bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Thermal Stimulation to Enhance Shale Gas Recovery through a Novel Conceptual Model
Authors: Xue Liang , Dai Cheng , Wang Lei , Chen Xiaoxia
Published: February 2019

To investigate the effect of thermal stimulation on shale gas recovery, a novel conceptual model coupling shale gas flow and temperature is proposed. The adsorption process is nonisothermal, and adsorption capacity changes with temperature. The local thermal nonequilibrium can explicitly describe the convective heat exchange between rock and fluids. The fluid flow model takes Knudsen diffusion, slippage effect, and non-Darcy flow into account. The complex geometry of fracture network due to hydraulic fracturing can also be considered. A series of synthetic tests are designed to demonstrate the model performance. The results show that the dynamic characteristics of heat diffusion and pressure spread can be reasonably obtained. Gas recovery decreases with the increase of volumetric heat transfer coefficient, and there exists a threshold value of the effect of volumetric heat transfer coefficient on gas recovery. Gas recovery increases with the gas and rock thermal conductivity and decreases with heat capacity of rock, but the decrease level becomes insignificant when heat capacity of rock is sufficiently high. Increasing the heating temperature and decreasing the production pressure are beneficial to enhance shale gas recovery, but the rate of recovery enhancement tends to decrease for sufficiently high heating temperature.
Ability of 18F-FDG PET/CT Radiomic Features to Distinguish Breast Carcinoma from Breast Lymphoma
Authors: Ou Xuejin , Wang Jian , Zhou Ruofan , Zhu Sha , Pang Fuwen , Zhou Yi , Tian Rong , Ma Xuelei
Published: February 2019

Purpose. To investigate the value of SUV metrics and radiomic features based on the ability of 18F-FDG PET/CT in differentiating between breast lymphoma and breast carcinoma. Methods. A total of 67 breast nodules from 44 patients who underwent 18F-FDG PET/CT pretreatment were retrospectively analyzed. Radiomic parameters and SUV metrics were extracted using the LIFEx package on PET and CT images. All texture parameters were divided into six groups: histogram (HISTO), SHAPE, gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), neighborhood gray-level different matrix (NGLDM), and gray-level zone-length matrix (GLZLM). Receiver operating characteristics (ROC) curves were generated to evaluate the discriminative ability of each parameter, and the optimal parameter in each group was selected to generate a new predictive variable by using binary logistic regression. PET predictive variable, CT predictive variable, the combination of PET and CT predictive variables, and SUVmax were compared in terms of areas under the curve (AUCs), sensitivity, specificity, and accuracy. Results. Except for SUVmin (p=0.971), the averages of FDG uptake metrics of lymphoma were significantly higher than those of carcinoma (p≤0.001), with the following median values: SUVmean, 4.75 versus 2.38 g/ml (P<0.001); SUVstd, 2.04 versus 0.88 g/ml (P=0.001); SUVmax, 10.69 versus 4.76 g/ml (P=0.001); SUVpeak, 9.15 versus 2.78 g/ml (P<0.001); TLG, 42.24 versus 9.90 (P<0.001). In the ROC curves analysis based on radiomic features and SUVmax, the AUC for SUVmax was 0.747, for CT texture parameters was 0.729, for PET texture parameters was 0.751, and for the combination of CT and PET texture parameters was 0.771. Conclusion. The SUV metrics in 18FDG PET/CT images showed a potential ability in the differentiation between breast lymphoma and carcinoma. The combination of SUVmax and PET/CT texture analysis may be promising to provide an effectively discriminant modality for the differential diagnosis of breast lymphoma and carcinoma, even for the differentiation of subtypes of lymphoma.
Impregnation of ZnO onto a Vegetal Activated Carbon from Algerian Olive Waste: A Sustainable Photocatalyst for Degradation of Ethyl Violet Dye
Authors: Abdessemed Ala , Rasalingam Shivatharsiny , Abdessemed Sanna , Djebbar Kamel El Zin , Koodali Ranjit
Published: February 2019

This study is aimed at developing a simple and low-cost method to fabricate ZnO-loaded porous activated carbon (AC-ZnO) prepared from the Algerian olive-waste cakes and utilize it as a photocatalyst for the degradation of Ethyl Violet dye. The synthesized AC-ZnO material was characterized using powder X-ray diffraction, BET surface area measurements, Raman microscopy, thermogravimetric analysis, UV-visible diffuse reflectance spectroscopy, and zeta potential measurements. The degradation efficiency was evaluated with Ethyl Violet (EV) dye in aqueous solution under UV irradiation supplied by a Xenon arc lamp through a Pyrex glass filter (cutoff 280 nm), and the degraded products were identified by using electrospray ionization mass spectroscopy. Additional experiments were carried out under N2 flow and with isopropyl alcohol to examine the role of superoxide and hydroxyl radicals, respectively. The amount of ●OH radical formed on irradiated AC-ZnO was tested with terephthalic acid which can act as a chemical trap for the ●OH radicals. The results from this study indicate that the AC-ZnO is a potential catalyst for the pollutant removal and the ●OH radicals are the key species for the degradation of EV. Further, this study opens up an opportunity to produce cheaper activated carbon support from olive wastes for environmental remediation applications.
Cherry Anthocyanins Regulate NAFLD by Promoting Autophagy Pathway
Authors: Chu Qiang , Zhang Shuang , Chen Meng , Han Wen , Jia Ruoyi , Chen Wen , Zheng Xiaodong
Published: February 2019

Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease that threatens human health, and present therapies remain limited due to the lack of effective drugs. Lipid metabolic disturbance and oxidative stress have strong links to the development of NAFLD, while autophagy was generally accepted as a key regulatory mechanism on these steps. Our previous studies indicated that cherry anthocyanins (CACN) protected against high fat diet-induced obesity and NALFD in C57BL/6 mice, while the underlying molecule mechanism is still unclear. Thus, in this study, we show that CACN protect against oleic acid- (OA-) induced oxidative stress and attenuate lipid droplet accumulation in NAFLD cell models. According to the results of a transmission electron microscope (TEM), western blot, immunofluorescence (IF), and adenovirus transfection (Ad-mCherry-GFP-LC3B), autophagy is in accordance with the lipid-lowering effect induced by CACN. Further studies illustrate that CACN may activate autophagy via mTOR pathways. In addition, an autophagy inhibitor, 3-methyladenine (3-MA), was applied and the result suggested that autophagy indeed participates in the lipid clearance process in OA-induced lipid accumulation. All these results indicate that the positive effects of CACN on OA-induced hepatic lipid accumulation are mediated via activating autophagy, showing a potential target for the therapeutic strategy of NAFLD.
Study on the Rolling‐Type Microvibration Isolation Mechanisms Based on Completely Elastic Contact
Authors: Guan Gaofeng , Xu Dengfeng , Zhu Yu , Yu Qiang , Li Qiang
Published: February 2019

The previous models of rolling‐type mechanisms were built based on rigid contact and pure rolling motion, but when applied to ground microvibration isolation, a large error in the natural frequency was sometimes observed in the experiments. A new model of a common mechanism based on completely elastic contact is developed, and the expression of the natural frequency is provided under a microvibration condition. The experiments and analysis show that the proposed model is more accurate than the previous model, and the natural frequency is independent of the payload. The analysis shows that the proposed model is only suitable in the range of completely elastic contact, and the load range is provided after comparing the experimental results with existing theory.
Transpedicular Endoscopic Surgery for Highly Downmigrated L5-S1 Disc Herniation
Authors: Krzok Guntram
Published: February 2019

Endoscopic surgery for highly downmigrated disc herniation at level L5-S1 is a challenging technique. Most surgeons prefer the interlaminar access because of the special anatomy of the L5-S1 disc level, i.e., narrow neuroforamen and large interlaminar window. Transforaminal access to the neuroforamen L5-S1 is difficult in cases with high iliac crest. Here, the access to the highly downmigrated disc herniation with the recently reported technique of transpedicular endoscopic surgery by Krzok et al. was described. In 3 cases with highly downmigrated disc herniation of L5-S1, the sequester was removed successfully through the bone hole of S1 pedicle. This technique is demanding for experienced endoscopic surgeons.
Dynamic Model of the Hot Strip Rolling Mill Vibration Resulting from Entry Thickness Deviation and Its Dynamic Characteristics
Authors: Wang Xinxin , Yan Xiaoqiang
Published: February 2019

The vibration demolding of the crystallizer leads to slab thickness deviation in continuous casting processes. Therefore, in this paper, the dynamic model of the hot strip rolling mill vibration resulting from entry thickness deviation is proposed and its dynamic characteristics are studied. First, the dynamic model of vertical vibration in the hot strip rolling mill is established based on Sims’ rolling force model. Then, the model validity is certified by comparing the simulation with field test data from a 1580 hot strip rolling mill. Finally, we investigate the influence of model parameters on the dynamic characteristics of hot strip rolling mill vibration resulting from entry thickness deviation. The result indicates that hot strip rolling mill vibration resulting from entry thickness deviation can be reduced by increasing the area of the hydraulic cylinder piston side and the entry thickness as well as by decreasing the deformation resistance, rolling speed, and equivalent stiffness.
Application of Bee Evolutionary Genetic Algorithm to Maximum Likelihood Direction‐of‐Arrival Estimation
Authors: Fan Xinnan , Pang Linbin , Shi Pengfei , Li Guangzhi , Zhang Xuewu
Published: February 2019

The maximum likelihood (ML) method achieves an excellent performance for DOA estimation. However, its computational complexity is too high for a multidimensional nonlinear solution search. To address this issue, an improved bee evolutionary genetic algorithm (IBEGA) is applied to maximize the likelihood function for DOA estimation. First, an opposition‐based reinforcement learning method is utilized to achieve a better initial population for the BEGA. Second, an improved arithmetic crossover operator is proposed to improve the global searching performance. The experimental results show that the proposed algorithm can reduce the computational complexity of ML DOA estimation significantly without sacrificing the estimation accuracy.
A Building‐Block‐Based Genetic Algorithm for Solving the Robots Allocation Problem in a Robotic Mobile Fulfilment System
Authors: Zhang Jingtian , Yang Fuxing , Weng Xun
Published: February 2019

Robotic mobile fulfilment system (RMFS) is an efficient and flexible order picking system where robots ship the movable shelves with items to the picking stations. This innovative parts‐to‐picker system, known as Kiva system, is especially suited for e‐commerce fulfilment centres and has been widely used in practice. However, there are lots of resource allocation problems in RMFS. The robots allocation problem of deciding which robot will be allocated to a delivery task has a significant impact on the productivity of the whole system. We model this problem as a resource‐constrained project scheduling problem with transfer times (RCPSPTT) based on the accurate analysis of driving and delivering behaviour of robots. A dedicated serial schedule generation scheme and a genetic algorithm using building‐blocks‐based crossover (BBX) operator are proposed to solve this problem. The designed algorithm can be combined into a dynamic scheduling structure or used as the basis of calculation for other allocation problems. Experiment instances are generated based on the characteristics of RMFS, and the computation results show that the proposed algorithm outperforms the traditional rule‐based scheduling method. The BBX operator is rapid and efficient which performs better than several classic and competitive crossover operators.
Tough and Fatigue-Resistant Hydrogels with Triple Interpenetrating Networks
Authors: Wang Jilong , Wei Junhua , Su Siheng , Qiu Jingjing
Published: February 2019

Biomimetic hydrogels with triple networks have been developed via in situ polymerization and addition of graphene oxide (GO) nanosheets, which achieve improved toughness and superior fatigue resistance, simultaneously. Compared with pristine calcium alginate/polyacrylamide double network (DN) hydrogels, the integration of a calcium-induced graphene oxide network enhances the crosslinking degree of triple network (TN) hydrogels with improved compressive strength by 172% and toughness by 174%. In addition, cyclic compressive loading-unloading curves depict excellent fatigue resistance because of reversible calcium alginate and calcium-induced GO networks, whereas high strength and toughness of traditional DN gels derive from the first sacrificial network, which leads to inferior fatigue resistance. Toughness of these TN gels was still kept at 110 kJ m−3 at the fifth cycle which is equal to that of articular cartilages. The swelling property of these DN and TN hdyrogels is also systematically explored, which exhibits that GO can reduce the swelling to maintain the mechanical properties of TN gels. The internal fracture mechanisms of these TN hydrogels are studied via swelling tests of precompressed and as-prepared gels. These synergistic effects of the reversible ions crosslinking polymer network and nanofillers open a new platform to design supertough and fatigue-resistant hydrogels. In addition, these TN hydrogels are talented replacements for load-bearing parts, like cartilage due to its high toughness and superior fatigue resistance.
Impact of Transport Cost and Travel Time on Trade under China-Pakistan Economic Corridor (CPEC)
Authors: Alam Khalid Mehmood , Li Xuemei , Baig Saranjam
Published: February 2019

China is the second biggest economy in the world and almost 40% of its trade in 2016 is transported through the South China Sea. China needs a small, secure, and low-cost path to trade with Europe and the Middle East and China-Pakistan Economic Corridor (CPEC) is a feasible solution to this requirement. This research analyzes the effect of CPEC on trade in terms of transport cost and travel time. In addition, the study compares the existing routes and the new CPEC route. The research methodology consists of qualitative and descriptive statistical methods. The variables (transport cost and travel time) are calculated and compared for both the existing route and new CPEC route. The results show that transport cost for 40-foot container between Kashgar and destination ports in the Middle East is decreased by about $1450 dollars and for destination ports in Europe is decreased by $1350 dollars. Additionally, travel time is decreased by 21 to 24 days for destination ports in the Middle East and 21 days for destination ports in Europe. The distance from Kashgar to destination ports in the Middle East and Europe is decreased by 11,000 to 13,000 km.
The Action Control Model for Robotic Fish Using Improved Extreme Learning Machine
Authors: Zhang XueXi , Chen ShuiBiao , Cai ShuTing , Xiong XiaoMing , Hu Zefeng
Published: February 2019

To achieve fast and accurate adjustment of robotic fish, this paper proposes state prediction model based on the extreme learning machine optimized by particle swarm algorithm. The proposed model can select desirable actions for robotic fish according to precisely predicted states, “adjusting position” or “pushing ball” defined herein. Specifically, the extreme learning machine (ELM) is leveraged to predict the state of robotic fish, from the observations of current surrounding environment. As the outputs in ELM are varying with the randomly initialized parameters, particle swarm optimization (PSO) algorithm further improves the accuracy and robustness of the ELM by optimizing initial parameters. The empirical results on URWPGSim2D simulation platform indicate that the robotic fish tends to carry out appropriate actions using the state prediction model so that we can complete the game efficiently. It proves that the proposed model can make best use of the real‐time information of robotic fish and water polo and derive fulfilling action strategy in various scenarios, which meet the requirements of motion control for robotic fish.
The Association between Toxoplasma gondii Infection and Risk of Parkinson’s Disease: A Systematic Review and Meta-Analysis
Authors: Zhou Zonglei , Zhou Ruzhen , Li Kunpeng , Wei Wen , Zhang Zengqiao , Zhu Yan , Luan Rongsheng
Published: February 2019

Background. Several studies have investigated the association between Toxoplasma gondii (T. gondii) infection and risk of Parkinson’s disease (PD) with inconsistent results. Clarifying this relation might be useful for better understanding of the risk factors and the relevant mechanisms of PD, thus a meta-analysis was conducted to explore whether exposure to T. gondii is associated with an increased risk of PD. Methods. We conducted this meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A rigorous literature selection was performed by using the databases of PubMed, Embase, Web of Science, Cochrane Library, and ScienceDirect. Odds ratio (OR) and corresponding 95% confidential interval (CI) were pooled by using fixed-effects models. Sensitivity analysis, publication bias test, and methodological quality assessment of studies were also performed. Results. Seven studies involving 1086 subjects were included in this meta-analysis. Pooled data by using fixed-effects models suggested both latent infection (OR, 1.17; 95% CI, 0.86 to 1.58; P=0.314) and acute infection (OR, 1.13; 95% CI, 0.30 to 4.35; P=0.855) were not associated with PD risk. Stable and robust estimates were confirmed by sensitivity analysis. No publication bias was found by visual inspection of the funnel plot, Begg’s, and Egger’s test. Conclusions. This meta-analysis does not support any possible association between T. gondii infection and risk of PD. Researches are still warranted to further explore the underlying mechanisms of T. gondii in the pathogenesis of PD and their causal relationship.
Effects of Crimp and Textile Architecture on the Stiffness and Strength of Composites with 3D Reinforcement
Authors: Stig Fredrik , Hallström Stefan
Published: February 2019

The aim of this study is to experimentally determine how the weave architecture and yarn crimp affect the measured tensile stiffness and strength of composites containing 3D textile reinforcement. It is shown that both the stiffness and strength decrease nonlinearly with increasing 3D crimp. The ultimate strength of specimens containing nominally straight yarns and specimens containing crimped yarns can differ more than a factor of 3, and the stress causing onset of damage can be affected even more. Adding nominally straight stuffer yarns into a 3D-woven reinforcement significantly increases the fibre volume fraction, the stiffness, and the strength of the composite. However, since the stuffer yarns are virtually straight and thus stiffer than the warp yarns, they attract the load and reach their strength at relatively lower strain than the warp yarns. The reinforcement architecture varies between the surfaces and the interior of the studied textiles, which has corresponding influence on the local stiffness. The onset of failure is predicted satisfactorily accurate with relatively simple estimations. The ultimate strength is a result of extensive damage progression and thus more dubious to predict.
Arthroscopic Excision of Intra-Articular Osteoid Osteoma at the Elbow
Authors: Hatta Taku , Hosaka Masami , Watanuki Munenori , Yano Toshihisa , Yoshida Shinichirou , Watanabe Mika , Hitachi Shin , Itoi Eiji
Published: February 2019

Osteoid osteoma (OO) apparent in the intra-articular region of the elbow is very rare. Although computed tomography-guided excision and radiofrequency ablation have been recognized as useful treatment options, arthroscopic excision has recently received focus as an alternative strategy for lesions close to neurovascular structures or intra- and juxta-articular lesions. We herein report a 17-year-old female who underwent arthroscopic treatment for intra-articular OO located at the olecranon/coronoid fossa. Her symptoms included elbow pain that was exacerbated at night and contracture of elbow flexion-extension, and she was diagnosed with intra-articular OO after 12 months of symptomatic history. Arthroscopically, thorough synovectomy for both the anterior and posterior aspects of the joint enabled definition of the tumor margin with hyperemic alteration and excision of the lesion as an en bloc specimen. At the 12-month follow-up, the patient had no recurrence of elbow limitation or pain. This case report describes the advantages of arthroscopic treatment, including a low-invasive approach and easy accessibility to the whole intra-articular space, which can provide clear visualization of the tumorous lesion.
MnTE-2-PyP Attenuates TGF-β-Induced Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Inhibiting the Smad2/3 Signaling Pathway
Authors: Yang Yu , Zhang Pei , Yan Ruicheng , Wang Qi , Fang Erhu , Wu Hongxue , Li Shijun , Tan Haiyan , Zhou Xing , Ma Xianxiong , Tang Yu , Huang Yongming , Deng Rui , Liu Ying , Tong Shilun , Wang Zhihua , Oberley-Deegan Rebecca E. , Tong Qiang
Published: February 2019

Background. As a key step in enhancing cancer cell invasion and metastasis, epithelial-mesenchymal transition (EMT) plays an important role in colorectal cancer progression. EMT is triggered by a variety of signaling pathways, among which the transforming growth factor β (TGF-β) signaling pathway has been implicated as a primary inducer. Accumulating evidence demonstrates that MnTE-2-PyP (chemical name: manganese(III) meso-tetrakis-(N-ethylpyridinium-2-yl), a superoxide dismutase (SOD) mimetic, inhibits TGF-β signaling; however, its ability to inhibit TGF-β-induced EMT in colorectal cancer has not yet been explored. Methods. To verify our hypothesis that MnTE-2-PyP attenuates TGF-β-induced EMT, human colorectal cancer cells were treated with TGF-β in the presence or absence of MnTE-2-PyP. Cells were analyzed by several techniques including western blotting, real-time quantitative PCR, transwell assay, and wound healing assay. Results. MnTE-2-PyP reverses cell phenotypes induced by TGF-β in colon cancer cells. MnTE-2-PyP treatment significantly reduced the expression of mesenchymal markers but maintained epithelial marker expression. Mechanistically, MnTE-2-PyP suppressed the phosphorylated Smad2/3 protein levels induced by TGF-β in SW480 cells, but MnTE-2-PyP failed to suppress TGF-β-induced Slug and Snail expression in colorectal cells. Furthermore, MnTE-2-PyP effectively suppressed TGF-β-mediated cell migration and invasion and the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in colorectal cells. Conclusion. Taken together, we provide an in-depth mechanism by which MnTE-2-PyP inhibits colorectal cancer progression, supporting an important role for MnTE-2-PyP as an effective and innovative antitumor agent to enhance treatment outcomes in colorectal cancer.
Fischer-Clifford Matrices and Character Table of the Maximal Subgroup (29:(L3(4)):2 of U6(2):2
Authors: Prins Abraham Love , Monaledi Ramotjaki Lucky
Published: February 2019

The automorphism group U6(2):2 of the unitary group U6(2)≅Fi21 has a maximal subgroup G¯ of the form (29:(L3(4)):2 of order 20643840. In this paper, Fischer-Clifford theory is applied to the split extension group G¯ to construct its character table. Also, class fusion from G¯ into the parent group U6(2):2 is determined.
Tumor Cell Escape from Therapy-Induced Senescence as a Model of Disease Recurrence after Dormancy
Authors: Saleh Tareq , Tyutyunyk-Massey Liliya , Gewirtz David A.
Published: February 2019

Senescence, a durable form of growth arrest, represents a primary response to numerous anticancer therapies. Although the paradigm that senescence is “irreversible” has largely withstood the findings of tumor cell recovery from what has been termed “pseudo-senescence” or “senescence-like arrest,” a review of the literature suggests that therapy-induced senescence in tumor cells is not obligatorily a permanent cell fate. Consequently, we propose that senescence represents one avenue whereby tumor cells evade the direct cytotoxic impact of therapy, thereby allowing for prolonged survival in a dormant state, with the potential to recover self-renewal capacity and contribute to disease recurrence.
Brain Tumor Microenvironment and Host State: Implications for Immunotherapy
Authors: Tomaszewski William , Sanchez-Perez Luis , Gajewski Thomas F. , Sampson John H.
Published: February 2019

Glioblastoma (GBM) is a highly lethal brain tumor with poor responses to immunotherapies that have been successful in more immunogenic cancers with less immunosuppressive tumor microenvironments (TME). The GBM TME is uniquely challenging to treat due to tumor cell–extrinsic components that are native to the brain, as well as tumor-intrinsic mechanisms that aid in immune evasion. Lowering the barrier of immunosuppression by targeting the genetically stable tumor stroma presents opportunities to treat the tumor in a way that circumvents the complications of targeting a constantly mutating tumor with tumor antigen–directed therapies. Tumor-associated monocytes, macrophages, and microglia are a stromal element of particular interest. Macrophages and monocytes compose the bulk of infiltrating immune cells and are considered to have protumor and immunosuppressive effects. Targeting these cells or other stromal elements is expected to convert what is considered the “cold” TME of GBM to a more “hot” TME phenotype. This conversion could increase the effectiveness of what have become conventional frontline immunotherapies in GBM—creating opportunities for better treatment through combination therapy.
Molecular Subtype Not Immune Response Drives Outcomes in Endometrial Carcinoma
Authors: Talhouk Aline , Derocher Heather , Schmidt Pascal , Leung Samuel , Milne Katy , Gilks C. Blake , Anglesio Michael S. , Nelson Brad H. , McAlpine Jessica N.
Published: February 2019

Purpose:

Tumors with high mutation load are thought to engender stronger immune responses, which in turn promote prolonged patient survival. To investigate this, we assessed tumor-infiltrating lymphocytes (TILs) and immunosuppressive factors across the 4 molecular subtypes of endometrial cancer, which have characteristic mutation rates ranging from low to ultra-high.

Experimental Design:

A total of 460 endometrial cancers were stratified by ProMisE (Proactive Molecular Risk Classifier in Endometrial cancer) into 4 molecular subtypes: mismatch repair-deficient (MMRd), POLE mutant (POLE), p53 abnormal (p53abn), and p53 wild-type (p53wt). Immune markers (CD3, CD8, CD79a, CD138, PD-1, PD-L1, FoxP3, IDO-1) were quantified by multiplex IHC and tested for associations with ProMisE subtype, survival, and other clinicopathologic parameters.

Results:

Two major TIL patterns were observed. TILhigh tumors harbored dense T- and B-lineage infiltrates and multiple immunosuppressive features and were common in molecular subtypes associated with high mutation load (MMRd and POLE); however, equally strong responses were seen in significant numbers of p53abn and p53wt tumors, which have characteristically low mutation loads. TILlow tumors were generally devoid of immunologic features and were more prevalent in p53abn and p53wt endometrial cancers, yet were also seen in MMRd and POLE subtypes. In multivariable models involving ProMisE subtype, T-cell markers, and TIL clusters, only ProMisE showed independent prognostic significance.

Conclusions:

Immune response correlates with endometrial cancer molecular subtype but does not carry independent prognostic significance. Profound variation in immune response is seen across and within endometrial cancer molecular subtypes, suggesting that assessment of immune response rather than molecular subtype may better predict response to immunotherapy.

See related commentary by Mullen and Mutch, p. 2366
Phase I Immunotherapy Trial with Two Chimeric HER-2 B-Cell Peptide Vaccines Emulsified in Montanide ISA 720VG and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors
Authors: Bekaii-Saab Tanios , Wesolowski Robert , Ahn Daniel H. , Wu Christina , Mortazavi Amir , Lustberg Maryam , Ramaswamy Bhuvaneswari , Fowler Jeffrey , Wei Lai , Overholser Jay , Kaumaya Pravin T.P.
Published: February 2019

Purpose:

This first-in-human phase I study (NCT 01417546) evaluated the safety profile, optimal immunologic/biological dose (OID/OBD), and immunogenicity of the combination of two peptide B-cell epitope vaccines engineered to represent the trastuzumab- and pertuzumab-binding sites. Although trastuzumab and pertuzumab have been approved for clinical use, patients often develop resistance to these therapies. We have advanced a new paradigm in immunotherapy that focuses on humoral responses based on conformational B-cell epitope vaccines.

Patients and Methods:

The vaccine is comprised of two chimeric HER-2 B-cell peptide vaccines incorporating a “promiscuous T-cell epitope.” Patients were immunized with the vaccine constructs emulsified with nor-muramyl-dipeptide adjuvant in a water-in-oil Montanide ISA 720VG vehicle. Eligible patients with metastatic and/or recurrent solid tumors received three inoculations every 3 weeks.

Results:

Forty-nine patients with a median of 4 prior lines of chemotherapy received at least 1 vaccination. Twenty-eight patients completed the 3 vaccination regimens. Six patients received 1 six-month boost after the regimen, and one patient received 7 six-month boosts. No serious adverse reactions or dose-limiting toxicities were observed. The vaccine was well tolerated with dose level 2 as the recommended phase II dose. The most common related toxicity in all patients was injection-site reactions (24%). Two patients had a partial response, 14 had stable disease, and 19 had progressive disease.

Conclusions:

The study vaccine is safe, exhibits antitumor activity, and shows preliminary indication that peptide vaccination may avoid therapeutic resistance and offer a promising alternative to monoclonal antibody therapies.
Patterns of Lymph Node Metastasis in Differentiated Thyroid Cancer; Clinical Implications with Particular Emphasis on the Emerging Role of Compartment-Oriented Lymph Node Dissection
Authors: Sakorafas George H. , Koureas Andreas , Mpampali Iliana , Balalis Dimitrios , Nasikas Dimitrios , Ganztzoulas Sotirios
Published: February 2019

Recent advances in modern imaging allow an accurate identification of involved or suspicious lymph nodes within the nodal compartments of the neck. Careful ultrasonographic lymphatic mapping of the neck by an experienced radiologist allows a targeted, compartment-oriented (or selective) lymph node dissection to be performed instead of the more extensive modified radical lymph node dissection. Compartment-oriented lymph node dissection necessitates the close cooperation of an experienced radiologist with a particular interest in thyroid and neck ultrasonography. There is emerging evidence that this more conservative strategy allows local control of the disease while at the same time morbidity is minimized and a better cosmetic result is achieved. Further investigation is needed to establish the precise role of this interesting surgical approach.
Comparisons of the Mucosal Healing Process between Flat and Protruded Type after Endoscopic Submucosal Dissection for Gastric Neoplasms
Authors: Kim In Sung , Shin Sung Jae , Noh Choong-Kyun , Jung Min Wuk , Park Hye Lin , Kang Je Wuk , Lee Jae Eun , Lim Sun Gyo , Lee Kee Myung , Lee Kwang Jae , Cho Hyo Jung , Yang Min Jae , Kim Soon Sun , Hwang Jae Chul , Cheong Jae Youn , Yoo Byung Moo , Kim Jin Hong , Cho Sung Won
Published: February 2019

Background/Aims: The mucosal healing process after endoscopic submucosal dissection (ESD) is mostly scarring change (flat type), but a protruded lesion is occasionally found. We investigated the factors influencing the mucosal healing process, such as the flat and protruded types. Methods: A total of 2,096 ESD cases were performed from February 2005 to December 2013, and 1,757 underwent follow-up endoscopy after 3 months to check the healing type of the ulceration. We retrospectively reviewed the medical charts to analyze demographic, endoscopic, and pathological findings between the 2 groups. Results: Forty-eight cases were of the protruded type and 1,709 were of the flat type. In univariate analysis, the protruded type was found more in the antrum, anterior wall, and greater curvature (p < 0.001). In protruded types, the Helicobacter pylori (H. pylori) infection rate was lower (p < 0.017), the mean length of ESD specimen was shorter (p < 0.012), the fibrosis rate was lower (p < 0.033), and the mean number of hot biopsy and clips during ESD were less (p < 0.008 and p < 0.001 respectively). Conclusions: The healing type of mucosal ulceration after ESD seemed to be influenced by location, specimen size, and the presence of an H. pylori infection.
Bili-Uéré: A Chimpanzee Behavioural Realm in Northern Democratic Republic of Congo
Authors: Hicks Thurston C. , Kühl Hjalmar S. , Boesch Christophe , Dieguez Paula , Ayimisin Ayuk Emmanuel , Fernandez Rumen Martin , Zungawa Donatienne Barubiyo , Kambere Mbangi , Swinkels Jeroen , Menken Steph B.J. , Hart John , Mundry Roger , Roessingh Peter
Published: February 2019

To improve our understanding of the evolutionary origins of culture and technology in humans, it is vital that we document the full extent of behavioural diversity in our great ape relatives. About half of the world’s remaining chimpanzees (Pan spp.) live in the Democratic Republic of Congo (DRC), yet until now we have known almost nothing about their behaviour. Here we describe the insect-related tool technology of Bili-Uéré chimpanzees (Pan troglodytes schweinfurthii) inhabiting an area of at least a 50,000-km2 area in northern DRC, as well as their percussive technology associated with food processing. Over a 12-year period, we documented chimpanzee tools and artefacts at 20 survey areas and gathered data on dung, feeding remains and sleeping nests. We describe a new chimpanzee tool kit: long probes used to harvest epigaeic driver ants (Dorylus spp.), short probes used to extract ponerine ants and the arboreal nests of stingless bees, wands to dip for D. kohli and stout digging sticks used to access underground meliponine bee nests. Epigaeic Dorylus tools were significantly longer than the other tool types, and D. kohli tools were significantly thinner. Tools classified as terrestrial honey-digging sticks were a significant predictor for brushed and blunted tool ends, consistent with their presumed use. We describe two potential new tool types, an “ant scoop” and a “fruit hammer.” We document an extensive percussive technology used to process termite mounds of Cubitermes sp. and Thoracotermes macrothorax and hard-shelled fruits such as Strychnos, along with evidence of the pounding open of African giant snails and tortoises. We encountered some geographic variation in behaviour: we found honey-digging tools, long driver ant probes and fruit-pounding sites only to the north of the Uele River; there were more epigaeic Dorylus tools to the north and more ponerine ant tools to the south. We found no evidence of termite-fishing, despite the availability of Macrotermes muelleri mounds throughout the region. This lack of evidence is consistent with the results of dung washes, which revealed a substantial proportion of driver ants, but no evidence of Macrotermes or other termites. Our results allow us to describe a new chimpanzee behavioural complex, characterised by a general similarity of multiple behaviours across a large, ecologically diverse region but with subtle differences in prey choice and techniques. We propose that this widespread and related suite of behaviours be referred to as the Bili-Uéré Chimpanzee Behavioural Realm. Possible explanations for this pattern are a recent chimpanzee expansion across the region and the interconnectedness of this population across at least the entirety of northern DRC.
A Family-Based Rare Haplotype Association Method for Quantitative Traits
Authors: Datta Ananda S. , Lin Shili , Biswas Swati
Published: February 2019

Background: The variants identified in genome-wide association studies account for only a small fraction of disease heritability. A key to this “missing heritability” is believed to be rare variants. Specifically, we focus on rare haplotype variant (rHTV). The existing methods for detecting rHTV are mostly population-based, and as such, are susceptible to population stratification and admixture, leading to an inflated false-positive rate. Family-based methods are more robust in this respect. Methods: We propose a method for detecting rHTVs associated with quantitative traits called family-based quantitative Bayesian LASSO (famQBL). FamQBL can analyze any type of pedigree and is based on a mixed model framework. We regularize the haplotype effects using Bayesian LASSO and estimate the posterior distributions using Markov chain Monte Carlo methods. Results: We conduct simulation studies, including analyses of Genetic Analysis Workshop 18 simulated data, to study the properties of famQBL and compare with a standard family-based haplotype association test implemented in FBAT (family-based association test) software. We find famQBL to be more powerful than FBAT with well-controlled false-positive rates. We also apply famQBL to the Framingham Heart Study data and detect an rHTV associated with diastolic blood pressure. Conclusion: FamQBL can help uncover rHTVs associated with quantitative traits.
A Rare Case of Mixed Adenoneuroendocrine Carcinoma (MANEC) of the Gastroesophageal Junction with HER2/neu Overexpression and Distinct Orbital and Optic Nerve Toxicity after Intravenous Administration of Cisplatin
Authors: Golombek Thomas , Henker Robert , Rehak Matus , Quäschling Ulf , Lordick Florian , Knödler Maren
Published: February 2019

Background: Mixed adenoneuroendocrine carcinomas (MANECs) are rare malignancies with both neuroendocrine and non-neuroendocrine components. To date, the prognosis of gastroenteropancreatic MANECs remains dismal, and treatment options are mainly based on guidelines for the treatment of pure neuroendocrine carcinomas or small cell lung cancer. Established first-line therapy in the metastatic situation is cisplatin and etoposide. Platinum derivatives are known to cause a variety of side effects also involving the visual system. Severe orbital and optic nerve toxicities have been described mainly after intracarotid infusion of cisplatin. Case Report: Herein we report a rare case of a 60-year-old male patient suffering from MANEC of the gastroesophageal junction with HER2/neu overexpression who developed severe orbital and ocular neurotoxicity (grade 3 according to CTCAE v4.03) after intravenous cisplatin. Conclusion: We discuss diagnostic approaches and differential diagnoses in this clinical situation. Before starting treatment with intravenous and topical steroids, it is crucial to rule out meningeal and cerebral spread as well as paraneoplastic and endocrine syndromes.
Phase II Study of S-1 plus Cisplatin as First-Line Therapy in Patients with Metastatic Esophageal Carcinoma
Authors: Sun Si , Yu Hui , Wang Huijie , Zhang Hai , Wu Xianghua , Wang Jialei , Chang Jianhua
Published: February 2019

Background: Patients with metastatic esophageal squamous cell cancer (ESCC) need safer and more efficacious treatments. The aim of this phase II study was to investigate the efficacy and safety of S-1 plus cisplatin as first-line therapy in metastatic ESCC. Patients and Methods: 50 patients with metastatic ESCC who had not received prior systemic chemotherapy for metastatic disease were enrolled. Patients received S-1 at 40 mg/m2 divided into 2 daily doses for 14 days and cisplatin at 75 mg/m2 on day 1 or 25 mg/m2 on days 1-3 intravenously, repeated every 21 days with a maximum of 6 cycles. Results: 47 patients were assessable for response and 18 patients achieved a partial response, giving an overall response rate of 38.3%. Among those who had objective responses, a large percentage (72.2%) quickly showed remarkable tumor shrinkage during the first 2 cycles. 18 (38.3%) patients had stable disease. The median progression-free survival was 5.6 months, and the median overall survival was 12.0 months. Toxicity was mild to moderate and generally tolerable. Conclusion: The combination of S-1 plus cisplatin was a well-tolerated and convenient chemotherapy regimen with promising efficacy.
Big Data Research in Pediatric Neurosurgery: Content, Statistical Output, and Bibliometric Analysis
Authors: Oravec Chesney S. , Motiwala Mustafa , Reed Kevin , Jones Tamekia L. , Klimo Jr. Paul
Published: February 2019

Background/Aims: We sought to describe pediatric “big data” publications since 2000, their statistical output, and clinical implications. Methods: We searched 4 major North American neurosurgical journals for articles utilizing non-neurosurgery-specific databases for clinical pediatric neurosurgery research. Articles were analyzed for descriptive and statistical information. We analyzed effect sizes (ESs), confidence intervals (CIs), and p values for clinical relevance. A bibliometric analysis was performed using several key citation metrics. Results: We identified 74 articles, which constituted 1.7% of all pediatric articles (n = 4,436) published, with an exponential increase after 2013 (53/74, 72%). The Healthcare Cost and Utilization Project (HCUP) databases were most frequently utilized (n = 33); hydrocephalus (n = 19) was the most common study topic. The statistical output (n = 49 studies with 464 ESs, 456 CIs, and 389 p values) demonstrated that the majority of the ESs (253/464, 55%) were categorized as small; half or more of the CI spread (CIS) values and p values were high (274/456, 60%) and very strong (195/389, 50%), respectively. Associations with a combination of medium-to-large ESs (i.e., magnitude of difference), medium-to-high CISs (i.e., precision), and strong-to-very strong p values comprised only 20% (75/381) of the reported ESs. The total number of citations for the 74 articles was 1,115 (range per article, 0–129), with the median number of citations per article being 8.5. Four studies had > 50 citations, and 2 of them had > 100 citations. The calculated h-index was 16, h-core citations were 718, the e-index was 21.5, and the Google i10-index was 34. Conclusions: There has been a dramatic increase in the use of “big data” in the pediatric neurosurgical literature. Reported associations that may, as a group, be of greatest interest to practitioners represented only 20% of the total output from these publications. Citations were weighted towards a few highly cited publications.
Intraokulare Entzündung nach IVOM
Authors: Feltgen Nicolas
Published: February 2019

Purpose: To report a cluster of high incidence of noninfectious inflammatory reaction shortly after bevacizumab injection.Methods: Data were collected from medical records of consecutive patients who underwent bevacizumab injections and presented with acute uveitis within 1-4 days. Results: All 7 patients were injected intravitreally with bevacizumab from different batches and presented with visual deterioration. One patient with anterior uveitis complained of pain. None had hypopyon. Three patients with vitritis underwent a vitreous tap with an intravitreal injection of vancomycin and ceftazidime for possible infectious endophthalmitis. All patients received intensive topical antibiotic drops and steroids, and the intraocular inflammation resolved completely within 1 month. Five patients continued to receive bevacizumab injections without recurrent episodes. Conclusions: Our series demonstrates an incidence of noninfectious inflammatory reaction shortly after bevacizumab injection that is higher than that reported in the literature. The cause is more likely the preparation process in the same compounding pharmacy.
Eye Optics in Semiaquatic Mammals for Aerial and Aquatic Vision
Authors: Mass Alla M. , Supin Alexander Ya
Published: February 2019

Based on anatomical measurements of refractive structures in the eye, the positions of focused images were computed for several groups of semiaquatic mammals: rodents, a nonpinniped semiaquatic carnivore (the sea otter), and pinniped carnivores (seals, sea lions, and the walrus). In semiaquatic rodents, eye optics enable emmetropia in the air but cause substantial hypermetropia in the water. In semiaquatic carnivores, there are several mechanisms for amphibious vision that focus images on the retina in both air and water. These mechanisms include the potential for a substantial change in the lens shape of sea otters and the presence of the corneal emmetropic window in pinnipeds. The results suggest that several groups of mammals that independently adapted to aquatic environments vary in how their visual systems adapted to aquatic vision.
Impact of Preoperative Systemic Corticosteroids on the Histology and Diagnosis of Eosinophilic Chronic Rhinosinusitis
Authors: Akiyama Kosuke , Makihara Seiichiro , Uraguchi Kensuke , Samukawa Yasushi , Oka Aiko , Hoshikawa Hiroshi
Published: February 2019

Background: The histological changes corticosteroids induce in nasal polyps, and whether these changes have an impact on the diagnosis of eosinophilic chronic rhinosinusitis (ECRS), currently remain unclear. Objectives: A prospective controlled multicenter trial was conducted to evaluate the efficacy of the low-dose and short-term oral prednisolone (oPSL) treatment for tissue eosinophil infiltrations in ECRS. Methods: Subjects with ECRS diagnosed by previous biopsies received a low dose of oPSL for 3 days (PSL 3) or 7 days (PSL 7) before surgery. Changes in the tissue eosinophil count after these treatments were evaluated. Furthermore, the percent change of tissue eosinophil count from baseline and its impact on the diagnosis defined by the JESREC study were examined. Results: There were 23 and 21 subjects in the PSL 3 and PSL 7 groups, respectively. Polyp scores, clinical symptom scores, and the proportion of blood eosinophils significantly decreased after the treatment, and no significant differences were observed between the groups. The entire tissue eosinophil count tended to be slightly decreased in both groups without reaching a statistically significant value. The median percent change of tissue eo­sinophil count from baseline was 83.6%, and only the posttreatment proportion of blood eosinophil showed a mild correlation with it. Seven out of 44 nasal polyp specimens collected from the superficial part of the middle meatus showed < 70 eosinophils/high-power field; therefore, the false negative rate was 15.9%, but decreased to 11.4% when other parts were included in the histological evaluation. Conclusions: Low-dose and short-term oPSL did not appear to markedly affect the tissue eosinophil count in ECRS patients; however, the potential for misdiagnoses due to the effects of oPSL cannot be rejected. The diagnosis of ECRS prior to the administration of corticosteroids or tissue evaluations using multiple tissue parts is desirable.