bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of heritability for nine common cancers using data from genome‐wide association studies in Chinese population
Authors: Dai Juncheng , Shen Wei , Wen Wanqing , Chang Jiang , Wang Tongmin , Chen Haitao , Jin Guangfu , Ma Hongxia , Wu Chen , Li Lian , Song Fengju , Zeng YiXin , Jiang Yue , Chen Jiaping , Wang Cheng , Zhu Meng , Zhou Wen , Du Jiangbo , Xiang Yongbing , Shu Xiao‐Ou , Hu Zhibin , Zhou Weiping , Chen Kexin , Xu Jianfeng , Jia Weihua , Lin Dongxin , Zheng Wei , Shen Hongbing 
Published: September 2016

The familial aggregation indicated the inheritance of cancer risk. Recent genome‐wide association studies (GWASs) have identified a number of common single‐nucleotide polymorphisms (SNPs). Following heritability analyses have shown that SNPs could explain a moderate amount of variance for different cancer phenotypes among Caucasians. However, little information was available in Chinese population. We performed a genome‐wide complex trait analysis for common cancers at nine anatomical sites in Chinese population (14,629 cancer cases vs. 17,554 controls) and estimated the heritability of these cancers based on the common SNPs. We found that common SNPs explained certain amount of heritability with significance for all nine cancer sites: gastric cancer (20.26%), esophageal squamous cell carcinoma (19.86%), colorectal cancer (16.30%), lung cancer (LC) (15.17%), and epithelial ovarian cancer (13.31%), and a similar heritability around 10% for hepatitis B virus‐related hepatocellular carcinoma, prostate cancer, breast cancer and nasopharyngeal carcinoma. We found that nearly or less than 25% change was shown when removing the regions expanding 250 kb or 500 kb upward and downward of the GWAS‐reported SNPs. We also found strong linear correlations between variance partitioned by each chromosome and chromosomal length only for LC (R2 = 0.641, p = 0.001) and esophageal squamous cell cancer (R2 = 0.633, p = 0.002), which implied us the complex heterogeneity of cancers. These results indicate polygenic genetic architecture of the nine common cancers in Chinese population. Further efforts should be made to discover the hidden heritability of different cancer types among Chinese.
Genetically encoded photocrosslinkers for identifying and mapping protein‐protein interactions in living cells
Authors: Yang Yi , Song Haiping , Chen Peng R. 
Published: September 2016

AbstractProtein‐protein interactions (PPIs) play pivotal roles in regulation of many biological processes. Conventional methods are capable of investigating stable and strong interactions within protein complexes, but remain difficult for studying dynamic, transient, and weak PPIs. Herein we review photo‐affinity unnatural amino acids that can be site‐specifically incorporated into a protein of interest to covalently trap noncovalent PPIs under living conditions. A newly developed cleavable photocrosslinker from our group will also be introduced, which facilitated the prey‐bait separation for better enrichment and identification of photocrosslinked PPI complexes. © 2016 IUBMB Life, 68(11):879–886, 2016
Direct and label‐free detection of the human growth hormone in urine by an ultrasensitive bimodal waveguide biosensor
Authors: González‐Guerrero Ana Belén , Maldonado Jesús , Dante Stefania , Grajales Daniel , Lechuga Laura M. 
Published: September 2016

A label‐free interferometric transducer showing a theoretical detection limit for homogeneous sensing of 5 × 10–8 RIU, being equivalent to a protein mass coverage resolution of 2.8 fg mm–2, is used to develop a high sensitive biosensor for protein detection. The extreme sensitivity of this transducer combined with a selective bioreceptor layer enables the direct evaluation of the human growth hormone (hGH) in undiluted urine matrix in the 10 pg mL–1 range.
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Comparative evaluation of a heparin‐citrate anticoagulation for LDL‐apheresis in two primary apheresis systems
Authors: Handschel Doris , Etienne Janssens Michiel , Gericke Marion , De Reys Stef , Borberg Helmut 
Published: September 2016

AbstractBACKGROUND: As COBE Spectra has been replaced in many parts of the world, we describe a new protocol for low‐density lipoprotein (LDL)‐apheresis performed on familial hypercholesterolemia patients for the Spectra Optia platform. METHODS: For all procedures, after administering a bolus of heparin of 2,500 U, 10,000 U of heparin added to a 600 ml ACD‐A bag was used as anticoagulant (AC). In a first phase (A), 16 apheresis procedures with COBE Spectra using an inlet:AC ratio of 25:1 were compared to 18 LDL‐apheresis treatments with Spectra Optia at split Inlet:AC ratios of 16:1/18:1 or 20:1/25:1. Platelet activation and coagulation markers were assessed. In a follow‐up phase (B), 20 procedures on Spectra Optia using an inlet:AC ratio of 20:1 were performed. RESULTS: Although coagulation markers and platelet activation analyzed were similar in both apheresis devices used, COBE Spectra procedures did not show any visual clumping in the sets. Visual analysis of clumping was highest in the Spectra Optia's 20:1/25:1 AC regimen (5/8 procedures). For the lowest Spectra Optia, AC regimen and during the follow‐up phase reversible clump formation in the disposable set was similar (1/10 procedures). Clumping was successfully reversed in all cases by temporarily lowering the inlet:AC ratio to 18:1. Blood cell counts (WBC, Plt, Hct) were similar for both COBE Spectra and Spectra Optia procedures. Spectra Optia had a significantly higher plasma removal efficiency versus COBE Spectra (84% vs.75%, P < .05). No serious adverse events were observed. CONCLUSION: Apheresis procedures on the Spectra Optia system with low‐dose heparin‐citrate anticoagulation are feasible and safe.
Evaluation of Evolocumab (AMG 145), a Fully Human Anti‐PCSK9 IgG2 Monoclonal Antibody, in Subjects With Hepatic Impairment
Authors: Gibbs John P. , Slatter J. Greg , Egbuna Ogo , Geller Michelle , Hamilton Lisa , Dias Clapton S. , Xu Ren Y. , Johnson Jessica , Wasserman Scott M. , Emery Maurice G. 
Published: September 2016

AbstractEvolocumab binds PCSK9, increasing low‐density lipoprotein cholesterol (LDL‐C) receptors and lowering LDL‐C. Target‐mediated evolocumab elimination is attributable to PCSK9 binding. As circulating PCSK9 and LDL‐C levels are primarily regulated by the liver, we compared evolocumab pharmacokinetics, pharmacodynamics, and safety in individuals with and without hepatic impairment. An open‐label, parallel‐group study evaluated the pharmacokinetics of evolocumab in hepatic‐impaired (Child‐Pugh Class A or B) or healthy adults. Participants were classified as having no, mild, or moderate hepatic impairment (n = 8/group) and received a single 140‐mg evolocumab dose. Assessments of unbound evolocumab and PCSK9 were made predose and postdose. Adverse events were monitored throughout the study. No significant association was observed between baseline PCSK9 and increasing level of hepatic impairment. No difference in extent and time course of PCSK9 or LDL‐C reduction was observed despite an apparent decrease in mean unbound evolocumab exposure with increasing hepatic impairment (Jonckheere‐Terpstra trend test; maximum serum concentration P = .18; area under the curve P = .09). Maximum reductions were observed in moderately impaired subjects vs healthy individuals: mean maximum serum concentration –34%; mean area under the concentration‐time curve (AUC) –47%. On average, unbound PCSK9 serum concentrations fell by >80% at 4 hours after a single evolocumab dose. Mean (95% confidence interval) maximum LDL‐C reductions in the healthy, mild, and moderate groups were –57% (–64% to –48%), –70% (–75% to –63%), and –53% (–61% to –43%), respectively. No safety risks were identified. These results support evolocumab use without dose adjustment in patients with active liver disease and mild or moderate hepatic impairment.
A haploid HSV‐1 genome platform for vector development: testing of the tetracycline‐responsive switch shows interference by infected cell protein 0
Authors: Khalique Hena , López Marco Jorge , Lim Filip 
Published: September 2016

AbstractBackgroundAlthough herpes simplex virus type 1 (HSV‐1) has outstanding properties for gene delivery vectors and its genome is available in bacterial artificial chromosomes (BACs) for mutagenesis studies, one impediment is the presence of approximately 15.4 kb of DNA sequences that are duplicated in the HSV‐1 genome, complicating vector construction and stability.MethodsAs a useful platform for building HSV‐1 vectors, we have constructed a fully haploid HSV‐1 genome BAC by deletion of one of these repeats, confirming that viral propagation in culture is not impaired. We used this ΔIR mutant to subsequently investigate whether the insertion of tetracycline‐responsive tetO elements into the ICP34.5–ICP0 gene region can be used to control HSV‐1 lytic replication.ResultsThe results of the present study show that ΔIR mutants deleted for ICP34.5 are viable for replication but not when the ICP0 promoter is also disrupted, thus indicating that regulation of infected cell protein 0 (ICP0) levels in the absence of ICP34.5 could be a viable means for controlling growth of HSV‐1 vectors. Surprisingly, however, the tetO elements inserted into the ICP0 promoter did not confer ligand responsiveness to growth or ICP0 expression. Further analysis by transfection experiments revealed that ICP0 itself interferes with the tetracycline switch and reduces the the inducibility of this system.ConclusionsOur new haploid HSV‐1 BAC is a useful platform for building multiply deleted HSV‐1 vectors. Deletion of the gene for ICP34.5 in this backbone renders viral growth dependent on ICP0, although ICP0 expression could not be regulated by tet‐responsive transcriptional regulators.
Effect of silybin on the fibrillation of hen egg‐white lysozyme
Authors: Zeng Hua‐jin , Miao Min , Yang Ran , Qu Ling‐bo 
Published: September 2016

AbstractIn this study, the fibrillation of hen egg‐white lysozyme (HEWL) in the absence and presence of different concentrations of silybin was studied by thioflavin T spectroscopy, Congo red binding assays, 8‐anilino‐1‐naphthalenesulfonic acid (ANS) fluorescence assay, circular dichroism, and transmission electron microscopy. The experimental results indicated that not only the fibrillation of HEWL at high temperature (65°C) and low pH (pH = 2.0) could be inhibited effectively by silybin but also the inhibition of HEWL by silybin followed a dose‐dependent manner. Molecular docking studies indicated that 2 possible binding modes could be found in the interaction between silybin and HEWL via van der Waals forces and electrostatic forces as well as hydrogen bonding. One of these 2 conformations was directly entered into the cavity of HEWL (binding site I); the other was bound to the surface of HEWL (binding site II). In this way, silybin could not only increase the hydrophobicity of the cavity or the surface of HEWL but also influence the microenvironment of the binding site, which was able to stabilize the structure of HEWL and delay the process of HEWL fibrosis.
Mid‐elevation ecosystems of Panama: future uncertainties in light of past global climatic variability
Authors: Correa‐Metrio Alexander , Vélez Maria I. , Escobar Jaime , St‐Jacques Jeannine‐Marie , López‐Pérez Minerva , Curtis Jason , Cosford Jason 
Published: September 2016

ABSTRACTModern changes in regional climates will result in high ecosystem turnover and substantial biodiversity rearrangements. Understanding these changes requires palaeoecological studies at temporal resolutions comparable to the time window at which modern climate change is occurring. Here we present a multi‐proxy, high‐resolution record of forest and lake ecosystem change that occurred during the last 1100 years at middle elevations in Panama. From ∼900 to 1400 CE, regional forest and lake ecosystems were characterized by high seasonality, probably associated with both high El Niño activity and higher global temperatures. At ∼1400 CE, an abrupt transition marked the decoupling of forest and lake responses, with forest responding mostly to local patterns of human occupation, and lake trophic status being controlled mostly by the regional precipitation–evaporation balance, possibly associated with solar irradiance. Factors that played important roles in shaping regional ecosystems during the last 1100 years will probably again play critical roles within the coming decades, i.e. higher precipitation seasonality and higher temperatures. Past responses of the system, together with pervasive human activities, suggest that future conditions will simplify mid‐elevation forests. Given the importance of these geographical locations as hotspots of biological diversity, substantial losses of global biodiversity are foreseen.
Fungal contribution in chondroradionecrosis of the larynx
Authors: Worthen Mary , Jusufbegovic Mia , Bumpous Jeffrey M. , Vaughn Andrew , Cash Elizabeth , Yang Xiu , Fichandler Craig , Tennant Paul 
Published: September 2016

ObjectiveTo assess the prevalence of invasive fungal elements in the specimens of patients who underwent salvage total laryngectomy for chondroradionecrosis (CRN) in the absence of recurrent or persistent malignancy.Study DesignRetrospective chart review.SettingTertiary academic medical center.MethodsOne hundred fifty‐nine patients were identified who underwent salvage total laryngectomy. Pathology reports were reviewed, and all laryngectomy specimens that did not contain residual malignancy were reevaluated for evidence of invasive fungal elements.ResultsTwelve of 159 (7.5%) patients who underwent total laryngectomy after primary radiotherapy or chemoradiotherapy had no evidence of residual malignancy. Each of these specimens contained histopathologic evidence of CRN; invasive fungal elements were identified in 25%. There was no statistical difference in demographic or treatment‐related variables between patients who underwent salvage total laryngectomy with evidence of persistent or recurrent malignancy in the laryngectomy specimen versus patients without evidence of tumor on final histopathologic analysis. Patients with evidence of ulceration or necrosis in the laryngectomy specimen had reduced overall survival, irrespective of the presence of persistent malignancy (hazard ratio = 2.923, 95% confidence interval = 1.023–8.352, P = .045).ConclusionAmong salvage total laryngectomy patients, no difference was identified between patients who underwent total laryngectomy for recurrent or persistent malignancy after primary radiotherapy and those who received total laryngectomy without evidence of malignancy in their specimens. Invasive fungal elements were detected in several laryngectomy specimens that did not contain residual malignancy. Empiric antifungal therapy may therefore benefit patients diagnosed with CRN who are at risk for progression to nonfunctional larynx. Patients with evidence of ulceration or necrosis in the salvage laryngectomy specimen had worse overall survival.Level of Evidence4. Laryngoscope, 127:E159–E165, 2017
Evaluation of the American college of surgeons thyroid and parathyroid ultrasound course: Results of a web‐based survey
Authors: Sharma Giriraj K. , Sofferman Robert A. , Armstrong William B. 
Published: September 2016

Objectives/HypothesisThe American College of Surgeons Thyroid and Parathyroid Ultrasound Skills‐Oriented Course (TPUSC) was designed to teach surgeons how to interpret and perform office‐based head and neck ultrasound (HNUS). The objective of this study was to survey attendees of the TPUSC to evaluate the usefulness of the course, to track surgeon performed HNUS practice patterns, and to help identify potential roadblocks to incorporation of HNUS into a surgeon's practice.Study DesignCross‐sectional survey.MethodsA Web‐based survey was sent to 952 surgeons who completed the TPUSC between 2010 and 2014. Questions included surgeon specialty, practice type, Likert scale rating of the TPUSC, competency with different HNUS procedures, and current HNUS practice patterns.ResultsThe response rate was 24%. On a scale from 1 (not useful) to 5 (extremely valuable), the mean course usefulness rating was 4.2. Educational goals were met for 194 (92%) surgeons, and 162 (77%) surgeons reported performing HNUS in their practice. Of 48 surgeons not performing HNUS, 24 (50%) attributed insufficient time in their clinic schedule, and 21 (44%) attributed high equipment costs.ConclusionsThe TPUSC is a valuable educational experience for surgeons seeking to gain proficiency in HNUS. The majority of TPUSC graduates gain competency with at least one type of HNUS procedure following the course.Level of EvidenceNA Laryngoscope, 127:1950–1958, 2017
State‐of‐the‐art all‐silicon sub‐bandgap photodetectors at telecom and datacom wavelengths
Authors: Casalino Maurizio , Coppola Giuseppe , De La Rue Richard M. , Logan Dylan F. 
Published: September 2016

AbstractSilicon‐based technologies provide an ideal platform for the monolithic integration of photonics and microelectronics. In this context, a variety of passive and active silicon photonic devices have been developed to operate at telecom and datacom wavelengths, at which silicon has minimal optical absorption ‐ due to its bandgap of 1.12 eV. Although in principle this transparency window limits the use of silicon for optical detection at wavelengths above 1.1 μm, in recent years tremendous advances have been made in the field of all‐silicon sub‐bandgap photodetectors at telecom and datacom wavelengths. By taking advantage of emerging materials and novel structures, these devices are becoming competitive with the more well‐established technologies, and are opening new and intriguing perspectives. In this paper, a review of the state‐of‐the‐art is presented. Devices based on defect‐mediated absorption, two‐photon absorption and the internal photoemission effect are reported, their working principles are elucidated and their performance discussed and compared.
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Biomaterial‐Based Approaches to Address Vein Graft and Hemodialysis Access Failures
Authors: Boire Timothy C. , Balikov Daniel A. , Lee Yunki , Guth Christy M. , Cheung‐Flynn Joyce , Sung Hak‐Joon 
Published: September 2016

Veins used as grafts in heart bypass or as access points in hemodialysis exhibit high failure rates, thereby causing significant morbidity and mortality for patients. Interventional or revisional surgeries required to correct these failures have been met with limited success and exorbitant costs, particularly for the US Centers for Medicare & Medicaid Services. Vein stenosis or occlusion leading to failure is primarily the result of neointimal hyperplasia. Systemic therapies have achieved little long‐term success, indicating the need for more localized, sustained, biomaterial‐based solutions. Numerous studies have demonstrated the ability of external stents to reduce neointimal hyperplasia. However, successful results from animal models have failed to translate to the clinic thus far, and no external stent is currently approved for use in the US to prevent vein graft or hemodialysis access failures. This review discusses current progress in the field, design considerations, and future perspectives for biomaterial‐based external stents. More comparative studies iteratively modulating biomaterial and biomaterial‐drug approaches are critical in addressing mechanistic knowledge gaps associated with external stent application to the arteriovenous environment. Addressing these gaps will ultimately lead to more viable solutions that prevent vein graft and hemodialysis access failures.
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Clinical exome sequencing in early‐onset generalized dystonia and large‐scale resequencing follow‐up
Authors: Zech Michael , Boesch Sylvia , Jochim Angela , Weber Sandrina , Meindl Tobias , Schormair Barbara , Wieland Thomas , Lunetta Christian , Sansone Valeria , Messner Michael , Mueller Joerg , Ceballos‐Baumann Andres , Strom Tim M. , Colombo Roberto , Poewe Werner , Haslinger Bernhard , Winkelmann Juliane 
Published: September 2016

ABSTRACTBackgroundDystonia is clinically and genetically heterogeneous. Despite being a first‐line testing tool for heterogeneous inherited disorders, whole‐exome sequencing has not yet been evaluated in dystonia diagnostics. We set up a pilot study to address the yield of whole‐exome sequencing for early‐onset generalized dystonia, a disease subtype enriched for monogenic causation.MethodsClinical whole‐exome sequencing coupled with bioinformatics analysis and detailed phenotyping of mutation carriers was performed on 16 consecutive cases with genetically undefined early‐onset generalized dystonia. Candidate pathogenic variants were validated and tested for cosegregation. The whole‐exome approach was complemented by analyzing 2 mutated yet unestablished causative genes in another 590 dystonia cases.ResultsWhole‐exome sequencing detected clinically relevant mutations of known dystonia‐related genes in 6 generalized dystonia cases (37.5%), among whom 3 had novel variants. Reflecting locus heterogeneity, identified unique variants were distributed over 5 genes (GCH1, THAP1, TOR1A, ANO3, ADCY5), of which only 1 (ANO3) was mutated recurrently. Three genes (GCH1, THAP1, TOR1A) were associated with isolated generalized dystonia, whereas 2 (ANO3, ADCY5) gave rise to combined dystonia‐myoclonus phenotypes. Follow‐up screening of ANO3 and ADCY5 revealed a set of distinct variants of interest, the pathogenicity of which was supported by bioinformatics testing and cosegregation work.ConclusionsOur study identified whole‐exome sequencing as an effective strategy for molecular diagnosis of early‐onset generalized dystonia and offers insights into the heterogeneous genetic architecture of this condition. Furthermore, it provides confirmatory evidence for a dystonia‐relevant role of ANO3 and ADCY5, both of which likely associate with a broader spectrum of dystonic expressions than previously thought. © 2016 International Parkinson and Movement Disorder Society.
Orbital stability of solitary waves of the coupled Klein–Gordon–Zakharov equations
Authors: Zheng Xiaoxiao , Shang Yadong , Peng Xiaoming 
Published: September 2016

This paper investigates the orbital stability of solitary waves for the coupled Klein–Gordon–Zakharov (KGZ) equationsurn:x-wiley:mma:media:mma4187:mma4187-math-0001whereα ≠ 0. Firstly, we rewrite the coupled KGZ equations to obtain its Hamiltonian form. And then, we present a pair of sech‐type solutions of the coupled KGZ equations. Because the abstract orbital stability theory presented by Grillakis, Shatah, and Strauss (1987) cannot be applied directly, we can extend the abstract stability theory and use the detailed spectral analysis to obtain the stability of the solitary waves for the coupled KGZ equations. In our work,α = 1,β = 0 are advisable. Hence, we can also obtain the orbital stability of solitary waves for the classical KGZ equations which was studied by Chen. Copyright © 2016 John Wiley & Sons, Ltd.