bluuebunny/crossref_metadata_2025 huggingface dataset:
The art of talking about science: beginning to teach physiology students how to communicate with nonscientists
Authors: Petzold Andrew M. , Dunbar Robert L.
Published: April 2018

The ability to clearly disseminate scientific knowledge is a skill that is necessary for any undergraduate student within the sciences. Traditionally, this is accomplished through the instruction of scientific presentation or writing with a focus on peer-to-peer communication at the expense of teaching communication aimed at a nonscientific audience. One of the ramifications of focusing on peer-to-peer communication has presented itself as an apprehension toward scientific knowledge within the general populace. This apprehension can be seen in a variety of venues, including the traditional media, popular culture, and education, which generally paint scientists as aloof and with an inability to discuss scientific issues to anyone other than other scientists. This paper describes a curriculum designed to teach Introduction to Anatomy and Physiology students the tools necessary for communicating complex concepts that were covered during the semester using approachable language. Students were assessed on their word usage in associated writing activities, the student’s ability to reduce complexity of their statements, and performance in an informal scientific presentation to a lay audience. Results showed that this pedagogical approach has increased students’ ability to reduce the complexity of their language in both a written and oral format. This, in turn, led to evaluators reporting greater levels of understanding of the topic presented following the presentation.
Loss of biliverdin reductase-A promotes lipid accumulation and lipotoxicity in mouse proximal tubule cells
Authors: Adeosun Samuel O. , Gordon Darren M. , Weeks Mary Frances , Moore Kyle H. , Hall John E. , Hinds Terry D. , Stec David E.
Published: April 2018

Obesity and increased lipid availability have been implicated in the development and progression of chronic kidney disease. One of the major sites of renal lipid accumulation is in the proximal tubule cells of the kidney, suggesting that these cells may be susceptible to lipotoxicity. We previously demonstrated that loss of hepatic biliverdin reductase A (BVRA) causes fat accumulation in livers of mice on a high-fat diet. To determine the role of BVRA in mouse proximal tubule cells, we generated a CRISPR targeting BVRA for a knockout in mouse proximal tubule cells (BVRA KO). The BVRA KO cells had significantly less metabolic potential and mitochondrial respiration, which was exacerbated by treatment with palmitic acid, a saturated fatty acid. The BVRA KO cells also showed increased intracellular triglycerides which were associated with higher fatty acid uptake gene cluster of differentiation 36 as well as increased de novo lipogenesis as measured by higher neutral lipids. Additionally, neutrophil gelatinase-associated lipocalin 1 expression, annexin-V FITC staining, and lactate dehydrogenase assays all demonstrated that BVRA KO cells are more sensitive to palmitic acid-induced lipotoxicity than wild-type cells. Phosphorylation of BAD which plays a role in cell survival pathways, was significantly reduced in palmitic acid-treated BVRA KO cells. These data demonstrate the protective role of BVRA in proximal tubule cells against saturated fatty acid-induced lipotoxicity and suggest that activating BVRA could provide a benefit in protecting from obesity-induced kidney injury.
Sphingosine-1-phosphate pathway in renal fibrosis
Authors: Zhang Xiwen , Ritter Joseph K. , Li Ningjun
Published: April 2018

Renal fibrosis is defined as the excessive deposition and modification of extracellular matrix (ECM) in the renal parenchyma in response to injury and inflammation, resulting in renal function loss. This condition is common to many chronic kidney diseases occurring under diverse pathological conditions, such as diabetic and hypertensive nephropathy. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in the regulation of cardiovascular functions and the pathogenesis of various cardiovascular diseases. S1P has also been considered an important regulator of fibrotic diseases, playing significant roles in the differentiation of fibroblasts to myofibroblasts and in the induction of inflammatory responses during the early stages of fibrotic diseases. This minireview summarizes recent research findings regarding the importance of the sphingosine kinase-1-S1P-S1P receptor axis and its interactions with other classic fibrotic signaling pathways and the immune inflammatory response to reveal novel therapeutic targets for the treatment or prevention of renal fibrosis.
Emphasizing the “positive” in positive reinforcement: using nonbinary rewarding for training monkeys on cognitive tasks
Authors: Fischer Benjamin , Wegener Detlef
Published: April 2018

Nonhuman primates constitute an indispensable model system for studying higher brain functions at the neurophysiological level. Studies involving these animals elucidated the neuronal mechanisms of various cognitive and executive functions, such as visual attention, working memory, and decision-making. Positive reinforcement training (PRT) constitutes the gold standard for training animals on the cognitive tasks employed in these studies. In the laboratory, PRT is usually based on application of a liquid reward as the reinforcer to strengthen the desired behavior and absence of the reward if the animal’s response is wrong. By trial and error, the monkey may adapt its behavior and successfully reduce the number of error trials, and eventually learn even very sophisticated tasks. However, progress and success of the training strongly depend on reasonable error rates. If errors get too frequent, they may cause a drop in the animal’s motivation to cooperate or its adaptation to high error rates and poor overall performance. We introduce in this report an alternative training regime to minimize errors and base the critical information for learning on graded rewarding. For every new task rule, the feedback to the animal is provided by different amounts of reward to distinguish the desired, optimal behavior from less optimal behavior. We applied this regime in different situations during training of visual attention tasks and analyzed behavioral performance and reaction times to evaluate its effectiveness. For both simple and complex behaviors, graded rewarding was found to constitute a powerful technique allowing for effective training without trade-off in accessible task difficulty or task performance.

NEW & NOTEWORTHY Laboratory training of monkeys usually builds on providing a fixed amount of reward for the desired behavior, and no reward otherwise. We present a nonbinary, graded reward schedule to emphasize the positive, desired behavior and to keep errors on a moderate level. Using data from typical training situations, we demonstrate that graded rewards help to effectively guide the animal by success rather than errors and provide a powerful new tool for positive reinforcement training.
Endoscopic Vacuum-Assisted Closure Therapy in Patients with Anastomotic Leakage after Esophagectomy: A Single-Center Experience
Authors: Noh Soo Min , Ahn Ji Yong , Lee Jeong Hoon , Jung Hwoon-Yong , AlGhamdi Zeead , Kim Hyeong Ryul , Kim Yong-Hee
Published: April 2018

Aim. To study the efficacy of E-VAC therapy for patients with anastomotic leakage after esophagectomy. Methods. Between January 2013 and April 2017, 12 patients underwent E-VAC therapy for the management of postoperative leakage. Their clinical features and endoscopic procedure details, therapy results, adverse events, and survival were investigated. Results. All 12 patients were male and the median age was 57 years (interquartile range 51.5–62.8 years). The reasons for esophageal surgery were esophageal cancer (83.3%), gastrointestinal stromal tumor (8.3%), and esophageal diverticulum (8.3%). Prior to E-VAC therapy, 6 patients had undergone failed primary surgical repair and the median duration from esophagectomy to leakage discovery was 13.5 days (IQR 6–207 days). The median duration of E-VAC therapy was 25 days (IQR 13.5–34.8 days) and the average sponge exchange rate was 2.7 times during the treatment period. After E-VAC therapy, 8 patients (66.7%) had complete leakage closure, 3 (25%) had a decreased leakage size, and 1 (8.3%) was unchanged. The three patients with a decreased leakage size after E-VAC therapy were treated with endoscopic and conservative management without further surgery. Conclusion. With proper patient selection, E-VAC therapy is a feasible and safe method for the treatment of anastomotic leakage after esophagectomy.
Characterization of Polypropylene Green Composites Reinforced by Cellulose Fibers Extracted from Rice Straw
Authors: Dinh Vu Ngo , Thi Tran Hang , Duy Nguyen Toan
Published: April 2018

Polypropylene (PP) based green composites containing 10, 20, 30, 40 and 50 wt% of cellulose fibers (CFs) which were extracted from rice straw were successfully prepared by melt blend method. The CFs washed with H2O2 after alkaline extraction showed lower water absorption than that not washed with H2O2. The thermal, mechanical, and biodegradation properties of composites were also investigated. The 10% weight loss temperature of the composites was decreased with the increasing CFs content, but all the composites showed over 300°C. Young’s modulus and flexural properties of PP were improved by blending PP with CFs. The pure PP showed no degradability, but the PP/CFs composites degraded from about 3 to 23 wt%, depending on CFs content after being buried in soil for 50 days. These PP/CFs composites with high thermal, mechanical properties and biodegradability may be useful as green composite materials for various environmental fields.
Preventive and Therapeutic Role of Functional Ingredients of Barley Grass for Chronic Diseases in Human Beings
Authors: Zeng Yawen , Pu Xiaoying , Yang Jiazhen , Du Juan , Yang Xiaomeng , Li Xia , Li Ling , Zhou Yan , Yang Tao
Published: April 2018

Barley grass powder is the best functional food that provides nutrition and eliminates toxins from cells in human beings; however, its functional ingredients have played an important role as health benefit. In order to better cognize the preventive and therapeutic role of barley grass for chronic diseases, we carried out the systematic strategies for functional ingredients of barley grass, based on the comprehensive databases, especially the PubMed, Baidu, ISI Web of Science, and CNKI, between 2008 and 2017. Barley grass is rich in functional ingredients, such as gamma‐aminobutyric acid (GABA), flavonoids, saponarin, lutonarin, superoxide dismutase (SOD), K, Ca, Se, tryptophan, chlorophyll, vitamins (A, B1, C, and E), dietary fiber, polysaccharide, alkaloid, metallothioneins, and polyphenols. Barley grass promotes sleep; has antidiabetic effect; regulates blood pressure; enhances immunity; protects liver; has anti‐acne/detoxifying and antidepressant effects; improves gastrointestinal function; has anticancer, anti‐inflammatory, antioxidant, hypolipidemic, and antigout effects; reduces hyperuricemia; prevents hypoxia, cardiovascular diseases, fatigue, and constipation; alleviates atopic dermatitis; is a calcium supplement; improves cognition; and so on. These results support that barley grass may be one of the best functional foods for preventive chronic diseases and the best raw material of modern diet structure in promoting the development of large health industry and further reveal that GABA, flavonoids, SOD, K‐Ca, vitamins, and tryptophan mechanism of barley grass have preventive and therapeutic role for chronic diseases. This paper can be used as a scientific evidence for developing functional foods and novel drugs for barley grass for preventive chronic diseases.
UV-fs-LA-ICP-MS Analysis of CO2-Rich Fluid Inclusions in a Frozen State: Example from the Dahu Au-Mo Deposit, Xiaoqinling Region, Central China
Authors: Jian Wei , Albrecht Moritz , Lehmann Bernd , Mao Jingwen , Horn Ingo , Li Yanhe , Ye Huishou , Li Zongyan , Fang Guanguan , Xue Yongsheng
Published: April 2018

The recently developed technique of ultraviolet femtosecond laser ablation inductively coupled plasma mass spectrometry (UV-fs-LA-ICP-MS) combined with a freezing cell is expected to improve the analysis of CO2-rich fluid inclusions by decreasing their internal pressure and avoiding the common problem of uncontrolled explosive fluid release on ablation. Here, we report the application of this technique through the case study of CO2-rich fluid inclusions from the quartz vein-style Au-Mo deposit of Dahu in the Xiaoqinling region of central China. The concentrations of Li, B, Na, Al, K, Ca, Mn, Fe, Cu, Zn, Rb, Sr, Mo, Ag, Te, Cs, Ba, Au, Pb, and Bi were analyzed in 124 (not all for Al and Ca) fluid inclusions, which have low to moderate salinity and multiphase composition (liquid H2O + liquid CO2  ± vapor CO2  ± solids). The Dahu fluids are dominated by Na and K. The concentrations of Mo are always below the detection limit from 0.005 to 2 ppm (excluding values obtained from fluid inclusions with accidentally trapped solids). The Dahu ore fluids differ from metamorphic fluids in compositions and most likely represent two separate pulses of spent fluids evolved from an unexposed and oxidized magmatic system. The UV-fs-LA-ICP-MS analysis of fluid inclusions in a frozen state improves the overpressure problem of CO2-rich fluid inclusions during laser ablation. The transformation of gaseous and liquid CO2 into the solid state leads to a significant decline in the internal pressure of the fluid inclusions, while femtosecond laser pulses generate a minimal heat input in the sample and thus maintain the frozen state during ablation. Transient signals of CO2-rich fluid inclusions obtained in this study typically had one or multiple peaks lasting for more than 15 seconds, without an initial short signal spike as obtained by ns-LA-ICP-MS analysis of CO2-rich fluid inclusions at room temperature.
Investigation of the Effect of Neck Muscle Active Force on Whiplash Injury of the Cervical Spine
Authors: Yan Yu , Huang Jing , Li Fan , Hu Lin
Published: April 2018

The objective of the present study is to investigate the influence of neck muscle activation on whiplash neck injury of the occupants of a passenger vehicle under different severities of frontal and rear-end impact collisions. The finite element (FE) model has been used as a versatile tool to simulate and understand the whiplash injury mechanism for occupant injury prevention. However, whiplash injuries and injury mechanisms have rarely been investigated in connection with neck active muscle forces, which restricts the complete reappearance and understanding of the injury mechanism. In this manuscript, a mixed FE human model in a sitting posture with an active head-neck was developed. The response of the cervical spine under frontal and rear-end collision conditions was then studied using the FE model with and without neck muscle activation. The effect of the neck muscle activation on the whiplash injury was studied based on the results of the FE simulations. The results indicated that the neck active force influenced the head-neck dynamic response and whiplash injury during a collision, especially in a low-speed collision.
A Postmenopausal Woman with Giant Ovarian Serous Cyst Adenoma: A Case Report with Brief Literature Review
Authors: Fatema Nishat , Mubarak Al Badi Muna
Published: April 2018

Giant (>10 cm) ovarian cyst is a rare finding. In the literature, a few cases of giant ovarian cysts have been mentioned sporadically, especially in elderly patients. We report a 57-year-old postmenopausal woman with a giant left ovarian cyst measuring 43 × 15 × 9 cm. She was referred to us from the local health center in view of palpable pelvic mass for six-month period. Considering the age and menopausal state, we performed a total abdominal hysterectomy and bilateral salpingo-oophorectomy with excision of the giant left ovarian cyst intact and successfully without any significant complication. On histopathological examination, the cyst was confirmed as benign serous cystadenoma of the ovary. During the management of these high-risk cases of multidisciplinary approach, intraoperative and postoperative strict vigilance is necessary to avoid unwanted complications.
Energy Spectrum of Shallow Donor in Elongated InAs/GaAs Volcano-Shaped Quantum Dot
Authors: García L. F. , Escorcia R. A. , Mikhailov I. D.
Published: April 2018

We study the effect of the nonparabolicity of the conduction band on the spectral properties of the shallow donor in elongated InAs/GaAs quantum dots with volcano-shaped profile in the framework of the Kane model by using a simple semiempiric relation between geometrical parameters of the quantum dot profile and the confinement potential, governing the in-plane electron’s movement. We represent the solution of the Schrödinger equation in the form of double Bessel-Fourier series expansion. We show that the nonparabolicity of dispersion of the conduction band, given by the Kane formula, conduces to significant lowering of the donor energies and to stronger confinement of the electron within the quantum dot. Calculated results for the energies as functions of the electric and magnetic fields for different quantum dot dimensions were compared with those obtained in the effective mass approximation. Our results exhibit a high sensibility of the probability density of electron distribution in volcano-shaped quantum dot to the variation of the external magnetic and electric fields.
Weight‐Aware Sensor Deployment in Wireless Sensor Networks for Smart Cities
Authors: Xie Mingshan , Bai Yong , Hu Zhuhua , Shen Chong
Published: April 2018

During the construction of wireless sensor networks (WSNs) for smart cities, a preliminary survey of the relative criticalness within the monitored area can be performed. It is a challenge for deterministic sensor deployment to balance the tradeoff of sensing reliability and cost. In this paper, based on the sensing accuracy of the sensor, we establish a reliability model of the sensing area which is divided into sensing grids, and different weights are allocated to those grids. We employ a practical evaluation criterion using seesaw mapping for determining the weights of sensing grids. We further formulate and solve an optimization problem for maximizing the trust degree of the WSNs. With our proposed method, the efficient deployment of sensors can be realized. Simulation results show that our proposed deployment strategy can achieve higher trust degree with reduced sensor deployment cost and lower number of sensors at a certain miss probability threshold.
Virtual Simulation Analysis of Rigid‐Flexible Coupling Dynamics of Shearer with Clearance
Authors: Chen Hongyue , Zhang Kun , Piao Mingbo , Wang Xin , Mao Jun , Song Qiushuang
Published: April 2018

A model for virtual simulation analysis of the rigid‐flexible coupling of a shearer has been developed with the objective of addressing problems associated with lifetime mismatch and low reliability of pin rows of a scraper conveyor and the corresponding support mechanism of a shearer. Simulations were performed using the experimental roller load as stimulus. Results of the analysis demonstrate that the vertical cutting force on the roller serves to reduce the load on the plane support plates during shearer cutting, and the force on the right plane support plate is considerably smaller compared to that on the left plane support plate along the direction of motion of the shearer. Owing to action of the roller‐traction load, loads acting on the two guiding support plates increase significantly along the direction of shearer motion. Mechanical characteristics of the support mechanism were determined through experiments, and the accuracy of the virtual simulation model was verified. Simultaneously, mechanical characteristics of the shearer support mechanism were studied under varying pitch and roll angles. This study was performed to provide a base for analyzing the mechanical characteristics as well as optimizing the structural design of the shearer. Through fatigue‐life analysis of the support plate and subsequent optimization of the support plate structure, the life of the guide support plate was found to have been extended by approximately 1.5 times.
RP-Ring: A Heterogeneous Multi-FPGA Accelerator
Authors: Guo Shuaizhi , Wang Tianqi , Tao Linfeng , Tian Teng , Xiang Zikun , Jin Xi
Published: April 2018

To reduce the cost of designing new specialized FPGA boards as direct-summation MOND (Modified Newtonian Dynamics) simulator, we propose a new heterogeneous architecture with existing FPGA boards, which is called RP-ring (reconfigurable processor ring). This design can be expanded conveniently with any available FPGA board and only requires quite low communication bandwidth between FPGA boards. The communication protocol is simple and can be implemented with limited hardware/software resources. In order to avoid overall performance loss caused by the slowest board, we build a mathematical model to decompose workload among FPGAs. The dividing of workload is based on the logic resource, memory access bandwidth, and communication bandwidth of each FPGA chip. Our accelerator can achieve two orders of magnitude speedup compared with CPU implementation.
MPPT for Photovoltaic System Using Nonlinear Controller
Authors: Iftikhar Ramsha , Ahmad Iftikhar , Arsalan Muhammad , Naz Neelma , Ali Naghmash , Armghan Hammad
Published: April 2018

Photovoltaic (PV) system generates energy that varies with the variation in environmental conditions such as temperature and solar radiation. To cope up with the ever increasing demand of energy, the PV system must operate at maximum power point (MPP), which changes with load as well as weather conditions. This paper proposes a nonlinear backstepping controller to harvest maximum power from a PV array using DC-DC buck converter. A regression plane is formulated after collecting the data of the PV array from its characteristic curves to provide the reference voltage to track MPP. Asymptotic stability of the system is proved using Lyapunov stability criteria. The simulation results validate the rapid tracking and efficient performance of the controller. For further validation of the results, it also provides a comparison of the proposed controller with conventional perturb and observe (P&O) and fuzzy logic-based controller (FLBC) under abrupt changes in environmental conditions.
Effect of Repeated Injection of Iodixanol on Renal Function in Healthy Wistar Rats Using Functional MRI
Authors: Wang Yongfang , Ren Ke , Xie Lizhi , Sun Wenge , Liu Yi , Li Songbai
Published: April 2018

Purpose. To determine the optimal time interval of repeated intravenous injections of iodixanol in rat model and to identify the injury location and causes of renal damage in vivo. Materials and Methods. Rats were randomly divided into Control group, Group 1 with one iodixanol injection, and Group 2 with two iodixanol injections. Group 2 was subdivided into 3 cohorts according to the interval between the first and second iodixanol injections as 1, 3, and 5 days, respectively. Blood oxygen level-dependent (BOLD) imaging and diffusion weighted imaging (DWI) were performed at 1 hour, 1 day, 3 days, 5 days, and 10 days after the application of solutions. Results. Compared with Group 1 (7.2%), Group 2 produced a remarkable R2⁎ increment at the inner stripe of the renal outer medulla by 15.37% (P=0.012), 14.83% (P=0.046), and 13.53% (P>0.05), respectively, at 1 hour after repeated injection of iodixanol. The severity of BOLD MRI to detect renal hypoxia was consistent with the expression of HIF-1α and R2⁎ was well correlated with HIF-1α expression (r=0.704). The acute tubular injury was associated with urinary NGAL and increased significantly at 1 day. Conclusions. Repetitive injection of iodixanol within a short time window can induce acute kidney injury, the impact of which on renal damage in rats disappears gradually 3–5 days after the injections.
Comparison of the Oocyte Quality Derived from Two-Dimensional Follicle Culture Methods and Developmental Competence of In Vitro Grown and Matured Oocytes
Authors: Lee Jaewang , Kim Eun Jung , Kong Hyun Sun , Youm Hye Won , Kim Seul Ki , Lee Jung Ryeol , Suh Chang Suk , Kim Seok Hyun
Published: April 2018

In vitro follicle growth (IVFG) is an emerging fertility preservation technique, which can obtain fertilizable oocytes from an in vitro culture system in female. This study aimed to compare efficiency of the most widely used two-dimensional follicle culture methods [with or without oil layer (O+ or O− group)]. Preantral follicles were isolated from mice and randomly assigned. Follicles were cultured for 10 days and cumulus-oocyte complexes harvested 16–18 hours after hCG treatment. Follicle and oocyte growth, hormones in spent medium, meiotic spindle localization, expression of reactive oxygen species (ROS), mitochondrial activity, and gene expression were evaluated. In follicle growth, survival, pseudoantral cavity formation, ovulation, and oocyte maturation were also significantly higher in O+ group than O− group. Hormone production was significantly higher in follicles cultured in O+ than O−. There were no significant differences in mRNA expression related to development. On the other hand, the level of ROS was increased while the mitochondrial activity of in vitro grown matured oocyte was less than in vivo matured oocytes. In conclusion, follicle culture with O+ group appears to be superior to the culture in O− group in terms of follicle growth, development, oocyte growth, maturation, and microorganelles in oocyte.
Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma
Authors: Jovanovic Milan , Gajovic Nevena , Zdravkovic Natasa , Jovanovic Marina , Jurisevic Milena , Vojvodic Danilo , Maric Veljko , Arsenijevic Aleksandar , Jovanovic Ivan
Published: April 2018

Background and Objectives. The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. Methods. Concentrations of galectin-3, TNF-α, TGF-β, IL-10, and IL-1β were analyzed in samples of blood and stool of 60 patients with CRC. Results. Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-β and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. Conclusions. Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.
Mobile Spectroscopy in Archaeometry: Some Case Study
Authors: Crupi Vincenza , D’Amico Sebastiano , Denaro Lucia , Donato Paola , Majolino Domenico , Paladini Giuseppe , Persico Raffaele , Saccone Mauro , Sansotta Carlo , Spagnolo Grazia Vera , Venuti Valentina
Published: April 2018

We provide an overview of recent results obtained by the innovative application of mobile spectroscopy for in situ investigation in archaeometry. Its growing relevance is linked to the great advantages of avoiding the transport and eventual damage of precious artifacts and of allowing the analysis of those specimens that are, for example, built into infrastructures or in some way permanently affixed. In this context, some case studies of combined instrumental approaches, involving X-ray fluorescence (XRF) and Raman spectroscopy, integrated by infrared thermography (IRT), are, in particular, discussed: the archaeological site of Scifì (Forza d’Agrò, province of Messina, Italy) and the Abbey of SS. Pietro e Paolo d’Agrò (Casalvecchio Siculo, province of Messina, Italy). In the first case, the elemental composition, as obtained by XRF, of two types of mortars belonging to two different chronological phases, dated back between the 3rd and the 5th century AD, allowed us to hypothesize a same origin area of their raw materials and a different production technique. Again, the combined use of XRF and Raman spectroscopies, supported by IRT technique, on pottery fragments of Greek-Hellenistic age and late imperial period, furnished important information concerning the receipts for the pigmenting agents of the finishing layer, allowing in some cases their unambiguous identification. In the second case, XRF data collected on bricks and stones from the external facade of the abbey allowed us to make some hypothesis concerning the provenance of their constituents materials, supposed to be in the area of valley of the river Agrò.
Emergence of Pituitary Adenoma in a Child during Surveillance: Clinical Challenges and the Family Members’ View in anAIPMutation-Positive Family
Authors: Marques Pedro , Barry Sayka , Ronaldson Amy , Ogilvie Arla , Storr Helen L. , Goadsby Peter J. , Powell Michael , Dang Mary N. , Chahal Harvinder S. , Evanson Jane , Kumar Ajith V. , Grieve Joan , Korbonits Márta
Published: April 2018

Introduction. Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 15–30% of familial isolated pituitary adenomas (FIPAs). We report a FIPA kindred with a heterozygous deletion inAIP, aiming to highlight the indications and benefits of genetic screening, variability in clinical presentations, and management challenges in this setting.Patients. An 18-year-old male was diagnosed with a clinically nonfunctioning pituitary adenoma (NFPA). Two years later, his brother was diagnosed with a somatolactotrophinoma, and a small Rathke’s cleft cyst and a microadenoma were detected on screening in their 17-year-old sister. Following amenorrhoea, their maternal cousin was diagnosed with hyperprolactinaemia and two distinct pituitary microadenomas. A 12-year-old niece developed headache and her MRI showed a microadenoma, not seen on a pituitary MRI scan 3 years earlier.Discussion. Out of the 14 members harbouring germlineAIPmutations in this kindred, 5 have pituitary adenoma. Affected members had different features and courses of disease. Bulky pituitary and not fully suppressed GH on OGTT can be challenging in the evaluation of females in teenage years. Multiple pituitary adenomas with different secretory profiles may arise in the pituitary of these patients. Small, stable NFPAs can be present in mutation carriers, similar to incidentalomas in the general population. Genetic screening and baseline review, with follow-up of younger subjects, are recommended inAIPmutation-positive families.
Evolution Mechanism of Metallic Dioxide MO2 (M = Mn, Ti) from Nanorods to Bulk Crystal: First-Principles Research
Authors: Zhao Pengsen , Li Guifa , Li Bingtian , Zheng Haizhong , Lu Shiqiang , Peng Ping
Published: April 2018

Using first-principle calculations, the surface energy, cohesive energy, and electronic properties of α-MnO2 and rutile TiO2 nanorods and microfacets were investigated and clarified to, in the first instance, determine the evolution mechanism. The results show that the surface energies of α-MnO2 nanorods and microfacets conform to function 1.0401 Jm−2 + N × 0.608 Jm−2, while the surface energies of the rutile TiO2 nanorods and microfacets are governed by a 1.0102 × 1.1997 rule. Their electronic properties, such as the Mulliken population and Mulliken charge, can only be normalized by their surface areas to attain a linear function. Meanwhile, the surface energy of α-MnO2 with the nanostructure closely conforms to the function for normalized Mulliken population and Mulliken charge as f(x)=102.9×x+0.101 with an R2 value of 0.995. Thus, our research into the evolution mechanism affecting the surface effect of nanometer materials will be useful for investigating the intrinsic mechanism of the nanometer effect and doping process of metallic dioxide catalysts.
Association of Metformin with Breast Cancer Incidence and Mortality in Patients with Type II Diabetes: A GRADE-Assessed Systematic Review and Meta-analysis
Authors: Tang Grace H. , Satkunam Meloja , Pond Gregory R. , Steinberg Gregory R. , Blandino Giovanni , Schünemann Holger J. , Muti Paola
Published: April 2018

Background: Preclinical data suggest that metformin may reduce breast cancer incidence and improve cancer prognosis. However, the current evidence in observational studies is inconclusive. A systematic review and meta-analysis was conducted to assess the effect of metformin on the incidence of breast cancer and all-cause mortality in patients with type II diabetes (T2D).

Methods: A literature search was performed on Medline, EMBASE, and the Cochrane library from inception to November 2016. Outcomes were incidence of breast cancer and all-cause mortality. Risk of bias and overall certainty of evidence was assessed using the Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development, and Evaluation (GRADE), respectively. Meta-analyses were performed using the most fully adjusted ORs or HRs and 95% confidence intervals (95% CI) as effect measures.

Results: A total of 12 observational studies were included for breast cancer incidence and 11 studies for all-cause mortality. No significant association was found between metformin exposure and incidence of breast cancer (OR = 0.93; 95% CI, 0.85–1.03; I2 = 35%). A 45% risk reduction was observed for all-cause mortality (HR = 0.55; 95% CI, 0.44–0.70; I2 = 81%). Presence of publication bias is strongly suspected for both outcomes using Egger's funnel plots.

Conclusions: The use of metformin may improve overall survival in patients with T2D and breast cancer. No effect of metformin on the incidence of breast cancer was observed. Interpretation of results is limited by the observational nature of the studies and resulting biases.

Impact: Clinical trials are warranted to determine the role of metformin in breast cancer risk reduction and prognosis. Cancer Epidemiol Biomarkers Prev; 27(6); 627–35. ©2018 AACR.
Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent
Authors: Piulats Josep M. , Vidal August , García-Rodríguez Francisco J. , Muñoz Clara , Nadal Marga , Moutinho Catia , Martínez-Iniesta María , Mora Josefina , Figueras Agnés , Guinó Elisabet , Padullés Laura , Aytés Àlvaro , Molleví David G. , Puertas Sara , Martínez-Fernández Carmen , Castillo Wilmar , Juliachs Merce , Moreno Victor , Muñoz Purificación , Stefanovic Milica , Pujana Miguel A. , Condom Enric , Esteller Manel , Germà Josep R. , Capella Gabriel , Farré Lourdes , Morales Albert , Viñals Francesc , García-del-Muro Xavier , Cerón Julián , Villanueva Alberto
Published: April 2018

Purpose: To investigate the genetic basis of cisplatin resistance as efficacy of cisplatin-based chemotherapy in the treatment of distinct malignancies is often hampered by intrinsic or acquired drug resistance of tumor cells.

Experimental Design: We produced 14 orthoxenograft transplanting human nonseminomatous testicular germ cell tumors (TGCT) in mice, keeping the primary tumor features in terms of genotype, phenotype, and sensitivity to cisplatin. Chromosomal and genetic alterations were evaluated in matched cisplatin-sensitive and their counterpart orthoxenografts that developed resistance to cisplatin in nude mice.

Results: Comparative genomic hybridization analyses of four matched orthoxenografts identified recurrent chromosomal rearrangements across cisplatin-resistant tumors in three of them, showing gains at 9q32-q33.1 region. We found a clinical correlation between the presence of 9q32-q33.1 gains in cisplatin-refractory patients and poorer overall survival (OS) in metastatic germ cell tumors. We studied the expression profile of the 60 genes located at that genomic region. POLE3 and AKNA were the only two genes deregulated in resistant tumors harboring the 9q32-q33.1 gain. Moreover, other four genes (GCS, ZNF883, CTR1, and FLJ31713) were deregulated in all five resistant tumors independently of the 9q32-q33.1 amplification. RT-PCRs in tumors and functional analyses in Caenorhabditis elegans (C. elegans) indicate that the influence of 9q32-q33.1 genes in cisplatin resistance can be driven by either up- or downregulation. We focused on glucosylceramide synthase (GCS) to demonstrate that the GCS inhibitor DL-threo-PDMP resensitizes cisplatin-resistant germline-derived orthoxenografts to cisplatin.

Conclusions: Orthoxenografts can be used preclinically not only to test the efficiency of drugs but also to identify prognosis markers and gene alterations acting as drivers of the acquired cisplatin resistance. Clin Cancer Res; 24(15); 3755–66. ©2018 AACR.
Risk Assessment after Neoadjuvant Chemotherapy in Luminal Breast Cancer Using a Clinicomolecular Predictor
Authors: Loibl Sibylle , Weber Karsten , Huober Jens , Krappmann Kristin , Marmé Frederik , Schem Christian , Engels Knut , Pfitzner Berit Maria , Kümmel Sherko , Furlanetto Jenny , Hartmann Arndt , Darb-Esfahani Silvia , Müller Volkmar , Staebler Annette , von Minckwitz Gunter , Kronenwett Ralf , Denkert Carsten
Published: April 2018

Purpose: This study aimed to evaluate a modified EPclin test (mEPclin), a combination of EndoPredict (EP) score, post-neoadjuvant pathologic tumor size and nodal status, for predicting the risk of distance recurrence after neoadjuvant chemotherapy (NACT) in patients with residual estrogen receptor (ER)–positive/HER2-negative breast cancer. We also compared the prognostic power of the mEPclin with that of the CPS-EG score.

Experimental Design: A total of 428 formalin-fixed, paraffin-embedded tumor samples from GeparTrio and GeparQuattro studies were evaluated for mRNA expression of eight cancer-related and three reference genes. The mEPclin score was computed using a modified algorithm and predefined cut-off values were used to classify each patient at low or high risk. Primary endpoint was disease-free survival (DFS).

Results: A higher continuous mEPclin score was significantly associated with increased risk of relapse [HR, 2.16; 95% confidence interval (CI), 1.86–2.51; P < 0.001] and death (HR, 2.28; 95% CI, 1.90–2.75; P < 0.001). Similarly, patients classified at high risk by dichotomous mEPclin showed significantly poorer DFS and overall survival compared with those at low risk. In contrast with CPS-EG, the mEPclin remained significantly prognostic for DFS in multivariate analysis (HR, 2.13; 95% CI, 1.73–2.63; P < 0.001). Combining CPS-EG and other clinicopathological variables with mEPclin yielded a significant improvement of the prognostic power for DFS versus without mEPclin (c-indices: 0.748 vs. 0.660; P < 0.001).

Conclusions: The mEPclin score independently predicted the risk of distance recurrence and provided additional prognostic information to the CPS-EG score to assess more accurately the prognosis after NACT in the luminal non-pCR patient population. Therefore, this approach can be used to select patients for additional post-neoadjuvant therapies. Clin Cancer Res; 24(14); 3358–65. ©2018 AACR.
Prevalent Homozygous Deletions of Type I Interferon and Defensin Genes in Human Cancers Associate with Immunotherapy Resistance
Authors: Ye Zhenqing , Dong Haidong , Li Ying , Ma Tao , Huang Haojie , Leong Hon Sing , Eckel-Passow Jeanette , Kocher Jean-Pierre A. , Liang Han , Wang Liguo
Published: April 2018

Purpose: Homozygous deletions play important roles in carcinogenesis. The genome-wide screening for homozygously deleted genes in many different cancer types with a large number of patient specimens representing the tumor heterogeneity has not been done.

Experimental Design: We performed integrative analyses of the copy-number profiles of 10,759 patients across 31 cancer types from The Cancer Genome Atlas project.

Results: We found that the type-I interferon, α-, and β-defensin genes were homozygously deleted in 19 cancer types with high frequencies (7%–31%, median = 12%; interquartile range = 10%–16.5%). Patients with homozygous deletion of interferons exhibited significantly shortened overall or disease-free survival time in a number of cancer types, whereas patients with homozygous deletion of defensins did not significantly associate with worse overall or disease-free survival. Gene expression analyses suggested that homozygous deletion of interferon and defensin genes could activate genes involved in oncogenic and cell-cycle pathways but repress other genes involved in immune response pathways, suggesting their roles in promoting tumorigenesis and helping cancer cells evade immune surveillance. Further analysis of the whole exomes of 109 patients with melanoma demonstrated that the homozygous deletion of interferon (P = 0.0029, OR = 11.8) and defensin (P = 0.06, OR = 2.79) genes are significantly associated with resistance to anti-CTLA4 immunotherapy.

Conclusions: Our analysis reveals that the homozygous deletion of interferon and defensin genes is prevalent in human cancers, and importantly this feature can be used as a novel prognostic biomarker for immunotherapy resistance. Clin Cancer Res; 24(14); 3299–308. ©2018 AACR.
Change in Topoisomerase 1–Positive Circulating Tumor Cells Affects Overall Survival in Patients with Advanced Breast Cancer after Treatment with Etirinotecan Pegol
Authors: Rugo Hope S. , Cortes Javier , Awada Ahmad , O'Shaughnessy Joyce , Twelves Chris , Im Seock-Ah , Hannah Alison , Lu Lin , Sy Sherwin , Caygill Katie , Zajchowski Deborah A. , Davis Darren W. , Tagliaferri Mary , Hoch Ute , Perez Edith A.
Published: April 2018

Purpose: Preplanned exploratory analyses were performed to identify biomarkers in circulating tumor cells (CTC) predictive of response to the topoisomerase 1 inhibitor etirinotecan pegol (EP).

Experimental Design: The BEACON trial treated patients with metastatic breast cancer (MBC) with EP or treatment of physician's choice (TPC). Blood from 656 of 852 patients (77%) was processed with ApoStream to enrich for CTCs. A multiplex immunofluorescence assay measured expression of candidate response biomarkers [topoisomerase 1 (Top1), topoisomerase 2 (Top2), Ki67, RAD51, ABCG2, γH2AX, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL)] in CTCs. Patients were classified as Top1 low (Top1Lo) or Top1 high (Top1Hi) based on median CTC Top1 expression. Correlation of CTC biomarker expression at baseline, cycle 2 day 1 (C2D1), and cycle 4 day 1 with overall survival (OS) was investigated using Cox regression and Kaplan–Meier analyses.

Results: Overall, 98% of samples were successfully processed, of which 97% had detectable CTCs (median, 47–63 CTCs/mL; range, 0–2,020 CTCs/mL). Top1, Top2, and TUNEL expression was detected in 52% to 90% of samples; no significant associations with OS were observed in pretreatment samples for either group. EP-treated patients with low C2D1Top1+ CTCs had improved OS compared with those with higher positivity (14.1 months vs. 11.0 months, respectively; HR, 0.7; P = 0.02); this difference was not seen in TPC-treated patients (HR, 1.12; P = 0.48). Patients whose CTCs decreased from Top1Hi to Top1Lo at C2D1 had the greatest OS benefit from EP (HR, 0.57; P = 0.01).

Conclusions: CTC Top1 expression following EP treatment may identify patients with MBC most likely to have an OS benefit. Clin Cancer Res; 24(14); 3348–57. ©2018 AACR.
Isolation and Characterization of a Lytic Bacteriophage (vB_PmiS-TH) and Its Application in Combination with Ampicillin against Planktonic and Biofilm Forms of Proteus mirabilis Isolated from Urinary Tract Infection
Authors: Yazdi Mahsa , Bouzari Majid , Ghaemi Ezzat Allah
Published: April 2018

Proteus mirabilis is one of the most common causes of urinary tract infection (UTI), particularly in patients undergoing long-term catheterization. Phage vB_PmiS-TH was isolated from wastewater with high lytic activity against P. mirabilis (TH) isolated from UTI. The phage had rapid adsorption, a large burst size (∼260 PFU per infected cell), and high stability at a wide range of temperatures and pH values. As analyzed by transmission electron microscopy, phage vB_PmiS-TH had an icosahedral head of ∼87 × 62 nm with a noncontractile tail about 137 nm in length and 11 nm in width. It belongs to the family Siphoviridae. Combination of the phage vB_PmiS-TH with ampicillin had a higher removal activity against planktonic cells of P. mirabilis (TH) than the phage or the antibiotic alone. Combination of the phage at a multiplicity of infection of 100 with a high dose of ampicillin (246 µg/mL) showed the highest biofilm removal activity after 24 h. This study demonstrates that using a combination of phage and antibiotic could be significantly more effective against planktonic and biofilm forms of P. mirabilis (TH).
Abnormal Expression of PICT-1 and Its Codon 389 Polymorphism Is a Risk Factor for Human Endometrial Cancer
Authors: Yoshimoto Masafumi , Tokuda Aoi , Nishiwaki Kunihiko , Sengoku Kazuo , Yaginuma Yuji
Published: April 2018

Objective: The protein interacting with carboxyl terminus-1 (PICT-1) gene has been implicated as a tumor suppressor gene, and its alterations have been reported in several cancers. This study investigated the association of PICT-1 alterations with endometrial carcinogenesis. Methods: We analyzed the entire coding region of the PICT-1 gene using polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing to examine PICT-1 mutations in endometrial cancer. Western blotting and immunohistochemical staining were performed to analyze the protein expression and cellular localization of PICT-1 in endometrial cancer cell lines and patient samples. Results: The codon 389 polymorphism of PICT-1 increased the risk of endometrial cancer. Interestingly, 2 of 13 endometrial cancers somatically acquired this mutation compared to normal counterparts. Immunohistochemical staining revealed lower levels of PICT-1 in samples from atypical endometrial hyperplasia and endometrial cancer tissues compared to normal endometrial tissues (p < 0.01). This decrease in PICT-1 expression was significantly correlated with histological grade and lymph node metastasis (p < 0.05). Conclusions: The findings of this study suggest that disruption of PICT-1 protein expression and codon 389 polymorphism can contribute to the pathogenesis or neoplastic progression of endometrial cancer.