bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of RNA Interference Targeting NET-1 Combination with Sorafenib for Hepatocellular Carcinoma TherapyIn VitroandIn Vivo
Authors: He Song , Wei Ying-ze , Wang Gui-lan , Xu Yu-yin , Zhou Jia-ming , Zhang Yi-xin , Chen Li
Published: November 2013

The aim of this study is to explore the inhibitory effects of RNA interference (RNAi) targeting NET-1 or combined with sorafenib on HCCin vitroandin vivoand the possible underlying mechanisms. The expressions of NET-1 mRNA and protein were detected by RT-QPCR and western blot. The ability of proliferation was determined by CCK-8 assay. Apoptosis was examined by flow cytometry (FCM). Abilities of migration and invasion were measured by scratch-wound assay and transwell assay. MHCC97H cells with stable transfection of NET-1shRNA were injected subcutaneously to prepare nude mice model of HCC and Caspase-3, Caspase-8, and Caspase-9 mRNAs of tumor tissues in different groups were examined. NET-1 mRNA and protein were reduced sharply in MHCC97H cells transfected with NET-1shRNA. The abilities of proliferation and migration were inhibited and apoptosis was promoted in either NET-1shRNA or sorafenib as compared with untreated cellsin vitroandin vivo(P<0.05). The mRNA levels of caspase-3, caspase-8, and caspase-9 of tumor tissues were reduced in different treatment groups compared with untreated group, particularly in combination group. (P<0.05). The combination NET-1shRNA with sorafenib dramatically enhanced the effects of sorafenib antitumor ,which may involve in blocking ras signaling pathway and stimulating apoptotic pathways simultaneously.
Usefulness of Traditional Serum Biomarkers for Management of Breast Cancer Patients
Authors: Mirabelli Peppino , Incoronato Mariarosaria
Published: November 2013

The measurement of serum tumor markers levels in breast cancer (BC) patients is an economic and noninvasive diagnostic assay frequently requested by clinical oncologists to get information about the presence or absence of disease as well as its evolution. Despite their wide use in clinical practice, there is still an intense debate between scientific organizations about the real usefulness for patient monitoring during followup as well as response to therapy evaluation in case of advanced BC. In this review, we want to highlight the current recommendations published by scientific organizations about the use of “established” BC serum markers (CEA, TPA, TPS, CIFRA-21, CA15-3, and s-HER2) in clinical oncology practice. Moreover, we will focus on recent papers evidencing the usefulness of tumor markers levels measurement as a guide for the prescription and diagnostic integration of molecular imaging exams such as those performed by hybrid 18-fluorofeoxyglucose-positron emission tomography with integrated computed tomography. This technology is nowadays able to detect early cancer lesions undetectable by conventional morphological imaging investigation and most likely responsible for increasing of serum tumor markers levels.
Influence of Physical Activity and Nutrition on Obesity‐Related Immune Function
Authors: Huang Chun-Jung , Zourdos Michael C. , Jo Edward , Ormsbee Michael J.
Published: November 2013

Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF‐α, CRP, and IL‐6. Consequently, obesity is now characterized as a state of chronic low‐grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity‐immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity‐related immune function with specific focus on inflammation.
Zebra Finch Glucokinase Containing Two Homologous Halves Is an In Silico Chimera
Authors: Victorovich Khrustalev Vladislav , Vladimirovich Lelevich Sergey , Victorovich Barkovsky Eugene
Published: November 2013

Chimerical nature of the gene annotated as Zebra finch (Taeniopygia guttata) glucokinase (hexokinase IV) has been proved in this study. N-half of the protein encoded by that gene shows similarity with glucokinase from other vertebrates, while its C-half shows similarity with C-halves of hexokinases II. We mapped 7 new exons coding for N-half of hexokinase II and 4 new exons coding for glucokinase of Zebra finch. Finally, we reconstructed normal genes coding for Zebra finch glucokinase and hexokinase II which are situated in “head-to-tail” orientation on the chromosome 22. Because of the error in gene annotation, exons encoding N-half of normal glucokinase have been fused with exons encoding C-half of normal hexokinase II, even though they are separated from each other by the sequence 98066 nucleotides in length.
Italian Residential Buildings: Economic Assessments for Biomass Boilers Plants
Authors: Carlini Maurizio , Castellucci Sonia , Cocchi Silvia , Allegrini Elena , Li Ming
Published: November 2013

Biomass is increasingly used for energy generation since it represents a useful alternative to fossil fuel in order to face the pollutions and the global warming problem. It can be exploited for heating purposes and for supplying domestic hot water. The most common applications encompass wood and pellet boilers. The economic aspect is becoming an important issue in order to achieve the ambitious targets set by the European Directives on Renewable Sources. Thus, the present paper deals with the economic feasibility of biomass boiler plants with specific regard to an existing residential building. An Italian case study is further investigated, focusing the attention on European and national regulations on energy efficiency and considering the recent public incentives and supporting measures. The main thermoclimatic parameters—that is, heating degree days (HDDs), building thermal insulation and thermal needs—are taken into account. Moreover, the following economic indicators are calculated: cumulative cash flow, discounted cumulative cash flow, payback period (PP), net present value (NPV), Internal rate of return (IRR), discounted payback period (DPP), and profit index (PI).
Geometric Distribution Weight Information Modeled Using Radial Basis Function with Fractional Order for Linear Discriminant Analysis Method
Authors: Chen Wen-Sheng , Zhang Chu , Chen Shengyong
Published: November 2013

Fisher linear discriminant analysis (FLDA) is a classic linear feature extraction and dimensionality reduction approach for face recognition. It is known that geometric distribution weight information of image data plays an important role in machine learning approaches. However, FLDA does not employ the geometric distribution weight information of facial images in the training stage. Hence, its recognition accuracy will be affected. In order to enhance the classification power of FLDA method, this paper utilizes radial basis function (RBF) with fractional order to model the geometric distribution weight information of the training samples and proposes a novel geometric distribution weight information based Fisher discriminant criterion. Subsequently, a geometric distribution weight information based LDA (GLDA) algorithm is developed and successfully applied to face recognition. Two publicly available face databases, namely, ORL and FERET databases, are selected for evaluation. Compared with some LDA-based algorithms, experimental results exhibit that our GLDA approach gives superior performance.
High Expression and Purification of Amino-Terminal Fragment of Human Amyloid Precursor Protein inPichia pastorisand Partial Analysis of Its Properties
Authors: Li Wei , Gao Xiang , Ren Junle , An Ting , Liu Yan
Published: November 2013

The cleaved amino-terminal fragment of human amyloid precursor protein (N-APP) binds death receptor 6 (DR6) and triggers a caspase-dependent self-destruction process, which was suggested to contribute to Alzheimer’s disease. To investigate the N-APP-DR6-induced degeneration pathway at the molecular level, obtaining abundant and purified N-APP is fundamental and critical. The recombinant N-APP has been produced in mammalian expression system. However, the cost and yield disadvantages of mammalian expression system make it less ideal for protein mass production. Here, we successfully expressed and purified recombinant N-terminal 18-285 amino acid residues of human amyloid precursor protein from the methylotrophic yeastPichia pastoriswith a high yield of 50 mg/L. Flow cytometry indicated the purified N-APP-induced obvious apoptosis of human neuroblastoma SHEP cells.
Functional Status in Behavioral Variant Frontotemporal Dementia: A Systematic Review
Authors: Lima-Silva Thais Bento , Bahia Valéria Santoro , Nitrini Ricardo , Yassuda Mônica Sanches
Published: November 2013

The aim was to conduct a systematic review of studies that described the functional profile of patients with behavioral variant frontotemporal dementia (bvFTD), published between 2000 and 2013. The bibliographic search was conducted using the terms “frontotemporal dementia” and “frontotemporal lobar degeneration” in combination with “independence,” “functionality,” “basic activities of daily living,” “disability,” and scales that measure functional performance: “Disability Assessment for Dementia-DAD,” “Functional Activities Questionnaire (FAQ),” “Direct Assessment of Functional Status (DAFS).” To be included in the review, the study had to mention the characterization of the functional status of patients with bvFTD in the objectives of the study, using a previously validated instrument of functional assessment. Fourteen studies met this criterion. The reviewed studies suggested that individuals with bvFTD have greater functional impairment when compared to those with other subtypes of frontotemporal lobar degeneration or Alzheimer’s disease. The studies documented a significant association between cognitive impairment and measures of functionality in these patients. The cognitive profile of patients may predict faster functional decline.
Periodontal Plastic Microsurgery in the Treatment of Deep Gingival Recession after Orthodontic Movement
Authors: Kahn Sérgio , Rodrigues Walmir Júnio de Pinho Reis , Barceleiro Marcos de Oliveira
Published: November 2013

Gingival recession is a condition that affects a large portion of the young and adult population and negatively affects the aesthetic aspects of the smile. Many factors are related to its development, including orthodontic movement beyond the osseous limits. Many treatment options have been proposed to cover the exposed root surface. The aim of this article was to describe three cases where a subepithelial connective tissue graft was performed, using a microsurgical technique, in the treatment of deep gingival recession after orthodontic treatment. This technique resulted in successful root coverage and keratinized tissue gain, improving the gingival esthetic pattern.
Nonlinear Instability for a Leslie-Gower Predator-Prey Model with Cross Diffusion
Authors: Zhang Lina , Fu Shengmao
Published: November 2013

A rigorous mathematical characterization for early-stage spatial and temporal patterns formation in a Leslie-Gower predator-prey model with cross diffusion is investigated. Given any general perturbation near an unstable constant equilibrium, we prove that its nonlinear evolution is dominated by the corresponding linear dynamics along a fixed finite number of the fastest growing modes.
A Comprehensive Focus on Global Spectrum ofBRCA1andBRCA2Mutations in Breast Cancer
Authors: Karami Fatemeh , Mehdipour Parvin
Published: November 2013

Breast cancer (BC) is the most common cancer of women all over the world.BRCA1andBRCA2gene mutations comprise the most important genetic susceptibility of BC. Except for few common mutations, the spectrum ofBRCA1andBRCA2mutations is heterogeneous in diverse populations. 185AGdel and 5382insC are the most importantBRCA1andBRCA2alterations which have been encountered in most of the populations. After those Ashkenazi founder mutations, 300T>G also demonstrated sparse frequency in African American and European populations. This review affords quick access to the most frequent alterations among various populations which could be helpful in BRCA screening programs.
On Weak‐BCC‐Algebras
Authors: Thomys Janus , Zhang Xiaohong
Published: November 2013

We describe weak‐BCC‐algebras (also called BZ‐algebras) in which the condition (x∗y)∗z = (x∗z)∗y is satisfied only in the case when elements x, y belong to the same branch. We also characterize ideals, nilradicals, and nilpotent elements of such algebras.
Bcl2 Induces DNA Replication Stress by Inhibiting Ribonucleotide Reductase
Authors: Xie Maohua , Yen Yun , Owonikoko Taofeek K. , Ramalingam Suresh S. , Khuri Fadlo R. , Curran Walter J. , Doetsch Paul W. , Deng Xingming
Published: November 2013

DNA replication stress is an inefficient DNA synthesis process that leads replication forks to progress slowly or stall. Two main factors that cause replication stress are alterations in pools of deoxyribonucleotide (dNTP) precursors required for DNA synthesis and changes in the activity of proteins required for synthesis of dNTPs. Ribonucleotide reductase (RNR), containing regulatory hRRM1 and catalytic hRRM2 subunits, is the enzyme that catalyzes the conversion of ribonucleoside diphosphates (NDP) to deoxyribonucleoside diphosphates (dNDP) and thereby provides dNTP precursors needed for the synthesis of DNA. Here, we demonstrate that either endogenous or exogenous expression of Bcl2 results in decreases in RNR activity and intracellular dNTP, retardation of DNA replication fork progression, and increased rate of fork asymmetry leading to DNA replication stress. Bcl2 colocalizes with hRRM1 and hRRM2 in the cytoplasm and directly interacts via its BH4 domain with hRRM2 but not hRRM1. Removal of the BH4 domain of Bcl2 abrogates its inhibitory effects on RNR activity, dNTP pool level, and DNA replication. Intriguingly, Bcl2 directly inhibits RNR activity by disrupting the functional hRRM1/hRRM2 complex via its BH4 domain. Our findings argue that Bcl2 reduces intracellular dNTPs by inhibiting ribonucleotide reductase activity, thereby providing insight into how Bcl2 triggers DNA replication stress. Cancer Res; 74(1); 212–23. ©2013 AACR.
The ATP-Competitive mTOR Inhibitor INK128 Enhances In Vitro and In Vivo Radiosensitivity of Pancreatic Carcinoma Cells
Authors: Hayman Thomas J. , Wahba Amy , Rath Barbara H. , Bae Heekyong , Kramp Tamalee , Shankavaram Uma T. , Camphausen Kevin , Tofilon Philip J.
Published: November 2013

Purpose: Radiotherapy remains a primary treatment modality for pancreatic carcinoma, a tumor characterized by aberrant mTOR activity. Given the regulatory role of mTOR in gene translation, in this study, we defined the effects of the clinically relevant, ATP-competitive mTOR inhibitor, INK128 on the radiosensitivity of pancreatic carcinoma cell lines.

Experimental Design: Clonogenic survival was used to determine the effects of INK128 on in vitro radiosensitivity of three pancreatic carcinoma cell lines and a normal fibroblast cell line with mTOR activity defined using immunoblots. DNA double-strand breaks were evaluated according to γH2AX foci. The influence of INK128 on radiation-induced gene translation was determined by microarray analysis of polysome-bound mRNA. Leg tumor xenografts grown from pancreatic carcinoma cells were evaluated for mTOR activity, eIF4F cap complex formation, and tumor growth delay.

Results: INK128, while inhibiting mTOR activity in each of the cell lines, enhanced the in vitro radiosensitivity of the pancreatic carcinoma cells but had no effect on normal fibroblasts. The dispersal of radiation-induced γH2AX foci was inhibited in pancreatic carcinoma cells by INK128 as were radiation-induced changes in gene translation. Treatment of mice with INK128 resulted in an inhibition of mTOR activity as well as cap complex formation in tumor xenografts. Whereas INK128 alone had no effect of tumor growth rate, it enhanced the tumor growth delay induced by single and fractionated doses of radiation.

Conclusion: These results indicate that mTOR inhibition induced by INK128 enhances the radiosensitivity of pancreatic carcinoma cells and suggest that this effect involves the inhibition of DNA repair. Clin Cancer Res; 20(1); 110–9. ©2013 AACR.
NEDD9 Depletion Leads to MMP14 Inactivation by TIMP2 and Prevents Invasion and Metastasis
Authors: McLaughlin Sarah L. , Ice Ryan J. , Rajulapati Anuradha , Kozyulina Polina Y. , Livengood Ryan H. , Kozyreva Varvara K. , Loskutov Yuriy V. , Culp Mark V. , Weed Scott A. , Ivanov Alexey V. , Pugacheva Elena N.
Published: November 2013

The scaffolding protein NEDD9 is an established prometastatic marker in several cancers. Nevertheless, the molecular mechanisms of NEDD9-driven metastasis in cancers remain ill-defined. Here, using a comprehensive breast cancer tissue microarray, it was shown that increased levels of NEDD9 protein significantly correlated with the transition from carcinoma in situ to invasive carcinoma. Similarly, it was shown that NEDD9 overexpression is a hallmark of highly invasive breast cancer cells. Moreover, NEDD9 expression is crucial for the protease-dependent mesenchymal invasion of cancer cells at the primary site but not at the metastatic site. Depletion of NEDD9 is sufficient to suppress invasion of tumor cells in vitro and in vivo, leading to decreased circulating tumor cells and lung metastases in xenograft models. Mechanistically, NEDD9 localized to invasive pseudopods and was required for local matrix degradation. Depletion of NEDD9 impaired invasion of cancer cells through inactivation of membrane-bound matrix metalloproteinase MMP14 by excess TIMP2 on the cell surface. Inactivation of MMP14 is accompanied by reduced collagenolytic activity of soluble metalloproteinases MMP2 and MMP9. Reexpression of NEDD9 is sufficient to restore the activity of MMP14 and the invasive properties of breast cancer cells in vitro and in vivo. Collectively, these findings uncover critical steps in NEDD9-dependent invasion of breast cancer cells.

Implications: This study provides a mechanistic basis for potential therapeutic interventions to prevent metastasis. Mol Cancer Res; 12(1); 69–81. ©2013 AACR.
Tumor-Promoting and -Suppressive Roles of Autophagy in the Same Mouse Model of BrafV600E-Driven Lung Cancer
Authors: Chen Song , Guan Jun-Lin
Published: November 2013

Summary: Although a role of autophagy in cancer development and progression has received increasing appreciation in recent years, there are still significantly uncertain and conflicting results about its tumor-suppressive and -promoting functions, and, more importantly, a lack of understanding of mechanisms underlying these opposing activities. The work presented by Strohecker and colleagues uses an innovative approach to address these challenges by examining the effects of inactivating the key autophagy gene Atg7 at different stages of oncogenic development in a BrafV600E-driven mouse lung cancer model. The authors show that autophagy blockage initially accelerated tumor development, but suppressed tumor progression in later stages, converting adenomas to oncocytomas and increasing mouse survival. Importantly, they identify a critical role of glutamine dependency in the suppression of BrafV600E-induced cancer, thus revealing an important mechanism by which autophagy may promote tumor progression in different cellular contexts. Cancer Discov; 3(11); 1225–7. ©2013 AACR.

See related article by Strohecker et al., p. 1272
Risk Factors for Cesarean Delivery after Induction of Labor in Nulliparous Women with an Unfavorable Cervix at or beyond 41 Weeks of Gestation
Authors: Son Ga Hyun , Kim Jeong Hyeon , Kwon Ja Young , Kim Young Han , Park Yong Won
Published: November 2013

Aims: To investigate risk factors for cesarean section (CS) following labor induction in nulliparas with an unfavorable cervix at or beyond 41 weeks of gestation. Methods: In this retrospective cohort study, a total of 276 nulliparas with an unfavorable cervix (Bishop score ≤6) who underwent labor induction for prolonged pregnancies were included out of a total of 646 patients who delivered ≥41 weeks (2002-2011). Results: 82 (29.7%) patients of the 276 delivered by CS. The patients who underwent CS had less cervical dilatation and a lower Bishop score on admission than those patients who delivered vaginally (0.76 ± 0.47 vs. 0.92 ± 0.58 cm, p = 0.03 and 1.16 ± 1.25 vs. 1.51 ± 1.34, p = 0.04, respectively). Neonatal birth weight and biparietal diameter (BPD) were significantly smaller in the vaginal delivery group (3,414.93 ± 361.37 vs. 3,534.81 ± 383.05 g, p = 0.01 and 9.43 ± 0.35 vs. 9.65 ± 0.42 cm, p < 0.01). After multiple logistic regression analysis, maternal height, BPD, and early rupture of membranes (ROM) were independently related with CS. Early ROM was defined as spontaneous ROM that occurred before the onset of the active phase of labor. Conclusion: Maternal height, BPD, and early ROM were risk factors for CS following labor induction in nulliparas at or beyond 41 weeks of gestation.
Use of an Artificial Neural Network for Diagnosis of Facial Pain Syndromes: An Update
Authors: McCartney Shirley , Weltin Markus , Burchiel Kim J.
Published: November 2013

Background: Based on a classification scheme for facial pain syndromes and a binomial (yes/no) facial pain questionnaire, we previously reported on the ability of an artificial neural network (ANN) to recognize and correctly diagnose patients with different facial pain syndromes. Objectives: We now report on an updated questionnaire, the development of a secure web-based neural network application and details of ANNs trained to diagnose patients with different facial pain syndromes. Methods: Online facial pain questionnaire responses collected from 607 facial pain patients (395 female, 65%, ratio F/M 1.86/1) over 5 years and 7 months were used for ANN training. Results: Sensitivity and specificity of the currently running ANN for trigeminal neuralgia type 1 and trigeminal neuralgia type 2 are 92.4 and 62.5% and 87.8 and 96.4%, respectively. Sensitivity and specificity are 86.7 and 95.2% for trigeminal neuropathic pain, 0 and 100% for trigeminal deafferentation pain and 100% for symptomatic trigeminal neuralgia and postherpetic neuralgia. Sensitivity is 50% for nervus intermedius neuralgia (NIN) and 0% for atypical facial pain (AFP), glossopharyngeal neuralgia (GPN) and temporomandibular joint disorder (TMJ). Specificity for AFP, NIN and TMJ is 99% and for GPN, 100%. Conclusions: We demonstrate the utilization of question-based historical self-assessment responses used as inputs to design an ANN for the purpose of diagnosing facial pain syndromes (outputs) with high accuracy.
Changes in Body Composition in Patients with Chronic Obstructive Pulmonary Disease: Do They Influence Patient-Related Outcomes?
Authors: Rutten Erica P.A. , Calverley Peter M.A. , Casaburi Richard , Agusti Alvar , Bakke Per , Celli Bartolome , Coxson Harvey O. , Crim Courtney , Lomas David A. , MacNee William , Miller Bruce E. , Rennard Stephan I. , Scanlon Paul D. , Silverman Edwin K. , Tal-Singer Ruth , Vestbo Jørgen , Watkins Michael L. , Wouters Emiel F.M. ,   on behalf of the ECLIPSE Investigators (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints)
Published: November 2013

Aims: The follow-up of the ECLIPSE study, a prospective longitudinal study to identify and define parameters that predict disease progression over 3 years in chronic obstructive pulmonary disease (COPD), allows the examination of the effect of body composition changes on COPD-related outcomes. Methods: Body composition and health status were established in 2,115 COPD patients, 327 smoking and 239 nonsmoking controls at baseline and 3 years, while mortality was recorded in year 2 and 3 in the COPD patients. Associations between fat free mass index (FFMI) and fat mass index (FMI) changes to deterioration in health status and mortality were determined. Results: Change in FFMI and FMI over 3 years was small and comparable between the groups. Underweight and obese patients had the worst health status. Worsening health status was associated with FFMI decrease in underweight patients and FMI increase in overweight/obese patients. While overweight patients had the lowest mortality, FFMI or FMI decrease was associated with a higher mortality. Conclusion: Changes in body composition over 3 years were small and comparable in COPD patients and control subjects. Nevertheless, muscle mass decline in underweight and fat mass increase in overweight/obese patients is associated with worsening health status. Overweight is associated with decreased mortality, but muscle mass and fat mass decline are detrimental for mortality.
A Miniature Optical Neuronavigation System for CT-Guided Stereotaxy
Authors: von Jako Christopher R. , Perlaki Gabor , Orsi Gergely , Schwarcz Attila , Dóczi Tamás
Published: November 2013

Background and Objective: Neuronavigation devices have progressed over the past 2 decades, but logistical limitations remain for many stereotactic procedures. We describe our technique and accuracy for a novel miniature optical tracking system which overcomes these limitations. Method: The minioptical tracking system uses a miniature video camera mounted on a rigid cannula to determine cannula location and orientation relative to a patient-attached sticker containing reference markers. A CT scan is used to register these markers to the anatomy and a user-selected target. A computer displays the cannula guidance information to the target. Bench testing was performed on 225 targets in a custom test phantom and additional testing was performed on 20 small targets in an anthropomorphic head phantom to determine the practical accuracy and workflow. Results: The phantom study demonstrated that 3-D navigation accuracy is 1.41 ± 0.53 mm. There was a 100% head phantom study success rate for the 20 small targets. Conclusions: The resulting accuracy data demonstrated good correlation with the CT data, and the clinical simulation workflow indicated its potential usefulness for common neurosurgical applications. Furthermore, this small-footprint tracking technology does not experience the traditional environmentally induced issues or the requirement of pin-based head fixation, allowing for use in the neurointensive care unit and the emergency department.
Treatment of Advanced Cutaneous Squamous Cell Carcinomas with Epidermal Growth Factor Receptor Inhibitors
Authors: Alter M. , Satzger I. , Mattern A. , Kapp A. , Gutzmer R.
Published: November 2013

In advanced cutaneous squamous cell carcinoma (cSCC), efficient medical treatment options are limited in case surgery and radiotherapy failed, particularly since most patients are of higher age and suffer from comorbidities. In many tumor entities, the epidermal growth factor receptor (EGFR) has been established as an important therapeutic target, and blockade of EGFR signaling by monoclonal antibodies or small molecules achieves a therapeutic benefit. EGFR expression is also often dysregulated in cSCC. We report here two patients with advanced cSCC treated with the EGFR inhibitor cetuximab and summarize the current published experience with the use of EGFR inhibitors in cSCC.
Impact of Different Operational Definitions on Mild Cognitive Impairment Rate and MMSE and MoCA Performance in Transient Ischaemic Attack and Stroke
Authors: Pendlebury Sarah T. , Mariz Jose , Bull Linda , Mehta Ziyah , Rothwell Peter M.
Published: November 2013

Background: Mild cognitive impairment (MCI) is at least as prevalent as dementia after transient ischaemic attack (TIA)/stroke and is increasingly recognised as an important outcome in observational studies and randomised trials. However, there is no consensus on how impairment should be defined, and numerous different criteria exist. Previous studies have shown that different criteria for cognitive impairment impact on prevalence rates in epidemiological studies. However, there are few data on how operational differences within established criteria (e.g. Petersen-MCI) affect measured impairment rates and the performance of short cognitive tests such as the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), particularly in cerebrovascular disease. We therefore evaluated the effect of different operational definitions on measured rates of Petersen-MCI and on reliability of short cognitive tests in patients with TIA and stroke. Methods: Consecutive patients underwent the MMSE, MoCA and neuropsychological battery ≥1 year after TIA or stroke in a population-based study. MCI was defined using the Petersen method and subclassified as single or multiple domain, both with (original) and without (modified) subjective memory impairment. Different cut-offs (>1, >1.5 and >2 standard deviations, SD) on a given test relative to published norms were compared together with use of single versus multiple tests to define domain impairment. Results: 91 non-demented subjects completed neuropsychological testing (mean age ± SD 69.7 ± 11.6 years, 54 male, 49 stroke) at a mean of 3.1 ± 1.9 years after the index event. Rates of cognitive impairment ranged from 14/91 (15%) for MCI-original at >2 SD cut-off to 61/91 (67%) MCI-modified at >1 SD cut-off, and the proportion of MCI that was multiple domain varied, e.g. 24/46 (52%) versus only 5/27 (20%) at 1 versus 2 SD cut-off for MCI-modified. Requirement for subjective memory complaint approximately halved estimates [e.g. 17 (19%) vs. 39 (43%) for MCI at 1.5 SD cut-off, single test definition], whereas use of multiple tests versus a single test to define a cognitive domain had less impact. In general, diagnostic accuracy was higher, and optimal cut-offs lower, on MMSE and MoCA for multiple-domain versus single-domain MCI, but the MoCA appeared superior for detecting MCI-modified, whereas the MMSE performed well in detecting MCI-original. Conclusion: Even within established criteria for MCI, differences in operational methodology result in 4-fold variation in MCI estimates. Optimal MMSE and MoCA cut-offs are lower, and reliability more similar, when criteria for MCI are more stringent. Our findings have implications for sample size and adjusted relative risk calculations in randomised trials and for comparisons between studies.
Leptin and Ghrelin Levels in Children before and after Adenoidectomy or Adenotonsillectomy
Authors: Karalok Zeynep Selen , Akdag Mehmet , Turhan Murat , Uzun Gulbahar , Ozdem Sebahat , Dinc Oktay , Bircan Iffet
Published: November 2013

Background and Aim: Accelerated weight gain after (adeno)tonsillectomy has been reported in a number of studies. Whether (adeno)tonsillectomy is also a risk factor for development of overweight is unknown. We investigated serum leptin and plasma ghrelin levels before and 1 year after (adeno)tonsillectomy operation in children. Materials and Methods: We studied 31 patients and 29 age- and sex-matched healthy control children. Auxologic evaluation and biochemical investigations were performed before surgery and 1 year later. Results: One year after surgery, height SDS (p = 0.001) and weight SDS (p = 0.004) were significantly increased in both groups. No changes in BMI SDS (p = 0.105) were observed. Preoperative leptin levels were significantly higher in patients than controls (p < 0.001). IGF-1, IGFBP-3, HOMA-IR and ghrelin values were not significantly different between the groups. One year after surgery, IGF-1 (p = 0.001) and IGFBP-3 (p = 0.001) were significantly increased, while ghrelin (p < 0.001) was significantly decreased. Postoperative leptin levels of patients were also significantly higher than preoperative values (p = 0.036). Conclusion: Significantly higher leptin levels in patients compared to control both before and 1 year after an obstruction-relieving surgery suggested that higher levels might be due to leptin resistance in these patients. Based on our findings we recommend measurement of leptin levels longitudinally for at least 5 years after adenotonsillectomy.
Trends of Menarcheal Age in Women in the Reproductive Age and Menopause in Shanghai
Authors: Jin Feng , Shao Hongfang , Tao Minfang
Published: November 2013

Aim: To explore the factors affecting menarcheal age by investigating two groups of women differing in age by 10-15 years in Shanghai. Methods: Data on 5,207 women were collected from January 2011 to May 2012: 2,151 women of reproductive age from the Obstetrical Department and 3,056 women in menopause from the Medical Center of the Sixth Hospital of Shanghai City. General data and data on menarcheal age and medical history were collected. The two groups were divided into subgroups from <10 to ≥20 years, i.e. 12 subgroups in total, respectively. SPSS 17.0 software was used to examine statistical differences. Results: The onset of menarcheal age of reproductive age women was 0.5 years earlier than that of menopause women (p < 0.05). In the early menarche age group (<13 years old), there were more reproductive age and high-educated women. Correlation analysis found the current body mass index in menopausal women was significantly negatively correlated with their menarcheal age (r = -0.033, p < 0.05). Conclusions: There was a downward trend in menarcheal age in women of Shanghai and its surrounding areas. Economic environment and education background were the main factors affecting menarcheal age, and menarcheal age may be considered as a predictor of adult obesity.
In vivo and protease-activated receptor-1-mediated platelet activation but not response to antiplatelet therapy predict two-year outcomes after peripheral angioplasty with stent implantation
Authors: Steiner Sabine , Seidinger Daniela , Koppensteiner Renate , Panzer Simon , Kopp Christoph W. , Gremmel Thomas
Published: November 2013

Data linking the response to antiplatelet therapy with clinical outcomes after angioplasty and stenting for lower extremity artery disease (LEAD) are scarce. Moreover, associations of in vivo and thrombin-inducible platelet activation with the occurrence of adverse events have not been investigated in these patients, so far. We therefore assessed clinical outcomes and on-treatment platelet reactivity by four test systems in 108 patients receiving dual antiplatelet therapy after infrainguinal angioplasty and stenting for LEAD. Further, in vivo and thrombin receptor-activating peptide (TRAP)-6-inducible glycoprotein (GP) IIb/IIIa activation and P-selectin expression were measured as sensitive parameters of platelet activation. The primary endpoint was defined as the composite of atherothrombotic events and target vessel restenosis or reocclusion. Residual platelet reactivity to adenosine diphosphate and arachidonic acid was similar between patients without and with adverse outcomes within two-year follow-up (all p>0.05). Further, the occurrence of clinical endpoints did not differ significantly between patients without and with high on-treatment residual platelet reactivity by all test systems (all p>0.05). In contrast, in vivo and TRAP-6-inducible platelet activation were significantly more pronounced in patients with subsequent adverse events (all p<0.05), and high levels of platelet activation were independent predictors of the primary endpoint (adjusted hazard ratios: 3.5 for high in vivo activated GPIIb/IIIa, 2.9 for high TRAP-6-inducible activated GPIIb/IIIa, 2.3 for high in vivo P-selectin, and 3 for high TRAP-6-inducible P-selectin; all p<0.05). In conclusion, in vivo and protease-activated receptor-1-mediated platelet activation predict two-year clinical outcomes in stable patients undergoing angioplasty and stenting for LEAD.
Association of Novel Biomarkers of Cardiovascular Stress With Left Ventricular Hypertrophy and Dysfunction: Implications for Screening
Authors: Xanthakis Vanessa , Larson Martin G. , Wollert Kai C. , Aragam Jayashri , Cheng Susan , Ho Jennifer , Coglianese Erin , Levy Daniel , Colucci Wilson S. , Michael Felker G. , Benjamin Emelia J. , Januzzi James L. , Wang Thomas J. , Vasan Ramachandran S.
Published: November 2013

Background

Currently available screening tools for left ventricular (
LV
) hypertrophy (
LVH
) and systolic dysfunction (
LVSD
) are either expensive (echocardiography) or perform suboptimally (B‐type natriuretic peptide [
BNP
]). It is unknown whether newer biomarkers are associated with
LVH
and
LVSD
and can serve as screening tools.

Methods and Results

We studied 2460
F
ramingham Study participants (mean age 58 years, 57% women) with measurements of biomarkers mirroring cardiac biomechanical stress (soluble
ST
‐2 [
ST
2], growth differentiation factor‐15 [
GDF
‐15] and high‐sensitivity troponin I [hsTnI]) and
BNP
. We defined
LVH
as
LV
mass/height
2
≥the sex‐specific 80th percentile and
LVSD
as mild/greater impairment of
LV
ejection fraction (
LVEF
) or a fractional shortening <0.29. Adjusting for standard risk factors in logistic models,
BNP
,
GDF
‐15, and hsTnI were associated with the composite echocardiographic outcome (
LVH
or
LVSD
), odds ratios (
OR
) per
SD
increment in log‐biomarker 1.29, 1.14, and 1.18 (95%
CI
: 1.15 to 1.44, 1.004 to 1.28, and 1.06 to 1.31), respectively. The C‐statistic for the composite outcome increased from 0.765 with risk factors to 0.770 adding
BNP
, to 0.774 adding novel biomarkers. The continuous Net Reclassification Improvement was 0.212 (95%
CI
: 0.119 to 0.305,
P
<0.0001) after adding the novel biomarkers to risk factors plus
BNP
.
BNP
was associated with
LVH
and
LVSD
in multivariable models, whereas
GDF
‐15 was associated with
LVSD
(
OR
1.41, 95%
CI
: 1.16 to 1.70), and hsTnI with
LVH
(
OR
1.22, 95%
CI
: 1.09 to 1.36).
ST
2 was not significantly associated with any outcome.

Conclusions

Our community‐based investigation suggests that cardiac stress biomarkers are associated with
LVH
and
LVSD
but may have limited clinical utility as screening tools.
Periprocedural Hemodynamic Depression Is Associated With a Higher Number of New Ischemic Brain Lesions After Stenting in the International Carotid Stenting Study-MRI Substudy
Authors: Altinbas Aysun , Algra Ale , Bonati Leo H. , Brown Martin M. , Kappelle L. Jaap , de Borst Gert Jan , Hendrikse Jeroen , van der Tweel Ingeborg , van der Worp H. Bart
Published: November 2013

Background and Purpose—

Carotid artery stenting (CAS) is associated with a higher risk of both hemodynamic depression and new ischemic brain lesions on diffusion-weighted imaging than carotid endarterectomy (CEA). We assessed whether the occurrence of hemodynamic depression is associated with these lesions in patients with symptomatic carotid stenosis treated by CAS or CEA in the randomized International Carotid Stenting Study (ICSS)-MRI substudy.

Methods—

The number and total volume of new ischemic lesions on diffusion-weighted imaging 1 to 3 days after CAS or CEA was measured in the ICSS-MRI substudy. Hemodynamic depression was defined as periprocedural bradycardia, asystole, or hypotension requiring treatment. The number of new ischemic lesions was the primary outcome measure. We calculated risk ratios and 95% confidence intervals per treatment with Poisson regression comparing the number of lesions in patients with or without hemodynamic depression.

Results—

A total of 229 patients were included (122 allocated CAS; 107 CEA). After CAS, patients with hemodynamic depression had a mean of 13 new diffusion-weighted imaging lesions, compared with a mean of 4 in those without hemodynamic depression (risk ratio, 3.36; 95% confidence interval, 1.73–6.50). The number of lesions after CEA was too small for reliable analysis. Lesion volumes did not differ between patients with or without hemodynamic depression.

Conclusions—

In patients treated by CAS, periprocedural hemodynamic depression is associated with an excess of new ischemic lesions on diffusion-weighted imaging. The findings support the hypothesis that hypoperfusion increases the susceptibility of the brain to embolism.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN25337470.
Sabinaria, a new genus of palms (Cryosophileae, Coryphoideae, Arecaceae) from the Colombia-Panama border
Authors: Bernal Rodrigo , Galeano Gloria
Published: November 2013

The new palm genus Sabinaria (Cryosophileae, Coryphoideae, Arecaceae) and the new species Sabinaria magnifica from the Colombia-Panama border are described and illustrated. Sabinaria differs from other genera in the tribe in the leaf blades with a single deep, medial, abaxial split, and short abaxial splits in each segment, mostly unisexual flowers with biseriate perianth, calyx connate with the corolla at a single place on its margin, large, tightly appressed, persistent rachis bracts that hide the pistillate flowers, and fruits tightly packed and hidden among leaf bases, often covered by litter.  Se describen e ilustran el nuevo género de palmas Sabinaria (Cryosophileae, Coryphoideae, Arecaceae) y la nueva especie Sabinaria magnifica, de la frontera entre Colombia y Panamá. Sabinaria difiere de otros géneros en la tribu por la lámina foliar con una sola división abaxial central y cortas divisiones abaxiales en cada uno de los segmentos, flores principalmente unisexuales con perianto biseriado, cáliz connato con la corola en un solo punto en su margen, grandes brácteas del raquis fuertemente adpresas y persistentes, que ocultan las flores pistiladas, y frutos apiñados, ocultos entre las bases de las hojas y a menudo cubiertos por hojarasca.
Redescription of the subgenus Parancistrum Verhoeff, 1943, an eastern Mediterranean lineage of the millipede genus Megaphyllum Verhoeff, 1894 (Diplopoda: Julida: Julidae: Brachyiulini)
Authors: VAGALINSKI BOYAN , LAZÁNYI ESZTER , GOLOVATCH SERGEI
Published: November 2013

The subgenus Parancistrum Verhoeff, 1943 is redefined on the basis of the examination of type and non-type material. The subgenus is currently settled to comprise 6 species, of which Megaphyllum arcuatum sp. n. is described as new, while M. adanense (Verhoeff, 1943) syn. n. and M. palaestinum (Jawłowski, 1931) syn. n. are established as junior subjective synonyms of M. curvifolii (Verhoeff, 1898) and M. genezarethanum (Verhoeff, 1923) comb. nov., respectively. A neotype is designed for Chromatoiulus tenenbaumi Jawłowski, 1931 under ICZN Article 75.1. The distribution pattern of the studied group is discussed, and some preliminary phylogenetic ideas about Megaphyllum and the tribe Brachyiulini are presented.
First recorded cave-dwelling terrestrial isopods (Isopoda: Oniscidea) in Iran with a description of a new species
Authors: KASHANI GHASEM M. , MALEKHOSSEINI MOHAMMAD-JAVAD , SADEGHI SABER
Published: November 2013

Cave-dwelling terrestrial isopods from the province of Kohgiluyeh and Boyerahmad, southwestern Iran, are reported here. These include three accidental and one troglobitic species namely Protracheoniscus gakalicus n. sp., which is also the first recorded troglobitic species from the genus Protracheoniscus. The new species is readily distinguished by the lack of eyes and pigmentation.
The Coherence and Impact of Meridional Heat Transport Anomalies in the Atlantic Ocean Inferred from Observations*
Authors: Kelly Kathryn A. , Thompson LuAnne , Lyman John
Published: November 2013

Observations of thermosteric sea level (TSL) from hydrographic data, equivalent water thickness (EWT) from the Gravity Recovery and Climate Experiment (GRACE), and altimetric sea surface height (SSH) are used to infer meridional heat transport (MHT) anomalies for the Atlantic Ocean. An “unknown control” version of a Kalman filter in each of eight regions extracts smooth estimates of heat transport convergence (HTC) from discrepancies between the response to monthly surface heat and freshwater fluxes and observed mass and heat content. Two models are used: model A using only the heat budget for 1993–2010 and model B using both heat and mass budgets for 2003–10. Based on the small contributions of mass to SSH, model A is rerun using SSH in place of TSL to improve temporal resolution and data consistency. Estimates of MHT are derived by summing the HTC from north to south assuming either negligible anomalies at 67°N or setting MHT to observed values near 40°N. Both methods show that MHT is highly coherent between 35°S and 40°N. The former method gives a large drop in coherence north of 40°N while the latter method gives a less dramatic drop. Estimated anomalies in MHT comparable to or larger than that recently observed at the Rapid Climate Change and Meridional Overturning Circulation and Heatflux Array (RAPID/MOCHA) line at 26.5°N have occurred multiple times in this 18-yr period. Positive anomalies in coherent MHT correspond to increased heat loss in the North Atlantic subtropical gyre demonstrating the feedback of oceanic heat transport anomalies on air–sea fluxes. A correlation of MHT with the Antarctic Oscillation suggests a southern source for the coherent MHT anomalies.
Two Years of Observations of Warm-Core Anticyclones in the Labrador Sea and Their Seasonal Cycle in Heat and Salt Stratification
Authors: de Jong M. F. , Bower A. S. , Furey H. H.
Published: November 2013

Between 25 September 2007 and 28 September 2009, a heavily instrumented mooring was deployed in the Labrador Sea, offshore of the location where warm-core, anticyclonic Irminger rings are formed. The 2-year time series offers insight into the vertical and horizontal structure of newly formed Irminger rings and their heat and salt transport into the interior basin. In 2 years, 12 Irminger rings passed by the mooring. Of these, 11 had distinct properties, while 1 anticyclone likely passed the mooring twice. Eddy radii (11–35 km) were estimated using the dynamic height signal of the anticyclones (8–18 cm) together with the observed velocities. The anticyclones show a seasonal cycle in core properties when observed (1.9°C in temperature and 0.07 in salinity at middepth) that has not been described before. The temperature and salinity are highest in fall and lowest in spring. Cold, fresh caps, suggested to be an important source of freshwater, were seen in spring but were almost nonexistent in fall. The heat and freshwater contributions by the Irminger rings show a large spread (from 12 to 108 MJ m−2 and from −0.5 to −4.7 cm, respectively) for two reasons. First, the large range of radii leads to large differences in transported volume. Second, the seasonal cycle leads to changes in heat and salt content per unit volume. This implies that estimates of heat and freshwater transport by eddies should take the distribution of eddy properties into account in order to accurately assess their contribution to the restratification.