bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased neuromuscular consistency in gait and balance after partnered, dance-based rehabilitation in Parkinson’s disease
Authors: Allen Jessica L. , McKay J. Lucas , Sawers Andrew , Hackney Madeleine E. , Ting Lena H.
Published: April 2017

Here we examined changes in muscle coordination associated with improved motor performance after partnered, dance-based rehabilitation in individuals with mild to moderate idiopathic Parkinson’s disease. Using motor module (a.k.a. muscle synergy) analysis, we identified changes in the modular control of overground walking and standing reactive balance that accompanied clinically meaningful improvements in behavioral measures of balance, gait, and disease symptoms after 3 wk of daily Adapted Tango classes. In contrast to previous studies that revealed a positive association between motor module number and motor performance, none of the six participants in this pilot study increased motor module number despite improvements in behavioral measures of balance and gait performance. Instead, motor modules were more consistently recruited and distinctly organized immediately after rehabilitation, suggesting more reliable motor output. Furthermore, the pool of motor modules shared between walking and reactive balance increased after rehabilitation, suggesting greater generalizability of motor module function across tasks. Our work is the first to show that motor module distinctness, consistency, and generalizability are more sensitive to improvements in gait and balance function after short-term rehabilitation than motor module number. Moreover, as similar differences in motor module distinctness, consistency, and generalizability have been demonstrated previously in healthy young adults with and without long-term motor training, our work suggests commonalities in the structure of muscle coordination associated with differences in motor performance across the spectrum from motor impairment to expertise.

NEW & NOTEWORTHY We demonstrate changes in neuromuscular control of gait and balance in individuals with Parkinson’s disease after short-term, dance-based rehabilitation. Our work is the first to show that motor module distinctness, consistency, and generalizability across gait and balance are more sensitive than motor module number to improvements in motor performance following short-term rehabilitation. Our results indicate commonalities in muscle coordination improvements associated with motor skill reacquisition due to rehabilitation and motor skill acquisition in healthy individuals.
A distributed neural network model for the distinct roles of medial and lateral HVC in zebra finch song production
Authors: Galvis Daniel , Wu Wei , Hyson Richard L. , Johnson Frank , Bertram Richard
Published: April 2017

Zebra finch song consists of a string of syllables repeated in a nearly invariant sequence. We propose a neural network organization that can explain recent data indicating that the medial and lateral portions of the premotor cortical nucleus HVC have different roles in zebra finch song production. Our model explains these data, as well as data on the effects on song of cooling HVC, and makes predictions that we test in the singing bird.
Subacute Disseminated Intravascular Coagulation in a Patient with Liver Metastases of a Renal Cell Carcinoma
Authors: van der Wekken L. C. , Loffeld R. J. L. F.
Published: April 2017

Disseminated intravascular coagulation (DIC) is a syndrome characterised by simultaneous bleeding and thromboembolic formation. Its acute form is associated with severe bacterial infections and hematological malignancies. It has a fulminant presentation with prolonged bleeding times and diffuse thrombosis. On the other hand, chronic DIC can be asymptomatic for long periods of time and can be seen in patients with disseminated malignancies. This case report describes a patient who developed DIC within one week and bled profusely from venipuncture wounds. An underlying hepatogenic metastasised renal cell carcinoma appeared to be the cause. This is an uncommon and diagnostically challenging presentation.
An Integrating Approach for Genome-Wide Screening of MicroRNA Polymorphisms Mediated Drug Response Alterations
Authors: Wang Xianyue , Jiang Hong , Wu Wei , Zhang Rongxin , Wu Lingxiang , Chen Huan , Li Pengping , Nie Yumin , Shao Jiaofang , Li Yan , Lin Xue , Lv Sali , Wang Qh , Hu Jie
Published: April 2017

MicroRNAs (miRNAs) are a class of evolutionarily conserved small noncoding RNAs, ~22 nt in length, and found in diverse organisms and play important roles in the regulation of mRNA translation and degradation. It was shown that miRNAs were involved in many key biological processes through regulating the expression of targets. Genetic polymorphisms in miRNA target sites may alter miRNA regulation and therefore result in the alterations of the drug targets. Recent studies have demonstrated that SNPs in miRNA target sites can affect drug efficiency. However, there are still a large number of specific genetic variants related to drug efficiency that are yet to be discovered. We integrated large scale of genetic variations, drug targets, gene interaction networks, biological pathways, and seeds region of miRNA to identify miRNA polymorphisms affecting drug response. In addition, harnessing the abundant high quality biological network/pathways, we evaluated the cascade distribution of tarSNP impacts. We showed that the predictions can uncover most of the known experimentally supported cases as well as provide informative candidates complementary to existing methods/tools. Although there are several existing databases predicting the gain or loss of targeting function of miRNA mediated by SNPs, such as PolymiRTS, miRNASNP, MicroSNiPer, and MirSNP, none of them evaluated the influences of tarSNPs on drug response alterations. We developed a user-friendly online database of this approach named Mir2Drug.
Inhibition of Cardiac Hypertrophy Effects in D‐Galactose‐Induced Senescent Hearts by Alpinate Oxyphyllae Fructus Treatment
Authors: Chang Yung-Ming , Chang Hen-Hong , Lin Hung-Jen , Tsai Chin-Chuan , Tsai Chuan-Te , Chang Hsin-Nung , Lin Shu-Luan , PadmaViswanadha Vijaya , Chen Ray-Jade , Huang Chih-Yang
Published: April 2017

Aging is a complex physiological phenomenon accelerated by ROS accumulation, with multisystem decline and increasing vulnerability to degenerative diseases and death. Cardiac hypertrophy is a key pathophysiological component that accompanies the aging process. Alpinate Oxyphyllae Fructus (Alpinia oxyphylla MIQ, AOF) is a traditional Chinese medicine, which provides cardioprotective activity against aging, hypertension, and cerebrovascular disorders. In this study, we found the protective effect of AOF against cardiac hypertrophy in D‐galactose‐induced aging rat model. The results showed that treating rats with D‐galactose resulted in pathological hypertrophy as evident from the morphology change, increased left ventricular weight/whole heart weight, and expression of hypertrophy‐related markers (MYH7 and BNP). Both concentric and eccentric cardiac hypertrophy signaling proteins were upregulated in aging rat model. However, these pathological changes were significantly improved in AOF treated group (AM and AH) in a dose‐dependent manner. AOF negatively modulated D‐galactose‐induced cardiac hypertrophy signaling mechanism to attenuate ventricular hypertrophy. These enhanced cardioprotective activities following oral administration of AOF reflect the potential use of AOF for antiaging treatments.
Effects of the Slot Harmonics on the Stator Current in an Induction Motor with Bearing Fault
Authors: Song Xiangjin , Hu Jingtao , Zhu Hongyu , Zhang Jilong
Published: April 2017

Bearing faults are the most frequent faults of induction motors. The current spectrum analysis is an easy and popular method for the monitoring and detection of bearing faults. After a presentation of the existing fault models, this paper illustrates an analytical approach to evaluate the effects of the slot harmonics on the stator current in an induction motor with bearing fault. Simple and clear theoretical analysis results in some new current characteristic frequencies. Experimental tests with artificial bearing outer raceway fault are carried out by measuring stator current signals. The experimental results by spectral analysis of the stator current agree well with the theoretical inference.
Culture of iPSCs Derived Pancreatic β-Like Cells In Vitro Using Decellularized Pancreatic Scaffolds: A Preliminary Trial
Authors: Wan Jian , Huang Yan , Zhou Pengcheng , Guo Yibing , Wu Cen , Zhu Shajun , Wang Yao , Wang Lei , Lu Yuhua , Wang Zhiwei
Published: April 2017

Diabetes mellitus is a disease which has affected 415 million patients in 2015. In an effort to replace the significant demands on transplantation and morbidity associated with transplantation, the production of β-like cells differentiated from induced pluripotent stem cells (iPSCs) was evaluated. This approach is associated with promising decellularized scaffolds with natural extracellular matrix (ECM) and ideal cubic environment that will promote cell growth in vivo. Our efforts focused on combining decellularized rat pancreatic scaffolds with mouse GFP+-iPSCs-derived pancreatic β-like cells, to evaluate whether decellularized scaffolds could facilitate the growth and function of β-like cells. β-like cells were differentiated from GFP+-iPSCs and evaluated via cultivating in the dynamic circulation perfusion device. Our results demonstrated that decellularized pancreatic scaffolds display favorable biochemical properties. Furthermore, not only could the scaffolds support the survival of β-like cells, but they also accelerated the expression of the insulin as compared to plate-based cell culture. In conclusion, these results suggest that decellularized pancreatic scaffolds could provide a suitable platform for cellular activities of β-like cells including survival and insulin secretion. This study provides preliminary support for regenerating insulin-secreting organs from the decellularized scaffolds combined with iPSCs derived β-like cells as a potential clinical application.
Online Adaptive Optimal Control of Vehicle Active Suspension Systems Using Single‐Network Approximate Dynamic Programming
Authors: Fu Zhi-Jun , Li Bin , Ning Xiao-Bin , Xie Wei-Dong
Published: April 2017

In view of the performance requirements (e.g., ride comfort, road holding, and suspension space limitation) for vehicle suspension systems, this paper proposes an adaptive optimal control method for quarter‐car active suspension system by using the approximate dynamic programming approach (ADP). Online optimal control law is obtained by using a single adaptive critic NN to approximate the solution of the Hamilton‐Jacobi‐Bellman (HJB) equation. Stability of the closed‐loop system is proved by Lyapunov theory. Compared with the classic linear quadratic regulator (LQR) approach, the proposed ADP‐based adaptive optimal control method demonstrates improved performance in the presence of parametric uncertainties (e.g., sprung mass) and unknown road displacement. Numerical simulation results of a sedan suspension system are presented to verify the effectiveness of the proposed control strategy.
Selecting a Multicriteria Inventory Classification Model to Improve Customer Order Fill Rate
Authors: Iqbal Qamar , Malzahn Don , Whitman Lawrence E.
Published: April 2017

Multicriteria models have been proposed for inventory classification in previous studies. However, it is important to make a decision when a particular multicriteria inventory classification model should be preferred over other models and also if the highest performing model remains the highest performing at all times. Companies always look for ways to improve customer order fulfillment process. This paper shows how better inventory classification can improve customer order fill rate in variable settings. The method to compare the inventory classification models with regard to improving customer order fill rate is proposed. The cut-off point is calculated which indicates when a model currently in use should be dropped in favor of another model to increase revenue by filling more orders. Sensitivity analysis is also performed to determine how holding cost and demand uncertainty affect the performance metric. Finally, regression analysis and hypothesis testing inform the decision-maker of how a model’s performance differs from other models at various values of holding cost and standard deviation of demand.
Donor Impurity-Related Optical Absorption in GaAs Elliptic-Shaped Quantum Dots
Authors: Londoño M. A. , Restrepo R. L. , Ojeda J. H. , Vinh Phuc Huynh , Mora-Ramos M. E. , Kasapoglu E. , Morales A. L. , Duque C. A.
Published: April 2017

The conduction band and electron-donor impurity states in elliptic-shaped GaAs quantum dots under the effect of an externally applied electric field are calculated within the effective mass and adiabatic approximations using two different numerical approaches: a spectral scheme and the finite element method. The resulting energies and wave functions become the basic information needed to evaluate the interstate optical absorption in the system, which is reported as a function of the geometry, the electric field strength, and the temperature.
Synthesis of Gold Nanoparticles Dispersed in Palm Oil Using Laser Ablation Technique
Authors: Sadrolhosseini Amir Reza , Abdul Rashid Suraya , Zakaria Azmi
Published: April 2017

Gold nanoparticles have more applications in biology, medicine, and industry. In this study, gold nanoparticles were synthesized in pure palm oil using laser ablation technique. Gold nanoparticles were fabricated in different temperature, and the effect of the temperature on the particle size was investigated. Consequently, the tail of the carbonyl band of fatty acids was capped gold nanoparticles, and spherically shaped gold nanoparticles with size range of 8.92 to 19.73 nm were formed in palm oil. The temperature caused the agglomeration of nanoparticles while the particle size increased with an increase in the temperature.
Normalizing Item‐Based Collaborative Filter Using Context‐Aware Scaled Baseline Predictor
Authors: Ma Wenming , Shi Junfeng , Zhao Ruidong
Published: April 2017

Item‐based collaborative filter algorithms play an important role in modern commercial recommendation systems (RSs). To improve the recommendation performance, normalization is always used as a basic component for the predictor models. Among a lot of normalizing methods, subtracting the baseline predictor (BLP) is the most popular one. However, the BLP uses a statistical constant without considering the context. We found that slightly scaling the different components of the BLP separately could dramatically improve the performance. This paper proposed some normalization methods based on the scaled baseline predictors according to different context information. The experimental results show that using context‐aware scaled baseline predictor for normalization indeed gets better recommendation performance, including RMSE, MAE, precision, recall, and nDCG.
Bovine Tooth Discoloration Induced by Endodontic Filling Materials for Primary Teeth
Authors: Xavier Samantha Rodrigues , Pilownic Katerine Jahnecke , Gastmann Andressa Heberle , Echeverria Mariana Silveira , Romano Ana Regina , Geraldo Pappen Fernanda
Published: April 2017

Objective.This study evaluated the discoloration potential of endodontic materials used in primary teeth.Material and Methods.Dentine-enamel blocks were prepared from 75 bovine teeth, assorted in five experimental groups (n=15). The tested materials included an MTA-based material; zinc oxide and eugenol cement (ZOE); Vitapex; and calcium hydroxide thickened with zinc oxide (Calen + ZO). The color measurements were performed using a spectrophotometer at the following intervals: prior to (T0) and after placement of the filling (T1) and after 1 week (T2), 1 month (T3), 3 months (T4), 6 months (T5), and 9 months (T6). Data were submitted to ANOVA with repeated measures and Tukey’s test.Results.The time had a significant effect on the color variation (ΔE00⁎) (p<0.0001). The effect of the materials on the color variation (ΔE00⁎) was statistically significant (p=0.004). Interactions between time and materials demonstrated a significant effect on the values (ΔE00⁎) (p<0.0001). The ZOE cement showed the highest darkening effect (p=0.018).Conclusion.The MTA-based material showed the smallest discoloration during the experimental time; however, it was similar to the other materials and to the control group. Zinc oxide and eugenol showed higher discoloration.
Dispersion of High Concentrations of Carbon Nanofibers in Portland Cement Mortars
Authors: Hogancamp Joshua , Grasley Zachary
Published: April 2017

This research focuses on creating and maintaining a stable dispersion of carbon nanofibers (CNFs) in portland cement based materials. A microfine cement is used in conjunction with an untraditional dispersion method to encourage and stabilize the dispersion of CNFs in concentrations up to 5% by mass of cement. A computational simulation was utilized to examine an effect called geometric clustering on the dispersion of CNFs among Type I/II and microfine cement grains. The geometric clustering simulation revealed a higher achievable dispersion for microfine cement than for Type I/II cement. Scanning electron microscopy (SEM) was used to quantify the dispersion of CNFs among Type I/II and microfine cement grains. SEM image analysis indicated excessive CNF clumping among Type I/II cement grains, while the dispersion of hybrid microfine cement mortar continued to improve as the concentration of CNFs increased up to 5% by mass of cement. Mortar cube elastic stiffness and mortar prism flexure tests revealed that high concentrations of CNFs had detrimental effects in hybrid Type I/II cement mortar, whereas similar concentrations of CNFs had negligible or beneficial effects in hybrid microfine cement mortar.
The p53/p21 Complex Regulates Cancer Cell Invasion and Apoptosis by Targeting Bcl-2 Family Proteins
Authors: Kim Eun Mi , Jung Chan-Hun , Kim Jongdoo , Hwang Sang-Gu , Park Jong Kuk , Um Hong-Duck
Published: April 2017

The tumor suppressor p53 binds prosurvival Bcl-2 family proteins such as Bcl-w and Bcl-XL to liberate Bax, which in turn exerts proapoptotic or anti-invasive functions depending on stress context. On the basis of our previous finding that p53 interacts with p21, we investigated the possible involvement of p21 in these functions. Here, we report that although p53 can bind Bcl-w alone, it requires p21 to liberate Bax to suppress cell invasion and promote cell death. p21 bound Bcl-w, forming a p53/p21/Bcl-w complex in a manner that maintained all pairwise p53/p21, p21/Bcl-w, and p53/Bcl-w interactions. This allowed Bax liberation from the complex. Accordingly, a p53 derivative incapable of binding p21 failed to mediate radiotherapy-induced tumor cell death in mice. Bcl-XL also served as a target of the cooperative action of p53 and p21. Overall, our findings indicate that the p53/p21 complex rather than p53 itself regulates cell invasion and death by targeting Bcl-2 proteins. We propose that the p53/p21 complex is a functional unit that acts on multiple cell components, providing a new foundation for understanding the tumor-suppressing functions of p53 and p21. Cancer Res; 77(11); 3092–100. ©2017 AACR.
Thyroid-Stimulating Hormone, Thyroid Hormones, and Risk of Papillary Thyroid Cancer: A Nested Case–Control Study
Authors: Huang Huang , Rusiecki Jennifer , Zhao Nan , Chen Yingtai , Ma Shuangge , Yu Herbert , Ward Mary H. , Udelsman Robert , Zhang Yawei
Published: April 2017

Background: The effects of thyroid-stimulating hormone (TSH) and thyroid hormones on the development of human papillary thyroid cancer (PTC) remain poorly understood.

Methods: The study population consisted of 741 (341 women, 400 men) histologically confirmed PTC cases and 741 matched controls with prediagnostic serum samples stored in the Department of Defense Serum Repository. Concentrations of TSH, total T3, total T4, and free T4 were measured in serum samples. Conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI).

Results: The median time between blood draw and PTC diagnosis was 1,454 days. Compared with the middle tertile of TSH levels within the normal range, serum TSH levels below the normal range were associated with an elevated risk of PTC among women (OR, 3.74; 95% CI, 1.53–9.19) but not men. TSH levels above the normal range were associated with an increased risk of PTC among men (OR, 1.96; 95% CI, 1.04–3.66) but not women. The risk of PTC decreased with increasing TSH levels within the normal range among both men and women (Ptrend = 0.0005 and 0.041, respectively).

Conclusions: We found a significantly increased risk of PTC associated with TSH levels below the normal range among women and with TSH levels above the normal range among men. An inverse association between PTC and TSH levels within the normal range was observed among both men and women.

Impact: These results could have significant clinical implications for physicians who are managing patients with abnormal thyroid functions and those with thyroidectomy. Cancer Epidemiol Biomarkers Prev; 26(8); 1209–18. ©2017 AACR.
Spectrum of Immune-Related Conditions Associated with Risk of Keratinocyte Cancers among Elderly Adults in the United States
Authors: Yanik Elizabeth L. , Pfeiffer Ruth M. , Freedman D. Michal , Weinstock Martin A. , Cahoon Elizabeth K. , Arron Sarah T. , Chaloux Matthew , Connolly M. Kari , Nagarajan Priyadharsini , Engels Eric A.
Published: April 2017

Background: Elevated keratinocyte carcinoma risk is present with several immune-related conditions, e.g., solid organ transplantation and non-Hodgkin lymphoma. Because many immune-related conditions are rare, their relationships with keratinocyte carcinoma have not been studied.

Methods: We used Medicare claims to identify cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) cases in 2012, and controls matched on sex and age. All subjects were aged 65 to 95 years, of white race, and had attended ≥1 dermatologist visit in 2010–2011. Immune-related conditions were identified during 1999–2011 using Medicare claims. Associations were estimated with logistic regression, with statistical significance determined after Bonferroni correction for multiple comparisons.

Results: We included 258,683 SCC and 304,903 BCC cases. Of 47 immune-related conditions, 21 and 9 were associated with increased SCC and BCC risk, respectively. We identified strongly elevated keratinocyte carcinoma risk with solid organ transplantation (SCC OR = 5.35; BCC OR = 1.94) and non-Hodgkin lymphoma (SCC OR = 1.62; BCC OR = 1.25). We identified associations with common conditions, e.g., rheumatoid arthritis [SCC OR = 1.06, 95% confidence interval (95% CI), 1.04–1.09] and Crohn's disease (SCC OR = 1.33, 95% CI, 1.27–1.39; BCC OR = 1.10, 95% CI, 1.05–1.15), and rare or poorly characterized conditions, e.g., granulomatosis with polyangiitis (SCC OR = 1.88; 95% CI, 1.61–2.19), autoimmune hepatitis (SCC OR = 1.81; 95% CI, 1.52–2.16), and deficiency of humoral immunity (SCC OR = 1.51, 95% CI, 1.41–1.61; BCC OR = 1.22, 95% CI, 1.14–1.31). Most conditions were more positively associated with SCC than BCC. Associations were generally consistent regardless of prior keratinocyte carcinoma history.

Conclusions: Many immune-related conditions are associated with elevated keratinocyte carcinoma risk and appear more tightly linked to SCC.

Impact: Immunosuppression or immunosuppressive treatment may increase keratinocyte carcinoma risk, particularly SCC. Cancer Epidemiol Biomarkers Prev; 26(7); 998–1007. ©2017 AACR.
Cervical Infection with Cutaneous Beta and Mucosal Alpha Papillomaviruses
Authors: Sichero Laura , El-Zein Mariam , Nunes Emily M. , Ferreira Silvaneide , Franco Eduardo L. , Villa Luisa L.
Published: April 2017

Background: Alpha-human papillomavirus (α-HPV) plays a causal role in cervical cancer, but little is known about the epidemiology of genital Beta-human papillomavirus (β-HPV) infection.

Methods: We used Luminex and PCR hybridization to detect β- and α-HPVs prevalence at enrollment and 12-month follow-up in cervical samples from 505 women enrolled in the Ludwig-McGill cohort study. We compared epidemiologic correlates of both β- and α-HPVs and compared genotypes between these genera with respect to co-occurrence and association with cervical cytologic abnormalities.

Results: Infection with β-HPV types was more prevalent than that with α-HPV types at both visits (cumulative prevalences: 27.3% vs. 21.6%, respectively, P = 0.034). β-HPVs were mostly transient; however, only 1.98% women retained their original positivity at 12 months, whereas persistence was higher for α-HPVs (5.15%; P = 0.007). Age, parity, and sexual activity variables were predictors of α-HPV but not of β-HPV. α- and β-HPV types occurred independently. Increased risk of cervical abnormalities was restricted to women infected with α-9 or α-6 HPV types. We found no epidemiologic correlates for β-HPV infections.

Conclusions: Detection of β-HPV types in the cervix tends to occur as random and transient episodes not explained via the sexual-transmission correlates that characterize infections by α-HPVs.

Impact: Although it is plausible that β-HPVs may play a direct or indirect carcinogenic role, the lack of epidemiologic correlates for detection episodes of these viruses and lack of association with cervical lesions speak against their ancillary role as sexually transmitted agents in cervical carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(8); 1312–20. ©2017 AACR.
Characterization of an Immunogenic Mutation in a Patient with Metastatic Triple-Negative Breast Cancer
Authors: Assadipour Yasmine , Zacharakis Nikolaos , Crystal Jessica S. , Prickett Todd D. , Gartner Jared J. , Somerville Robert P.T. , Xu Hui , Black Mary A. , Jia Li , Chinnasamy Harshini , Kriley Isaac , Lu Lily , Wunderlich John R. , Zheng Zhili , Lu Yong-Chen , Robbins Paul F. , Rosenberg Steven A. , Goff Stephanie L. , Feldman Steven A.
Published: April 2017

Purpose: The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There are limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic nonsynonymous mutations in a patient with triple-negative breast cancer (TNBC) to identify and isolate mutation-reactive TILs for possible use in adoptive cell transfer.

Experimental Design: A TNBC metastasis was resected for TIL generation and whole-exome sequencing. Tandem minigenes or long 25-mer peptides encoding selected mutations were electroporated or pulsed onto autologous antigen-presenting cells, and reactivity of TIL was screened by upregulation of CD137 and IFNγ ELISPOT. The nature of the T-cell response against a unique nonsynonymous mutation was characterized.

Results: We identified 72 nonsynonymous mutations from the tumor of a patient with TNBC. CD4+ and HLA-DRB1*1501–restricted TILs isolated from this tumor recognized a single mutation in RBPJ (recombination signal binding protein for immunoglobulin kappa J region). Analysis of 16 metastatic sites revealed that the mutation was ubiquitously present in all samples.

Conclusions: Breast cancers can express naturally processed and presented unique nonsynonymous mutations that are recognized by a patient's immune system. TILs recognizing these immunogenic mutations can be isolated from a patient's tumor, suggesting that adoptive cell transfer of mutation-reactive TILs could be a viable treatment option for patients with breast cancer. Clin Cancer Res; 23(15); 4347–53. ©2017 AACR.
Biological Role and Therapeutic Targeting of TGF-β3 in Glioblastoma
Authors: Seystahl Katharina , Papachristodoulou Alexandros , Burghardt Isabel , Schneider Hannah , Hasenbach Kathy , Janicot Michel , Roth Patrick , Weller Michael
Published: April 2017

Transforming growth factor (TGF)-β contributes to the malignant phenotype of glioblastoma by promoting invasiveness and angiogenesis and creating an immunosuppressive microenvironment. So far, TGF-β1 and TGF-β2 isoforms have been considered to act in a similar fashion without isoform-specific function in glioblastoma. A pathogenic role for TGF-β3 in glioblastoma has not been defined yet. Here, we studied the expression and functional role of endogenous and exogenous TGF-β3 in glioblastoma models. TGF-β3 mRNA is expressed in human and murine long-term glioma cell lines as well as in human glioma-initiating cell cultures with expression levels lower than TGF-β1 or TGF-β2 in most cell lines. Inhibition of TGF-β3 mRNA expression by ISTH2020 or ISTH2023, two different isoform-specific phosphorothioate locked nucleic acid (LNA)-modified antisense oligonucleotide gapmers, blocks downstream SMAD2 and SMAD1/5 phosphorylation in human LN-308 cells, without affecting TGF-β1 or TGF-β2 mRNA expression or protein levels. Moreover, inhibition of TGF-β3 expression reduces invasiveness in vitro. Interestingly, depletion of TGF-β3 also attenuates signaling evoked by TGF-β1 or TGF-β2. In orthotopic syngeneic (SMA-560) and xenograft (LN-308) in vivo glioma models, expression of TGF-β3 as well as of the downstream target, plasminogen-activator-inhibitor (PAI)-1, was reduced, while TGF-β1 and TGF-β2 levels were unaffected following systemic treatment with TGF-β3-specific antisense oligonucleotides. We conclude that TGF-β3 might function as a gatekeeper controlling downstream signaling despite high expression of TGF-β1 and TGF-β2 isoforms. Targeting TGF-β3 in vivo may represent a promising strategy interfering with aberrant TGF-β signaling in glioblastoma. Mol Cancer Ther; 16(6); 1177–86. ©2017 AACR.
Sleep Duration across the Adult Lifecourse and Risk of Lung Cancer Mortality: A Cohort Study in Xuanwei, China
Authors: Wong Jason Y. , Bassig Bryan A. , Vermeulen Roel , Hu Wei , Ning Bofu , Seow Wei Jie , Ji Bu-Tian , Downward George S. , Katki Hormuzd A. , Barone-Adesi Francesco , Rothman Nathaniel , Chapman Robert S. , Lan Qing
Published: April 2017

Sufficient sleep duration is crucial for maintaining normal physiological function and has been linked to cancer risk; however, its contribution to lung cancer mortality is unclear. Therefore, we evaluated the relationship between average sleep duration in various age-periods across the adult lifecourse, and risk of lung cancer mortality in Xuanwei, China. An ambidirectional cohort study was conducted in 42,422 farmers from Xuanwei, China. Participants or their surrogates were interviewed in 1992 to assess average sleep hours in the age periods of 21–30, 31–40, 41–50, 51–60, 61–70, and ≥71 years, which were categorized as ≤7, 8 (reference), 9, and ≥10 hours/day. Vital status was followed until 2011. Sex-specific Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for lung cancer mortality in 1994–2011, adjusted for demographic, anthropometric, medical, and household characteristics. J-shaped relationships were found between average sleep duration and lung cancer mortality. The patterns were consistent across sex, age periods, and fuel usage. Compared with sleeping 8 hours/day on average, ≤7 hours/day was associated with significantly increased HRs ranging from 1.39 to 1.58 in ages ≥41 years in men, and 1.29 to 2.47 in ages ≥51 years in women. Furthermore, sleeping ≥10 hours/day was associated with significantly increased HRs ranging from 2.44 to 3.27 in ages ≥41 year in men, and 1.31 to 2.45 in ages ≤60 years in women. Greater and less than 8 hours/day of sleep in various age-periods may be associated with elevated risk of lung cancer mortality in Xuanwei, China. Cancer Prev Res; 10(6); 327–35. ©2017 AACR.
Serological Reactivity and Identification of Immunoglobulin E-Binding Polypeptides of Ganoderma applanatum Crude Spore Cytoplasmic Extract in Puerto Rican Subjects
Authors: Vilá-Héreter Frances , Rivera-Mariani Félix E. , Bolaños-Rosero Benjamín
Published: April 2017

Background: The allergenic potential of Ganoderma applanatum basidiospores has been demonstrated previously in Puerto Rico. However, basidiomycete allergens are not available for inclusion in allergy diagnostic panels. Therefore, we sought to confirm allergic sensitization to G. applanatum crude spore cytoplasmic extract through reactivity in serological assays and detection of immunoglobulin E (IgE)-binding polypeptides. Methods: Via an indirect ELISA, serological reactivity was compared between groups of individuals with different allergic profiles. Group 1 (n = 51) consisted of individuals with sIgE to the allergens included in the diagnostic panels; group 2 (n = 14) comprised individuals with no sIgE to the allergens tested; and group 3 (n = 22) included individuals with no allergic history. To visualize IgE-binding polypeptides, group 1 sera were examined via Western blotting (WB). Polypeptide bands with the highest reactivity were analyzed by mass spectrometry (MS) for putative identification. Results: The serological reactivity of group 1 was significantly higher than that of group 3 in an indirect ELISA (p = 0.03). Sixty-five percent of group 1 individuals showed reactivity to polypeptide bands in WB. Bands of 81 and 56 kDa had the highest reactivity proportions among the reactive sera, followed by a 45-kDa band. MS analysis of these 3 polypeptides suggests that they are basidiomycete-derived enzymes with aconitate hydratase, catalase, and enolase functions. Conclusions:G. applanatum spores have allergenic components recognized by Puerto Rican individuals, which could eventually be considered as markers in cases of fungal allergy and be included in diagnostic allergen panels in Puerto Rico and tropical regions.
Association between Brain and Kidney Near-Infrared Spectroscopy and Early Postresuscitation Mortality in Asphyxiated Newborn Piglets
Authors: Solevåg Anne Lee , Schmölzer Georg M. , Nakstad Britt , Saugstad Ola Didrik , Cheung Po-Yin
Published: April 2017

Background: Early outcome predictors after delivery room cardiopulmonary resuscitation (CPR) of asphyxiated newborns are needed. Objectives: To investigate if cerebral (rScO2) and renal (rSrO2) tissue oxygen saturation 30 min after return of spontaneous circulation (ROSC) are different between surviving versus nonsurviving piglets with asphyxia-induced cardiac arrest and CPR. Further, to investigate the relationship of rScO2 and rSrO2 to cardiac output (CO), blood pressure (BP), and biochemical variables 30 min and 4 h after ROSC. Methods: Anesthetized, mechanically ventilated piglets (1-3 days, 1.7-2.4 kg) were used. rScO2, rSrO2, SpO2, right common carotid artery flow, and arterial BP were measured continuously. CO was measured with echocardiography. The piglets were asphyxiated until cardiac arrest and resuscitated. Piglets that survived 4 h after ROSC (n = 12) were compared with piglets that died before planned euthanasia at 4 h (n = 13). Left ventricular, and kidney and brain tissue lactate were analyzed. Correlations between variables were assessed. Results: Thirty minutes after ROSC, median rSrO2 (43% [n = 10] vs. 25% [n = 2], p = 0.003) but not rScO2 (46% [41-55] [n = 10] vs. 40% [22-45] [n = 5], p = 0.08) was higher in survivors than in nonsurvivors. Arterial lactate was negatively correlated and pH positively correlated with rScO2 and rSrO2. Left ventricular, but not kidney or brain lactate was negatively correlated with rScO2 and rSrO2. There was no correlation between CO or BP and rScO2 or rSrO2. Conclusions: Despite satisfactory CO and BP vital organ oxygenation can be poor. Tissue oxygen saturation, pH, and lactate, as measures of anaerobic metabolism, may reflect vital organ oxygenation and outcome.
A Randomized Trial Comparing Triple versus Single Uterine Tourniquet in Open Myomectomy
Authors: Al Ragip Atakan , Yapca Omer E. , Gumusburun Neset
Published: April 2017

Background: Single and triple uterine tourniquet significantly reduces blood loss during myomectomy and both are highly effective. Triple tourniquet, however, blocks ovarian circulation and there is doubt that it causes ischemic damage to ovaries. These 2 methods have not been compared by a randomised controlled study yet. The purpose of this study was to compare triple uterine tourniquet with single tourniquet in terms of blood loss during open myomectomy. Material and Methods: Women were randomized to triple (n = 24) or to single tourniquet (n = 24) at open myomectomy. All women with a myomatous uterus greater than 12 weeks of gestation were eligible to be part of the study. The primary outcome of the study was the amount of blood loss during surgery. Sample size was set to detect a 250 mL difference in blood loss with 80% power at α = 0.05. We also compared the change in anti-Müllerian Hormone (AMH) levels before and after surgery. Results: There was no significant difference in the outcome of blood loss between triple and single uterine tourniquet (322 ± 223 vs. 426 ± 355 mL, p = 0.230). Change in AMH was not different between the groups. Conclusions: There is no clinically significant difference between triple and single uterine tourniquets on blood loss at open myomectomy.
Vaginal Neoplasia Induced by an Unusual Papillomavirus Subtype in a Woman with Inherited Chromosomally Integrated Human Herpesvirus Type 6A
Authors: Pichon Maxime , Gaymard Alexandre , Lebail-Carval Karine , Frobert Emilie , Beaufils Etienne , Chene Gautier , Tommasino Massimo , Lina Bruno , Gaucherand Pascal , Gautheret-Dejean Agnès , Bonnafous Pascale , Gheit Tarik , Buenerd Annie , Lamblin Gery , Mekki Yahia
Published: April 2017

We describe here a case of high-grade vaginal squamous lesion in a 54-year-old woman with a papillomaviruses (HPV) genital infection that developed from a cervical low-grade squamous intraepithelial lesion (SIL) to a high-grade SIL (H-SIL) on cytological examination. A colposcopy exam led to the detection of suspect vaginal lesions with granulomatous infiltrations, which were classified as a Vaginal Intra-Epithelial Neoplasia grade 2 after pathologists' analyses. After a laser vaginal surgery and a loop excision of the transformation zone, the analyses of the anatomical pieces using a near-complete HPV screening panel revealed an HPV-4 infection that was not detected before in cervical smears. This HPV-infection is associated with a high human herpesvirus type 6A (HHV-6A) viral load in the same anatomical piece. The presence of an inherited chromosomally integrated HHV-6A (iciHHV-6A) was proved in this patient by real-time polymerase chain reaction on hair follicles and nail. This case suggests reconsidering both the benign nature of low-grade lesions in the female genital tract and the well-known “good” prognosis of low-risk HPV infection, especially when iciHHV-6A is diagnosed. This clinical course insists on the benefits of the multiplex panel use or global sequencing in order to optimize biological testing sensitivity, and so enhance clinical management of infection-induced neoplasia.
Contemporaneidades do Ensino de Anatomia Humana
Authors: Schultz Michele
Published: April 2017

As estratégias de ensino devem respeitar a formação profissional e acompanhar a dinâmica sociocultural. A forma de passar e adquirir conhecimento mudou ao longo dos séculos, mas a disciplina de Anatomia Humana pauta-se pelo tradicionalismo e aplica métodos muito semelhantes aos adotados no século XIII, quando ela foi criada. Neste relato, questiona-se a efetividade do ensino tradicional de Anatomia Humana, baseado na memorização, e se apresentam estratégias alternativas utilizadas em cursos de graduação da Escola de Artes, Ciências e Humanidades da Universidade de São Paulo. Tais estratégias estão baseadas em preceitos que conduzam a/o estudante à condição de protagonista de seu aprendizado, construído a partir de suas experiências e futuras competências profissionais
P2X
7
Deficiency Blocks Lesional Inflammasome Activity and Ameliorates Atherosclerosis in Mice
Authors: Stachon Peter , Heidenreich Adrian , Merz Julian , Hilgendorf Ingo , Wolf Dennis , Willecke Florian , von Garlen Sunaina , Albrecht Philipp , Härdtner Carmen , Ehrat Nicolas , Hoppe Natalie , Reinöhl Jochen , von zur Mühlen Constantin , Bode Christoph , Idzko Marco , Zirlik Andreas
Published: April 2017

Background:

Extracellular adenosine triphosphate (ATP) binds as a danger signal to purinergic receptor P2X
7
and promotes inflammasome assembly and interleukin-1β expression. We hypothesized a functional role of the signal axis ATP–P2X
7
in inflammasome activation and the chronic inflammation driving atherosclerosis.

Methods:

P2X
7
-competent and P2X
7
-deficient macrophages were isolated and stimulated with lipopolysaccharide, ATP, or both. To assess whether P2X
7
may have a role in atherosclerosis, P2X
7
expression was analyzed in aortic arches from low density lipoprotein receptor
-/-
mice consuming a high-cholesterol or chow diet. P2X
7
+/+
and P2X
7
−/−
low density lipoprotein receptor
−/−
mice were fed a high-cholesterol diet to investigate the functional role of P2X
7
knockout in atherosclerosis. Human plaques were derived from carotid endarterectomy and stained against P2X
7
.

Results:

Lipopolysaccharide or ATP stimulation alone did not activate caspase 1 in isolated macrophages. However, priming with lipopolysaccharide, followed by stimulation with ATP, led to an activation of caspase 1 and interleukin-1β in P2X
7
-competent macrophages. In contrast, P2X
7
-deficient macrophages showed no activation of caspase 1 after sequential stimulation while still expressing a basal amount of interleukin-1β. P2X
7
receptor was higher expressed in murine atherosclerotic lesions, particularly by lesional macrophages. After 16 weeks of a high-cholesterol diet, P2X
7
-deficient mice showed smaller atherosclerotic lesions than P2X
7
-competent mice (0.162 cm
2
±0.023 [n=9], P2X
7
−/−
low density lipoprotein receptor
−/−
: 0.084 cm
2
±0.01 [n=11],
P
=0.004) with a reduced amount of lesional macrophages. In accord with our in vitro findings, lesional caspase 1 activity was abolished in P2X
7
−/−
mice. In addition, intravital microscopy revealed reduced leukocyte rolling and adhesion in P2X
7
-deficient mice. Last, we observe increased P2X
7
expression in human atherosclerotic lesions, suggesting that our findings in mice are relevant for human disease.

Conclusions:

P2X
7
deficiency resolved plaque inflammation by inhibition of lesional inflammasome activation and reduced experimental atherosclerosis. Therefore, P2X
7
represents an interesting potential new target to combat atherosclerosis.
The Meaning of Airspace Sovereignty Today – A Case Study on Demilitarisation and Functional Airspace Blocks
Authors: Åkermark Sia Spiliopoulou
Published: April 2017

As a result of the eu Single European Sky directives, European states adopted regional agreements on functional airspace blocks. The Agreement on the North European Functional Airspace Block (nefab) was signed in 2012 by Estonia, Finland, Latvia and Norway. The nature of the agreement is mixed and involves civil as well as military actors. nefab seems to operate in practice in a hybrid mode, sometimes looking like a private international enterprise and sometimes more like a public international organisation. Does the highly technical nature of the agreement keep issues of political and legal relevance outside the range of democratic control? To what extent can such hybrid, functional, technical regimes of international cooperation affect the understandings and the exercise of sovereignty, and what is the effect of the NEFAB-regime on older legal obligations such as the demilitarisation and neutralisation regime of the Åland Islands?
New species of the genus Gnathochorisis Förster (Hymenoptera: Ichneumonidae: Orthocentrinae) from the Neotropical Region
Authors: HUMALA ANDREI E.
Published: April 2017

The Neotropical species of the genus Gnathochorisis (Ichneumonidae: Orthocentrinae) are reviewed, seven species: G. enodis sp. nov., G. khalaimi sp. nov. from Mexico, G. intercalaris sp. nov., G. punctata sp. nov., G. rufa sp. nov., G. rufithorax sp. nov. from French Guiana, and G. dilleri sp. nov. from Peru are described and illustrated, and one species G. laticincta comb. nov. is transferred from the genus Symplecis. A key to the Neotropical Gnathochorisis species is provided.
Five new species of the leafhopper genus Thagria Melichar (Hemiptera: Cicadellidae: Coelidiinae) from China
Authors: WANG XIU-DAN , ZHANG YA-LIN
Published: April 2017

Five new species of genus Thagria are described, illustrated and photographed: T. gansuensis sp. nov., T. menglana sp. nov., T. melanoloma sp. nov., T. incurvata sp. nov., and T. crena sp. nov.
Correlation of Symptoms, Clinical Signs, and Biomarkers of Inflammation in Postsurgical Chronic Rhinosinusitis
Authors: Racette Samuel D. , Wijewickrama Rohan C. , Jayaprakash Vijayvel , Sherris David A. , Santos Carlos , Kita Hirohito , O’Donnell Frank E. , Ponikau Jens U.
Published: April 2017

Objective:

The study aimed to evaluate symptoms described by patients with chronic rhinosinusitis with polypoid changes/nasal polyps and their correlation with computed tomography (CT), nasal endoscopy, and intranasal biomarkers.

Study Design:

Prospective multicenter study symptom data from postsurgical adult chronic rhinosinusitis study participants with recurrent disease refractory to medical therapy were analyzed in comparison with objective data.

Methods:

Using logistic regression analysis, participant-rated 16-question surveys from 258 participants were assessed for correlation with nasal endoscopy scores, CT percentage of sinus occlusion, and intranasal biomarkers of fungal antigens (Alternaria and Aspergillus), eosinophilic inflammation (eosinophil-derived neurotoxin [EDN] and major basic protein [MBP]), and inflammatory cytokines (interleukins 5 and 13).

Results:

Study participant assessments revealed increased CT occlusion in participants presenting with greater inability to smell ( P < .019). Mucosal inflammation identified on nasal endoscopy was positively correlated with congestion ( P < .028), runny nose ( P < .002), and ear pain ( P < .007). Elevated EDN was positively correlated in patients with bothersome congestion ( P < .031) and runny nose ( P < .011). Sneezing was positively correlated with multiple markers: Alternaria ( P < .024), interleukin-13 ( P < .027), MBP ( P < .034), and interleukin-5 ( P < .019).

Conclusion:

Nasal endoscopy, not CT imaging, has the strongest correlation with the 2 cardinal symptoms of congestion and runny nose in CRS patients; these correlate with biomarkers of eosinophilic inflammation.