bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal splice isoform of CD44 (CD44s) promotes EMT/invasion and imparts stem‐like properties to ovarian cancer cells
Authors: Bhattacharya Rahul , Mitra Tulika , Ray Chaudhuri Susri , Roy Sib Sankar 
Published: November 2017

AbstractIncreased metastasis and a precipitous recurrence contribute to the lethality of ovarian cancer (OC). Several molecular mechanisms including aberrant‐splicing have been closely associated with the extent of cancer progression. Numerous gene transcripts are differentially spliced in cancer cells, CD44 being one of them. CD44 splice isoforms contribute to the aggressiveness and gain of stem‐like properties in different cancer types, but their role in ovarian cancer remains to be elucidated. We observed augmented CD44 levels in human ovarian cancer patient samples correlated with enhanced expression of the mesenchymal spliced variant CD44s (standard) and a concurrent decrease in the epithelial variants (CD44v). Moreover, CD44s was upregulated upon TGFβ1‐induced EMT, which was mediated through the downregulation of the splicing factor, ESRP1. Furthermore, overexpression of this mesenchymal isoform in the OC cells induced EMT and invasion, followed by the gain of stem‐like characteristics and chemoresistance. Since all these phenomena render lethality to this disease type, CD44s can be attributed for playing a major role in deregulated‐splicing mediated ovarian cancer progression.
The mitochondrial metabolic reprogramming agent trimetazidine as an ‘exercise mimetic’ in cachectic C26‐bearing mice
Authors: Molinari Francesca , Pin Fabrizio , Gorini Stefania , Chiandotto Sergio , Pontecorvo Laura , Penna Fabio , Rizzuto Emanuele , Pisu Simona , Musarò Antonio , Costelli Paola , Rosano Giuseppe , Ferraro Elisabetta 
Published: November 2017

AbstractBackgroundCancer cachexia is characterized by muscle depletion and exercise intolerance caused by an imbalance between protein synthesis and degradation and by impaired myogenesis. Myofibre metabolic efficiency is crucial so as to assure optimal muscle function. Some drugs are able to reprogram cell metabolism and, in some cases, to enhance metabolic efficiency. Based on these premises, we chose to investigate the ability of the metabolic modulator trimetazidine (TMZ) to counteract skeletal muscle dysfunctions and wasting occurring in cancer cachexia.MethodsFor this purpose, we used mice bearing the C26 colon carcinoma as a model of cancer cachexia. Mice received 5 mg/kg TMZ (i.p.) once a day for 12 consecutive days. A forelimb grip strength test was performed and tibialis anterior, and gastrocnemius muscles were excised for analysis. Ex vivo measurement of skeletal muscle contractile properties was also performed.ResultsOur data showed that TMZ induces some effects typically achieved through exercise, among which is grip strength increase, an enhanced fast‐to slow myofibre phenotype shift, reduced glycaemia, PGC1α up‐regulation, oxidative metabolism, and mitochondrial biogenesis. TMZ also partially restores the myofibre cross‐sectional area in C26‐bearing mice, while modulation of autophagy and apoptosis were excluded as mediators of TMZ effects.ConclusionsIn conclusion, our data show that TMZ acts like an ‘exercise mimetic’ and is able to enhance some mechanisms of adaptation to stress in cancer cachexia. This makes the modulation of the metabolism, and in particular TMZ, a suitable candidate for a therapeutic rehabilitative protocol design, particularly considering that TMZ has already been approved for clinical use.
Effect of novel chelating agents on the push‐out bond strength of calcium silicate cements to the simulated root‐end cavities
Authors: Ballal Nidambur Vasudev , Ulusoy Özgür İlke , Chhaparwal Shubha , Ginjupalli Kishore 
Published: November 2017

AbstractTo compare the effects of different chelating agents on the push‐out bond strength of calcium silicate‐based cements to the simulated root‐end cavities. Root‐end cavities were prepared on the roots of fifty extracted maxillary anterior teeth. The specimens were then randomly divided into 5 groups (n = 10) based on the final irrigation regimen: Group 1: 17% EDTA, Group 2: 7% maleic acid, Group 3: QMix, Group 4: 2.25% peracetic acid (PAA), Group 5: 0.9% saline. Then, the samples from each group were subdivided into two groups (n = 5) based on the apical filling material. In group 1, root‐end cavities of all samples were filled with Biodentine and in group 2, with MTA. Each sample was horizontally sectioned to produce two discs of ∼1 mm thick per specimen. The maximum load required for the dislodgement of 100 retrofillings was recorded. The specimens were examined under scanning electron microscope after debonding to assess the type of bond failure. Data were statistically analyzed using Kruskal Wallis and Mann Whitney U tests. Irrigation with saline resulted in higher bond strength compared to the other irrigants in the retrograde cavities obturated with MTA or Biodentine (p < .05). In MTA group, there was no significant difference between the test irrigants (p > .05). EDTA and PAA groups showed higher dislodgement resistance values than the other test irrigants, when Biodentine was used as a filling. The type of irrigation solution influences the bond strength of the root‐end fillings.
Relationship between preoperative breast MRI and surgical treatment of non‐metastatic breast cancer
Authors: Onega Tracy , Weiss Julie E. , Goodrich Martha E. , Zhu Weiwei , DeMartini Wendy B. , Kerlikowske Karla , Ozanne Elissa , Tosteson Anna N.A. , Henderson Louise M. , Buist Diana S.M. , Wernli Karen J. , Herschorn Sally D. , Hotaling Elise , O'Donoghue Cristina , Hubbard Rebecca 
Published: November 2017

Background and ObjectivesMore extensive surgical treatments for early stage breast cancer are increasing. The patterns of preoperative MRI overall and by stage for this trend has not been well established.MethodsUsing Breast Cancer Surveillance Consortium registry data from 2010 through 2014, we identified women with an incident non‐metastatic breast cancer and determined use of preoperative MRI and initial surgical treatment (mastectomy, with or without contralateral prophylactic mastectomy (CPM), reconstruction, and breast conserving surgery ± radiation). Clinical and sociodemographic covariates were included in multivariable logistic regression models to estimate adjusted odds ratios and 95% confidence intervals.ResultsOf the 13 097 women, 2217 (16.9%) had a preoperative MRI. Among the women with MRI, results indicated 32% higher odds of unilateral mastectomy compared to breast conserving surgery and of mastectomy with CPM compared to unilateral mastectomy. Women with preoperative MRI also had 56% higher odds of reconstruction.ConclusionPreoperative MRI in women with DCIS and early stage invasive breast cancer is associated with more frequent mastectomy, CPM, and reconstruction surgical treatment. Use of more extensive surgical treatment and reconstruction among women with DCIS and early stage invasive cancer whom undergo MRI warrants further investigation.
Critical evaluation of the American Joint Commission on Cancer (AJCC) 8th edition staging system for patients with Hepatocellular Carcinoma (HCC): A Surveillance, Epidemiology, End Results (SEER) analysis
Authors: Kamarajah Sivesh K. , Frankel Timothy L. , Sonnenday Christopher , Cho Clifford S. , Nathan Hari 
Published: November 2017

BackgroundRecently, the American Joint Committee on Cancer (AJCC) released its 8th edition changes to the staging system for hepatocellular cancer (HCC). We sought to validate the 8th edition staging system and compare the performance to the 7th edition using a population‐based data set.MethodsUsing the Surveillance, Epidemiology and End Results (SEER) database (1998‐2013), patients undergoing resection or transplant for non‐metastatic HCC were identified. Overall survival was estimated using the Kaplan‐Meier method and compared using log‐rank tests. Concordance indices (c‐indices) were calculated from Cox proportional hazards models to evaluate discriminatory power.ResultsThe study included 8918 patients resected (63%) or transplanted (37%) for HCC. Nodal staging was performed in 19%, of whom 5% had positive nodes. The c‐index for the AJCC 8th edition staging system was 0.60, similar to that for the 7th edition (0.59). Survival was better for solitary tumors >2 cm with vascular invasion than for multifocal tumors <5 cm (median not reached vs 57 months, P < 0.0001), although the staging system groups these tumors together as T2. For multifocal tumors ≤5 cm, those with vascular invasion had worse survival than those without (median 42 vs 50 months, P < 0.001), although the staging system draws no such distinction.ConclusionThe AJCC 8th edition staging system for HCC performs similarly to the 7th edition. Future revisions should consider substratification of early HCC, specifically by distinguishing solitary tumors >2 cm from multifocal tumors ≤5 cm, and by considering the prognostic impact of vascular invasion in multifocal tumors ≤5 cm. Future studies should aim to validate these findings.
Acoustic Characterization and Enhanced Ultrasound Imaging of Long‐Circulating Lipid‐Coated Microbubbles
Authors: Li Hongbo , Yang Yanye , Zhang Meimei , Yin Liping , Tu Juan , Guo Xiasheng , Zhang Dong 
Published: November 2017

ObjectivesA long‐circulating lipid‐coated ultrasound (US) contrast agent was fabricated to achieve a longer wash‐out time and gain more resistance against higher–mechanical index sonication. Systemic physical, acoustic, and in vivo imaging experiments were performed to better understand the underlying mechanism enabling the improvement of contrast agent performance by adjusting the physical and acoustic properties of contrast agent microbubbles.MethodsBy simply altering the gas core, a kind of US contrast agent microbubble was synthesized with a similar lipid‐coating shell as SonoVue microbubbles (Bracco SpA, Milan, Italy) to achieve a longer wash‐out time and higher inertial cavitation threshold. To bridge the structure‐performance relationship of the synthesized microbubbles, the imaging performance of the microbubbles was assessed in vivo with SonoVue as a control group. The size distribution and inertial cavitation threshold of the synthesized microbubbles were characterized, and the shell parameters of the microbubbles were determined by acoustic attenuation measurements. All of the measurements were compared with SonoVue microbubbles.ResultsThe synthesized microbubbles had a spherical shape, a smooth, consistent membrane, and a uniform distribution, with an average diameter of 1.484 μm. According to the measured attenuation curve, the synthesized microbubbles resonated at around 2.8 MHz. Although the bubble's shell elasticity (0.2 ± 0.09 N/m) was comparable with SonoVue, it had relatively greater viscosity and inertial cavitation because of the different gas core. Imaging studies showed that the synthesized microbubbles had a longer circulation time and a better chance of fighting against rapid collapse than SonoVue.ConclusionsNano/micrometer long‐circulating lipid‐coated microbubbles could be fabricated by simply altering the core composition of SonoVue microbubbles with a higher–molecular weight gas. The smaller diameter and higher inertial cavitation threshold of the synthesized microbubbles might make it easier to access deep‐seated organs and give prolonged imaging enhancement in the liver.
Ecotypic variation in population dynamics of reintroduced bighorn sheep
Authors: Bleich Vernon C. , Sargeant Glen A. , Wiedmann Brett P. 
Published: November 2017

ABSTRACTSelection of bighorn sheep (Ovis canadensis) for translocation historically has been motivated by preservation of subspecific purity rather than by adaptation of source stocks to similar environments. Our objective was to estimate cause‐specific, annual, and age‐specific mortality of introduced bighorn sheep that originated at low elevations in southern British Columbia, Canada (BC ecotype), or in the Missouri River Breaks region of central Montana, USA (MT ecotype). In North Dakota, USA, mortality was similar and typically low for adult female bighorn sheep from Montana (0.09 ± 0.029 [SE]) and British Columbia (0.08 ± 0.017) during 2000–2016. Median life expectancy was 11 years for females that reached adulthood (2 yrs old); however, mortality accelerated with age and reached 86% by age 16. Mortalities resulted primarily from low rates of predation, disease, accidents, and unknown natural causes (<0.04 [upper 90% CI]). Similar survival rates of female bighorn sheep from female bighorn sheep from British Columbia and Montana, coupled with greater recruitment of bighorn sheep from Montana, resulted in a greater projected rate of increase for the MT ecotype (λ = 1.21) than for the BC ecotype (1.02), and a more youthful age structure. These results support translocation of bighorn sheep from areas that are environmentally similar to areas that will be stocked. Potential benefits include more rapid population growth, greater resilience to and more rapid recovery from density‐independent losses, an increased possibility that rapidly growing populations will expand into adjacent habitat, increased hunter opportunity, increased connectivity among herds, and a more complete restoration of ecosystem processes. © 2017 The Wildlife Society.
Vantage point counts and monitoring roe deer
Authors: Zaccaroni Marco , Dell'Agnello Filippo , Ponti Giulia , Riga Francesco , Vescovini Chiara , Fattorini Lorenzo 
Published: November 2017

ABSTRACTVantage point counts (VPCs) are adopted to estimate the densities of roe deer (Capreolus capreolus) populations for harvest management. Thus, counts should be performed only within blocks without woodlands where it is possible to relate counts to block sizes. Alternatively, if VPCs are simply carried out on all blocks in a study region, the expectations of total counts could be used as relative abundance indices. In most cases, surveying all blocks is too demanding because of the number of observers required, time, and organization. Therefore, VPCs are performed only on a portion of the blocks, and relative abundance indices are estimated from these counts. If the blocks are selected by means of probabilistic sampling schemes, then statistically sound estimators of total count expectations can be adopted. Therefore, the estimation of the sampling errors, construction of confidence intervals, and assessment of change are possible, together with a post hoc power analysis for evaluating the probability of failing to detect a change in the expectations. Our objective in this study is to consider sampling strategies that allow the performance of all these statistical steps and to check the performance of these strategies on a hunting district located in Tuscany, Italy, in which all the blocks were surveyed in 2013 and 2014. The results provide evidence of the imprecision of the estimators. Even for large sampling fractions of 40–50%, the relative standard errors never decreased below 20%, and the corresponding powers in detecting a change of 30% at a level were <0.65. Our results highlight the need for efficient and robust alternative strategies. © 2017 The Wildlife Society.
The Gordian knot of mountain lion predation and bighorn sheep
Authors: Rominger Eric M. 
Published: November 2017

ABSTRACTThe objective of this review is to generate a synthesis of research conducted on predation of bighorn sheep (Ovis canadensis) and to suggest directions for future research relative to current knowledge gaps and a novel hypothesis. This review is primarily based on literature from the last 60 years on desert bighorn sheep (O. c. nelsoni), Rocky Mountain bighorn sheep (O. c. canadensis), and mountain lion (Puma concolor) predation. Although, many predators kill bighorn sheep, only mountain lions are currently considered to be the primary proximate cause of mortality for many bighorn sheep populations. The ultimate cause of this phenomenon has vexed wildlife managers for >40 years. There are 3 primary reasons for increased predation on bighorn sheep by mountain lions. First, there is an increased presence of mountain lions in habitats where they were historically absent or rare because of the expansion of mule deer (Odocoileus hemionus) following the extensive conversion of fire‐maintained grasslands to shrublands in the late‐1800s. Second, is the extirpation of the 2 dominant apex carnivores (wolves [Canis lupus] and grizzly bears [Ursus arctos]) during this same time period and a hypothesized numerical response of mountain lions to those extirpations. Finally, the response of mountain lions to the cessation of >70 years of intensive predator control has often resulted in unsustainable mountain lion‐bighorn sheep ratios, especially for desert bighorn sheep. Additionally, the effect of mountain lion predation is exacerbated by declines in bighorn sheep that do not result in declines in mountain lions because of their ability to prey switch to mule deer, elk (Cervus canadensis), or domestic cattle; kleptoparasitism of mountain lions kills, by ursids and canids, resulting in higher kill rates for mountain lions; and a possible ecological trap where adaptations derived over evolutionary time are no longer adaptive because of human‐induced changes in the sympatric apex predator guild. Control of mountain lions, when mountain lion‐ungulate ratios are high, might be required to protect small or endangered bighorn sheep populations, and to produce bighorn sheep for restoration efforts. © 2017 The Wildlife Society.
Head and neck paragangliomas: A two‐decade institutional experience and algorithm for management
Authors: Smith Joshua D. , Harvey Rachel N. , Darr Owen A. , Prince Mark E. , Bradford Carol R. , Wolf Gregory T. , Else Tobias , Basura Gregory J. 
Published: November 2017

ObjectivesParagangliomas of the head and neck and cranial base are typically benign, slow‐growing tumors arising within the jugular foramen, middle ear, carotid bifurcation, or vagus nerve proper. The objective of this study was to provide a comprehensive characterization of our institutional experience with clinical management of these tumors and posit an algorithm for diagnostic evaluation and treatment.MethodsThis was a retrospective cohort study of patients undergoing treatment for paragangliomas of the head and neck and cranial base at our institution from 2000–2017. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic work‐up, pre‐treatment cranial nerve palsy, treatment modality, utilization of preoperative angiographic embolization, complications of treatment, tumor control and recurrence, and hereditary status (ie, succinate dehydrogenase mutations) were collected and summarized.ResultsThe mean (SD) age of our cohort was 51.8 (±16.1) years with 123 (63.4%) female patients and 71 (36.6%) male patients. Catecholamine‐secreting lesions were found in nine (4.6%) patients. Fifty‐one patients underwent genetic testing, with mutations identified in 43 (20 SDHD, 13 SDHB, 7 SDHD, 1 SDHA, SDHAF2, and NF1). Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were variably employed as treatment approaches across anatomic subsites.ConclusionAn algorithmic approach to clinical management of these tumors, derived from our longitudinal institutional experience and current empiric evidence, may assist otolaryngologists, radiation oncologists, and geneticists in the care of these complex neoplasms.Level of Evidence4
Perception and Respiratory Responses of the Upper Airway Mechanism to Added Resistance With Aging
Authors: Murtolahti Siiri , Crouse Ulla K. , Pahkala Riitta , Warren Donald W. , Laine‐Alava Maija T. 
Published: November 2017

ObjectivesTo assess breathing behaviors and perception of added respiratory loads in young compared to old individuals, and to determine whether aging affects the perception and response to changes in nasal airway resistance.Study designIn a clinical study, 40 young (11–20 years) and 40 older (59–82 years) subjects were evaluated during rest breathing and during the application of added airway resistance loads.MethodsThe pressure‐flow technique was used to measure airflow rate (mL/s) and oral‐nasal pressures (cmH2O) to calculate nasal resistance (cmH2O/L/s). To create calibrated resistance loads for the test conditions, we used a device modified from a precision iris diaphragm.ResultsDuring rest breathing airflow rate was significantly lower for the younger group compared to older group. Using the loading device, 11–20‐year‐olds detected increased resistance at the level of 2.26 cmH2O/L/s compared to 4.55 cmH2O/L/s in 59–82‐year‐olds. In contrast to the younger group, mean airflow rate was higher during expiration than during inspiration among 59–82‐year‐olds except at rest breathing.ConclusionsThe data revealed that the perception and respiratory response to increased airway resistance changed with aging. Younger subjects were more sensitive to changes within the airway. In both groups, subjects responded to increased airway resistance by decreasing airflow rate. However, expiratory phase became more active than inspiratory phase only in the older group.Level of EvidenceN/A
Phase processing for quantitative susceptibility mapping of regions with large susceptibility and lack of signal
Authors: Fortier Véronique , Levesque Ives R. 
Published: November 2017

PurposePhase processing impacts the accuracy of quantitative susceptibility mapping (QSM). Techniques for phase unwrapping and background removal have been proposed and demonstrated mostly in brain. In this work, phase processing was evaluated in the context of large susceptibility variations (Δχ) and negligible signal, in particular for susceptibility estimation using the iterative phase replacement (IPR) algorithm.MethodsContinuous Laplacian, region‐growing, and quality‐guided unwrapping were evaluated. For background removal, Laplacian boundary value (LBV), projection onto dipole fields (PDF), sophisticated harmonic artifact reduction for phase data (SHARP), variable‐kernel sophisticated harmonic artifact reduction for phase data (V‐SHARP), regularization enabled sophisticated harmonic artifact reduction for phase data (RESHARP), and 3D quadratic polynomial field removal were studied. Each algorithm was quantitatively evaluated in simulation and qualitatively in vivo. Additionally, IPR‐QSM maps were produced to evaluate the impact of phase processing on the susceptibility in the context of large Δχ with negligible signal.ResultsQuality‐guided unwrapping was the most accurate technique, whereas continuous Laplacian performed poorly in this context. All background removal algorithms tested resulted in important phase inaccuracies, suggesting that techniques used for brain do not translate well to situations where large Δχ and no or low signal are expected. LBV produced the smallest errors, followed closely by PDF.ConclusionResults suggest that quality‐guided unwrapping should be preferred, with PDF or LBV for background removal, for QSM in regions with large Δχ and negligible signal. This reduces the susceptibility inaccuracy introduced by phase processing. Accurate background removal remains an open question. Magn Reson Med 79:3103–3113, 2017. © 2017 International Society for Magnetic Resonance in Medicine.