bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Lordotic Angle of a Cage on Sagittal Alignment and Clinical Outcome in One Level Posterior Lumbar Interbody Fusion with Pedicle Screw Fixation
Authors: Lee Ji-Ho , Lee Dong-Oh , Lee Jae Hyup , Shim Hee Jong
Published: January 2015

This study aims to assess the differences in the radiological and clinical results depending on the lordotic angles of the cage in posterior lumbar interbody fusion (PLIF). We reviewed 185 segments which underwent PLIF using two different lordotic angles of 4° and 8° of a polyetheretherketone (PEEK) cage. The segmental lordosis and total lumbar lordosis of the 4° and 8° cage groups were compared preoperatively, as well as on the first postoperative day, 6th and 12th months postoperatively. Clinical assessment was performed using the ODI and the VAS of low back pain. The pre- and immediate postoperative segmental lordosis angles were 12.9° and 12.6° in the 4° group and 12° and 12.0° in the 8° group. Both groups exhibited no significant different segmental lordosis angle and total lumbar lordosis over period and time. However, the total lumbar lordosis significantly increased from six months postoperatively compared with the immediate postoperative day in the 8° group. The ODI and the VAS in both groups had no differences. Cages with different lordotic angles of 4° and 8° showed insignificant results clinically and radiologically in short-level PLIF surgery. Clinical improvements and sagittal alignment recovery were significantly observed in both groups.
Aggressive Extraocular Sebaceous Carcinoma Recurring after Mohs Micrographic Surgery
Authors: Grigoryan Konstantin V. , Leithauser Laurel , Gloster Hugh M.
Published: January 2015

Sebaceous carcinomas (SC) are rare adnexal tumors with possible aggressive behavior usually arising in the head and neck region of adults in the seventh decade of life. Treatment has traditionally been with surgical excision with 5-6 mm wide margins but Mohs micrographic surgery (MMS) has also been reported as an effective treatment modality. We present a case of a Caucasian female renal transplant patient with a rapidly enlarging nodule on the left preauricular cheek that was excised with MMS with negative margins. The tumor recurred rapidly and metastasized ultimately leading to the death of the patient. There was some disagreement amongst pathologists as to the possible nature of the diagnosis with the original biopsy being labeled as a poorly differentiated carcinoma. We aim to highlight the potential aggressive nature of SC and review the features of the neoplasm including histological features that help in making the diagnosis.
Mining Experiential Patterns from Game-Logs of Board Game
Authors: Wang Liang , Wang Yu , Li Yan
Published: January 2015

In board games, game-logs record past game processes, which can be regarded as an accumulation of experience. Similar to a real person, a computer player can gradually increase its skill by learning from game-logs. Therefore, the game becomes more interesting. This paper proposes an extensible approach to mine experiential patterns from increasing game-logs. The computer player improves its strategies by utilizing these growing patterns, just as it acquires experience. To evaluate the effect and performance of the approach, we designed a sample board game as a test platform and elaborated an experiment consisting of a series of tests. Experimental results show that our approach is effective and efficient.
Zero Discharge Performance of an Industrial Pilot-Scale Plant Treating Palm Oil Mill Effluent
Authors: Wang Jin , Mahmood Qaisar , Qiu Jiang-Ping , Li Yin-Sheng , Chang Yoon-Seong , Chi Li-Na , Li Xu-Dong
Published: January 2015

Palm oil is one of the most important agroindustries in Malaysia. Huge quantities of palm oil mill effluent (POME) pose a great threat to aqueous environment due to its very high COD. To make full use of discharged wastes, the integrated “zero discharge” pilot-scale industrial plant comprising “pretreatment-anaerobic and aerobic process-membrane separation” was continuously operated for 1 year. After pretreatment in the oil separator tank, 55.6% of waste oil in raw POME could be recovered and sold and anaerobically digested through 2 AnaEG reactors followed by a dissolved air flotation (DAF); average COD reduced to about 3587 mg/L, and biogas production was 27.65 times POME injection which was used to generate electricity. The aerobic effluent was settled for 3 h or/and treated in MBR which could remove BOD3(30°C) to less than 20 mg/L as required by Department of Environment of Malaysia. After filtration by UF and RO membrane, all organic compounds and most of the salts were removed; RO permeate could be reused as the boiler feed water. RO concentrate combined with anaerobic surplus sludge could be used as biofertilizer.
Monitoring the Modifications of the Vitreous Humor Metabolite Profile after Death: An Animal Model
Authors: Rosa Maria Francesca , Scano Paola , Noto Antonio , Nioi Matteo , Sanna Roberta , Paribello Francesco , De-Giorgio Fabio , Locci Emanuela , d’Aloja Ernesto
Published: January 2015

We applied a metabolomic approach to monitor the modifications occurring in goat vitreous humor (VH) metabolite composition at different times (0, 6, 12, 18, and 24 hours) after death. The1H-NMR analysis of the VH samples was performed for the simultaneous determination of several metabolites (i.e., the metabolite profile) representative of the VHstatusat different times. Spectral data were analyzed by Principal Component Analysis (PCA) and by Orthogonal Projection to Latent Structures (OPLS) regression technique. PCA and OPLS suggested that different spectral regions were involved in time-related changes. The major time-related compositional changes, here detected, were the increase of lactate, hypoxanthine, alanine, total glutathione, choline/phosphocholine, creatine, andmyo-inositol and the decrease of glucose and 3-hydroxybutyrate. We attempted a speculative interpretation of the biological mechanisms underlying these changes. These results show that multivariate statistical approach, based on1H NMR metabolite profiling, is a powerful tool for detecting ongoing differences in VH composition and may be applied to investigate several physiological and pathological conditions.
The Type III Secretion System (T3SS) ofChlamydophila psittaciIs Involved in the Host Inflammatory Response by Activating the JNK/ERK Signaling Pathway
Authors: He Qing-zhi , Zeng Huai-cai , Huang Yan , Hu Yan-qun , Wu Yi-mou
Published: January 2015

Chlamydophila psittaci(C. psittaci) is a human zoonotic pathogen, which could result in severe respiratory disease. In the present study, we investigated the role and mechanism of the type III secretion system (T3SS) ofC. psittaciin regulating the inflammatory response in host cells.C. psittaci-infected THP-1 cells were incubated with the specific T3SS inhibitor INP0007, inhibitors of ERK, p38, or JNK, and the levels of inflammatory cytokines were analyzed using Q-PCR and ELISA. The levels of ERK, p38, and JNK phosphorylation were analyzed by Western blot. Our results verified that INP0007 inhibited chlamydial growthin vitro, but the coaddition of exogenous iron completely reversed the growth deficit. INP0007 inhibited the growth ofC. psittaciand decreased the levels of IL-8, IL-6, TNF-α, and IL-1β. Exogenous iron restored the chlamydial growth but not the production of inflammatory cytokines. These results demonstrated that the expression of inflammatory cytokines during infection was associated with the T3SS which reduced by incubation with ERK and JNK inhibitors, but not with p38 inhibitor. We concluded that the T3SS elicited inflammatory responses by activating the JNK or ERK signaling pathways in the infection ofC. psittaci.
Dictionary-Based, Clustered Sparse Representation for Hyperspectral Image Classification
Authors: Qin Zhen-tao , Yang Wu-nian , Yang Ru , Zhao Xiang-yu , Yang Teng-jiao
Published: January 2015

This paper presents a new, dictionary-based method for hyperspectral image classification, which incorporates both spectral and contextual characteristics of a sample clustered to obtain a dictionary of each pixel. The resulting pixels display a common sparsity pattern in identical clustered groups. We calculated the image’s sparse coefficients using the dictionary approach, which generated the sparse representation features of the remote sensing images. The sparse coefficients are then used to classify the hyperspectral images via a linear SVM. Experiments show that our proposed method of dictionary-based, clustered sparse coefficients can create better representations of hyperspectral images, with a greater overall accuracy and a Kappa coefficient.
Synthesis and Photocatalytic Activity of Mo-Doped TiO2Nanoparticles
Authors: Huang Ji-guo , Guo Xue-ting , Wang Bo , Li Lin-yang , Zhao Mei-xia , Dong Li-li , Liu Xing-juan , Huang Yu-ting
Published: January 2015

The undoped and Mo-doped TiO2nanoparticles were synthesized by sol-gel method. The as-prepared samples were characterized by X-ray diffraction (XRD), diffuse reflectance UV-visible absorption spectra (UV-vis DRS), X-ray photoelectron spectra (XPS), and transmission electron microscopy (TEM). The photocatalytic activity was evaluated by photocatalytic degradation of methylene blue under irradiation of a 500 W xenon lamp and natural solar light outdoor. Effects of calcination temperatures and Mo doping amounts on crystal phase, crystallite size, lattice distortion, and optical properties were investigated. The results showed that most of Mo6+took the place of Ti4+in the crystal lattice of TiO2, which inhibited the growth of crystallite size, suppressed the transformation from anatase to rutile, and led to lattice distortion of TiO2. Mo doping narrowed the band gap (from 3.05 eV of TiO2to 2.73 eV of TiMo0.02O) and efficiently increased the optical absorption in visible region. Mo doping was shown to be an efficient method for degradation of methylene blue under visible light, especially under solar light. When the calcination temperature was 550°C and the Mo doping amount was 2.0%, the Mo-doped TiO2sample exhibited the highest photocatalytic activity.
Solubility Characteristics and Slow-Release Mechanism of Nitrogen from Organic-Inorganic Compound Coated Urea
Authors: Zou Hongtao , Ling Yao , Dang Xiuli , Yu Na , Zhang YuLing , Zhang YuLong , Dong Jianghui
Published: January 2015

A soil incubation method was used to investigate the solubility characteristics and slow-release mechanism of organic-inorganic compound coated urea at temperature of 10, 20, and 30°C. The membrane microstructure with and without incubation was tested via scanning electron microscopy (SEM). Slow release of nitrogen (N) from different inorganic minerals was analysed by the activation energy from the nutrient solubility system. The rate of nitrogen solubility increased with temperature increasing. The first-order reaction kinetic equation described the solubility process of coated urea. The rate constantkalso increased with temperature increasing. Moreover, the SEM images showed that the microstructure of the coating layer changed into a flocculent structure and the number of tiny pores and holes on the membrane surface increased significantly with temperature increasing, which increased N solubility rate. The Arrhenius equation indicated that activation energy was closely related tokduring the solubility process; the activation energy was reduced withkrising, which resulted in N solubility rate increasing. Overall, the N solubility rate of coated urea was affected by temperature.
Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model
Authors: Koskimäki Janne , Tarkia Miikka , Ahtola-Sätilä Tuula , Saloranta Lasse , Simola Outi , Forsback Ari-Pekka , Laakso Aki , Frantzén Janek
Published: January 2015

Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. Thein vitrocharacteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implantsin vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant.
Effectiveness of Functional Electrical Stimulation in Improving Clinical Outcomes in the Upper Arm following Stroke: A Systematic Review and Meta-Analysis
Authors: Vafadar Amir K. , Côté Julie N. , Archambault Philippe S.
Published: January 2015

Background.Different therapeutic methods are being used to prevent or decrease long-term impairments of the upper arm in stroke patients. Functional electrical stimulation (FES) is one of these methods, which aims to stimulate the nerves of the weakened muscles so that the resulting muscle contractions resemble those of a functional task.Objectives.The objective of this study was to review the evidence for the effect of FES on (1) shoulder subluxation, (2) pain, and (3) upper arm motor function in stroke patients, when added to conventional therapy.Methods.From the 727 retrieved articles, 10 (9 RCTs, 1 quasi-RCT) were selected for final analysis and were rated based on the PEDro (Physiotherapy Evidence Database) scores and the Sackett’s levels of evidence. A meta-analysis was performed for all three considered outcomes.Results.The results of the meta-analyses showed a significant difference in shoulder subluxation in experimental groups compared to control groups, only if FES was applied early after stroke. No effects were found on pain or motor function outcomes.Conclusion.FES can be used to prevent or reduce shoulder subluxation early after stroke. However, it should not be used to reduce pain or improve upper arm motor function after stroke.
A Case of Primary Renal Carcinoid Tumor
Authors: Tanaka Toshikazu , Yamamoto Hayato , Imai Atsushi , Shingo Hatakeyama , Yoneyama Takahiro , Koie Takuya , Hashimoto Yasuhiro , Ohyama Chikara
Published: January 2015

Primary renal carcinoid tumors are extremely rare kidney lesions, with fewer than 100 reported cases previously. We describe a 75-year-old man with an incidentally detected cystic renal mass. Computed tomography showed a 3 cm tumor with a cystic component enhanced with contrast. No evidence of metastasis was detected. We treated the patient with radical nephrectomy. Pathological examinations revealed a cellular arrangement specific to carcinoid tumor and positive for chromogranin A, neural cell adhesion molecule, and somatostatin receptor type 2. The tumor cells had a mitotic count of 4 mitoses/10 high-power fields, and the level of the proliferation marker Ki-67 was 5%. The pathological diagnosis was renal neuroendocrine tumor grade 2. No local recurrence and no systemic metastasis were detected during the 18-month follow-up period. To our knowledge, this is the 6th case of renal neuroendocrine grade 2 tumor reported thus far.
Breast MRI in Patients with Unilateral Bloody and Serous-Bloody Nipple Discharge: A Comparison with Galactography
Authors: Manganaro Lucia , D’Ambrosio Ilaria , Gigli Silvia , Di Pastena Francesca , Giraldi Guglielmo , Tardioli Stefano , Framarino Marialuisa , Porfiri Lucio Maria , Ballesio Laura
Published: January 2015

Purpose. Assessing the role of breast MRI compared to galactography in patients with unilateral bloody or serous-bloody nipple discharge.Materials and Methods. Retrospective study including 53 unilateral discharge patients who performed galactography and MRI. We evaluated the capability of both techniques in identifying pathology and distinguishing between nonmalignant and malignant lesions. Lesions BIRADS 1/2 underwent follow-up, while the histological examination after surgery has been the gold standard to assess pathology in lesions BIRADS 3/4/5. The ROC analysis was used to test diagnostic MRI and galactography ability.Results. After surgery and follow-up, 8 patients had no disease (15%), 23 papilloma (43%), 11 papillomatosis (21%), 5 ductal cancer in situ (10%), and 6 papillary carcinoma (11%) diagnoses. Both techniques presented 100% specificity; MRI sensitivity was 98% versus 49% of galactography. Considering MRI, we found a statistical association between mass enhancement and papilloma (P<0.001; AUC 0.957; CI 0.888–1.025), ductal enhancement and papillomatosis (P<0.001; AUC 0.790; CI 0.623–0.958), segmental enhancement and ductal cancer in situ (P=0.007; AUC 0.750; CI 0.429–1.071), and linear enhancement and papillary cancer (P=0.011).Conclusions. MRI is a valid tool to detect ductal pathologies in patients with suspicious bloody or serous-bloody discharge showing higher sensitivity and specificity compared to galactography.
Effect of Rat Medicated Serum Containing Zuo Gui Wan and/or You Gui Wan on the Differentiation of Stem Cells Derived from Human First Trimester Umbilical Cord into Oocyte-Like CellsIn Vitro
Authors: Hu Xiang , Lu Hua , Deng Yan-li , Wan Qian , Yie Shang-mian
Published: January 2015

Zuo Gui Wan (ZGW) and You Gui Wan (YGW) are two classic formulas used in clinical treatment of infertility in traditional Chinese medicine (TCM). However, the actions of the formulas remain to be proven at the cellular and molecular levels. In this study, we investigate whether the two formulas have any effect on germ cell formation and differentiation by culturing rat medicated serums containing YGW or ZGW with stem cells derived from human first trimester umbilical cord. Our results showed that while the normal rat serums had no significant effects, the rat medicated serums had significant effects on the differentiation of the stem cells into oocyte-like cells (OLCs) based on (1) cell morphological changes that resembled purative cumulus-oocyte complexes (COCs); (2) expressions of specific markers that were indicative of germ cell formation and oocyte development; and (3) estradiol production by the COC-like cells. Furthermore, ZGW medicated serums exhibited more obvious effects on specific gene expressions of germ cells, whereas YGW medicated serums showed stronger effects on estradiol production. Accordingly, our study provides evidence demonstrating for the first time that one of molecular and cellular actions of YGW or ZGW in treating human reproductive dysfunctions may be through an enhancement of neooogenesis.
Smaller Anterior Cruciate Ligament Diameter Is a Predictor of Subjects Prone to Ligament Injuries: An Ultrasound Study
Authors: Mahajan Parag Suresh , Chandra Prem , Negi Vidya Chander , Jayaram Abhilash Pullincherry , Hussein Sheik Akbar
Published: January 2015

Purpose. To test if diameter of normal anterior cruciate ligament (ACL) can be measured by ultrasound (US), to see if there is a relationship between smaller ACL diameter and ACL injury, and to assess agreement between radiologists in measuring ACL diameter in cases and matched controls.Materials and Methods. In this ethics committee-approved study, maximum diameter of ACL near tibial insertion site was measured by static and dynamic US study in 25 normal contralateral knees of subjects who suffered noncontact ACL injury and in 25 matched control subjects.Results. ACL was visualized as a thick linear hypoechoic band inserted approximately 11 mm caudal to the tibial plateau and the intercondylar eminence. Maximum diameter of contralateral ACL near tibial insertion site among injured subjects was significantly smaller than in noninjured subjects (0.62 ± 0.07 cm versus 0.81 ± 0.06 cm;P<0.0001). In the regression analysis, the diameter of ACL near tibial insertion site was found significantly proportional to body weight and not significantly associated to height, gender, and age.Conclusion. Diameter of normal ACL near tibial insertion site can be measured by US and the maximum diameter is significantly smaller among subjects with noncontact ACL injury. US is a promising modality that can be used as an excellent screening test to detect subjects especially aspiring athletes prone to ACL injury. Very strong agreement was observed between radiologists in measuring ACL diameter.
Transgenic Sugarcane Resistant toSorghum mosaic virusBased on Coat Protein Gene Silencing by RNA Interference
Authors: Guo Jinlong , Gao Shiwu , Lin Qinliang , Wang Hengbo , Que Youxiong , Xu Liping
Published: January 2015

As one of the critical diseases of sugarcane, sugarcane mosaic disease can lead to serious decline in stalk yield and sucrose content. It is mainly caused byPotyvirus sugarcane mosaic virus(SCMV) and/orSorghum mosaic virus(SrMV), with additional differences in viral strains. RNA interference (RNAi) is a novel strategy for producing viral resistant plants. In this study, based on multiple sequence alignment conducted on genomic sequences of different strains and isolates of SrMV, the conserved region of coat protein (CP) genes was selected as the target gene and the interference sequence with size of 423 bp in length was obtained through PCR amplification. The RNAi vector pGII00-HACP with an expression cassette containing both hairpin interference sequence andcp4-epspsherbicide-tolerant gene was transferred to sugarcane cultivar ROC22 viaAgrobacterium-mediated transformation. After herbicide screening, PCR molecular identification, and artificial inoculation challenge, anti-SrMV positive transgenic lines were successfully obtained. SrMV resistance rate of the transgenic lines with the interference sequence was 87.5% based on SrMV challenge by artificial inoculation. The genetically modified SrMV-resistant lines of cultivar ROC22 provide resistant germplasm for breeding lines and can also serve as resistant lines having the same genetic background for study of resistance mechanisms.
Voluminous Omental Inflammatory Myofibroblastic Tumor in an Elderly Man: A Case Report and Literature Review
Authors: Cianci Pasquale , Ambrosi Antonio , Fersini Alberto , Tartaglia Nicola , Lizzi Vincenzo , Sanguedolce Francesca , Parafioriti Antonina , Neri Vincenzo
Published: January 2015

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm of intermediate biologic potential, with uncertain etiology. This tumor occurs primarily in the lung, but the tumor may affect any organ system. A 75-year-old male was evaluated for voluminous palpable high abdominal mass with continuous and moderately abdominal pain, associated with abdominal distension for the last two months. Abdominal computed tomography showed a large (32×29×15 cm) heterogeneously enhanced mass with well-defined margins. At surgery, the mass originated from the greater omentum was completely excised. Histologically the tumor was a mesenchymal neoplasm in smooth muscle differentiation and was characterized by spindle-cell proliferation with lymphocytes, plasma cells, and rare eosinophils. Immunohistochemically, the tumor cells were positive for vimentin and smooth muscle actin and negative for anaplastic lymphoma kinase. Complete surgical resection of IMTs remains the mainstay of treatment associated with a low rate of recurrence. Final diagnosis should be based on histopathological and immunohistochemical findings. Appropriate awareness should be exercised by surgeons to abdominal IMTs in combination with constitutional symptoms, abnormal hematologic findings, and radiological definition, to avoid misdiagnosed.
Minimal Length Effects on Tunnelling from Spherically Symmetric Black Holes
Authors: Mu Benrong , Wang Peng , Yang Haitang
Published: January 2015

We investigate effects of the minimal length on quantum tunnelling from spherically symmetric black holes using the Hamilton-Jacobi method incorporating the minimal length. We first derive the deformed Hamilton-Jacobi equations for scalars and fermions, both of which have the same expressions. The minimal length correction to the Hawking temperature is found to depend on the black hole’s mass and the mass and angular momentum of emitted particles. Finally, we calculate a Schwarzschild black hole's luminosity and find the black hole evaporates to zero mass in infinite time.
Lentiviral-Mediated Silencing of Farnesyl Pyrophosphate Synthase through RNA Interference in Mice
Authors: Yang Jian , Zhao Chen-Ze , Chen Bin , Chen Fei , Han Jie , Hu Shen-Jiang
Published: January 2015

Farnesyl pyrophosphate synthase (FPPS) plays a vital role in the mevalonate pathway and has been shown to be involved in hypertrophy and cardiovascular diseases. Lentivirus-mediated RNA interference (RNAi) to knock down a gene of interest has become a promising new tool for the establishment of transgenic animals. The interfering fragment, named pLVT202, was chosen from cardiomyocytes tested in vitro and was microinjected into the perivitelline space of zygotes from C57BL/6J mice via a lentivirus vehicle; 20 were identified as carrying copies of the transgene using the polymerase chain reaction (PCR). Real-time PCR and western blotting analysis showed that FPPS was downregulated in multiple tissues in the transgenic mice. The transgenic mouse model provides a novel means of studying the gene function of FPPS.
Elevation of Tim-3 and PD-1 Expression on T Cells Appears Early in HIV Infection, and Differential Tim-3 and PD-1 Expression Patterns Can Be Induced by Commonγ-Chain Cytokines
Authors: Zhang Zi-Ning , Zhu Ming-Lu , Chen Yan-Hong , Fu Ya-Jing , Zhang Tong-Wei , Jiang Yong-Jun , Chu Zhen-Xing , Shang Hong
Published: January 2015

Purpose. To explore the association between differential Tim-3 and PD-1 expression patterns and HIV disease progression, and to investigate the impact of commonγ-chain cytokines on Tim-3 and PD-1 expression patterns on T cells.Methods. Tim-3/PD-1 expression on the T cells of patients with early and chronic HIV infections was detected. The expression levels and functional profiles of T cells with differential Tim-3 and PD-1 expression patterns induced byγ-chain cytokines were studied.Results. The elevation of differential Tim-3 and PD-1 expression patterns on T cells appeared early in HIV infection. Co-expression of Tim-3 and PD-1 (Tim-3+PD-1+) correlates with more severe exhaustion of T cells during HIV infection. In vitro stimulation of commonγ-chain cytokines can induce differential expression patterns of Tim-3 and PD-1 on T cells. The enhancement of Tim-3 and PD-1 expression by commonγ-chain IL-2 can inhibit the function of T cells re-stimulated by HIV gag and TCR, not by the re-stimulation of IL-2.Conclusions. The elevation of differential Tim-3 and PD-1 expression patterns on T cells represents a state of T cell exhaustion and can be induced by commonγ-chain cytokines. These findings provide insights into HIV pathogenesis and help inform immune intervention strategies.
Serum/Plasma MicroRNAs as Biomarkers for HBV-Related Hepatocellular Carcinoma in China
Authors: Yin Wen , Zhao Yan , Ji Yong-Jing , Tong Li-Ping , Liu Ya , He Shui-Xiang , Wang Ai-Qin
Published: January 2015

MicroRNAs (miRNAs) are a group of small RNAs with a fundamental role in the regulation of gene expression. These RNAs have been shown to participate in various cellular and physiological processes, including cellular development, apoptosis, proliferation, and differentiation. Aberrant expression of several miRNAs was found to be involved in a large variety of neoplasms, including hepatocellular carcinoma (HCC). Previous studies have shown the existence of a large amount of stable miRNAs in human serum/plasma, which laid the foundation for studying the role of serum/plasma miRNAs in the diagnosis and prognosis of HCC. Here, we review the recent progress in research on serum miRNAs as biomarkers for HCC in Chinese patients.
Genetic and Pharmacologic Inhibition of eIF4E Reduces Breast Cancer Cell Migration, Invasion, and Metastasis
Authors: Pettersson Filippa , del Rincon Sonia V. , Emond Audrey , Huor Bonnie , Ngan Elaine , Ng Jonathan , Dobocan Monica C. , Siegel Peter M. , Miller Wilson H.
Published: January 2015

The translation initiation factor eIF4E is an oncogene that is commonly overexpressed in primary breast cancers and metastases. In this article, we report that a pharmacologic inhibitor of eIF4E function, ribavirin, safely and potently suppresses breast tumor formation. Ribavirin administration blocked the growth of primary breast tumors in several murine models and reduced the development of lung metastases in an invasive model. Mechanistically, eIF4E silencing or blockade reduced the invasiveness and metastatic capability of breast cancer cells in a manner associated with decreased activity of matrix metalloproteinase (MMP)-3 and MMP-9. Furthermore, eIF4E silencing or ribavirin treatment suppressed features of epithelial-to-mesenchymal transition, a process crucial for metastasis. Our findings offer a preclinical rationale to explore broadening the clinical evaluation of ribavirin, currently being tested in patients with eIF4E-overexpressing leukemia, as a strategy to treat solid tumors such as metastatic breast cancer. Cancer Res; 75(6); 1102–12. ©2015 AACR.
Trabectedin Efficacy in Ewing Sarcoma Is Greatly Increased by Combination with Anti-IGF Signaling Agents
Authors: Amaral Ana Teresa , Garofalo Cecilia , Frapolli Roberta , Manara Maria Cristina , Mancarella Caterina , Uboldi Sarah , Giandomenico Silvana Di , Ordóñez Jose Luis , Sevillano Victoria , Malaguarnera Roberta , Picci Piero , Hassan A. Bass , Alava Enrique De , D'Incalci Maurizio , Scotlandi Katia
Published: January 2015

Purpose: Goal of this study was to identify mechanisms that limit efficacy of trabectedin (ET-743, Yondelis) in Ewing sarcoma (EWS), so as to develop a clinical applicable combination therapy.

Experimental Design: By chromatin immunoprecipitation, we analyzed EWS–FLI1 binding to the promoters of several target genes, such as TGFβR2, CD99, insulin-like growth factor receptor 1 (IGF1R), and IGF1, both in vitro and in xenografts treated with trabectedin or doxorubicin. Combined therapy with trabectedin and anti-IGF1R agents (AVE1642 HAb; OSI-906) was tested in vitro and in xenografts.

Results: We confirm that both trabectedin and doxorubicin were able to strongly reduce EWS–FLI1 (both type I and type II) binding to two representative target genes (TGFβR2 and CD99), both in vitro and in xenografts. However, trabectedin, but not doxorubicin, was also able to increase the occupancy of EWS–FLI1 to IGF1R promoters, leading to IGF1R upregulation. Inhibition of IGF1R either by the specific AVE1642 human antibody or by the dual IGF1R/insulin receptor inhibitor OSI-906 (Linsitinib) greatly potentiate the efficacy of trabectedin in the 13 EWS cell lines here considered as well as in TC-71 and 6647 xenografts. Combined therapy induced synergistic cytotoxic effects. Trabectedin and OSI-906 deliver complementary messages that likely converge on DNA-damage response and repair pathways.

Conclusions: We showed that trabectedin may not only inhibit but also enhance the binding of EWS–FLI1 to certain target genes, leading to upregulation of IGF1R. We here provide the rationale for combining trabectedin to anti-IGF1R inhibitors. Clin Cancer Res; 21(6); 1373–82. ©2015 AACR.
The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood–Brain Barrier in Glioblastoma
Authors: Pokorny Jenny L. , Calligaris David , Gupta Shiv K. , Iyekegbe Dennis O. , Mueller Dustin , Bakken Katrina K. , Carlson Brett L. , Schroeder Mark A. , Evans Debra L. , Lou Zhenkun , Decker Paul A. , Eckel-Passow Jeanette E. , Pucci Vincenzo , Ma Bennett , Shumway Stuart D. , Elmquist William F. , Agar Nathalie Y.R. , Sarkaria Jann N.
Published: January 2015

Purpose: Wee1 regulates key DNA damage checkpoints, and in this study, the efficacy of the Wee1 inhibitor MK-1775 was evaluated in glioblastoma multiforme (GBM) xenograft models alone and in combination with radiation and/or temozolomide.

Experimental Design: In vitro MK-1775 efficacy alone and in combination with temozolomide, and the impact on DNA damage, was analyzed by Western blotting and γH2AX foci formation. In vivo efficacy was evaluated in orthotopic and heterotopic xenografts. Drug distribution was assessed by conventional mass spectrometry (MS) and matrix-assisted laser desorption/ionization (MALDI)-MS imaging.

Results: GBM22 (IC50 = 68 nmol/L) was significantly more sensitive to MK-1775 compared with five other GBM xenograft lines, including GBM6 (IC50 >300 nmol/L), and this was associated with a significant difference in pan-nuclear γH2AX staining between treated GBM22 (81% cells positive) and GBM6 (20% cells positive) cells. However, there was no sensitizing effect of MK-1775 when combined with temozolomide in vitro. In an orthotopic GBM22 model, MK-1775 was ineffective when combined with temozolomide, whereas in a flank model of GBM22, MK-1775 exhibited both single-agent and combinatorial activity with temozolomide. Consistent with limited drug delivery into orthotopic tumors, the normal brain to whole blood ratio following a single MK-1775 dose was 5%, and MALDI-MS imaging demonstrated heterogeneous and markedly lower MK-1775 distribution in orthotopic as compared with heterotopic GBM22 tumors.

Conclusions: Limited distribution to brain tumors may limit the efficacy of MK-1775 in GBM. Clin Cancer Res; 21(8); 1916–24. ©2015 AACR.
Non-Invasive Spectroscopic Determination of the Antioxidative Status of Gravidae and Neonates
Authors: Lademann Hanne , Gerber Bernd , Olbertz Dirk M. , Darvin Maxim E. , Stauf Leonie , Ueberholz Kirsten , Heinrich Verena , Lademann Jürgen , Briese Volker
Published: January 2015

Pregnancy and postpartum adaptation cause an increased formation of free radicals. This is associated with various perinatological diseases, e.g. necrotising enterocolitis. The human body has developed a protective system in the form of the antioxidative potential. The present study was the first to investigate the kinetics of the cutaneous antioxidative status in pregnant women and newborns using a non-invasive spectroscopic method. Eighteen pregnant women and their babies took part in the study. A light-emitting diode-based compact scanner system was used for quick non-invasive measurements of carotenoid antioxidants in human skin based on reflection spectroscopy. It could be shown that the antioxidative status of the expectant mothers significantly declined during labour (p < 0.001) and on day 1 after delivery (p < 0.01). Compared to the mothers, the newborns exhibited a significantly higher cutaneous carotenoid concentration on both day 1 (p < 0.01) and 5 (p < 0.01) after delivery. These results suggest that the oxidative stress due to postpartum adaptation is counteracted by an enhanced reservoir of carotenoid antioxidants in the subcutaneous fatty tissue. The peripartum cutaneous carotenoid level of mothers declines continuously, whereas term newborns show very high cutaneous antioxidant values.
High Sucrose Intake at 3 Years of Age Is Associated with Increased Salivary Counts of Mutans Streptococci and Lactobacilli, and with Increased Caries Rate from 3 to 16 Years of Age
Authors: Karjalainen Sára , Tolvanen Mimmi , Pienihäkkinen Kaisu , Söderling Eva , Lagström Hanna , Simell Olli , Niinikoski Harri
Published: January 2015

Objective: We aimed to study the long-term associations between sucrose intake (SI), selected representatives of the cariogenic oral flora, and the dental health of children from 3 to 16 years of age. Methods: At 7 months of age 1,062 infants (540 intervention; 522 controls) were included in the prospective, randomised STRIP-project aimed at restricting the child's saturated fat and cholesterol intake to prevent atherosclerosis when they become adults. At 3 years of age, every fifth child was invited (n = 178) to an oral sub-study, and 148 (78 boys) children attended. A restudy was conducted on 135 children aged 6, 127 aged 9, 114 aged 12 and 88 aged 16. SI using 4-day food records, plate-cultured mutans streptococci (MS), salivary lactobacilli (LB) and yeasts using commercial kits (Orion Diagnostica, Espoo Finland), toothbrushing frequency using fluoridated toothpaste and dental health expressed as d3mft/D3MFT were regularly recorded. Results: The SI of children whose intake was ≥10 E% (high SI) at 3 years remained high throughout the entire follow-up (p < 0.001, GLM for repeated measures) period, and they had higher salivary MS and LB counts (p = 0.024 and p = 0.068, respectively, GLM) than their counterparts whose SI was below 10 E% (low SI). No differences in toothbrushing habits were found between the high and low SI-groups. Caries-survival was strongly associated with low 6-year-counts of MS (p = 0.008, Cox regression analysis), and the d3mft/D3MFT-scores of the high SI-group were higher than those of the low SI-group (p = 0.046, GLM). Conclusions: High SI at 3 years was associated with high MS-counts (≥105 cfu/ml) and with a high risk for caries.
Microwave Ablation for Twin-Reversed Arterial Perfusion Sequence: A Novel Application of Technology
Authors: Stephenson Courtney D. , Temming Lorene A. , Pollack Rebecca , Iannitti David A.
Published: January 2015

Introduction: Twin-reversed arterial perfusion sequence is a rare complication of monochorionic pregnancies that is characterized by the presence of an acardiac mass perfused by an apparently normal pump twin. The risk of death to the pump twin has led to a range of therapeutic interventions aimed at separating their vascular connection. We report a novel application of microwave ablation for vessel coagulation in the treatment of twin-reversed arterial perfusion sequence. Material and Methods: Microwave ablation has been adopted by surgical subspecialties as a superior energy source for vessel and tissue ablation as it creates heat without a circuit and has less thermal spread. We describe the use of a 2.45-GHz microwave system using a 1.8-mm antenna to coagulate the intra-abdominal portion of umbilical vessels of the acardiac mass. Results: We report 6 cases of twin-reversed arterial perfusion sequence treated by microwave ablation. All patients were treated with microwave ablation with successful coagulation of intra-abdominal umbilical cord vessels of the acardiac mass with cessation of flow. Discussion: Microwave ablation is an excellent energy source for vessel coagulation due to its thermal properties and can be used effectively in the treatment of twin-reversed arterial perfusion sequence.
Natural History of Parkinson's Disease in the Province of Segovia: Disability in a 20 Years Longitudinal Study
Authors: Duarte Jacinto , García Olmos Luis Miguel , Mendoza Amelia , Martínez Pueyo Ángel , Clavería Luis Erik
Published: January 2015

Background: Parkinson's disease mainly affects the elderly population causing a progressive functional disability with motor, psychic, and cognitive deterioration. Objective: This study was carried out to evaluate disability caused by Parkinson's disease by analyzing the median time to reach Hoehn and Yahr stage III and to investigate predictor variables based on a 20-year longitudinal follow-up study. Methods: We examined 273 patients with Parkinson's disease recruited between 1978 and 1998. We performed a survival analysis using the Kaplan-Meier method to determine the time to disability and we used a Cox regression model to adjust prognosis factors. Results: The median time to reach Hoehn and Yahr stage III was 7.73 years (95% CI: 5.95-8.05). Independent predictors of disability were: age at onset, the hazard ratio (HR) = 1.10, 95% CI: 1.08-1.12; UPDRS II (activities of daily living) HR = 1.08, 95% CI: 1.03-1.14; and akinesia and rigidity at onset HR = 1.55, 95% CI: 1.07-2.24. Conclusions: Patients with Parkinson's disease evolve gradually toward disability, and prognostic factors of this evolution were identified.
The Relationship between Obstructive Sleep Apnea Syndrome and Apolipoprotein E Genetic Variants
Authors: Uyrum Ebru , Balbay Oner , Annakkaya Ali Nihat , Gulec Balbay Ege , Silan Fatma , Arbak Peri
Published: January 2015

Background: Clinical and epidemiological studies indicate that obstructive sleep apnea syndrome (OSAS) has a strong genetic basis. Objectives: To investigate the apolipoprotein E (APOE) alleles as a genetic risk factor in OSAS. Methods: A total of 73 patients (37 male) were included. All underwent full-night polysomnography and were evaluated for APOE alleles. Results: The mean age was 51 ± 12 years. Forty-two of the patients had OSAS. The APOE3 allele was found in 97.3% (71/73) of the study population. The most common APOE genotype was E3/E3 (55/73, 75.3%). Compared to the individuals with no APOE2 alleles (E3/E3, E3/E4), the individuals with at least one APOE2 allele (E2/E3, E2/E4) had a 9.37-fold greater OSAS risk (OR = 9.37, 95% CI 1.13-77.7, p = 0.019). The individuals with APOE2 alleles (E2/E3, E2/E4) compared to the individuals with only an E3/E3 allele genotype had a 10-fold greater OSAS risk (OR = 10.3, 95% CI 1.24-86.61, p = 0.0308). Compared to the individuals with no APOE4 alleles (E2/E3, E3/E3), the individuals with APOE4 alleles (E2/E4, E3/E4) had a high but insignificant risk for OSAS (OR = 2.9, 95% CI 0.55-15.05, p = 0.286). The individuals with APOE4 alleles (E2/E4, E3/E4) compared to APOE3 alleles (E3/E3) had an increased but insignificant risk for OSAS (OR = 3.62, 95% CI 0.96-19.05, p = 0.127). Conclusion: Specific APOE genotypes are associated with OSAS in a high-risk population.
Clinical Significance of First-Trimester Screening of the Retronasal Triangle for Identification of Primary Cleft Palate
Authors: Li Wei-Jing , Wang Xue-Qin , Yan Rui-Ling , Xiang Jing-Wen
Published: January 2015

Objective: To investigate the use of the retronasal triangle (RNT) for identification of orofacial cleft (OC) in the first trimester and the clinical application of three-dimensional (3D) ultrasound techniques for confirming the diagnosis of OC. Methods: A total of 5,054 women with singleton pregnancies underwent first-trimester screening for Down syndrome at 11-13+6 weeks. The RNT was scanned in each fetus, and 3D volumetric images of cases with abnormal or indeterminate RNT were obtained. Results: Satisfactory images were obtained from all cases. Seven cases (1.4‰) of abnormal RNT were diagnosed as OC in the first trimester, which were confirmed at a 16 weeks scan or at a postmortem examination. One case that was considered a normal RNT was diagnosed with OC at 22+2 weeks and after term delivery. Six cases of indeterminate RNT were diagnosed as normal by 3D ultrasound. Identification of OC by visualization of the RNT in the first trimester had a sensitivity of 87.5% and a specificity of 99.9%. Conclusion: The RNT is an important sonographic landmark that has a high sensitivity and specificity for the detection of OC in the first trimester. 3D ultrasound is an important tool that aids in confirming diagnosis of OC in the first and second trimesters.
Percutaneous Treatment of Common Bile Duct Stones: Results and Complications in 110 Consecutive Patients
Authors: Kint Johan F. , van den Bergh Janneke E. , van Gelder Rogier E. , Rauws Erik A. , Gouma Dirk J. , van Delden Otto M. , Laméris Johan S.
Published: January 2015

Background/Aims: Choledocholithiasis is a common complication of cholecystolithiasis, occurring in 15-20% of patients who have gallbladder stones. Endoscopic retrograde cholangio-pancreatography is the standard treatment. When this is not possible or not feasible, percutaneous transhepatic stone removal is an alternative treatment. In this retrospective study, we analyze 110 patients who were treated with percutaneous transhepatic removal of Common Bile Duct (CBD) stones. Patients and Methods: Between March 1998 and September 2013 110 patients (61 men, 49 women; aged 14-96, mean age 69.7 years) with confirmed bile duct stones were included. PTC was done using ultrasound and fluoroscopy. Balloon dilatation of the papilla was done with 8-12 mm balloons. If stone size exceeded 10 mm, mechanical lithotripsy was performed. Stones were then removed by percutaneous extraction or evacuation into the duodenum. Results: In 104 patients (104/110; 94.5%) total stone clearance of the CBD was achieved. A total of 12 complications occurred (10.9%), graded with the Clavien-Dindo scale as IVa, IVb, and V, respectively; hypoxia requiring resuscitation, sepsis and death due to ongoing cholangiosepsis (n = 1, 4, 1). Minor complications I, II, and IIIa included: small liver abscess, pleural empyema, transient hemobilia and mild fever (n = 1, 1, 2, 2). Conclusion: Percutaneous removal of CBD stones is an effective alternative treatment, when endoscopic treatment is contra-indicated, fails or is not feasible. It is effective, has a low complication rate and using deep sedation potentially requires only a very limited number of treatment sessions.
Cleft Lip/Palate, Short Stature, and Developmental Delay in a Boy with a 5.6-Mb Interstitial Deletion Involving 10p15.3p14
Authors: Gamba Bruno F. , Rosenberg Carla , Costa Silvia , Richieri-Costa Antonio , Ribeiro-Bicudo Lucilene A.
Published: January 2015

The chromosome interval 10p15.3p14 harbors about a dozen genes. This region has been implicated in a few well-known human phenotypes, namely HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) and DGS2 (DiGeorge syndrome 2), but a number of variable phenotypes have also been reported. Cleft lip/palate seems to be a very unusual finding within the clinical spectrum of patients with this deletion. Here, we report a male child born with short stature, cleft lip/palate, and feeding problems who was found to have a 5.6-Mb deletion at 10p15.3p14.
A Case of Pancreatic Intraepithelial Neoplasia That Was Difficult to Diagnose Preoperatively
Authors: Ito Hiroyuki , Kawaguchi Yoshiaki , Kawashima Yohei , Maruno Atsuko , Ogawa Masami , Hirabayashi Kenichi , Mine Tetsuya
Published: January 2015

A 63-year-old female patient presented to a local physician with pain in her back and epigastric region. An abdominal computed tomography (CT) scan revealed a pancreatic tumor, and the patient was referred to our hospital. Multiple imaging studies that included ultrasonography (US), CT, MRI, and endoscopic US revealed a cystic lesion 3-4 cm in size with node-like projections in the body of the pancreas. The distal main pancreatic duct was also found to be dilated. Endoscopic retrograde pancreatography revealed an irregular stenosis of the main pancreatic duct proximal to the cystic lesion, and malignancy was suspected. The patient was preoperatively diagnosed with pancreatic ductal carcinoma concomitant with intraductal papillary mucinous carcinoma, and a distal pancreatectomy was performed. Rapid pathological diagnosis during surgery revealed positive surgical margins for pancreatic intraepithelial neoplasia (PanIN). Further resection was performed twice, her surgical margin was positive and total pancreatectomy was ultimately conducted. Histopathological findings revealed diffuse microinvasive cancerous lesions corresponding to PanIN-2 (moderate dysplasia) to PanIN-3 (carcinoma in situ) throughout the pancreas. PanIN involves microlesions of the ductal epithelium that may precede pancreatic cancer. Ascertaining changes in PanIN using images provided by diagnostic modalities such as CT and US is challenging. Ductal stenosis and distal cystic lesions resulting from atrophy and fibrosis of pancreatic tissue were noted around PanIN. Considering the possibility of PanIN, a precancerous lesion during differential diagnosis will help to improve early detection and prognosis for patients with pancreatic cancer.