bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Removal: Efferocytosis
Authors: Henson Peter M.
Published: June 2017

In metazoans, removal of cells in situ is involved in larval maturation, metamorphosis, and embryonic development. In adults, such cell removal plays a role in the homeostatic maintenance of cell numbers and tissue integrity as well as in the response to cell injury and damage. This removal involves uptake of the whole or fragmented target cells into phagocytes. Depending on the organism, these latter may be near-neighbor tissue cells and/or professional phagocytes such as, in vertebrates, members of the myeloid family of cells, especially macrophages. The uptake processes appear to involve specialized and highly conserved recognition ligands and receptors, intracellular signaling in the phagocytes, and mechanisms for ingestion. The recognition of cells destined for this form of removal is critical and, significantly, is distinguished for the most part from the recognition of foreign materials and organisms by the innate and adaptive immune systems. In keeping with the key role of cell removal in maintaining tissue homeostasis, constant cell removal is normally silent, i.e., does not initiate a local tissue reaction. This article discusses these complex and wide-ranging processes in general terms as well as the implications when these processes are disrupted in inflammation, immunity, and disease.
The Scientific, Economic, and Social Impacts of the New Zealand Outbreak of Bacterial Canker of Kiwifruit (Pseudomonas syringaepv.actinidiae)
Authors: Vanneste Joel L.
Published: June 2017

The introduction of Pseudomonas syringae pv. actinidiae (Psa) severely damaged the New Zealand kiwifruit industry, which in 2010 was based on only two cultivars. Despite an extraordinarily quick and strong response by industry, government, and scientists to minimize the economic and social impacts, the economic consequences of this outbreak were severe. Although our understanding of Psa epidemiology and control methods increased substantively over the past six years, the kiwifruit industry largely recovered because of the introduction of a less-susceptible yellow-fleshed cultivar. The New Zealand population of Psa is clonal but has evolved rapidly since its introduction by exchanging mobile genetic elements, including integrative conjugative elements (ICEs), with the local bacterial populations. In some cases, this has led to copper resistance. It is currently believed that the center of origin of the pathogen is Japan or Korea, but biovar 3, which is responsible for the global outbreak, originated in China.
A Conversation with Emery Neal Castle
Authors: Castle Emery N. , Weber Bruce A. , Sandler Richard , Wu JunJie
Published: June 2017

This article presents the transcript of an interview with the eminent economist, Emery Neal Castle. Emery discusses his youth in rural Kansas and how it shaped him and his career. After several years in the US Army Air Force during World War II, Emery returned to Kansas State University for his undergraduate studies and then completed his PhD at Iowa State University. He eventually landed at Oregon State University (OSU) in the mid-1950s, where he taught farm management and developed early courses in water resource economics. Emery and colleagues nurtured what became a world-renowned resource economics program at OSU. Emery also spent a decade running the nonprofit public policy research organization Resources for the Future in Washington, DC. Throughout his long career, Emery made significant contributions to three subfields of applied economics: farm management, resource economics, and rural studies. Emery has received numerous awards for his impact on the profession and the agricultural economy.
Nkx2.5 is essential to establish normal heart rate variability in the zebrafish embryo
Authors: Harrington Jamie K. , Sorabella Robert , Tercek Abigail , Isler Joseph R. , Targoff Kimara L.
Published: June 2017

Heart rate variability (HRV) has become an important clinical marker of cardiovascular health and a research measure for the study of the cardiac conduction system and its autonomic controls. While the zebrafish ( Danio rerio) is an ideal vertebrate model for understanding heart development, HRV has only recently been investigated in this system. We have previously demonstrated that nkx2.5 and nkx2.7, two homologues of Nkx2–5 expressed in zebrafish cardiomyocytes, play vital roles in maintaining cardiac chamber-specific characteristics. Given observed defects in ventricular and atrial chamber identities in nkx2.5−/− embryos coupled with conduction system abnormalities in murine models of Nkx2.5 insufficiency, we postulated that reduced HRV would serve as a marker of poor cardiac health in nkx2.5 mutants and in other zebrafish models of human congenital heart disease. Using live video image acquisition, we derived beat-to-beat intervals to compare HRV in wild-type and nkx2.5−/− embryos. Our data illustrate that the nkx2.5 loss-of-function model exhibits increased heart rate and decreased HRV when compared with wild type during embryogenesis. These findings validate HRV analysis as a useful quantitative tool for assessment of cardiac health in zebrafish and underscore the importance of nkx2.5 in maintaining normal heart rate and HRV during early conduction system development.
The transcriptome of the Didelphis virginiana opossum kidney OK proximal tubule cell line
Authors: Eshbach Megan L. , Sethi Rahil , Avula Raghunandan , Lamb Janette , Hollingshead Deborah J. , Finegold David N. , Locker Joseph D. , Chandran Uma R. , Weisz Ora A.
Published: June 2017

The OK cell line derived from the kidney of a female opossum Didelphis virginiana has proven to be a useful model in which to investigate the unique regulation of ion transport and membrane trafficking mechanisms in the proximal tubule (PT). Sequence data and comparison of the transcriptome of this cell line to eutherian mammal PTs would further broaden the utility of this culture model. However, the genomic sequence for D. virginiana is not available and although a draft genome sequence for the opossum Monodelphis domestica (sequenced in 2012 by the Broad Institute) exists, transcripts sequenced from both species show significant divergence. The M. domestica sequence is not highly annotated, and the majority of transcripts are predicted rather than experimentally validated. Using deep RNA sequencing of the D. virginiana OK cell line, we characterized its transcriptome via de novo transcriptome assembly and alignment to the M. domestica genome. The quality of the de novo assembled transcriptome was assessed by the extent of homology to sequences in nucleotide and protein databases. Gene expression levels in the OK cell line, from both the de novo transcriptome and genes aligned to the M. domestica genome, were compared with publicly available rat kidney nephron segment expression data. Our studies demonstrate the expression in OK cells of numerous PT-specific ion transporters and other key proteins relevant for rodent and human PT function. Additionally, the sequence and expression data reported here provide an important resource for genetic manipulation and other studies on PT cell function using these cells.
Comparison of the VTA and LC response to methylphenidate: a concomitant behavioral and neuronal study of adolescent male rats
Authors: Karim Tahseen J. , Reyes-Vazquez Cruz , Dafny Nachum
Published: June 2017

Methylphenidate (MPD), also known as Ritalin, is a psychostimulant used to treat attention deficit hyperactivity disorder. However, it is increasingly being misused by normal adolescents for recreation and academic advantage. Therefore, it is important to elucidate the behavioral and neurophysiological effects of MPD in normal subjects. MPD inhibits the reuptake of catecholamines, mainly found in the ventral tegmental area (VTA) and locus coeruleus (LC). The VTA and LC normally mediate attention, motivation, and drug reward behaviors. Selective neuronal connections between the VTA and LC have been identified implicating regular interaction between the structures. The objective of this study was to compare the neuronal responses of the VTA and LC to MPD in normal adolescent rats. Animals were implanted with permanent electrodes in the VTA and LC, and neuronal units were recorded following acute and repetitive (chronic) saline or 0.6, 2.5, or 10.0 mg/kg MPD exposure. Animals displayed either behavioral sensitization or tolerance to all three doses of MPD. Acute MPD exposure elicited excitation in the majority of all VTA and LC units. Chronic MPD exposure elicited a further increase in VTA and LC neuronal activity in animals exhibiting behavioral sensitization and an attenuation in VTA and LC neuronal activity in animals exhibiting behavioral tolerance, demonstrating neurophysiological sensitization and tolerance, respectively. The similar pattern in VTA and LC unit activity suggests that the two structures are linked in their response to MPD. These results may help determine the exact mechanism of action of MPD, resulting in optimized treatment of patients.

NEW & NOTEWORTHY The same dose of 0.6, 2.5, and 10 mg/kg methylphenidate (MPD) elicits either behavioral sensitization or tolerance in adolescent rats. There is a direct correlation between the ventral tegmental area (VTA) and locus coeruleus (LC) neuronal response to chronic MPD exposure. Both the VTA and LC are involved in the behavioral and neurophysiological effects of chronic MPD.
Excitability and firing behavior of single slow motor axons transmitting natural repetitive firing of human motoneurons
Authors: Kudina Lydia P. , Andreeva Regina E.
Published: June 2017

Excitability of single slow axons was estimated by motor unit firing index in response to motor nerve stimulation, and its changes throughout a target interspike interval were explored during transmitting human motoneuron natural firing. It was found that axons exhibited early irresponsive, responsive, and later irresponsive periods. Findings question whether the traditionally described axonal excitability recovery cycle is realistic in natural motor control.
Activity of primate V1 neurons during the gap saccade task
Authors: Kim Kayeon , Lee Choongkil
Published: June 2017

The link between neural activity in monkey primary visual cortex (V1) and visually guided behavioral response is confirmed with the gap saccade paradigm. Results indicated that the variability in neural latency of V1 spike activity correlates with the gap effect on saccade latency and that the trial-to-trial variability in the state of V1 before the onset of saccade target correlates with the variability in neural and behavioral latencies.
High-frequency epidural stimulation across the respiratory cycle evokes phrenic short-term potentiation after incomplete cervical spinal cord injury
Authors: Gonzalez-Rothi Elisa J. , Streeter Kristi A. , Hanna Marie H. , Stamas Anna C. , Reier Paul J. , Baekey David M. , Fuller David D.
Published: June 2017

C2 spinal hemilesion (C2Hx) paralyzes the ipsilateral diaphragm, but recovery is possible through activation of “crossed spinal” synaptic inputs to ipsilateral phrenic motoneurons. We tested the hypothesis that high-frequency epidural stimulation (HF-ES) would potentiate ipsilateral phrenic output after subacute and chronic C2Hx. HF-ES (300 Hz) was applied to the ventrolateral C4 or T2 spinal cord ipsilateral to C2Hx in anesthetized and mechanically ventilated adult rats. Stimulus duration was 60 s, and currents ranged from 100 to 1,000 µA. Bilateral phrenic nerve activity and ipsilateral hypoglossal (XII) nerve activity were recorded before and after HF-ES. Higher T2 stimulus currents potentiated ipsilateral phasic inspiratory activity at both 2 and 12 wk post-C2Hx, whereas higher stimulus currents delivered at C4 potentiated ipsilateral phasic phrenic activity only at 12 wk ( P = 0.028). Meanwhile, tonic output in the ipsilateral phrenic nerve reached 500% of baseline values at the high currents with no difference between 2 and 12 wk. HF-ES did not trigger inspiratory burst-frequency changes. Similar responses occurred following T2 HF-ES. Increases in contralateral phrenic and XII nerve output were induced by C4 and T2 HF-ES at higher currents, but the relative magnitude of these changes was small compared with the ipsilateral phrenic response. We conclude that following incomplete cervical spinal cord injury, HF-ES of the ventrolateral midcervical or thoracic spinal cord can potentiate efferent phrenic motor output with little impact on inspiratory burst frequency. However, the substantial increases in tonic output indicate that the uninterrupted 60-s stimulation paradigm used is unlikely to be useful for respiratory muscle activation after spinal injury.

NEW & NOTEWORTHY Previous studies reported that high-frequency epidural stimulation (HF-ES) activates the diaphragm following acute spinal transection. This study examined HF-ES and phrenic motor output following subacute and chronic incomplete cervical spinal cord injury. Short-term potentiation of phrenic bursting following HF-ES illustrates the potential for spinal stimulation to induce respiratory neuroplasticity. Increased tonic phrenic output indicates that alternatives to the continuous stimulation paradigm used in this study will be required for respiratory muscle activation after spinal cord injury.
Synthesis and Characterization of Low Loss Dielectric Ceramics Prepared from Composite of Titanate Nanosheets with Barium Ions
Authors: Wypych-Puszkarz Aleksandra , Bobowska Izabela , Wrzesinska Angelika , Opasinska Agnieszka , Maniukiewicz Waldemar , Wojciechowski Piotr , Ulanski Jacek
Published: June 2017

We report a strategy for preparing barium titanate precursor, being the composite of titanate nanosheets (TN) with barium ions (Ba-TN), which subjected to step sintering allows obtaining TiO2 rich barium titanate ceramics of stoichiometry BaTi4O9 or Ba2Ti9O20. These compounds are important in modern electronics due to their required dielectric properties and grains’ size that can be preserved in nanometric range. The morphology studies, structural characterization, and dielectric investigations were performed simultaneously in each step of Ba-TN calcinations in order to properly characterize type of obtained ceramic, its grains’ morphology, and dielectric properties. The Ba-TN precursor can be sintered at given temperatures, so that its dielectric permittivity can be tuned between 25 and 42 with controlled temperature coefficients that change from negative 32 ppm/°C for Ba-TN sintered at 900°C up to positive 37 ppm/°C after calcination at 1300°C. XRD analysis and Raman investigations performed for the Ba-TN in the temperature range of 900÷1250°C showed that below 1100°C we obtained as a main phase BaTi4O9, whereas the higher calcinations temperature transformed Ba-TN into Ba2Ti9O20. Taking into account trend of device miniaturization and nanoscopic size requirements, temperatures of 900°C and 1100°C seem to be an optimal condition for Ba-TN precursor calcinations that guarantee the satisfactory value of dielectric permittivity (ε=26 and 32) and ceramic grains with a mean size of ~180 nm and ~550 nm, respectively.
Comparative Analysis of Local Control Prediction Using Different Biophysical Models for Non-Small Cell Lung Cancer Patients Undergoing Stereotactic Body Radiotherapy
Authors: Huang Bao-Tian , Zhang Wu-Zhe , Wu Li-Li , Lin Pei-Xian , Lu Jia-Yang
Published: June 2017

Purpose. The consistency for predicting local control (LC) data using biophysical models for stereotactic body radiotherapy (SBRT) treatment of lung cancer is unclear. This study aims to compare the results calculated from different models using the treatment planning data. Materials and Methods. Treatment plans were designed for 17 patients diagnosed with primary non-small cell lung cancer (NSCLC) using 5 different fraction schemes. The Martel model, Ohri model, and the Tai model were used to predict the 2-year LC value. The Gucken model, Santiago model, and the Tai model were employed to estimate the 3-year LC data. Results. We found that the employed models resulted in completely different LC prediction except for the Gucken and the Santiago models which exhibited quite similar 3-year LC data. The predicted 2-year and 3-year LC values in different models were not only associated with the dose normalization but also associated with the employed fraction schemes. The greatest difference predicted by different models was up to 15.0%. Conclusions. Our results show that different biophysical models influence the LC prediction and the difference is not only correlated to the dose normalization but also correlated to the employed fraction schemes.
Cardiopulmonary Signal Detection Based on Magnetic Induction
Authors: Yang Dan , Xu Bin , Qiao Hongyu , Wang Xu
Published: June 2017

Cardiopulmonary signal contains vital and rich physiological information, which is very useful for clinical diagnosis and home healthcare. Convectional monitoring methods still need uncomfortable sensors or are expensive for nonprofessional common consumers. In this paper, we proposed a cardiopulmonary signal detection method based on electromagnetic induction. Based on thoracic volume variation affecting the biological impedance, which can be detected by magnetic induction, our idea is to develop a not complicated and practical measuring platform and exploit the intrinsic properties of cardiopulmonary signals with respiratory and heart rate. We have some theoretical analysis about the relationship of thoracic volume with biological impedance, sensor-head parameters, and the optimal measuring position. Then a whole measuring system has been designed and evaluated. The respiratory and heart rate obtained from the proposed method are not significantly different from the reference method (noncontact BCG).
Preferred M2 Polarization by ASC-Based Hydrogel Accelerated Angiogenesis and Myogenesis in Volumetric Muscle Loss Rats
Authors: Huang Hong , Liu Jiejie , Hao Haojie , Chen Deyun , Zhizhong Ling , Li Meirong , Song Haijing , Xiang Rong , Jiang Chaoguang , Fu Xiaobing , Han Weidong
Published: June 2017

Volumetric muscle loss (VML) injury resulted from massive muscle defects and diseases for which there are still no effective therapeutic treatments. This study aimed to investigate the effects of rat adipose-derived mesenchymal stem cells (rASCs) and rASCs-conditioned medium- (CM-) based type I collagen hydrogel on macrophage (MP) transition, myogenesis, and vascularization in the rat VML model. Laser Doppler results demonstrated much higher blood flow in the rASC- and CM-based hydrogel groups. qRT-PCR, hematoxylin and eosin, immunofluorescence, and Sirius Red staining manifested that both rASCs and CM-based hydrogel implantation accelerated muscle repair with upregulated angiogenesis and myogenesis, attenuated inflammation while facilitating M2 transition, and decreased the collagen deposition compared with the hydrogel group. In vitro experiments indicated that factors secreted from polarized M2 MPs could accelerate the migration and tube formation capacities of HUVECs. These results suggested that rASCs exerted immunomodulatory effects on MPs which further enhanced the proangiogenic potential on ECs to promote myogenesis and angiogenesis during muscle repair. These fundamental results support further clinical applications of ASCs for muscle loss injury.
Coproduction of Research Questions and Research Evidence in Public Health: The Study to Prevent Teen Drinking Parties
Authors: Wolfson Mark , Wagoner Kimberly G. , Rhodes Scott D. , Egan Kathleen L. , Sparks Michael , Ellerbee Dylan , Song Eunyoung Y. , Debinski Beata , Terrillion Albert , Vining Judi , Yang Evelyn
Published: June 2017

Community-based participatory research (CBPR) provides a set of principles and practices intended to foster coproduction of knowledge. However, CBPR often has shortcomings when applied to population-level policy and practice interventions, including a focus on single communities and a lack of focus on policy change. At the same time, community trials focused on policy have shortcomings, including lack of stakeholder involvement in framing research questions and modest engagement in study implementation and interpretation and dissemination of results. We describe an attempt to hybridize CBPR and community trials by creating a partnership that included a national membership organization, a coalition advisory board, intervention and delayed intervention communities, and an academic study team, which collaborated on a study of community strategies to prevent underage drinking parties. We use qualitative and quantitative data to critically assess the partnership. Areas where the partnership was effective included (1) identifying a research question with high public health significance, (2) enhancing the intervention, and (3) improving research methods. Challenges included community coalition representatives’ greater focus on their own communities rather than the production of broader scientific knowledge. This model can be applied in future attempts to narrow the gap between research, policy, and practice.
Overexpression of miR-24 Is Involved in the Formation of Hypocoagulation State after Severe Trauma by Inhibiting the Synthesis of Coagulation Factor X
Authors: Chen Lu-Jia , Yang Lian , Cheng Xing , Xue Yin-Kai , Chen Li-Bo
Published: June 2017

Background. Dysregulation of microRNAs may contribute to the progression of trauma-induced coagulopathy (TIC). We aimed to explore the biological function that miRNA-24-3p (miR-24) might have in coagulation factor deficiency after major trauma and TIC. Methods. 15 healthy volunteers and 36 severe trauma patients (Injury Severity Score ≥ 16 were enrolled. TIC was determined as the initial international normalized ratio >1.5. The miR-24 expression and concentrations of factor X (FX) and factor XII in plasma were measured. In vitro study was conducted on L02 cell line. Results. The plasma miR-24 expression was significantly elevated by 3.17-fold (P=0.043) in major trauma patients and reduced after 3 days (P<0.01). The expression level was significantly higher in TIC than in non-TIC patients (P=0.040). Multivariate analysis showed that the higher miR-24 expression was associated with TIC. The plasma concentration of FX in TIC patients was significantly lower than in the non-TIC ones (P=0.030) and controls (P<0.01). A negative correlation was observed between miR-24 and FX. miR-24 transduction significantly reduced the FX level in the supernatant of L02 cells (P=0.030). Conclusions. miR-24 was overexpressed in major trauma and TIC patients. The negative correlation of miR-24 with FX suggested the possibility that miR-24 might inhibit the synthesis of FX during TIC.
Thermal Error Modeling of the CNC Machine Tool Based on Data Fusion Method of Kalman Filter
Authors: Wang Haitong , Li Tiemin , Cai Yonglin , Wang Heng
Published: June 2017

This paper presents a modeling methodology for the thermal error of machine tool. The temperatures predicted by modified lumped‐mass method and the temperatures measured by sensors are fused by the data fusion method of Kalman filter. The fused temperatures, instead of the measured temperatures used in traditional methods, are applied to predict the thermal error. The genetic algorithm is implemented to optimize the parameters in modified lumped‐mass method and the covariances in Kalman filter. The simulations indicate that the proposed method performs much better compared with the traditional method of MRA, in terms of prediction accuracy and robustness under a variety of operating conditions. A compensation system is developed based on the controlling system of Siemens 840D. Validated by the compensation experiment, the thermal error after compensation has been reduced dramatically.
Diagnosis and Management of Intraoperative Colorectal Anastomotic Leaks: A Global Retrospective Patient Chart Review Study
Authors: Schiff A. , Roy S. , Pignot M. , Ghosh S. K. , Fegelman E. J.
Published: June 2017

Background. This targeted chart review study reports the first ever detailed global account of clinical approaches adopted to detect and manage anastomotic leaks identified during surgery in routine clinical practice. Method. 156 surgeons from eight countries retrospectively extracted data from surgical records of 458 patients who underwent colorectal surgery with an identified intraoperative leak at the circular anastomosis. Demographic details, procedures, and outcomes were analyzed descriptively, by country. Results. Most surgeries were performed laparoscopically (57.6%), followed by open surgeries (35.8%). The burden of intraoperative leaks on the healthcare system is driven in large part by the additional interventions such as using a sealant, recreating the anastomosis, and diverting the anastomosis to a colostomy bag, undertaken to manage the leak. The mean duration of hospitalization was 19.9 days. Postoperative anastomotic leaks occurred in 62 patients (13.5%), most frequently 4 to 7 days after surgery. Overall, country-specific differences were observed in patient characteristics, surgical procedures, method of diagnosis of intraoperative leak, interventions, and length of hospital stay. Conclusion. The potential cost of time and material needed to repair intraoperative leaks during surgery is substantial and often hidden to the healthcare system, potentially leading to an underestimation of the impact of this complication.
Stressors and Coping Strategies of the Saudi Nursing Students in the Clinical Training: A Cross‐Sectional Study
Authors: Alsaqri Salman H.
Published: June 2017

Nursing students often encounter high levels of stress through clinical practice that may cause psychological or emotional problems during their professional life eventually affecting the quality of patient care they provide. The aims of the current study were to identify the level and types of stress perceived by nursing students in their clinical practice and to identify the coping strategies that students used to relieve their stress. A descriptive, cross‐sectional design was used in this study. A total of 200 students who were enrolled in the nursing program were taken as study respondents. Research data were collected using the Perceived Stress Scale (PSS) and the Coping Behavior Inventory (CBI). Data was analyzed using one‐way ANOVA test, Pearson’s test, and independent sample t‐test on SPSS version 22. Findings indicated that nursing students experienced a high level of stress. The most common coping strategy utilized by the students was problem solving, while avoidance was the least frequently used one. Saudi nursing students experienced stress levels above the mean in clinical training. The most common stressors were related to assignments and workload. The study recommends that clinical curriculum requirements and the workload of nursing students should be reviewed.
PNPLA3rs1010023 Predisposes Chronic Hepatitis B to Hepatic Steatosis but Improves Insulin Resistance and Glucose Metabolism
Authors: Pan Qin , Chen Mei-Mei , Zhang Rui-Nan , Wang Yu-Qin , Zheng Rui-Dan , Mi Yu-Qiang , Liu Wen-Bin , Shen Feng , Su Qing , Fan Jian-Gao
Published: June 2017

PNPLA3polymorphisms serve as the genetic basis of hepatic steatosis in normal population and lead to dysregulated glucose metabolism. Whether it underlies the hepatic steatosis and glucose homeostasis in chronic hepatitis B patients remains uncertain. Here, we investigated thePNPLA3polymorphisms in biopsy-proven chronic hepatitis B patients with (CHB+HS group,n=52) or without hepatic steatosis (CHB group,n=47) and non-CHB subjects with (HS group,n=37) or without hepatic steatosis (normal group,n=45). When compared to the TT genotype, C-allele atPNPLA3rs1010023 (CC and TC genotypes) conferred higher risk to hepatic steatosis in chronic hepatitis B patients (odds ratio (OR) = 1.768, 95% confidence interval (CI): 1.027–3.105;P=0.045) independent of age, gender, and body mass index. In contrast to their role in hepatic steatosis, CC and TC genotypes ofPNPLA3rs1010023 were correlated to significant improvement of homeostasis model assessment index (HOMA-IR) as compared to TT genotype in the CHB+HS group. Downregulated fasting blood glucose also characterized the CHB+HS patients with C-allele atPNPLA3rs1010023 (CC/TC versus TT: 4.81 ± 0.92 mmol/L versus 5.86 ± 2.11 mmol/L,P=0.02). These findings suggest thatPNPLA3rs1010023 may predispose chronic hepatitis B patients to hepatic steatosis but protects them from glucose dysregulation by attenuating insulin resistance.
An Out Space Accelerating Algorithm for Generalized Affine Multiplicative Programs Problem
Authors: Cai Lei , Tang Shuai , Yin Jingben , Hou Zhisong , Jiao Hongwei
Published: June 2017

This paper presents an out space branch-and-bound algorithm for solving generalized affine multiplicative programs problem. Firstly, by introducing new variables and constraints, we transform the original problem into an equivalent nonconvex programs problem. Secondly, by utilizing new linear relaxation technique, we establish the linear relaxation programs problem of the equivalent problem. Thirdly, based on the out space partition and the linear relaxation programs problem, we construct an out space branch-and-bound algorithm. Fourthly, to improve the computational efficiency of the algorithm, an out space reduction operation is employed as an accelerating device for deleting a large part of the investigated out space region. Finally, the global convergence of the algorithm is proved, and numerical results demonstrate the feasibility and effectiveness of the proposed algorithm.
Application of Numerical Modelling and Genetic Programming in Hydrocarbon Seepage Prediction and Control for Crude Oil Storage Unlined Rock Caverns
Authors: Ghotbi Ravandi Ebrahim , Rahmannejad Reza , Karimi-Nasab Saeed , Sarrafi Amir
Published: June 2017

Seepage control is a prerequisite for hydrocarbon storage in unlined rock caverns (URCs) where the seepage of stored products to the surrounding host rock and groundwater can cause serious environmental and financial problems. Practically seepage control is performed by permeability and hydrodynamic control methods. This paper employs numerical modelling and genetic programming (GP) for the purpose of seepage prediction and control method determination for the crude oil storage URCs based on the effective parameters including hydrogeologic characteristic of the rock and physicochemical properties of the hydrocarbons. Several levels for each parameter were considered and all the possible scenarios were modelled numerically for the two-phase mixture model formulation. The corresponding seepage values were evaluated to be used as genetic programming data base to generate representative equations for the hydrocarbon seepage value. The coefficients of determination (R2) and relative percent errors of the proposed equations show their ability in the seepage prediction and permeability or hydrodynamic control method determination and design. The results can be used for crude oil storage URCs worldwide.
Nonsurgical Treatment for Vocal Fold Leukoplakia: An Analysis of 178 Cases
Authors: Chen Min , Cheng Lei , Li Chang-jiang , Chen Jian , Shu Yi-lai , Wu Hai-tao
Published: June 2017

Objective. To assess the effectiveness and identify vocal fold leukoplakia types appropriate for nonsurgical treatment. Methods. The vocal fold leukoplakia in 178 patients was divided by gross appearance into three subtypes: flat and smooth, elevated and smooth, and rough. All patients received nonsurgical treatment including smoking and drinking cessation, voice rest, omeprazole, and Chinese medication therapy. The clinical response of three subtypes was assessed after a 6-month follow-up. Results. Vocal fold leukoplakia subtypes included flat and smooth (n=66; 37.1%), elevated and smooth (n=103; 57.9%), and rough (n=9; 5.0%). The rate of complete response was 80.3%, 66.0%, and 0.0% for the 3 lesion types, respectively (rough versus flat and smooth, P<0.001; rough versus elevated and smooth, P<0.001, Fisher’s exact test). The incidence of carcinoma in rough leukoplakia was significantly higher than that in smooth leukoplakia (44.4% versus 2.4%, P=0.002, Fisher’s exact test). Clinical type was the only significant factor for clinical response of nonsurgical treatment (P=0.005, ordinal logistic regression). Conclusions. The effectiveness of nonsurgical treatment for smooth vocal fold leukoplakia is better in comparison to rough vocal fold leukoplakia. Smooth leukoplakia could be managed with nonsurgical treatment; more aggressive treatments should be considered for rough leukoplakia.
Autologous and Nonautologous Blood Transfusion in Patients with Ruptured Ectopic Pregnancy and Severe Blood Loss
Authors: Huang Jingxian , Qin Dongquan , Gu Chunlin , Huang Yanjuan , Ma He , Huang Huageng , Huang Fanke , Ruan Jiaxin , Ling Mei
Published: June 2017

Background. There are some theoretical concerns for the use of intraoperative cell salvage (ICS) in patients with ectopic pregnancy. This study aimed to observe the impact of ICS on the coagulation function and clinical outcomes of patients with ruptured ectopic pregnancy and severe blood loss. Methods. This was a retrospective study of 225 patients with ruptured ectopic pregnancy and severe blood loss treated at the Third Affiliated Hospital of Guangxi Medical University between January 2012 and May 2016. Patients were grouped according to ICS (n=116) and controls (n=109, allogenic transfusion and no transfusion). Results. Compared with controls, patients with ICS had shorter hospitalization (P=0.007), lower requirement for allogenic blood products (P<0.001), and higher hemoglobin levels at discharge (P<0.001). There were no complications/ adverse reactions. In the ICS group, hemoglobin at discharge (−6.5%, P=0.002) and thrombin time (−3.7%, P=0.002) were decreased 24 h after surgery, while 24 h APTT was increased (+4.6%, P<0.001). In the control group, hemoglobin at discharge (−16.8%, P<0.001) was decreased after surgery and 24 h APTT was increased (+2.4%, P=0.045). At discharge, hemoglobin levels were higher in the ICS group (P<0.001). Conclusion. ICS was associated with good clinical outcomes in patients with ruptured ectopic pregnancy and severe blood loss.
Exploring EPR Parameters of 99Tc Complexes for Designing New MRI Probes: Coordination Environment, Solvent, and Thermal Effects on the Spectroscopic Properties
Authors: Pereira Bruna T. L. , Silva Érika Ferreira , Gonçalves Mateus A. , Mancini Daiana T. , Ramalho Teodorico C.
Published: June 2017

We have evaluated the solvent and thermal effects on spectroscopic parameters of 99Tc complexes coordinated to explicit water molecules. Molecular dynamics simulations were performed followed by hyperfine coupling constant calculations (Aiso). Our results show a significant increase of Aiso, which demonstrates that the studied compounds can be promising contrast agents in MRI.
Introducing a Novel Hybrid Artificial Intelligence Algorithm to Optimize Network of Industrial Applications in Modern Manufacturing
Authors: Azizi Aydin
Published: June 2017

Recent advances in modern manufacturing industries have created a great need to track and identify objects and parts by obtaining real-time information. One of the main technologies which has been utilized for this need is the Radio Frequency Identification (RFID) system. As a result of adopting this technology to the manufacturing industry environment, RFID Network Planning (RNP) has become a challenge. Mainly RNP deals with calculating the number and position of antennas which should be deployed in the RFID network to achieve full coverage of the tags that need to be read. The ultimate goal of this paper is to present and evaluate a way of modelling and optimizing nonlinear RNP problems utilizing artificial intelligence (AI) techniques. This effort has led the author to propose a novel AI algorithm, which has been named “hybrid AI optimization technique,” to perform optimization of RNP as a hard learning problem. The proposed algorithm is composed of two different optimization algorithms: Redundant Antenna Elimination (RAE) and Ring Probabilistic Logic Neural Networks (RPLNN). The proposed hybrid paradigm has been explored using a flexible manufacturing system (FMS), and results have been compared with Genetic Algorithm (GA) that demonstrates the feasibility of the proposed architecture successfully.
An Immunosuppressive Dendritic Cell Subset Accumulates at Secondary Sites and Promotes Metastasis in Pancreatic Cancer
Authors: Kenkel Justin A. , Tseng William W. , Davidson Matthew G. , Tolentino Lorna L. , Choi Okmi , Bhattacharya Nupur , Seeley E. Scott , Winer Daniel A. , Reticker-Flynn Nathan E. , Engleman Edgar G.
Published: June 2017

Pancreatic ductal adenocarcinoma (PDAC) after complete surgical resection is often followed by distant metastatic relapse for reasons that remain unclear. In this study, we investigated how the immune response at secondary sites affects tumor spread in murine models of metastatic PDAC. Early metastases were associated with dense networks of CD11b+CD11c+MHC-II+CD24+CD64lowF4/80low dendritic cells (DC), which developed from monocytes in response to tumor-released GM-CSF. These cells uniquely expressed MGL2 and PD-L2 in the metastatic microenvironment and preferentially induced the expansion of T regulatory cells (Treg) in vitro and in vivo. Targeted depletion of this DC population in Mgl2DTR hosts activated cytotoxic lymphocytes, reduced Tregs, and inhibited metastasis development. Moreover, blocking PD-L2 selectively activated CD8 T cells at secondary sites and suppressed metastasis, suggesting that the DCs use this particular pathway to inhibit CD8 T-cell–mediated tumor immunity. Phenotypically similar DCs accumulated at primary and secondary sites in other models and in human PDAC. These studies suggest that a discrete DC subset both expands Tregs and suppresses CD8 T cells to establish an immunosuppressive microenvironment conducive to metastasis formation. Therapeutic strategies to block the accumulation and immunosuppressive activity of such cells may help prevent PDAC progression and metastatic relapse after surgical resection. Cancer Res; 77(15); 4158–70. ©2017 AACR.
Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity
Authors: Emanuelli Andrea , Borroni Aurora P. , Apel-Sarid Liat , Shah Pooja A. , Ayyathan Dhanoop Manikoth , Koganti Praveen , Levy-Cohen Gal , Blank Michael
Published: June 2017

DNA topoisomerase IIα (Topo IIα) ensures genomic integrity and unaltered chromosome inheritance and serves as a major target of several anticancer drugs. Topo IIα function is well understood, but how its expression is regulated remains unclear. Here, we identify the E3 ubiquitin ligase Smurf2 as a physiologic regulator of Topo IIα levels. Smurf2 physically interacted with Topo IIα and modified its ubiquitination status to protect Topo IIα from the proteasomal degradation in dose- and catalytically dependent manners. Smurf2-depleted cells exhibited a reduced ability to resolve DNA catenanes and pathological chromatin bridges formed during mitosis, a trait of Topo IIα–deficient cells and a hallmark of chromosome instability. Introducing Topo IIα into Smurf2-depleted cells rescued this phenomenon. Smurf2 was a determinant of Topo IIα protein levels in normal and cancer cells and tissues, and its levels affected cell sensitivity to the Topo II–targeting drug etoposide. Our results identified Smurf2 as an essential regulator of Topo IIα, providing novel insights into its control and into the suggested tumor-suppressor functions of Smurf2. Cancer Res; 77(16); 4217–27. ©2017 AACR.
Targeting SRC Coactivators Blocks the Tumor-Initiating Capacity of Cancer Stem-like Cells
Authors: Rohira Aarti D. , Yan Fei , Wang Lei , Wang Jin , Zhou Suoling , Lu Andrew , Yu Yang , Xu Jianming , Lonard David M. , O'Malley Bert W.
Published: June 2017

Tumor-initiating cells (TIC) represent cancer stem-like cell (CSC) subpopulations within tumors that are thought to give rise to recurrent cancer after therapy. Identifying key regulators of TIC/CSC maintenance is essential for the development of therapeutics designed to limit recurrence. The steroid receptor coactivator 3 (SRC-3) is overexpressed in a wide range of cancers, driving tumor initiation, cell proliferation, and metastasis. Here we report that SRC-3 supports the TIC/CSC state and induces an epithelial-to-mesenchymal transition (EMT) by driving expression of the master EMT regulators and stem cell markers. We also show that inhibition of SRC-3 and SRC-1 with SI-2, a second-generation SRC-3/SRC-1 small-molecule inhibitor, targets the CSC/TIC population both in vitro and in vivo. Collectively, these results identify SRC coactivators as regulators of stem-like capacity in cancer cells and that these coactivators can serve as potential therapeutic targets to prevent the recurrence of cancer. Cancer Res; 77(16); 4293–304. ©2017 AACR.
β-Catenin Is a Candidate Therapeutic Target for Myeloid Neoplasms with del(5q)
Authors: Li Liping , Sheng Yue , Li Wenshu , Hu Chao , Mittal Nupur , Tohyama Kaoru , Seba Amber , Zhao You-Yang , Ozer Howard , Zhu Tongyu , Qian Zhijian
Published: June 2017

Deletion of the chromosome 5q [del(5q)] is one of the most common cytogenetic abnormalities observed in patients with de novo myelodysplastic syndromes (MDS) and therapy-related MDS or acute myeloid leukemia (t-MDS/tAML). Emerging evidence indicates that activation of the Wnt/β-catenin pathway contributes to the development of myeloid neoplasms with del(5q). Whether β-catenin is a potential therapeutic target for myeloid neoplasms with del(5q) has yet to be evaluated. Here, we report that genetic deletion of a single allele of β-catenin rescues ineffective hematopoiesis in an Apc haploinsufficient mouse model, which recapitulates several characteristic features of the preleukemic stage of myeloid neoplasms with a −5/del(5q). In addition, loss of a single allele of β-catenin reversed the defective self-renewal capacity of Apc-haploinsufficient hematopoietic stem cells and reduced the frequency of apoptosis induced by Apc haploinsufficiency. Suppression of β-catenin by indomethacin or β-catenin shRNA reduced proliferation and survival of human leukemia cell lines with del(5q) but not of control leukemia cell lines in vitro; β-catenin inactivation also inhibited leukemia progression in vivo in xenograft mice reconstituted with del(5q) leukemia cell lines. Inhibition of β-catenin also stunted growth and colony-forming abilities of primary bone marrow cells from del(5q) AML patients in vitro. Overall, our data support the idea that β-catenin could serve as a therapeutic target for the treatment of myeloid neoplasms with del(5q). Cancer Res; 77(15); 4116–26. ©2017 AACR.
Phase I Dose-Escalation and -Expansion Study of the BRAF Inhibitor Encorafenib (LGX818) in Metastatic BRAF-Mutant Melanoma
Authors: Delord Jean-Pierre , Robert Caroline , Nyakas Marta , McArthur Grant A. , Kudchakar Ragini , Mahipal Amit , Yamada Yasuhide , Sullivan Ryan , Arance Ana , Kefford Richard F. , Carlino Matteo S. , Hidalgo Manuel , Gomez-Roca Carlos , Michel Daniela , Seroutou Abdelkader , Aslanis Vassilios , Caponigro Giordano , Stuart Darrin D. , Moutouh-de Parseval Laure , Demuth Tim , Dummer Reinhard
Published: June 2017

Purpose: Encorafenib, a selective BRAF inhibitor (BRAFi), has a pharmacologic profile that is distinct from that of other clinically active BRAFis. We evaluated encorafenib in a phase I study in patients with BRAFi treatment-naïve and pretreated BRAF-mutant melanoma.

Experimental Design: The pharmacologic activity of encorafenib was first characterized preclinically. Encorafenib monotherapy was then tested across a range of once-daily (50–700 mg) or twice-daily (75–150 mg) regimens in a phase I, open-label, dose-escalation and -expansion study in adult patients with histologically confirmed advanced/metastatic BRAF-mutant melanoma. Study objectives were to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D), characterize the safety and tolerability and pharmacokinetic profile, and assess the preliminary antitumor activity of encorafenib.

Results: Preclinical data demonstrated that encorafenib inhibited BRAF V600E kinase activity with a prolonged off-rate and suppressed proliferation and tumor growth of BRAF V600E–mutant melanoma models. In the dose-escalation phase, 54 patients (29 BRAFi-pretreated and 25 BRAFi-naïve) were enrolled. Seven patients in the dose-determining set experienced dose-limiting toxicities. Encorafenib at a dose of 300 mg once daily was declared the RP2D. In the expansion phase, the most common all-cause adverse events were nausea (66%), myalgia (63%), and palmar–plantar erythrodysesthesia (54%). In BRAFi-naïve patients, the overall response rate (ORR) and median progression-free survival (mPFS) were 60% and 12.4 months [95% confidence interval (CI), 7.4–not reached (NR)]. In BRAFi-pretreated patients, the ORR and mPFS were 22% and 1.9 months (95% CI, 0.9–3.7).

Conclusions: Once-daily dosing of single-agent encorafenib had a distinct tolerability profile and showed varying antitumor activity across BRAFi-pretreated and BRAFi-naïve patients with advanced/metastatic melanoma. Clin Cancer Res; 23(18); 5339–48. ©2017 AACR.
Clinical and Genome-Wide Analysis of Cisplatin-Induced Peripheral Neuropathy in Survivors of Adult-Onset Cancer
Authors: Dolan M. Eileen , El Charif Omar , Wheeler Heather E. , Gamazon Eric R. , Ardeshir-Rouhani-Fard Shirin , Monahan Patrick , Feldman Darren R. , Hamilton Robert J. , Vaughn David J. , Beard Clair J. , Fung Chunkit , Kim Jeri , Fossa Sophie D. , Hertz Daniel L , Mushiroda Taisei , Kubo Michiaki , Einhorn Lawrence H. , Cox Nancy J. , Travis Lois B.
Published: June 2017

Purpose: Our purpose was to characterize the clinical influences, genetic risk factors, and gene mechanisms contributing to persistent cisplatin-induced peripheral neuropathy (CisIPN) in testicular cancer survivors (TCSs).

Experimental Design: TCS given cisplatin-based therapy completed the validated EORTC QLQ-CIPN20 questionnaire. An ordinal CisIPN phenotype was derived, and associations with age, smoking, excess drinking, hypertension, body mass index, diabetes, hypercholesterolemia, cumulative cisplatin dose, and self-reported health were examined for 680 TCS. Genotyping was performed on the Illumina HumanOmniExpressExome chip. Following quality control and imputation, 5.1 million SNPs in 680 genetically European TCS formed the input set. GWAS and PrediXcan were used to identify genetic variation and genetically determined gene expression traits, respectively, contributing to CisIPN. We evaluated two independent datasets for replication: Vanderbilt's electronic health database (BioVU) and the CALGB 90401 trial.

Results: Eight sensory items formed a subscale with good internal consistency (Cronbach α = 0.88). Variables significantly associated with CisIPN included age at diagnosis (OR per year, 1.06; P = 2 × 10−9), smoking (OR, 1.54; P = 0.004), excess drinking (OR, 1.83; P = 0.007), and hypertension (OR, 1.61; P = 0.03). CisIPN was correlated with lower self-reported health (OR, 0.56; P = 2.6 × 10−9) and weight gain adjusted for years since treatment (OR per Δkg/m2, 1.05; P = 0.004). PrediXcan identified lower expressions of MIDN and RPRD1B, and higher THEM5 expression as associated with CisIPN (P value for each < 5 × 10−6) with replication of RPRD1B meeting significance criteria (Fisher combined P = 0.0089).

Conclusions: CisIPN is associated with age, modifiable risk factors, and genetically determined expression level of RPRD1B. Further study of implicated genes could elucidate the pathophysiologic underpinnings of CisIPN. Clin Cancer Res; 23(19); 5757–68. ©2017 AACR.