bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear survivin expression correlates with endoglin-assessed microvascularisation in laryngeal carcinoma
Authors: Marioni Gino , Ottaviano Giancarlo , Marchese-Ragona Rosario , Fasanaro Elena , Tealdo Giulia , Zanotti Claudia , Randon Benedetto , Giacomelli Luciano , Stellini Edoardo , Blandamura Stella 
Published: April 2017

AimsSurvivin—a member of the family of inhibitor of apoptosis proteins that control cell division, apoptosis and metastasis—is overexpressed in virtually all human cancers, including laryngeal squamous cell carcinoma (LSCC). Recent findings also correlate survivin expression with the regulation of angiogenesis. The novel main aim of this study was a preliminary investigation into the potential role of survivin expression in LSCC neoangiogenesis, as determined by endoglin-assessed microvascular density (MVD).MethodsImmunohistochemical expression of nuclear survivin and endoglin-assessed MVD were ascertained by image analysis in 75 consecutive LSCCs.ResultsStatistical analysis disclosed a strong direct correlation between nuclear survivin expression and MVD. Patients whose nuclear survivin expression was ≥6.0% had a significantly higher LSCC recurrence rate, and a significantly shorter disease-free survival (DFS) than those with a nuclear survivin expression <6.0%. The LSCC recurrence rate was also higher and the DFS shorter in patients with endoglin-assessed MVD ≥6.89%. The OR for recurrence was 2.79 in patients with LSCC with a nuclear survivin expression ≥6.0%, and 12.31 in those with an MVD≥6.89%.ConclusionsSurvivin-targeting strategies to enhance tumour cell response to apoptosis and inhibit tumour growth should receive more attention with a view to developing agents for use in multimodality advanced LSCC treatment, or combined with conventional chemotherapy. Given the present preliminary evidence in LSCC, survivin targeting should also be further investigated for anti-angiogenic purposes, to reduce tumour blood flow and induce cancer necrosis.
Parameter optimization of flux-aided backing-submerged arc welding by using Taguchi method
Authors: Pu Juan , Yu Shengfu , Li Yuanyuan 
Published: April 2017

Flux-aided backing-submerged arc welding has been conducted on D36 steel with thickness of 20 mm. The effects of processing parameters such as welding current, voltage, welding speed and groove angle on welding quality were investigated by Taguchi method. The optimal welding parameters were predicted and the individual importance of each parameter on welding quality was evaluated by examining the signal-to-noise ratio and analysis of variance (ANOVA) results. The importance order of the welding parameters for the welding quality of weld bead was: welding current [Formula: see text] welding speed [Formula: see text] groove angle [Formula: see text] welding voltage. The welding quality of weld bead increased gradually with increasing welding current and welding speed and decreasing groove angle. The optimum values of the welding current, welding speed, groove angle and welding voltage were found to be 1050 A, 27 cm/min, 40[Formula: see text] and 34 V, respectively.
Synthesis and luminescence properties of red-emitting K2MgSiO4:Eu3+ phosphors
Authors: Yang Rong , Tang Huidong 
Published: April 2017

A novel phosphor, K2MgSiO4:Eu[Formula: see text], was synthesized by a solid-state reaction method. The phase formation was checked by X-ray powder diffraction. The photoluminescence excitation, emission spectra, decay curve and CIE coordinates of samples with different Eu[Formula: see text] ion concentrations were investigated in detail. The excitation spectra show a broad wavelength range of 225–470 nm. The K2MgSiO4:Eu[Formula: see text] phosphors exhibit highly red emission peaking at about 616 nm which is assigned to the 5D[Formula: see text]F2 transition of Eu[Formula: see text]ions under the excitation of near-ultraviolet (NUV) (394 nm) light. The critical quenching concentration of Eu[Formula: see text] doped in the K2MgSiO4: Eu[Formula: see text] phosphors was about 10 mol.% and the concentration quenching mechanism was dipole–dipole interactions between Eu[Formula: see text] ions. The results indicate that K2MgSiO4:Eu[Formula: see text] is a potential red phosphor candidate for NUV-pumped white light emitting diodes.
Superconductivity in nitrogen-doped 3C–SiC from first-principles calculations
Authors: Liu Ning , Wang Wenjun , Guo Liwei , Peng Tonghua , Chen Xiaolong 
Published: April 2017

The electronic structure and the lattice dynamics of N-doped 3C–SiC have been studied using the first-principles calculations. Electrons are introduced to the conduction band bottom at the X-point of the Brillouin zone. It is revealed that the acoustical modes and optical modes soften upon N doping. The softened acoustical modes contribute over twice of what the optical modes do to the electron–phonon coupling strength. We predict that the superconductivity will occur with N doping concentration beyond about 3 at.% and the transition temperature can reach 11.36 K upon doping of N at about 5 at.% for 3C–SiC.
Biomechanical impact of provisional stenting and balloon dilatation on coronary bifurcation: clinical implications
Authors: Chen Henry Y. , Al-Saadon Khalid , Louvard Yves , Kassab Ghassan S. 
Published: April 2017

In-stent restenosis (ISR) and stent thrombosis remain clinically significant problems for bifurcations. Although the role of wall shear stress (WSS) has been well investigated, the role of circumferential wall stresses (CWS) has not been well studied in provisional stenting with and without final kissing balloon (FKB). We hypothesized that the perturbation of CWS at the SB in provisional stenting and balloon dilatation is an important factor in addition to WSS, and, hence, may affect restenosis rates (i.e., higher CWS correlates with higher restenosis). To test this hypothesis, we developed computational models of stent, FKB at bifurcation, and finite element simulations that considered both fluid and solid mechanics of the vessel wall. We computed the stress ratio (CWS/WSS) to show potential correlation with restenosis in clinical studies (i.e., higher stress ratio correlates with higher restenosis). Our simulation results show that stenting in the main branch (MB) increases the maximum CWS in the side branch (SB) and, hence, yields a higher stress ratio in the SB, as compared with the MB. FKB dilatation decreases the CWS and increases WSS, which collectively lowers the stress ratio in the SB. The changes of stress ratio were correlated positively with clinical data in provisional stenting and FKB. Both fluid and solid mechanics need to be evaluated when considering various stenting techniques at bifurcations, as solid stresses also play an important role in clinical outcome. An integrative index of bifurcation mechanics is the stress ratio that considers both CWS and WSS. NEW & NOTEWORTHY Although the role of wall shear stress (WSS) has been well investigated, the role of circumferential wall stresses (CWS) has not been well studied in provisional stenting with and without final kissing balloon. Both fluid and solid mechanics need to be evaluated when considering various stenting techniques at bifurcations. An integrative index of bifurcation mechanics is the stress ratio that considers both CWS and WSS.
Temporal integration and 1/fpower scaling in a circuit model of cerebellar interneurons
Authors: Maex Reinoud , Gutkin Boris 
Published: April 2017

Inhibitory interneurons interconnected via electrical and chemical (GABAAreceptor) synapses form extensive circuits in several brain regions. They are thought to be involved in timing and synchronization through fast feedforward control of principal neurons. Theoretical studies have shown, however, that whereas self-inhibition does indeed reduce response duration, lateral inhibition, in contrast, may generate slow response components through a process of gradual disinhibition. Here we simulated a circuit of interneurons (stellate and basket cells) of the molecular layer of the cerebellar cortex and observed circuit time constants that could rise, depending on parameter values, to >1 s. The integration time scaled both with the strength of inhibition, vanishing completely when inhibition was blocked, and with the average connection distance, which determined the balance between lateral and self-inhibition. Electrical synapses could further enhance the integration time by limiting heterogeneity among the interneurons and by introducing a slow capacitive current. The model can explain several observations, such as the slow time course of OFF-beam inhibition, the phase lag of interneurons during vestibular rotation, or the phase lead of Purkinje cells. Interestingly, the interneuron spike trains displayed power that scaled approximately as 1/ f at low frequencies. In conclusion, stellate and basket cells in cerebellar cortex, and interneuron circuits in general, may not only provide fast inhibition to principal cells but also act as temporal integrators that build a very short-term memory.NEW & NOTEWORTHY The most common function attributed to inhibitory interneurons is feedforward control of principal neurons. In many brain regions, however, the interneurons are densely interconnected via both chemical and electrical synapses but the function of this coupling is largely unknown. Based on large-scale simulations of an interneuron circuit of cerebellar cortex, we propose that this coupling enhances the integration time constant, and hence the memory trace, of the circuit.
tRF/miR-1280 Suppresses Stem Cell–like Cells and Metastasis in Colorectal Cancer
Authors: Huang Bingqing , Yang Huipeng , Cheng Xixi , Wang Dan , Fu Shuyu , Shen Wencui , Zhang Qi , Zhang Lijuan , Xue Zhenyi , Li Yan , Da Yurong , Yang Qing , Li Zesong , Liu Li , Qiao Liang , Kong Ying , Yao Zhi , Zhao Peng , Li Min , Zhang Rongxin 
Published: April 2017

Abstract
Several studies have shown that tRNAs can be enzymatically cleaved to generate distinct classes of tRNA-derived fragments (tRF). Here, we report that tRF/miR-1280, a 17-bp fragment derived from tRNALeu and pre-miRNA, influences Notch signaling pathways that support the function of cancer stem-like cells (CSC) in colorectal cancer progression. tRF/miR-1280 expression was decreased in human specimens of colorectal cancer. Ectopic expression of tRF/miR-1280 reduced cell proliferation and colony formation, whereas its suppression reversed these effects. Mechanistic investigations implicated the Notch ligand JAG2 as a direct target of tRF/miR-1280 binding through which it reduced tumor formation and metastasis. Notably, tRF/miR-1280–mediated inactivation of Notch signaling suppressed CSC phenotypes, including by direct transcriptional repression of the Gata1/3 and miR-200b genes. These results were consistent with findings of decreased levels of miR-200b and elevated levels of JAG2, Gata1, Gata3, Zeb1, and Suz12 in colorectal cancer tissue specimens. Taken together, our results established that tRF/miR-1280 suppresses colorectal cancer growth and metastasis by repressing Notch signaling pathways that support CSC phenotypes. Furthermore, they provide evidence that functionally active miRNA can be derived from tRNA, offering potential biomarker and therapeutic uses. Cancer Res; 77(12); 3194–206. ©2017 AACR.
Landscape of Combination Immunotherapy and Targeted Therapy to Improve Cancer Management
Authors: Colli Leandro M. , Machiela Mitchell J. , Zhang Han , Myers Timothy A. , Jessop Lea , Delattre Olivier , Yu Kai , Chanock Stephen J. 
Published: April 2017

Abstract
Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet. To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic datasets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide nonsynonymous mutations (NsM) that exceed a proposed threshold for response to checkpoint inhibitors. Overall, 8.9% of cases displayed profiles that could benefit from combination therapy, which corresponded to approximately 11.2% of U.S. annual incident cancer cases. Frequently targetable mutations were in PIK3CA, BRAF, NF1, NRAS, and PTEN. We also noted a high burden of NsM in cases with targetable mutations in SMO, DDR2, FGFR1, PTCH1, FGFR2, and MET. Our results indicate that a significant proportion of solid tumor patients are eligible for immuno-targeted combination therapy, and they suggest prioritizing specific cancers for trials of certain targeted and checkpoint inhibitor drugs. Cancer Res; 77(13); 3666–71. ©2017 AACR.
The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity
Authors: Holbeck Susan L. , Camalier Richard , Crowell James A. , Govindharajulu Jeevan Prasaad , Hollingshead Melinda , Anderson Lawrence W. , Polley Eric , Rubinstein Larry , Srivastava Apurva , Wilsker Deborah , Collins Jerry M. , Doroshow James H. 
Published: April 2017

Abstract
To date, over 100 small-molecule oncology drugs have been approved by the FDA. Because of the inherent heterogeneity of tumors, these small molecules are often administered in combination to prevent emergence of resistant cell subpopulations. Therefore, new combination strategies to overcome drug resistance in patients with advanced cancer are needed. In this study, we performed a systematic evaluation of the therapeutic activity of over 5,000 pairs of FDA-approved cancer drugs against a panel of 60 well-characterized human tumor cell lines (NCI-60) to uncover combinations with greater than additive growth-inhibitory activity. Screening results were compiled into a database, termed the NCI-ALMANAC (A Large Matrix of Anti-Neoplastic Agent Combinations), publicly available at https://dtp.cancer.gov/ncialmanac. Subsequent in vivo experiments in mouse xenograft models of human cancer confirmed combinations with greater than single-agent efficacy. Concomitant detection of mechanistic biomarkers for these combinations in vivo supported the initiation of two phase I clinical trials at the NCI to evaluate clofarabine with bortezomib and nilotinib with paclitaxel in patients with advanced cancer. Consequently, the hypothesis-generating NCI-ALMANAC web-based resource has demonstrated value in identifying promising combinations of approved drugs with potent anticancer activity for further mechanistic study and translation to clinical trials. Cancer Res; 77(13); 3564–76. ©2017 AACR.
Conjunctival Ultraviolet Autofluorescence as a Measure of Past Sun Exposure in Children
Authors: Sun Cong , Pezic Angela , Mackey David A. , Carlin John B. , Kemp Andrew , Ellis Justine A. , Cameron Fergus J. , Rodda Christine P. , Dwyer Terence , Coroneo Minas T. , Ponsonby Anne-Louise 
Published: April 2017

Abstract
Background: Conjunctival ultraviolet autofluorescence (CUVAF) area detected from UVAF photographs is a recently developed potential marker for past sun exposure, but its relationship with sun-related factors has not been fully investigated.
Methods: The study included 339 healthy children ages 5 to 15 years in Melbourne, Australia. Data were collected by questionnaire and examination at school. CUVAF area was measured using a computer program and analyzed as a continuous and dichotomous outcome (any/none).
Results: Fifty-three children (15.6%) had detectable CUVAF, and the youngest age at which a child showed sun damage was 8 years. Compared with silicone skin cast score, there was good inter-grader agreement on CUVAF grading, with Cohen kappa 0.85 [95% confidence interval (CI), 0.65–1.00] for total CUVAF area using both eye photographs. Perfect intra-grader agreement was achieved. Fairer pigmentation, including medium/fair skin color [adjusted odds ratio (AOR), 3.42; 95% CI, 1.02–11.48 vs. dark/olive] and blue/gray eye color (AOR, 4.07; 95% CI, 1.73–9.55 vs. brown) was associated with increased odds of CUVAF. Increasing lifetime sunburn number (e.g., AOR, 2.89; 95% CI, 1.14–7.35 and 4.29; 1.04–17.76 for sunburns 2 to 4 and ≥ 5 times, respectively, vs. no sunburns, trend P = 0.004) and freckling by the end of last summer were associated with increased odds of CUVAF.
Conclusions: CUVAF area can be an a priori objective measure of past sun exposure in pediatric populations for future research.
Impact: To our knowledge, this is the first pediatric study that evaluated associations of sun-related risk factors with CUVAF. Cancer Epidemiol Biomarkers Prev; 26(7); 1146–53. ©2017 AACR.
Comparison of the Natural History of Genital HPV Infection among Men by Country: Brazil, Mexico, and the United States
Authors: Sudenga Staci L. , Torres B. Nelson , Silva Roberto , Villa Luisa L. , Lazcano-Ponce Eduardo , Abrahamsen Martha , Baggio Maria Luiza , Salmeron Jorge , Quiterio Manuel , Giuliano Anna R. 
Published: April 2017

Abstract
Background: Male genital human papillomavirus (HPV) prevalence and incidence has been reported to vary by geographical location. Our objective was to assess the natural history of genital HPV by country among men with a median of 48 months of follow-up.
Methods: Men ages 18–70 years were recruited from United States (n = 1,326), Mexico (n = 1,349), and Brazil (n = 1,410). Genital specimens were collected every 6 months and HPV genotyping identified 37 HPV genotypes. Prevalence of HPV was compared between the three countries using the Fisher exact test. Incidence rates and 95% confidence intervals were calculated. The median time to HPV clearance among men with an incident infection was estimated using the Kaplan–Meier method.
Results: The prevalence and incidence of the genital HPV types known to cause disease in males (HPV 16 and 6) was significantly higher among men from Brazil than men from Mexico. Prevalence and incidence of those genital HPV types in the United States varied between being comparable with those of Mexico or Brazil. Although genital HPV16 duration was significantly longer in Brazil (P = 0.04) compared with Mexico and the United States, HPV6 duration was shortest in Brazil (P = 0.03) compared with Mexico and the United States.
Conclusions: Men in Brazil and Mexico often have similar, if not higher prevalence of HPV compared with men from the United States.
Impact: Currently, there is no routine screening for genital HPV among males and while HPV is common in men, and most naturally clear the infection, a proportion of men do develop HPV-related diseases. Men may benefit from gender-neutral vaccine policies. Cancer Epidemiol Biomarkers Prev; 26(7); 1043–52. ©2017 AACR.
Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival
Authors: Boffa Daniel J. , Graf Ryon P. , Salazar Michelle C. , Hoag Jessica , Lu David , Krupa Rachel , Louw Jessica , Dugan Lyndsey , Wang Yipeng , Landers Mark , Suraneni Mahipal , Greene Stephanie B. , Magaña Marisa , Makani Samir , Bazhenova Lyudmila , Dittamore Ryan V. , Nieva Jorge 
Published: April 2017

Abstract
Background: Lung cancer treatment has become increasingly dependent upon invasive biopsies to profile tumors for personalized therapy. Recently, tumor expression of programmed death-ligand 1 (PD-L1) has gained interest as a potential predictor of response to immunotherapy. Circulating biomarkers present an opportunity for tumor profiling without the risks of invasive procedures. We characterized PD-L1 expression within populations of nucleated cells in the peripheral blood of lung cancer patients in hopes of expanding the role of liquid biopsy in this setting.
Methods: Peripheral blood samples from a multi-institutional prospective study of patients with clinical diagnosis of lung cancer were subjected to cytomorphometric and immunohistochemical evaluation using single-cell, automated slide-based, digital pathology. PD-L1 expression was determined by immunofluorescence.
Results: PD-L1 expression was detected within peripheral circulating cells associated with malignancy (CCAM) in 26 of 112 (23%) non–small cell lung cancer patients. Two distinct populations of nucleated, nonhematolymphoid, PD-L1–expressing cells were identified; cytokeratin positive (CK+, PD-L1+, CD45−) and cytokeratin negative (CK−, PD-L1+, CD45−) cells, both with cytomorphometric features (size, nuclear-to-cytoplasm ratio) consistent with tumor cells. Patients with &gt;1.1 PD-L1(+) cell/mL (n = 14/112) experienced worse overall survival than patients with ≤1.1 PD-L1(+) cell/mL (2-year OS: 31.2% vs. 78.8%, P = 0.00159). In a Cox model adjusting for stage, high PD-L1(+) cell burden remained a significant predictor of mortality (HR = 3.85; 95% confidence interval, 1.64–9.09; P = 0.002).
Conclusions: PD-L1 expression is detectable in two distinct cell populations in the peripheral blood of lung cancer patients and is associated with worse survival.
Impact: These findings could represent a step forward in the development of minimally invasive liquid biopsies for the profiling of tumors. Cancer Epidemiol Biomarkers Prev; 26(7); 1139–45. ©2017 AACR.
Enrichment of PI3K-AKT–mTOR Pathway Activation in Hepatic Metastases from Breast Cancer
Authors: Pierobon Mariaelena , Ramos Corinne , Wong Shukmei , Hodge K. Alex , Aldrich Jessica , Byron Sara , Anthony Stephen P. , Robert Nicholas J. , Northfelt Donald W. , Jahanzeb Mohammad , Vocila Linda , Wulfkuhle Julia , Gambara Guido , Gallagher Rosa I. , Dunetz Bryant , Hoke Nicholas , Dong Ting , Craig David W. , Cristofanilli Massimo , Leyland-Jones Brian , Liotta Lance A. , O'Shaughnessy Joyce A. , Carpten John D. , Petricoin Emanuel F. 
Published: April 2017

Abstract
Purpose: Little is known about the molecular signatures associated with specific metastatic sites in breast cancer. Using comprehensive multi-omic molecular profiling, we assessed whether alterations or activation of the PI3K–AKT–mTOR pathway is associated with specific sites of breast cancer metastasis.
Experimental Design: Next-generation sequencing–based whole-exome sequencing was coupled with reverse-phase protein microarray (RPPA) functional signaling network analysis to explore the PI3K–AKT–mTOR axis in 32 pretreated breast cancer metastases. RPPA-based signaling data were further validated in an independent cohort of 154 metastatic lesions from breast cancer and 101 unmatched primary breast tumors. The proportion of cases with PI3K–AKT–mTOR genomic alterations or signaling network activation were compared between hepatic and nonhepatic lesions.
Results: PIK3CA mutation and activation of AKT (S473) and p70S6K (T389) were detected more frequently among liver metastases than nonhepatic lesions (P &lt; 0.01, P = 0.056, and P = 0.053, respectively). However, PIK3CA mutations alone were insufficient in predicting protein activation (P = 0.32 and P = 0.19 for activated AKT and p70S6K, respectively). RPPA analysis of an independent cohort of 154 tumors confirmed the relationship between pathway activation and hepatic metastasis [AKT (S473), mTOR (S2448), and 4EBP1 (S65); P &lt; 0.01, P = 0.02, and P = 0.01, respectively]. Similar results were also seen between liver metastases and primary breast tumors [AKT (S473) P &lt; 0.01, mTOR (S2448) P &lt; 0.01, 4EBP1 (S65) P = 0.01]. This signature was lost when primary tumors were compared with all metastatic sites combined.
Conclusions: Breast cancer patients with liver metastasis may represent a molecularly homogenized cohort with increased incidence of PIK3CA mutations and activation of the PI3K–AKT–mTOR signaling network. Clin Cancer Res; 23(16); 4919–28. ©2017 AACR.