bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex- and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus
Authors: De Blasio Miles J. , Lanham Stuart A. , Blache Dominique , Oreffo Richard O. C. , Fowden Abigail L. , Forhead Alison J.
Published: February 2018

Widespread expression of leptin and its receptor in developing cartilage and bone suggests that leptin may regulate bone growth and development in the fetus. Using microcomputed tomography, this study investigated the effects of exogenous leptin and leptin receptor antagonism on aspects of bone structure in the sheep fetus during late gestation. From 125 to 130 days of gestation (term ~145 days), chronically catheterized singleton sheep fetuses were infused intravenously for 5 days with either saline (0.9% saline, n = 13), recombinant ovine leptin at two doses (0.6 mg·kg−1·day−1 LEP1, n = 10 or 1.4 mg·kg−1·day−1 LEP2, n = 7), or recombinant superactive ovine leptin receptor antagonist (4.6 mg·kg−1·day−1 SOLA, n = 6). No significant differences in plasma insulin-like growth factor-I, osteocalcin, calcium, inorganic phosphate, or alkaline phosphatase were observed between treatment groups. Total femur midshaft diameter and metatarsal lumen diameter were narrower in male fetuses treated with exogenous leptin. In a fixed length of femur midshaft, total and bone volumes were reduced by the higher dose of leptin; nonbone space volume was lower in both groups of leptin-treated fetuses. Leptin infusion caused increments in femur porosity and connectivity density, and vertebral trabecular thickness. Leptin receptor antagonism decreased trabecular spacing and increased trabecular number, degree of anisotrophy, and connectivity density in the lumbar vertebrae. The increase in vertebral porosity observed following leptin receptor antagonism was greater in the malecompared with female, fetuses. Therefore, leptin may have a role in the growth and development of the fetal skeleton, dependent on the concentration of leptin, sex of the fetus, and bone type examined.
Taste sensitivity to a mixture of monosodium glutamate and inosine 5′-monophosphate by mice lacking both subunits of the T1R1+T1R3 amino acid receptor
Authors: Blonde Ginger D. , Travers Susan P. , Spector Alan C.
Published: February 2018

The taste of l-glutamate and its synergism with 5′-ribonucleotides is thought to be primarily mediated through the T1R1+T1R3 heterodimer in some mammals, including rodents and humans. While knockout (KO) mice lacking either receptor subunit show impaired sensitivity to a range of monosodium glutamate (MSG) concentrations mixed with 2.5 mM inosine 5′-monophosphate (IMP) in amiloride, wild-type (WT) controls can detect this IMP concentration, hindering direct comparison between genotypes. Moreover, some residual sensitivity persists in the KO group, suggesting that the remaining subunit could maintain a limited degree of function. Here, C57BL/6J, 129X1/SvJ, and T1R1+T1R3 double KO mice ( n = 16 each to start the experiment) were trained in a two-response operant task in gustometers and then tested for their ability to discriminate 100 µM amiloride from MSG (starting with 0.6 M) and IMP (starting with 2.5 mM) in amiloride (MSG+I+A). Testing continued with successive dilutions of both MSG and IMP (in amiloride). The two WT strains were similarly sensitive to MSG+I+A ( P > 0.8). KO mice, however, were significantly impaired relative to either WT strain ( P < 0.01), although they were able to detect the highest concentrations. Thus, normal detectability of MSG+I+A requires an intact T1R1+T1R3 receptor, without regard for allelic variation in the T1R3 gene between the WT strains. Nevertheless, residual sensitivity by the T1R1+T1R3 KO mice demonstrates that a T1R-independent mechanism can contribute to the detectability of high concentrations of this prototypical umami compound stimulus.
Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high-fat-fed mice
Authors: Tan Wei Sheng , Mullins Thomas P. , Flint Melanie , Walton Sarah L. , Bielefeldt-Ohmann Helle , Carter David A. , Gandhi Meera R. , McDonald Hayley R. , Li Joan , Moritz Karen M. , Reichelt Melissa E. , Gallo Linda A.
Published: February 2018

There is an increased incidence of heart failure in individuals with diabetes mellitus (DM). The coexistence of kidney disease in DM exacerbates the cardiovascular prognosis. Researchers have attempted to combine the critical features of heart failure, using transverse aortic constriction, with DM in mice, but variable findings have been reported. Furthermore, kidney outcomes have not been assessed in this setting; thus its utility as a model of heart failure in DM and kidney disease is unknown. We generated a mouse model of obesity, hyperglycemia, and mild kidney pathology by feeding male C57BL/6J mice a high-fat diet (HFD). Cardiac pressure overload was surgically induced using transverse aortic constriction (TAC). Normal diet (ND) and sham controls were included. Heart failure risk factors were evident at 8-wk post-TAC, including increased left ventricular mass (+49% in ND and +35% in HFD), cardiomyocyte hypertrophy (+40% in ND and +28% in HFD), and interstitial and perivascular fibrosis (Masson’s trichrome and picrosirius red positivity). High-fat feeding did not exacerbate the TAC-induced cardiac outcomes. At 11 wk post-TAC in a separate mouse cohort, echocardiography revealed reduced left ventricular size and increased left ventricular wall thickness, the latter being evident in ND mice only. Systolic function was preserved in the TAC mice and was similar between ND and HFD. Thus combined high-fat feeding and TAC in mice did not model the increased incidence of heart failure in DM patients. This model, however, may mimic the better cardiovascular prognosis seen in overweight and obese heart failure patients.
Endurance exercise training and high-fat diet differentially affect composition of diacylglycerol molecular species in rat skeletal muscle
Authors: Kawanishi Noriaki , Takagi Kana , Lee Hyeon-Cheol , Nakano Daiki , Okuno Toshiaki , Yokomizo Takehiko , Machida Shuichi
Published: February 2018

Insulin resistance of peripheral muscle is implicated in the etiology of metabolic syndrome in obesity. Although accumulation of glycerolipids, such as triacylglycerol and diacylglycerol (DAG), in muscle contributes to insulin resistance in obese individuals, endurance-trained athletes also have higher glycerolipid levels but normal insulin sensitivity. We hypothesized that the difference in insulin sensitivity of skeletal muscle between athletes and obese individuals stems from changes in fatty acid composition of accumulated lipids. Here, we evaluated the effects of intense endurance exercise and high-fat diet (HFD) on the accumulation and composition of lipid molecular species in rat skeletal muscle using a lipidomic approach. Sprague-Dawley female rats were randomly assigned to three groups and received either normal diet (ND) in sedentary conditions, ND plus endurance exercise training, or HFD in sedentary conditions. Rats were fed ND or HFD between 4 and 12 wk of age. Rats in the exercise group ran on a treadmill for 120 min/day, 5 days/wk, for 8 wk. Soleus muscle lipidomic profiles were obtained using liquid chromatography/tandem mass spectrometry. Total DAG levels, particularly those of palmitoleate-containing species, were increased in muscle by exercise training. However, whereas the total DAG level in the muscle was also increased by HFD, the levels of DAG molecular species containing palmitoleate were decreased by HFD. The concentration of phosphatidylethanolamine molecular species containing palmitoleate was increased by exercise but decreased by HFD. Our results indicate that although DAG accumulation was similar levels in trained and sedentary obese rats, specific changes in molecular species containing palmitoleate were opposite.
Neural correlates of economic value and valuation context: an event-related potential study
Authors: Tyson-Carr John , Kokmotou Katerina , Soto Vicente , Cook Stephanie , Fallon Nicholas , Giesbrecht Timo , Stancak Andrej
Published: February 2018

The value of environmental cues and internal states is continuously evaluated by the human brain, and it is this subjective value that largely guides decision making. The present study aimed to investigate the initial value attribution process, specifically the spatiotemporal activation patterns associated with values and valuation context, using electroencephalographic event-related potentials (ERPs). Participants completed a stimulus rating task in which everyday household items marketed up to a price of £4 were evaluated with respect to their desirability or material properties. The subjective values of items were evaluated as willingness to pay (WTP) in a Becker-DeGroot-Marschak auction. On the basis of the individual’s subjective WTP values, the stimuli were divided into high- and low-value items. Source dipole modeling was applied to estimate the cortical sources underlying ERP components modulated by subjective values (high vs. low WTP) and the evaluation condition (value-relevant vs. value-irrelevant judgments). Low-WTP items and value-relevant judgments both led to a more pronounced N2 visual evoked potential at right frontal scalp electrodes. Source activity in right anterior insula and left orbitofrontal cortex was larger for low vs. high WTP at ∼200 ms. At a similar latency, source activity in right anterior insula and right parahippocampal gyrus was larger for value-relevant vs. value-irrelevant judgments. A stronger response for low- than high-value items in anterior insula and orbitofrontal cortex appears to reflect aversion to low-valued item acquisition, which in an auction experiment would be perceived as a relative loss. This initial low-value bias occurs automatically irrespective of the valuation context.

NEW & NOTEWORTHY We demonstrate the spatiotemporal characteristics of the brain valuation process using event-related potentials and willingness to pay as a measure of subjective value. The N2 component resolves values of objects with a bias toward low-value items. The value-related changes of the N2 component are part of an automatic valuation process.
Reference frames in the decisions of hand choice
Authors: Bakker Romy S. , Selen Luc P. J. , Medendorp W. Pieter
Published: February 2018

For the brain to decide on a reaching movement, it needs to select which hand to use. A number of body-centered factors affect this decision, such as the anticipated movement costs of each arm, recent choice success, handedness, and task demands. While the position of each hand relative to the target is also known to be an important spatial factor, it is unclear which reference frames coordinate the spatial aspects in the decisions of hand choice. Here we tested the role of gaze- and head-centered reference frames in a hand selection task. With their head and gaze oriented in different directions, we measured hand choice of 19 right-handed subjects instructed to make unimanual reaching movements to targets at various directions relative to their body. Using an adaptive procedure, we determined the target angle that led to equiprobable right/left hand choices. When gaze remained fixed relative to the body this balanced target angle shifted systematically with head orientation, and when head orientation remained fixed this choice measure shifted with gaze. These results suggest that a mixture of head- and gaze-centered reference frames is involved in the spatially guided decisions of hand choice, perhaps to flexibly bind this process to the mechanisms of target selection.

NEW & NOTEWORTHY Decisions of target and hand choice are fundamental aspects of human reaching movements. While the reference frames involved in target choice have been identified, it is unclear which reference frames are involved in hand selection. We tested the role of gaze- and head-centered reference frames in a hand selection task. Findings emphasize the role of both spatial reference frames in the decisions of hand choice, in addition to known body-centered computations such anticipated movement costs and handedness.
Lignocellulosic Composites Prepared Utilizing Aqueous Alkaline/Urea Solutions with Cold Temperatures
Authors: Tisserat Brent , Liu Zengshe , Haverhals Luke M.
Published: February 2018

Lignocellulosic composites (LCs) were fabricated by partially dissolving cotton to create a matrix that was reinforced with osage orange wood (OOW) particles and/or blue agave fibers (AF). LCs were composed of 15–35% cotton matrix and 65–85% OWW/AF reinforcement. The matrix was produced by soaking cotton wool in a cold aqueous alkaline/urea solvent and was stirred for 15 minutes at 350 rpm to create a viscous gel. The gel was then reinforced with lignocellulosic components, mixed, and then pressed into a panel mold. LC panels were soaked in water to remove the aqueous solvent and then oven dried to obtain the final LC product. Several factors involved in the preparation of these LCs were examined including reaction temperatures (−5 to −15°C), matrix concentration (15–35% cotton), aqueous solvent volume (45–105 ml/panel), and the effectiveness of employing various aqueous solvent formulations. The mechanical properties of LCs were determined and reported. Conversion of the cotton into a suitable viscous gel was critical in order to obtain LCs that exhibited high mechanical properties. LCs with the highest mechanical properties were obtained when the cotton wools were subjected to a 4.6% LiOH/15% urea solvent at −12.5°C using an aqueous solvent volume of 60 ml/panel. Cotton wool subjected to excessive cold alkaline solvents volumes resulted in irreversible cellulose breakdown and a resultant LC that exhibited poor mechanical properties.
Insights on Localized and Systemic Delivery of Redox‐Based Therapeutics
Authors: Buglak Nicholas E. , Batrakova Elena V. , Mota Roberto , Bahnson Edward S. M.
Published: February 2018

Reactive oxygen and nitrogen species are indispensable in cellular physiology and signaling. Overproduction of these reactive species or failure to maintain their levels within the physiological range results in cellular redox dysfunction, often termed cellular oxidative stress. Redox dysfunction in turn is at the molecular basis of disease etiology and progression. Accordingly, antioxidant intervention to restore redox homeostasis has been pursued as a therapeutic strategy for cardiovascular disease, cancer, and neurodegenerative disorders among many others. Despite preliminary success in cellular and animal models, redox‐based interventions have virtually been ineffective in clinical trials. We propose the fundamental reason for their failure is a flawed delivery approach. Namely, systemic delivery for a geographically local disease limits the effectiveness of the antioxidant. We take a critical look at the literature and evaluate successful and unsuccessful approaches to translation of redox intervention to the clinical arena, including dose, patient selection, and delivery approach. We argue that when interpreting a failed antioxidant‐based clinical trial, it is crucial to take into account these variables and importantly, whether the drug had an effect on the redox status. Finally, we propose that local and targeted delivery hold promise to translate redox‐based therapies from the bench to the bedside.
Study of Thermomechanical Properties of an Al‐Zn‐Based Composite Reinforced with Dodecaboride Particles
Authors: Colón Quintana José Luis , Soto Medina Sujeily , Hernández Marivic , Suárez Oscar Marcelo
Published: February 2018

The effect of the addition of AlB12 particles to gravity cast Al‐Zn alloys was studied and related to the composite deformation at high temperature. The characterization techniques of choice were thermomechanical analysis (TMA), Brinell hardness (HB), and optical microscopy. After homogenization treatment, Al‐5 wt.% Zn and Al‐10 wt.% Zn with 0, 2.08, 4.16 wt.% B samples were quenched in ice water and tested using a thermomechanical analyzer at different temperatures. It was found that after TMA treatment, Brinell hardness of the composites increased for higher concentrations of zinc and AlB12 particles, as expected. Such increment was not, however, uniform for all samples at higher temperature levels, suggesting a nonequilibrium interaction between reinforcing particles and zinc. This was further corroborated by TMA experiments, which revealed that for samples with Al‐10 wt.% Zn, high temperature deformation augmented as more AlB12 particles were present. After high temperature treatment, precipitation of zinc‐rich allotriomorphs was observed by the optical microscopy performed on the samples near or on the aluminum grain boundaries, which discarded the potential effect of fine precipitation due to aging.
A Multiobjective Decision-Making Method of Service Element Allocation of Customer Behavior
Authors: Xu Wei , Yu Yinyun , Zhang Qingshan
Published: February 2018

How to effectively configure the resources to maximize customer satisfaction is an important research topic in the service quality evaluation. This paper proposes a service quality evaluation under fuzzy environment method that takes customer satisfaction as the goal and considers enterprise resource constraints and customer fuzzy evaluation information at the same time. In this method, we first use expert Delphi method to get service elements and service items. Meanwhile, we design questionnaires to collect customer language fuzzy evaluation information and use FHAHP model to calculate the relative weight vector of the service items. Second, the customer is subdivided into market segmentation considering the customer total consumption and the service expectation value using the Logit model. Next, the customer satisfaction of the service schemes is calculated considering the customer’s expectation of the service schemes. Then, the maximum satisfaction of the customer group is calculated under the condition of enterprise resource constraint. Finally, an example is used to illustrate the feasibility and effectiveness of the proposed method.
Patient’s Decision to Disclose the Use of Traditional and Complementary Medicine to Medical Doctor: A Descriptive Phenomenology Study
Authors: Kelak Johny Anak , Cheah Whye Lian , Safii Razitasham
Published: February 2018

Nondisclosure of traditional and complementary medicine (T&CM) use may cause individual to be at risk of undue harm. This study aimed to explore patient’s experience and views on their decision to disclose the use of T&CM to the doctor. An exploratory qualitative study using in‐depth interview involving 10 primary care clinics attendees in Kuching was conducted. The results indicated that disclosure of T&CM use will motivate them to get information, increase doctor’s awareness, and get support from family and friends for disclosure. Fear of negative relationship and negative response from doctors was a barrier for disclosure. Doctor’s interpersonal and communication skills of being involved, treating patients respectfully, listening attentively, respecting privacy, and taking time for the patient were a critical component for disclosure. Intrapersonal trust regarding doctor influences their satisfaction on healthcare. Women are more open and receptive to a health concern and expressing negative emotions and tend to share problems, whereas men always described themselves as healthy, tended to keep their own personal feeling to themselves, and tended to not share. The doctor should consider gender differences in disclosure, their attitude towards T&CM use, and gained patient’s trust in the delivery of healthcare services. Good interpersonal and communication skills must be maintained between doctor and patients.
Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin‐Induced Diabetic Nephropathy of Rat
Authors: Geng Jianan , Yu Xiaoyan , Liu Chunyu , Sun Chengbo , Guo Menghuan , Li Zhen , Jin Yingli , Zou Yinggang , Yu Jinghua
Published: February 2018

Diabetic nephropathy (DN) is a major cause of end‐stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE) to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM) in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high‐dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase‐2 (MMP‐2) and the expression of tissue transglutaminase (tTG), which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin‐induced DN rat model, and HACE is a promising candidate to cure DN in clinic.
Realm of Thermoalkaline Lipases in Bioprocess Commodities
Authors: Lajis Ahmad Firdaus B.
Published: February 2018

For decades, microbial lipases are notably used as biocatalysts and efficiently catalyze various processes in many important industries. Biocatalysts are less corrosive to industrial equipment and due to their substrate specificity and regioselectivity they produced less harmful waste which promotes environmental sustainability. At present, thermostable and alkaline tolerant lipases have gained enormous interest as biocatalyst due to their stability and robustness under high temperature and alkaline environment operation. Several characteristics of the thermostable and alkaline tolerant lipases are discussed. Their molecular weight and resistance towards a range of temperature, pH, metal, and surfactants are compared. Their industrial applications in biodiesel, biodetergents, biodegreasing, and other types of bioconversions are also described. This review also discusses the advance of fermentation process for thermostable and alkaline tolerant lipases production focusing on the process development in microorganism selection and strain improvement, culture medium optimization via several optimization techniques (i.e., one-factor-at-a-time, surface response methodology, and artificial neural network), and other fermentation parameters (i.e., inoculums size, temperature, pH, agitation rate, dissolved oxygen tension (DOT), and aeration rate). Two common fermentation techniques for thermostable and alkaline tolerant lipases production which are solid-state and submerged fermentation methods are compared and discussed. Recent optimization approaches using evolutionary algorithms (i.e., Genetic Algorithm, Differential Evolution, and Particle Swarm Optimization) are also highlighted in this article.
Scenario Screen: A Dynamic and Context Dependent P300 Stimulator Screen Aimed at Wheelchair Navigation Control
Authors: Piña-Ramirez Omar , Valdes-Cristerna Raquel , Yanez-Suarez Oscar
Published: February 2018

P300 spellers have been widely modified to implement nonspelling tasks. In this work, we propose a “scenario” stimulation screen that is a P300 speller variation to command a wheelchair. Our approach utilized a stimulation screen with an image background (scenario snapshot for a wheelchair) and stimulation markers arranged asymmetrically over relevant landmarks, such as suitable paths, doors, windows, and wall signs. Other scenario stimulation screen features were green/blue stimulation marker color scheme, variable Interstimulus Interval, single marker stimulus mode, and optimized stimulus sequence generator. Eighteen able-bodied subjects participated in the experiment; 78% had no experience in BCI usage. A waveform feature analysis and a Mann–WhitneyUtest performed over the pairs of target and nontarget coherent averages confirmed that 94% of the subjects elicit P300 (p<.005) on this modified stimulator. Least Absolute Shrinkage and Selection Operator optimization and Linear Discriminant Analysis were utilized for the automatic detection of P300. For evaluation with unseen data, target detection was computed (median sensitivity = 1.00 (0.78–1.00)), together with nontarget discrimination (median specificity = 1.00 (0.98–1.00)). The scenario screen adequately elicits P300 and seems suitable for commanding a wheelchair even when users have no previous experience on the BCI spelling task.
Beyond Weight Loss: Establishing a Postbariatric Surgery Patient Support Group—What Do Patients Want?
Authors: Hameed Saira , Salem Victoria , Tan Tricia M. , Collins Alma , Shah Krishna , Scholtz Samantha , Ahmed Ahmed R. , Chahal Harvinder
Published: February 2018

Purpose. There are limited resources for long-term specialist follow-up after bariatric surgery. In selected centres, patients can access a postoperative support group, but there is no clear evidence to guide their delivery. Materials and Methods. A retrospective study of bariatric surgery patients (n = 152) who had been discharged from specialist follow-up (mean time since surgery 5.5 years), covering weight history, physical and psychosocial comorbidities, and the need for a postoperative bariatric support group. Results. Fifty-eight percent wanted a postbariatric surgery patient support group. This was not associated with operation type or the amount of weight lost or regained. However, those who wanted a support group were significantly more likely to be struggling to keep the weight off, to be unhappy with the way they look, or to be experiencing difficulties returning to work. Conclusions. These data point to an unmet patient requirement for a postoperative support group that is independent of weight loss success. More research is required to ascertain how such a group should be delivered, but our data would suggest that supporting patients with weight loss maintenance, body image, and return to work is an important part of postoperative care, and these needs extend well beyond the immediate period of specialist follow-up.
Influence of Rare Earth on Dynamic Recrystallization Behavior of As‐Cast 30Mn Steel
Authors: Yan Honghong , Hu Yong , Zhao Dawen
Published: February 2018

Based on casting‐rolling compound forming process, the effect of rare earth on dynamic recrystallization (DRX) of as‐cast 30Mn steel was investigated by the single‐pass hot compression tests performed using a Gleeble‐3500 thermomechanical simulator, and the deformation temperature range was 950°C–1150°C and strain rate range was 0.1–1 s−1. With the assistance of the process parameters, constitutive equations were used to obtain the activation energy and hot working equation. The dynamic recrystallization kinetics models of the tested steel were constructed. The results show that rare earth ferrosilicon alloy addition (0.2%, mass fraction) can delay the onset of DRX significantly and refine the hot deformation microstructures. All of the results indicate that the addition of rare earth into as‐cast 30Mn steel is helpful to prepare excellent cast slab for the casting‐rolling compound forming technology.
Oral Cancer Knowledge Assessment: Newly Graduated versus Senior Dental Clinicians
Authors: Pavão Spaulonci Gisele , Salgado de Souza Ricardo , Gallego Arias Pecorari Vanessa , Lauria Dib Luciano
Published: February 2018

The present study assessed the level of dentists’ knowledge regarding oral cancer in the city of São Paulo, Brazil. A questionnaire was used to compare the level of knowledge among newly graduated and senior clinicians. A total of 20,154 e-mails were correctly delivered to the dentists registered in the database of the Regional Dentistry Council of São Paulo, and 477 (2.36%) responses were received. This sample consisted of 84 newly graduated clinicians and 105 senior clinicians. For the statistical analysis, the chi-square test and the logistic regression analysis were performed withα = 0.05, and the results were described herein. According to their knowledge level, the results were statistically different between the groups, since 19% of the newly graduated clinicians were evaluated with knowledge grade A (excellent) in comparison to 6.7% of the senior clinicians. In spite of the results indicated that newly graduated clinicians’ knowledge regarding oral cancer was 2.1 times higher, 34.5% of the professionals in this group had regular or poor knowledge on the subject, and several questions relating to clinical characteristics and risk factors indicated that there still exist some knowledge gaps, demonstrating that there is a need for further studies and information activities addressing oral cancer.
Perillaldehyde Inhibits AHR Signaling and Activates NRF2 Antioxidant Pathway in Human Keratinocytes
Authors: Fuyuno Yoko , Uchi Hiroshi , Yasumatsu Mao , Morino-Koga Saori , Tanaka Yuka , Mitoma Chikage , Furue Masutaka
Published: February 2018

The skin covers the outer surface of the body, so the epidermal keratinocytes within it are susceptible to reactive oxygen species (ROS) generated by environmental pollutants such as benzo(a)pyrene (BaP), a potent activator of aryl hydrocarbon receptor (AHR). Antioxidant activity is generally mediated by the nuclear factor‐erythroid 2‐related factor‐2 (NRF2) and heme oxygenase‐1 (HO1) axis in human keratinocytes. Perillaldehyde is the main component of Perilla frutescens, which is a medicinal antioxidant herb traditionally consumed in East Asia. However, the effect of perillaldehyde on the AHR/ROS and/or NRF2/HO1 pathways remains unknown. In human keratinocytes, we found that perillaldehyde (1) inhibited BaP‐induced AHR activation and ROS production, (2) inhibited BaP/AHR‐mediated release of the CCL2 chemokine, and (3) activated the NRF2/HO1 antioxidant pathway. Perillaldehyde is thus potentially useful for managing inflammatory skin diseases or disorders related to oxidative stress.
Development and External Validation of Prediction Models for 10-Year Survival of Invasive Breast Cancer. Comparison with PREDICT and CancerMath
Authors: Karapanagiotis Solon , Pharoah Paul D.P. , Jackson Christopher H. , Newcombe Paul J.
Published: February 2018

Purpose: To compare PREDICT and CancerMath, two widely used prognostic models for invasive breast cancer, taking into account their clinical utility. Furthermore, it is unclear whether these models could be improved.

Experimental Design: A dataset of 5,729 women was used for model development. A Bayesian variable selection algorithm was implemented to stochastically search for important interaction terms among the predictors. The derived models were then compared in three independent datasets (n = 5,534). We examined calibration, discrimination, and performed decision curve analysis.

Results: CancerMath demonstrated worse calibration performance compared with PREDICT in estrogen receptor (ER)–positive and ER-negative tumors. The decline in discrimination performance was −4.27% (−6.39 to −2.03) and −3.21% (−5.9 to −0.48) for ER-positive and ER-negative tumors, respectively. Our new models matched the performance of PREDICT in terms of calibration and discrimination, but offered no improvement. Decision curve analysis showed predictions for all models were clinically useful for treatment decisions made at risk thresholds between 5% and 55% for ER-positive tumors and at thresholds of 15% to 60% for ER-negative tumors. Within these threshold ranges, CancerMath provided the lowest clinical utility among all the models.

Conclusions: Survival probabilities from PREDICT offer both improved accuracy and discrimination over CancerMath. Using PREDICT to make treatment decisions offers greater clinical utility than CancerMath over a range of risk thresholds. Our new models performed as well as PREDICT, but no better, suggesting that, in this setting, including further interaction terms offers no predictive benefit. Clin Cancer Res; 24(9); 2110–5. ©2018 AACR.
PIM Kinases Are a Potential Prognostic Biomarker and Therapeutic Target in Neuroblastoma
Authors: Brunen Diede , de Vries Romy C. , Lieftink Cor , Beijersbergen Roderick L. , Bernards René
Published: February 2018

The majority of high-risk neuroblastoma patients are refractory to, or relapse on, current treatment regimens, resulting in 5-year survival rates of less than 50%. This emphasizes the urgent need to identify novel therapeutic targets. Here, we report that high PIM kinase expression is correlated with poor overall survival. Treatment of neuroblastoma cell lines with the pan-PIM inhibitors AZD1208 or PIM-447 suppressed proliferation through inhibition of mTOR signaling. In a panel of neuroblastoma cell lines, we observed a marked binary response to PIM inhibition, suggesting that specific genetic lesions control responses to PIM inhibition. Using a genome-wide CRISPR-Cas9 genetic screen, we identified NF1 loss as the major resistance mechanism to PIM kinase inhibitors. Treatment with AZD1208 impaired the growth of NF1 wild-type xenografts, while NF1 knockout cells were insensitive. Thus, our data indicate that PIM inhibition may be a novel targeted therapy in NF1 wild-type neuroblastoma. Mol Cancer Ther; 17(4); 849–57. ©2018 AACR.
Extensive Lepromatous Lymphadenitis Preceding Lesions on the Face and Earlobes: An Unusual Presentation of Leprosy in Singapore
Authors: Yang Shi Yao Sam , Leong Wai Mun Sean , Kasunuran Cruz Maria Teresa , Huang Jing Xiang , Ho Sue-Ann Ju Ee , Aw Chen Wee Derrick , Merchant Reshma A.
Published: February 2018

Leprosy is also known as Hansen disease, as in some countries the diagnosis of leprosy carries a negative stigma and patients fear being shunned as outcasts. Presently, leprosy is primarily limited to specific geographical regions in resource-poor countries. As a result, there is increased difficulty for the younger generation of physicians today to correctly identify leprosy due to a lack of exposure and a low-index of suspicion, particularly in developed countries. In this case, the indurated lesions over the face demonstrated a preference for the outer lateral aspects over the maxillary areas, the nose bridge, and the pinna of the ears consistent with the organism’s preference for cooler regions of the body. This was also evident in the other skin lesions affecting the more acral regions of the limbs in the early stage of disease progression. There is a need to keep this infective condition as an alternate diagnosis to all unusual cutaneous lesions.
Photodynamic Therapy for Circumscribed Choroidal Haemangioma in a Scottish Cohort
Authors: Jamison Aaron , Cauchi Paul , Gilmour David F.
Published: February 2018

Purpose: The aim of this study was to evaluate the safety and efficacy of photodynamic therapy (PDT) with verteporfin as a treatment for circumscribed choroidal haemangioma (CCH). Procedures: This is a retrospective cohort study of all treatment-naïve patients undergoing PDT with verteporfin for CCH in a single centre between April 1, 2007, and September 30, 2016. Best corrected visual acuity (BCVA; using ETDRS letter score), optical coherence tomography (OCT) measurements and a subjective measurement of visual function were recorded before treatment, at 3-month follow-up and at each annual follow-up. Results: Seventeen Caucasian patients with CCH received PDT, with a re-treatment rate of 23.5% (n = 4). Mean (±SD) follow-up was 36.5 (±32.6) months (range 2–106). Mean (±SD) pre-PDT BCVA was 58.5 (±15.5) letters, with a mean improvement from baseline of 8.2 letters at 3 months, of 13.8 letters at 1 year, of 21.1 letters at 2 years and of 19.5 letters at 3 years of follow-up. Subjective visual improvement was noted in 67% at 3 months, in 93% at 1 year, in 86% at 2 years and in 100% at 3 years of follow-up. OCT demonstrated no intraretinal/subretinal fluid in 63% at 3 months, in 77% at 1 year, in 86% at 2 years and in 100% at 3 years of follow-up. No complications of PDT were noted during the study. Conclusions: PDT is a safe and effective treatment for CCH which results in both structural and functional improvements, and these findings are particularly applicable to patients of Caucasian ethnicity. OCT provides a useful and readily available option to monitor CCH disease activity and its response to PDT.
Concomitant Non-Small Cell Lung Cancer and Hairy Cell Leukemia in a Patient Harboring BRAF-V600E Mutation in Both Tissues: A Case Report
Authors: Mitsogianni Maria , Mitsimponas Nikolaos , Crespo Felipe , Hartmann Karl Axel , Klosterhalfen Bernd , Haase Sabine , Giagounidis Aristoteles
Published: February 2018

The BRAF-V600E mutation has been established as a signature alteration occurring almost universally in hairy cell leukemia. Moreover, it can be detected in a small percentage of patients with non-small cell lung cancer. We report the case of a patient with a metastatic BRAF-V600E-mutated lung adenocarcinoma suffering from concomitant hairy cell leukemia. The identification of an identical BRAF mutation in both malignancies raises physiopathological considerations and might offer unique therapeutic strategies for this group of patients.
TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of Tumor-Infiltrating Lymphocytes
Authors: Würfel Franziska , Erber Ramona , Huebner Hanna , Hein Alexander , Lux Michael P. , Jud Sebastian , Kremer Anita , Kranich Hannah , Mackensen Andreas , Häberle Lothar , Hack Carolin C. , Rauh Claudia , Wunderle Marius , Gaß Paul , Rabizadeh Shahrooz , Brandl Anna-Lisa , Langemann Hanna , Volz Bernhard , Nabieva Naiba , Schulz-Wendtland Rüdiger , Dudziak Diana , Beckmann Matthias W. , Hartmann Arndt , Fasching Peter A. , Rübner Matthias
Published: February 2018

Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype ‘lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.
Cardiovascular Risk Prediction Functions Underestimate Risk in HIV Infection
Authors: Triant Virginia A. , Perez Jeremiah , Regan Susan , Massaro Joseph M. , Meigs James B. , Grinspoon Steven K. , D’Agostino Ralph B.
Published: February 2018

Background:

Cardiovascular disease (CVD) risk is elevated in HIV-infected individuals, with contributions from both traditional and nontraditional risk factors. The accuracy of established CVD risk prediction functions in HIV is uncertain. We sought to assess the performance of 3 established CVD risk prediction functions in a longitudinal cohort of HIV-infected men.

Methods:

The FHS (Framingham Heart Study) functions for hard coronary heart disease (FHS CHD) and atherosclerotic CVD (FHS ASCVD) and the American College of Cardiology/American Heart Association ASCVD function were applied to the Partners HIV cohort. Risk scores were calculated between January 1, 2006, and December 31, 2008. Outcomes included CHD (myocardial infarction or coronary death) for the FHS CHD function and ASCVD (myocardial infarction, stroke, or coronary death) for the FHS ASCVD and American College of Cardiology/American Heart Association ASCVD functions. We investigated the accuracy of CVD risk prediction for each function when applied to the HIV cohort using comparison of Cox regression coefficients, discrimination, and calibration.

Results:

The HIV cohort was comprised of 1272 men followed for a median of 4.4 years. There were 78 (6.1%) ASCVD events; the 5-year incidence rate was 16.4 per 1000 person-years. Discrimination was moderate to poor as indicated by the low
c
statistic (0.68 for FHS CHD, 0.65 for American College of Cardiology/American Heart Association ASCVD, and 0.67 for FHS ASCVD). Observed CVD risk exceeded the predicted risk for each of the functions in most deciles of predicted risk. Calibration, or goodness of fit of the models, was consistently poor, with significant χ
2
P
values for all functions. Recalibration did not significantly improve model fit.

Conclusions:

Cardiovascular risk prediction functions developed for use in the general population are inaccurate in HIV infection and systematically underestimate risk in a cohort of HIV-infected men. Development of tailored CVD risk prediction functions incorporating traditional CVD risk factors and HIV-specific factors is likely to result in more accurate risk estimation to guide preventative CVD care.
Other Voices for the Conflict: Three Spanish texts about the Manchus and Their conquest of China
Authors: i Alemany Anna Busquets
Published: February 2018

The entry of the Manchus in the Chinese Empire introduced a new subject matter into the works about China that had been circulating in Europe until that time. In the second half of the XVII century, the Jesuits inundated the European scene with different publications centred on this historical event. In Spain, there were also texts that covered the changes in the Chinese dynasty right from the start. Specifically, information about the fall of the Ming dynasty basically came from three sources: the text by Bishop Juan de Palafox y Mendoza, Historia de la conquista de China por el Tártaro (1670, posthumous edition); the Hechos de la Orden de Predicadores en el Imperio de China (1667), by the Dominican Victorio Riccio, and the news collected by another Dominican, Fernández de Navarrete, in his Tratados históricos, políticos, éticos y religiosos de la monarquía de China (1676). The objective of this essay is to present these three authors and their works, analysing the information that they offer about the entry of the Manchus in China and the relation between them.
A new Reed Frog (Hyperoliidae: Hyperolius) from coastal northeastern Mozambique
Authors: CONRADIE WERNER , VERBURGT LUKE , PORTIK DANIEL M. , OHLER ANNEMARIE , BWONG BERYL A. , LAWSON LUCINDA P.
Published: February 2018

A new species of African reed frog (genus Hyperolius Rapp, 1842) is described from the Coastal Forests of the Eastern Africa Biodiversity Hotspot in northeastern Mozambique. It is currently only known from less than ten localities associated with the Mozambican coastal pans system, but may also occur in the southeastern corner of Tanzania. Phylogenetic reconstructions using the mitochondrial 16S marker revealed that it is the sister taxon of Hyperolius mitchelli (>5.6% 16S mtDNA sequence divergence) and forms part of a larger H. mitchelli complex with H. mitchelli and H. rubrovermiculatus. The new species is distinguished from other closely related Hyperolius species by genetic divergence, morphology, vocalisation, and dorsal colouration.
Additions to the Indonesian crab fauna of the genus Mariaplax Rahayu & Ng, 2014, and notes on Hexapus timika Rahayu & Ng, 2014 (Crustacea, Decapoda, Brachyura, Hexapodidae)
Authors: RAHAYU DWI LISTYO , WIDYASTUTI ERNAWATI
Published: February 2018

Hexapus timika Rahayu & Ng, 2014 is redescribed based on newly collected male and female specimens from Papua, Indonesia. Three new species from Jakarta Bay and Sunda Strait, Indonesia, are added to the genus Mariaplax, the richest genus in the family Hexapodidae, hitherto having 14 species. Mariaplax pitrai n. sp. has the carapace covered by small, closely-spaced tubercles and long ambulatory legs, resembling M. chenae Rahayu & Ng, 2014 but easily separated by the position of female vulvae. Mariaplax hispida n. sp. is unique for the presence of short stiff setae on the outer face of the chelipeds and pereopods 2−4. Mariaplax sundaica n. sp. is characterized by the broad carapace, covered entirely by tubercles, the longitudinal grooves present only on the meri of pereopods 2 and 3. A key to the species of Mariaplax is provided.
A new Candonopsini (Ostracoda) genus from subterranean waters of New South Wales (Australia)
Authors: KARANOVIC IVANA
Published: February 2018

The Australian Candonidae ostracod fauna has few surface water representatives, despite Australia being one of the principal centers of Candonidae biodiversity. The majority of Australian species live in subterranean waters, with most genera and one tribe being endemic to the continent. Species in Australia show Tethyan and Gondwana connections, with relatives living in European and Central/South American subterranean waters. I describe Hancockcandonopsis gen. nov. from boreholes in the alluvial aquifers of the Peel River and Hunter Valley, which at present contains five species, of which three are named, H. inachos sp. nov., H. io sp. nov., and H. tamworthi sp. nov., and two are left on the open nomenclature. All species are allopatric and short range endemics. The genus belongs to the almost cosmopolitan Candonopsini tribe, and the major generic autapomorphy is a hook-shaped h3-seta on the cleaning leg. Characters on the prehensile palps and hemipenis of Hancockcandonopsis indicate a close relationship with the Queensland genus Pioneercandonopsis Karanovic, 2005 and two West Indies genera, Cubacandona Danielopol, 1978 and Caribecandona Broodbaker, 1983. A cladistic analysis, based on 32 Candonopsini species and 24 morphological characters, is used to test phylogenetic relationships among Candonopsini genera globally. Several hypotheses about the historical biogeography of this tribe are discussed.