricle and to compare its mapping resolution within scar to standard 3.5-mm catheters (Smart-Touch Thermocool).

Methods and Results—

Three healthy swine and 11 swine with healed myocardial infarction underwent sequential mapping of the left ventricle with both catheters. Bipolar voltage amplitude in healthy tissue was similar between 3.5- and 1-mm multielectrode catheters with a 5th percentile of 1.61 and 1.48 mV, respectively. In swine with healed infarction, the total area of low bipolar voltage amplitude (defined as <1.5 mV) was 22.5% smaller using 1-mm multielectrode catheters (21.7 versus 28.0 cm2;
P
=0.003). This was more evident in the area of dense scar (bipolar amplitude <0.5 mV) with a 47% smaller very low–voltage area identified using 1-mm electrode catheters (7.1 versus 15.2 cm
2
;
P
=0.003). In this region, 1-mm multielectrode catheters recorded higher voltage amplitude (0.72±0.81 mV versus 0.30±0.12 mV;
P
<0.001). Importantly, 27% of these dense scar electrograms showed distinct triphasic electrograms when mapped using a 1-mm multielectrode catheter compared with fractionated multicomponent electrogram recorded with the 3.5-mm electrode catheter. In 8 mapped reentrant ventricular tachycardias, the circuits included regions of preserved myocardial tissue channels identified with 1-mm multielectrode catheters but not 3.5-mm electrode catheters. Pacing threshold within the area of low voltage was lower with 1-mm electrode catheters (0.9±1.3 mV versus 3.8±3.7 mV;
P
=0.001).

Conclusions—
Mapping with small closely spaced electrode catheters can improve mapping resolution within areas of low voltage.
Association of Central Adiposity With Adverse Cardiac Mechanics
Authors: Selvaraj Senthil , Martinez Eva E. , Aguilar Frank G. , Kim Kwang-Youn A. , Peng Jie , Sha Jin , Irvin Marguerite R. , Lewis Cora E. , Hunt Steven C. , Arnett Donna K. , Shah Sanjiv J. 
Published: June 2016

Background—
Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s′] and early diastolic [e′] tissue velocities).

Methods and Results—

We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m
2
, waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s′ velocity, and e′ velocity (
P
<0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status.

Conclusions—
In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics.
Cardiac Remodeling in Patients With Primary and Secondary Aldosteronism
Authors: Cesari Maurizio , Letizia Claudio , Angeli Paolo , Sciomer Susanna , Rosi Silvia , Rossi Gian Paolo 
Published: June 2016

Background—
Primary aldosteronism (PA) causes excess left ventricular (LV) hypertrophy and diastolic dysfunction; whether this occurs also in secondary aldosteronism (SA) without hypertension is unknown. We investigated the cardiac modifications in patients with preserved LV ejection fraction who had PA or SA.

Methods and Results—

We measured several Doppler echocardiography–derived variables, including tissue Doppler imaging (TDI) parameters and strain rate analysis, in 262 patients with PA, 117 with SA because of liver cirrhosis, and in 61 control healthy subjects. SA and PA patients showed markedly elevated aldosterone levels (67 versus 39 ng/dL, respectively; normal values <15 ng/dL) but contrasting values of plasma renin activity (15.00 versus 0.56 ng/mL/h;
P
<0.001). Compared with PA, SA patients showed higher heart rate, and lower blood pressure and vascular resistance values. Both PA and SA showed increased LV diameters, LV volumes, stroke volume, stroke work, and septal peak systolic tissue velocity, and had more LV hypertrophy (61% and 39%, respectively) and diastolic dysfunction (35% and 36%, respectively) than healthy subjects. Peak systolic septal strain (20% versus 23%;
P
=<0.001) and midwall fractional shortening (15.9% versus 16.7%;
P
=0.001) were lower in PA than in SA patients.

Conclusions—
Primary and secondary hyperaldosteronism correlate with LV enlargement and high prevalence of LV hypertrophy and diastolic dysfunction; a subclinical systolic dysfunction is evident only in PA. In SA, the high rate of LV hypertrophy, in spite of low peripheral resistances and low-to-normal blood pressure, could be accounted for the high renin and aldosterone values, and the work overload associated with a hyperdynamic circulatory state.
Image-Guided Placement of Osseointegrated Implants for Challenging Auricular, Orbital, and Rhinectomy Defects
Authors: Choi Kevin J. , Sajisevi Mirabelle B. , McClennen Jay , Kaylie David M. 
Published: June 2016

Objectives: Prosthetic reconstruction can restore the preoperative form and function after surgery for head and neck malignancies. We demonstrate the use of preoperative planning and intraoperative image guidance for placement of osseointegrated implants to restore craniofacial defects. Methods: A retrospective review of patients with craniofacial defects treated with image-guided placement of osseointegrated prosthetic implants was performed. Results: Case 1: 55-year-old male who underwent total auriculectomy with anterolateral thigh reconstruction. Case 2: 64-year-old male who required orbital exenteration and total auriculectomy with latissimus dorsi reconstruction. Case 3: 74-year-old male presented after a total rhinectomy. Cases 1 and 3 received adjuvant radiation prior to implantation. Case 2 underwent simultaneous placement of osseointegrated hearing and prosthetic implants. Computed tomography scans were used to perform preoperative planning to determine the optimal implant trajectories and sites. Complications included tissue overgrowth, delayed nonunion of implant, wound infection, and dehiscence. Conclusions: Defects following oncologic resection of head and neck malignancies can be difficult to achieve with native tissue alone. Osseointegrated implants offer an excellent means for reconstruction but can be challenging due to limited bone stock and anatomic landmarks. This can be overcome using intraoperative image guidance techniques for prosthetic reconstruction.
Detectability of BI-RADS category 3 or higher breast lesions and reading time on mammography: comparison between 5-MP and 8-MP LCD monitors
Authors: Yabuuchi Hidetake , Kawanami Satoshi , Kamitani Takeshi , Matsumura Tomomi , Yamasaki Yuzo , Morishita Junji , Honda Hiroshi 
Published: June 2016

Background Five-megapixel (MP) displays are recommended as soft copy devices for digital mammogram. An 8-MP liquid crystal display (LCD) (two 4-MP displays within one display) might offer the advantage of being able to view biplane mammography more easily than the dual planes of 5-MP LCDs. Purpose To compare detectability of Breast Imaging Reporting and Data System (BI-RADS) category 3 or higher lesions and reading time on mammography between 5- MP and 8-MP LCDs. Material and Methods The mammograms of 240 breasts of 120 patients including 60 breasts with BI-RADS category 3 or higher lesions and 180 breasts with normal or category 2 lesions were enrolled. All bilateral mammograms were displayed on bifacial 5-MP LCDs or an 8-MP LCD (two 4-MP displays within one display). Six radiologists assessed 240 breasts on each display. The observations were analyzed using receiver operating characteristic (ROC) analysis. A jack-knife method was used for statistical analysis. We employed a paired t-test to determine whether any significant differences existed in the reading time between two different displays. A P value < 0.05 was considered significant. Results The mean areas under the ROC curve obtained using 5-MP and 8-MP LCDs were 0.925 and 0.915, respectively, and there was no significant difference ( P = 0.46). There was also no significant difference in the reading time between two types of displays (57.8 min. vs. 51.5 min, P = 0.39). Conclusion The detectability of BI-RADS category 3 or higher lesions and reading time using an 8-MP LCD were comparable to those using a 5-MP LCD.
Health economic aspects of evaluation with diffusion weighted MR and MR colonography compared to standard evaluation with colonoscopy and CT before rectal cancer surgery
Authors: Achiam Michael P , Kjellberg Jakob , Rosenberg Jacob 
Published: June 2016

Background Colorectal cancer is a frequent type of cancer, and with the risk of synchronous disease, the need for a complete staging leads to an extensive and costly preoperative diagnostic evaluation. Previously we described a total preoperative evaluation using magnetic resonance (MR) colonography and diffusion-weighted MR of the liver. Purpose To compare the economic aspects of this modality with the standard evaluation in an analysis of the different cost drivers. Material and Methods Based on the results from previous studies, two calculations were performed, a theoretical cost calculation and a practical cost calculation. The cost drivers utilized are an average cost based on the cost of all procedures and diagnostic modalities performed in hospitalized patients (DRG) and outpatients (DAGS [Danish outpatient grouping system]) in Denmark. Results The total cost for a full colorectal evaluation and computed tomography (CT) scan of the thorax/abdomen was less for the new modality group in all theoretical models proposed; €225 using model A, €322 using model B, and €383 using model C. Using results from previous studies, the actual difference and the potential difference in cost between the two preoperative diagnostic modalities per patient were €312 and €712, respectively. Conclusion This cost analysis shows the cost effectiveness of the new modality as the future standard preoperative diagnostic work-up by reducing total cost and by having a higher sensitivity and completion rate.
Revision Hip Arthroscopy
Authors: Newman Justin T. , Briggs Karen K. , McNamara Shannen C. , Philippon Marc J. 
Published: June 2016

Background: As the number of hip arthroscopic surgeries being performed increases, so too does the prevalence of revision hip arthroscopic surgery. Hypothesis/Purpose: The purpose of this study was to compare outcomes in patients requiring revision hip arthroscopic surgery to patients undergoing primary hip arthroscopic surgery. The hypothesis was that patients undergoing revisions would demonstrate similar outcomes to those undergoing primary hip arthroscopic surgery. Study Design: Cohort study; Level of evidence, 2. Methods: Included in the study were patients undergoing revision hip arthroscopic surgery who did not have a history of prior open hip surgery. Each patient in the revision cohort was matched with 2 patients undergoing primary hip arthroscopic surgery. Preoperatively and at a minimum follow-up of 2 years, outcome scores were collected, including the Hip Outcome Score–Activities of Daily Living subscale (HOS-ADL), which was the primary outcome variable; modified Harris hip score (mHHS); Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); Hip Outcome Score–Sports subscale (HOS-Sports); and the 12-Item Short Form Health Survey (SF12). At follow-up, scores from the Tegner activity scale and patient self-reported satisfaction with surgical outcome were also collected. Results: A total of 246 patients in the revision cohort were matched with 492 patients in the primary cohort. In the revision cohort, 183 patients had 1 prior surgery, 45 had 2 surgeries, and 18 had ≥3 prior surgeries. Subsequent hip arthroscopic surgery was reported in 39 of 492 (8%) patients in the primary cohort and 5 of 246 (2%) patients in the revision cohort ( P = .001). Subsequent surgery was reported in 50 of 492 (10%) patients in the primary cohort and 15 of 246 (6%) patients in the revision cohort ( P = .07). Both groups saw significant improvement in outcome scores from preoperation to follow-up. The HOS-ADL was lower in the revision cohort preoperatively (65 vs 70) and postoperatively (79 vs 87) ( P = .001). This was also seen in the HOS-Sports, WOMAC, and SF12 physical component scores. Patients who had 1 prior hip arthroscopic procedure had higher postoperative mHHS (81 vs 75) compared with patients with >1 hip arthroscopic procedure; however, there was no difference in postoperative mHHS between the single-revision cohort and the primary cohort. In the revision group, patients whose HOS-ADL improved ≥10 points had greater joint space. Patients with greater improvement were more likely to have had a previous labral tear that was not repaired and to require capsular plication at revision. Conclusion: Patients who underwent revision hip arthroscopic surgery had significant improvement in outcome scores but did have lower scores compared with patients with primary hip arthroscopies. Patients with ≥2 revisions had lower outcomes. Improvement in the revision cohort was seen in patients with increased joint space, no prior labral repair, and capsular plication at revision.
Reduced breast cancer mortality after 20+ years of follow-up in the Swedish randomized controlled mammography trials in Malmö, Stockholm, and Göteborg
Authors: Nyström Lennarth , Bjurstam Nils , Jonsson Håkan , Zackrisson Sophia , Frisell Jan 
Published: June 2016

Objective To analyze the age- and trial-specific effects of the breast cancer screening trials with mammography in Malmö, Stockholm, and Göteborg. Methods The original trial files were linked to the Swedish Cancer and Cause of Death Registers to obtain date of breast cancer diagnosis and date and cause of death. Relative risks and 95% confidence intervals were calculated using the evaluation model (only breast cancers diagnosed between date of randomization and date when the first screening round of the control group was completed were included in the analysis). Results Women aged 40–70 at randomization in the Malmö I and II, Stockholm, and Göteborg trials were followed-up for an average of 30, 22, 25, and 24 years, respectively. The overview of all trials resulted in a significant decrease of 15% in breast cancer mortality. The variation by consecutive 10-year age group at randomization was small—from 21% in the age group 40–49 to 11% in the age group 50–59. After adjustment for age, there was a significant reduction in breast cancer mortality in the Göteborg trial (26%), and a non-significant reduction in the Malmö I and II and Stockholm trials (12%, 15%, and 5.8%, respectively). Conclusions The overview showed a 15% significant relative reduction in breast cancer mortality due to invitation to mammography screening. Heterogeneity in age, trial time, attendance rates, and length of screening intervals may have contributed to the variation in effect between the trials.
Functional inhibition of chemokine receptor CCR2 by dicer-substrate-siRNA prevents pain development
Authors: Bégin-Lavallée Valérie , Midavaine Élora , Dansereau Marc-André , Tétreault Pascal , Longpré Jean-Michel , Jacobi Ashley M , Rose Scott D , Behlke Mark A , Beaudet Nicolas , Sarret Philippe 
Published: June 2016

Background Accumulating evidence suggests that the C-C chemokine ligand 2 (CCL2, or monocyte chemoattractant protein 1) acts as a neuromodulator in the central nervous system through its binding to the C-C chemokine receptor 2 (CCR2). Notably, it is well established that the CCL2/CCR2 axis plays a key role in neuron-glia communication as well as in spinal nociceptive transmission. Gene silencing through RNA interference has recently emerged as a promising avenue in research and drug development, including therapeutic management of chronic pain. In the present study, we used 27-mer Dicer-substrate small interfering RNA (DsiRNA) targeting CCR2 and assessed their ability to reverse the nociceptive behaviors induced by spinal CCL2 injection or following intraplantar injection of complete Freund’s adjuvant. Results To this end, we first developed high-potency DsiRNAs designed to target different sequences distributed across the rat CCR2 (rCCR2) messenger RNA. For optimization, methyl groups were added to the two most potent DsiRNA candidates (Evader and M7 2′-O-methyl modified duplexes) in order to improve in vivo duplex stability and to reduce potential immunostimulatory activity. Our results demonstrated that all modified candidates formulated with the cell-penetrating peptide reagent Transductin showed strong RNAi activity following intrathecal delivery, exhibiting >50% rCCR2 knockdown in lumbar dorsal root ganglia. Accordingly, we found that these DsiRNA duplexes were able to reduce spinal microglia activation and were effective at blocking CCL2-induced mechanical hypersensitivity. Along with similar reductions of rCCR2 messenger RNA, both sequences and methylation patterns were similarly effective in inhibiting the CCL2 nociceptive action for the whole seven days testing period, compared to mismatch DsiRNA. DsiRNAs against CCR2 also reversed the hypernociceptive responses observed in the complete Freund’s adjuvant-induced inflammatory chronic pain model. Conclusion Altogether, these results validate CCR2 as a an appropriate molecular target for pain control and demonstrate that RNAi-based gene therapy represent an highly specific alternative to classical pharmacological approaches to treat central pathologies such as chronic pain.
Voluntary and evoked behavioral correlates in neuropathic pain states under different social housing conditions
Authors: Pitzer Claudia , Kuner Rohini , Tappe-Theodor Anke 
Published: June 2016

Background There is an urgent need to develop and incorporate novel behavioral tests in classically used preclinical pain models. Most rodent studies are based upon stimulus-evoked hindpaw measurements even though chronic pain is usually a day and night experience. Chronic pain is indeed a debilitating condition that influences the sociability and the ability for voluntary tasks, but the relevant behavioral readouts for these aspects are mostly under-represented in the literature. Moreover, we lack standardization in most behavioral paradigms to guarantee reproducibility and ensure adequate discussion between different studies. This concerns not only the combination, application, and duration of particular behavioral tasks but also the effects of different housing conditions implicating social isolation. Results Our aim was to thoroughly characterize the classically used spared nerve injury model for 12 weeks following surgery. We used a portfolio of classical stimulus-evoked response measurements, detailed gait analysis with two different measuring systems (Dynamic weight bearing (DWB) system and CatWalk), as well as observer-independent voluntary wheel running and home cage monitoring (Laboras system). Additionally, we analyzed the effects of social isolation in all behavioral tasks. We found that evoked hypersensitivity temporally matched changes in static gait parameters, whereas some dynamic gait parameters were changed in a time-dependent manner. Interestingly, voluntary wheel running behavior was not affected in spared nerve injury mice but by social isolation. Besides a reduced climbing activity, spared nerve injury mice did not showed tremendous alterations in the home cage activity. Conclusion This is the first longitudinal study providing detailed insights into various voluntary behavioral parameters related to pain and highlights the importance of social environment on spontaneous non-evoked behaviors in a mouse model of chronic neuropathy. Our results provide fundamental considerations for future experimental planning and discussion of pain-related behavioral changes.