bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending far and wide: the role of biopsy and staging in the management of ocular surface squamous neoplasia
Authors: Polski Ashley , Sibug Saber Maria , Kim Jonathan W. , Berry Jesse L.
Published: August 2018

Importance

Although the most recent American Joint Committee on cancer staging guidelines for ocular surface squamous neoplasia place a heightened emphasis on biopsy and histopathologic analysis, the interpretation and clinical relevance of these staging criteria are not always clear. We address limitations of using histopathologic analysis to predict clinical outcomes and suggest less‐invasive assessments.

Background

To investigate the impact of histopathologic depth of invasion on outcomes for tumours with the common presentation of multiple structure involvement.

Design

Retrospective chart review at tertiary institution.

Samples

Of 41 eyes with ocular surface squamous neoplasia between 2012 and 2017, 27 tumours involving multiple ocular structures clinically were included.

Methods

Biopsied tumours were determined to be invasive beyond the basement membrane or non‐invasive; non‐biopsied tumours were clinically identified with unknown depth of invasion. Outcomes were compared using Fisher's exact or Student's t tests.

Main Outcome Measures

Proportion of tumours cured, recurred and/or persisting.

Results

Twelve tumours (44%) received primary excisional biopsy, 10 (37%) received chemotherapy without biopsy and 5 (19%) received chemotherapy and biopsy. Clinical diagnosis was correct in all biopsied cases. While there were no significant differences in outcomes between invasive vs non‐invasive tumours or treatments, there was a trend toward larger basal diameter in recurrent tumours regardless of treatment.

Conclusions and Relevance

When ocular surface squamous neoplasia tumours with similar clinical involvement were compared, histopathologic depth of invasion was not predictive of clinical outcomes. Future staging criteria may consider the potential of largest basal dimension for more accurate prognostication.
Vascular endothelial growth factor activates neural stem cells through epidermal growth factor receptor signal after spinal cord injury
Authors: Liu Su‐Mei , Xiao Zhi‐Feng , Li Xing , Zhao Yan‐Nan , Wu Xian‐Ming , Han Jin , Chen Bing , Li Jia‐Yin , Fan Cai‐Xia , Xu Bai , Xue Xiao‐Yu , Xue Wei‐Wei , Yang Ying , Dai Jian‐Wu
Published: August 2018

Aims

Neural stem cells (NSCs) in the adult mammalian spinal cord are activated in response to spinal cord injury (SCI); however, mechanisms modulating this process are not clear. Here, we noticed SCI elevated expression of vascular endothelial growth factor (VEGF) and we aimed to validate the roles of VEGF in NSCs activation after SCI and investigated the related signals during the process.

Methods

In vitro we detected whether VEGF promoted spinal cord NSCs proliferation and investigated the involved signals; In vivo, we injected VEGF into rat spinal cord to check the NSCs activation.

Results

In vitro, VEGF triggered spinal cord NSCs proliferation and maintained self‐renewal. Further investigations demonstrated VEGF transactivated epidermal growth factor receptor (EGFR) through VEGF receptor 2 (VEGFR2) to promote spinal cord NSCs proliferation. In vivo, we injected VEGF into spinal cord by laminectomy to confirm the roles of VEGF‐VEGFR2‐EGFR signals in NSCs activation. VEGF significantly elevated the number of activated NSCs and increased EGFR phosphorylation. In contrast, intraspinal injection of specific inhibitors targeting EGFR and VEGFR2 decreased NSCs activation after SCI. Our results demonstrate that VEGF‐VEGFR2‐EGFR axis is important for NSCs activation after SCI, providing new insights into the mechanisms of spinal cord NSCs activation postinjury.
LncRNA SNHG4 promotes tumour growth by sponging miR‐224‐3p and predicts poor survival and recurrence in human osteosarcoma
Authors: Xu Ruida , Feng Fan , Yu Xiaosheng , Liu Zude , Lao Lifeng
Published: August 2018

Objective

Accumulating data show that dysregulation of long noncoding RNAs (lncRNAs) acts a critical role in a variety of malignancies. Among these lncRNAs, small nucleolar RNA host genes (SNHGs) are associated with tumour growth and progression. But, the molecular mechanisms by which SNHG4 contributes to osteosarcoma remain undocumented.

Methods

The association between lncRNA SNHG4 expression and clinicopathologic characteristics and prognosis in patients with osteosarcoma was analysed by TCGA RNA‐sequencing data. Cell viability and colony formation abilities were respectively assessed by MTT and colony formation assays. LncRNA SNHG4‐specific binding with miR‐224‐3p was verified by bioinformatic analysis, luciferase gene report, and RNA immunoprecipitation assays. Regulation relationship between SNHG4 and miR‐224‐3p expression was further evaluated by the rescue experiments.

Results

The expression level of lncRNA SNHG4 was significantly elevated in osteosarcoma samples and cell lines as compared with the adjacent normal tissues, and SNHG4 high expression was associated with tumour size (TS) and poor prognosis in patients with osteosarcoma. Knockdown of SNHG4 suppressed cell viability and invasive potential, whereas ectopic SNHG4 expression displayed the opposite effects. Moreover, we found that lncRNA SNHG4 acted as a sponge of miR‐224‐3p, and miR‐224‐3p mimic reversed SNHG4 induced tumour‐promoting effects in osteosarcoma cells. The expression of miR‐224‐3p depicted a negative correlation with SNHG4 in osteosarcoma samples and miR‐224‐3p low expression was associated with TS and poor survival in patients with osteosarcoma.

Conclusion

Our findings demonstrated that LncRNA SNHG4 promoted tumour growth by sponging miR‐224‐3p and represented a poor prognostic factor in patients with osteosarcoma.
Narciclasine induces autophagy‐dependent apoptosis in triple‐negative breast cancer cells by regulating the AMPK‐ULK1 axis
Authors: Cao Chuan , Huang Wei , Zhang Nan , Wu Fengbo , Xu Ting , Pan Xiaoli , Peng Cheng , Han Bo
Published: August 2018

Objectives

Autophagy and apoptosis are major types of eukaryotic programmed cell death, and regulating these processes holds promise for treating cancers. In this study, we explored the regulation mechanisms of narciclasine to autophagy and apoptosis processes in triple‐negative breast cancer.

Materials and Methods

Effects of narciclasine on proliferation, apoptosis, and autophagy of HCC‐1937 and MDA‐MB‐231 triple‐negative breast cancer (TNBC) cells were assessed using transmission electronic microscopy, flow cytometry following staining with Annexin V‐FITC and propidium iodide, RNA sequencing, real‐time PCR, and Western blotting. The ability of narciclasine to inhibit growth of human HCC1937 TNBC xenografts in mice was assessed, and potential mechanisms of inhibition were explored using immunohistochemistry.

Results

Narciclasine inhibited TNBC cell proliferation and induced autophagy‐dependent apoptosis in a dose‐dependent manner. These apoptotic effects could be reversed using autophagy inhibitors, including an AMPK inhibitor and ULK1 siRNA. Consistent with these in vitro results, narciclasine significantly inhibited TNBC tumour growth in mice by upregulating autophagy‐dependent apoptosis.

Conclusions

Our findings suggest that narciclasine regulates the AMPK‐ULK1 signalling axis to promote autophagy‐dependent apoptosis, demonstrating therapeutic potential against TNBC.
Preoperative expectations for health‐related quality of life after lung transplant
Authors: Aversa Meghan , Chowdhury Noori A. , Tomlinson George , Singer Lianne G.
Published: August 2018

How patients’ health‐related quality of life (HRQL) after lung transplant compares to their preoperative expectations is unclear. As part of a previously published prospective cohort study, we compared 328 subjects’ expectations for their post‐transplant HQRL with and without chronic lung allograft dysfunction (CLAD) to their actual HRQL scores after transplant, using the visual analog scale (VAS) and standard gamble (SG). Subjects’ expectations were considered met when the absolute difference between the expected and actual scores (the “expectation error”) was <0.1 units, based on the minimally important difference for VAS and SG. On average, subjects’ post‐transplant HRQL without CLAD met their expectations (mean expectation error: −0.09 units [VAS] and +0.02 units [SG]) and subjects’ post‐transplant HRQL with CLAD met or exceeded their expectations (mean expectation error: +0.08 units [VAS] and +0.19 units [SG]). When subjects developed CLAD stages 1 and 2, their HRQL was better than they expected (mean expectation error of each disease group: >+0.1 units). When subjects developed CLAD stage 3, their HRQL was as they expected (mean expectation error of each disease group except COPD and CF: within ± 0.1 units). Patients’ expectations for their HRQL after transplant are at least met and may be exceeded.
Cell blocks in cytopathology: An update
Authors: Nambirajan Aruna , Jain Deepali
Published: August 2018

The cell block (CB) offers many advantages over other cytological preparations, particularly for immunocytochemical and molecular testing. However, inconsistent cellularity remains the most common reason for dissatisfaction among cytopathologists. In recent years, there has been a surge in the demand for CBs imposed by the increasing number of minimally invasive procedures performed to obtain material for diagnostic, prognostic and predictive purposes from advanced stage cancer patients. However, routine preparation of CBs significantly increases laboratory work load, operating cost and sample turn‐around time. The objectives of our review were to: (a) identify scenarios where a CB is likely to improve diagnostic yield; (b) optimise CB preparatory methods; and (c) understand the factors influencing the success and validity of ancillary testing on various types of CBs. We performed an extensive literature search on CBs in cytology on internet search engines using the following keywords: cell block, cytoblock, cytology, cytopathology, methods, preparation, fixatives, diagnostic yield, ancillary and molecular studies. New CB methods, improvisations of previous CB methods, their utility for diagnosis, immunocytochemistry and molecular testing, and role in predictive biomarker testing are discussed in this review. CBs of good quality and cellularity outperform other cytology preparations in their reliability and versatility for ancillary testing. With many CB methods described in the literature, each with specific advantages and limitations, laboratories may choose to use one or more of the methods depending upon their infrastructure, expertise and workload.
Embryonic stage of obligatory diapause and effects of abiotic conditions on egg hatching in the balsam twig aphid, Mindarus abietinus
Authors: Doherty Jean‐François , Guay Jean‐Frédéric , Cloutier Conrad
Published: August 2018

Diapause‐mediated dormancy in overwintering insect eggs has rarely been studied with regard to the ecological factors controlling postdiapause development. In insects of temperate latitudes, water availability at the end of winter, in interaction with temperature, could control the resumption of development for insect stages in postdiapause quiescence. The balsam twig aphid, Mindarus abietinus Koch (Hemiptera: Aphididae), overwinters as eggs in southern Québec, Canada, on balsam fir, Abies balsamea (L.) Miller (Pinaceae), in Christmas tree plantations, where it is known as a pest. Previous work has shown that eggs of this aphid maintain low water content during winter, presumably to survive sub‐zero temperatures. Conversely, in late winter and early spring, they passively or actively absorb surrounding moisture, which is accompanied by notable changes in size, shape, and fresh mass. The primary objective here was to determine the embryonic stage at which winter diapause starts and is maintained in M. abietinus, a relatively primitive aphid. Secondly, we tested the hypothesis that free water availability to postdiapause eggs, in combination with temperatures above developmental threshold, is essential for embryonic development and hatching, by experimentally soaking field‐collected eggs in water at controlled frequencies. We observed that embryogenesis starts at the time of egg laying and stops after a few days, before the anatrepsis stage of blastokinesis is complete, when the germ band has not yet entirely immersed itself into the yolk. We also found that water surrounding overwintered eggs on fir shoots, in interaction with temperature regime, significantly increases M. abietinus egg hatching rates. Potential impacts of environmental factors such as precipitation are discussed in relation to M. abietinus egg hatching rates and potential for population growth in spring.
Mapping the imprint of biotic interactions on β‐diversity
Authors: Ohlmann Marc , Mazel Florent , Chalmandrier Loïc , Bec Stéphane , Coissac Eric , Gielly Ludovic , Pansu Johan , Schilling Vincent , Taberlet Pierre , Zinger Lucie , Chave Jérome , Thuiller Wilfried
Published: August 2018

Investigating how trophic interactions influence the β‐diversity of meta‐communities is of paramount importance to understanding the processes shaping biodiversity distribution. Here, we apply a statistical method for inferring the strength of spatial dependencies between pairs of species groups. Using simulated community data generated from a multi‐trophic model, we showed that this method can approximate biotic interactions in multi‐trophic communities based on β‐diversity patterns across groups. When applied to soil multi‐trophic communities along an elevational gradient in the French Alps, we found that fungi make a major contribution to the structuring of β‐diversity across trophic groups. We also demonstrated that there were strong spatial dependencies between groups known to interact specifically (e.g. plant‐symbiotic fungi, bacteria‐nematodes) and that the influence of environment was less important than previously reported in the literature. Our method paves the way for a better understanding and mapping of multi‐trophic communities through space and time.
Neurotrophic factors and status epilepticus
Authors: Simonato Michele
Published: August 2018

Because of their strong effects on cell survival and on synaptic function, neurotrophic factors (NTFs) have been hypothesized to be involved in some aspects of status epilepticus (SE) and in its possible consequences. This hypothesis has been explored mainly for 2 NTFs, namely fibroblast growth factor 2 (FGF‐2) and brain‐derived neurotrophic factor (BDNF). This article focuses on these 2 NTFs. I first summarize their biologic features and then describe existing evidence supporting their implication in SE and its outcomes. Available data support a direct implication of FGF‐2 and BDNF in SE and in its consequences. However, these NTFs have been found to exert some contrasting effects, for example, to favor seizures but protect from cell damage. A better understanding of the mechanisms of FGF‐2 and BDNF biosynthesis and signaling will be therefore instrumental for the development of therapeutic strategies that are not compromised by paradoxical side effects.
Modelling the invasion history of Sinanodonta woodiana in Europe: Tracking the routes of a sedentary aquatic invader with mobile parasitic larvae
Authors: Konečný Adam , Popa Oana P. , Bartáková Veronika , Douda Karel , Bryja Josef , Smith Carl , Popa Luis O. , Reichard Martin
Published: August 2018

Understanding the invasive potential of species outside their native range is one of the most pressing questions in applied evolutionary and ecological research. Admixture of genotypes of invasive species from multiple sources has been implicated in successful invasions, by generating novel genetic combinations that facilitate rapid adaptation to new environments. Alternatively, adaptive evolution on standing genetic variation, exposed by phenotypic plasticity and selected by genetic accommodation, can facilitate invasion success. We investigated the population genetic structure of an Asian freshwater mussel with a parasitic dispersal stage, Sinanodonta woodiana, which has been present in Europe since 1979 but which has expanded rapidly in the last decade. Data from a mitochondrial marker and nuclear microsatellites have suggested that all European populations of S. woodiana originate from the River Yangtze basin in China. Only a single haplotype was detected in Europe, in contrast to substantial mitochondrial diversity in native Asian populations. Analysis of microsatellite markers indicated intensive gene flow and confirmed a lower genetic diversity of European populations compared to those from the Yangtze basin, though that difference was not large. Using an Approximate Bayesian Modelling approach, we identified two areas as the probable source of the spread of S. woodiana in Europe, which matched historical records for its establishment. Their populations originated from a single colonization event. Our data do not support alternative explanations for the rapid recent spread of S. woodiana; recent arrival of a novel (cold‐tolerant) genotype or continuous propagule pressure. Instead, in situ adaptation, facilitated by repeated admixture, appears to drive the ongoing expansion of S. woodiana. We discuss management consequences of our results.
Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction
Authors: Ziegler A. L. , Freeman C. K. , Fogle C. A. , Burke M. J. , Davis J. L. , Cook V. L. , Southwood L. L. , Blikslager A. T.
Published: August 2018

Background

Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti‐inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo‐oxygenases (COX). COX‐1 is expressed constitutively and promotes gut barrier function, whereas COX‐2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX‐2 selective NSAIDs as compared with horses treated with flunixin meglumine.

Objectives

We hypothesised that treatment of post‐surgical SISO horses with firocoxib (COX‐2 selective) would reduce the signs of endotoxaemia to a greater extent than flunixin meglumine (nonselective COX inhibitor) while continuing to provide similar levels of pain control.

Study design

Blinded randomised clinical trial.

Methods

In addition to clinical monitoring, preoperative and 12‐, 24‐ and 48‐h post‐operative plasma samples were assessed for prostaglandin E2(PGE2), thromboxane B2(TXB2), TNF⍺ and soluble CD14 (sCD14).

Results

In 56 recruited SISO horses, either flunixin meglumine (1.1 mg/kg, i.v., q12h) or firocoxib (0.3 mg/kg, i.v. loading dose; 0.1 mg/kg, i.v., q24h) was given in the post‐operative period in three university hospitals from 2015 to 2017.

COX‐2 selectivity was confirmed by a relative lack of inhibition of the COX‐1 prostanoid TXB2by firocoxib and significant inhibition by flunixin meglumine (P = 0.014). Both drugs inhibited the COX‐2 prostanoid PGE2. There were no significant differences in pain scores between groups (P = 0.2). However, there was a 3.23‐fold increased risk (P = 0.04) of increased plasma sCD14 in horses treated with flunixin meglumine, a validated biomarker of equine endotoxaemia.

Main limitations

Horses were all treated with flunixin meglumine prior to referral. In addition, many horses were treated with lidocaine, which has been shown to mitigate the deleterious effects of flunixin meglumine.

Conclusions

In SISO cases, firocoxib reduced a biomarker of endotoxaemia as compared with flunixin meglumine while continuing to provide similar levels of pain control.
Beyond the Couple: A Qualitative Analysis of Successful In‐law Relationships in Iran
Authors: Cheraghi Mona , Mazaheri Mohammad A. , Motabi Fereshteh , Panaghi Leili , Sadeghi Mansoureh S.
Published: August 2018

In‐laws can play a significant role in the success or failure of marriages around the world. In the Middle East, recent quantitative research indicates that having trouble with in‐laws is a major predictor of divorce in Iran. To explore this further, we undertook a qualitative (grounded theory) analysis of in‐depth interviews with 17 Iranian daughters‐in‐law, five sons‐in‐law, three mothers‐in‐law, three fathers‐in‐law, and three expert family clinicians. Emergent concepts, themes, and coding categories were consistent with a Family Triad Model (FTM) of successful marital and in‐law relationships, wherein each spouse must (a) formwe‐ness with their partner, (b) establish flexible boundaries between themselves and their families of origin, and (c) join their in‐laws. A higher‐order core category suggested that optimal couple and family functioning depends on the coherence or balance of these functions across the triadic role components of spouse, child‐in‐law, and family‐in‐law (or family‐of‐origin). In the changing cultural context of Iran, where blood relations have traditionally held primacy over marital relations, such triadic coherence appears crucial to marital success, at least from the perspective of many women. OurFTMresults also highlight the importance of taking in‐laws into account when planning educational, preventative, or clinical interventions.
Endogenous debt maturity and rollover risk
Authors: Brancati Emanuele , Macchiavelli Marco
Published: August 2018

We empirically study the nature of rollover risk and show how banks manage it. Having to roll over debt does not lead to higher default risk per se. Only banks that lose significant access to new funding while having to roll over debt display higher default risk. We identify a factor that determines this buildup of risk: specifically, debt maturity shortening (forcing debt to be more frequently rolled over) and reduced access to new funding are both driven by market pessimism about banks’ future performance. We also provide evidence consistent with dynamic coordination risk.
Monitoring the acoustic activity of an aquatic insect population in relation to temperature, vegetation and noise
Authors: Desjonquères Camille , Rybak Fanny , Ulloa Juan Sebastian , Kempf Alexandre , Bar Hen Avner , Sueur Jérôme
Published: August 2018

Acoustic population monitoring is a noninvasive method that can be deployed continuously over long periods of time and at large spatial scales. One of the newly discovered threats acting on biological diversity is anthropogenic noise. High levels of anthropogenic noise occur in aquatic environments, yet their effects on animals living in freshwater habitats have very rarely been investigated.

Here, we used acoustic monitoring and automatic detection to assess the acoustic activity of a population of a soniferous freshwater insect.

The sounds emitted by the corixid Micronecta scholtzi were recorded in a Mediterranean pond with an array of 12 hydrophones. An automatic analysis based on a measure of the amplitude found in the frequency band of M. scholtzi was developed to assess the level of acoustic activity. We used functional linear models, accounting for the periodicity of the calling behaviour, to estimate the possible effect of temperature, vegetation and a noise due to an immersed engine.

The automatic analysis was validated as an efficient method to measure the acoustic activity. The monitoring revealed a clear 24‐hr pattern in the acoustic activity of M. scholtzi and three peaks of activity during the morning. Functional linear models revealed negative effects of both temperature and vegetation and showed that an engine noise, played back for 2 hr during the night, elicited an increase in the level of acoustic activity of the population. Moreover, a cross‐correlation procedure showed that noise delayed the acoustic activity of the population.

Our results suggest that acoustic survey and automatic detection are efficient methods to monitor the acoustic activity of an insect population especially in response to an anthropogenic disturbance.
Pivotal roles of environmental sensing and signaling mechanisms in plant responses to climate change
Authors: Bigot Servane , Buges Julie , Gilly Lauriane , Jacques Cécile , Le Boulch Pauline , Berger Marie , Delcros Pauline , Domergue Jean‐Baptiste , Koehl Astrid , Ley‐Ngardigal Béra , Tran Van Canh Loup , Couée Ivan
Published: August 2018

Climate change reshapes the physiology and development of organisms through phenotypic plasticity, epigenetic modifications, and genetic adaptation. Under evolutionary pressures of the sessile lifestyle, plants possess efficient systems of phenotypic plasticity and acclimation to environmental conditions. Molecular analysis, especially through omics approaches, of these primary lines of environmental adjustment in the context of climate change has revealed the underlying biochemical and physiological mechanisms, thus characterizing the links between phenotypic plasticity and climate change responses. The efficiency of adaptive plasticity under climate change indeed depends on the realization of such biochemical and physiological mechanisms, but the importance of sensing and signaling mechanisms that can integrate perception of environmental cues and transduction into physiological responses is often overlooked. Recent progress opens the possibility of considering plant phenotypic plasticity and responses to climate change through the perspective of environmental sensing and signaling. This review aims to analyze present knowledge on plant sensing and signaling mechanisms and discuss how their structural and functional characteristics lead to resilience or hypersensitivity under conditions of climate change. Plant cells are endowed with arrays of environmental and stress sensors and with internal signals that act as molecular integrators of the multiple constraints of climate change, thus giving rise to potential mechanisms of climate change sensing. Moreover, mechanisms of stress‐related information propagation lead to stress memory and acquired stress tolerance that could withstand different scenarios of modifications of stress frequency and intensity. However, optimal functioning of existing sensors, optimal integration of additive constraints and signals, or memory processes can be hampered by conflicting interferences between novel combinations and novel changes in intensity and duration of climate change‐related factors. Analysis of these contrasted situations emphasizes the need for future research on the diversity and robustness of plant signaling mechanisms under climate change conditions.
A geographical multivariable multilevel analysis of social exclusion among older people in China: Evidence from the China Longitudinal Aging Social Survey ageing study
Authors: Feng Zhixin , Phillips David R. , Jones Kelvyn
Published: August 2018

Social exclusion is increasingly considered to be a multi‐faceted concept involving more than simply material disadvantage among older people. The process of social exclusion may be driven by various factors and at different levels, including individual, household, group, community, country and global levels. Using data from the 2014 China Longitudinal Aging Social Survey focusing on respondents aged over 60, we employed multivariate multilevel models to simultaneously estimate four dimensions of social exclusion among older people. The results show that the social exclusion of older people varies not only among individuals but also among provinces. From an individual perspective, older people with lower educational attainment (often illiterate), in the lowest quintile of personal income and in poor health were the most likely to be excluded. From a geographical perspective, although there are no province‐level characteristics (social, economic and social security development) significantly related to the four dimensions of social exclusion, there is nevertheless significant unexplained variation for all dimensions of social exclusion at the province level. The negative relationships between exclusion from social relationships and exclusion from financial products, between subjective feeling of exclusion and social activities, and between subjective feeling of exclusion and exclusion from financial products at the provincial level indicate that a province may do well on one dimension of social exclusion but it will not automatically do well on the other dimensions.
GZ7 and GZ8 – Two Zircon Reference Materials for SIMS U‐Pb Geochronology
Authors: Nasdala Lutz , Corfu Fernando , Schoene Blair , Tapster Simon R. , Wall Corey J. , Schmitz Mark D. , Ovtcharova Maria , Schaltegger Urs , Kennedy Allen K. , Kronz Andreas , Reiners Peter W. , Yang Yue‐Heng , Wu Fu‐Yuan , Gain Sarah E. M. , Griffin William L. , Szymanowski Dawid , Chanmuang N. Chutimun , Ende Martin , Valley John W. , Spicuzza Michael J. , Wanthanachaisaeng Bhuwadol , Giester Gerald
Published: August 2018

Here, we document a detailed characterisation of two zircon gemstones, GZ7 and GZ8. Both stones had the same mass at 19.2 carats (3.84 g) each; both came from placer deposits in the Ratnapura district, Sri Lanka. The U‐Pb data are in both cases concordant within the uncertainties of decay constants and yield weighted mean 206Pb/238U ages (95% confidence uncertainty) of 530.26 Ma ± 0.05 Ma (GZ7) and 543.92 Ma ± 0.06 Ma (GZ8). Neither GZ7 nor GZ8 have been subjected to any gem enhancement by heating. Structure‐related parameters correspond well with the calculated alpha doses of 1.48 × 1018 g−1 (GZ7) and 2.53 × 1018 g−1 (GZ8), respectively, and the (U‐Th)/He ages of 438 Ma ± 3 Ma (2s) for GZ7 and 426 Ma ± 9 Ma (2s) for GZ8 are typical of unheated zircon from Sri Lanka. The mean U mass fractions are 680 μg g−1 (GZ7) and 1305 μg g−1 (GZ8). The two zircon samples are proposed as reference materials for SIMS (secondary ion mass spectrometry) U‐Pb geochronology. In addition, GZ7 (Ti mass fractions 25.08 μg g−1 ± 0.18 μg g−1; 95% confidence uncertainty) may prove useful as reference material for Ti‐in‐zircon temperature estimates.
Bayesian Monitoring Design for Streambed Heat Tracing: Numerical Simulation and Sandbox Experiments
Authors: Ju Lei , Zhang Jiangjiang , Wu Laosheng , Zeng Lingzao
Published: August 2018

Heat tracing methods have been widely employed for subsurface characterization. Nevertheless, there were very few studies regarding the optimal monitoring design for heat tracing in heterogeneous streambeds. In this study, we addressed this issue by proposing an efficient optimal design framework to collect the most informative diurnal temperature signal for Bayesian estimation of streambed hydraulic conductivities. The data worth (DW) was measured by the expected relative entropy between the prior and posterior distributions of the conductivity field. An adaptively refined Gaussian process surrogate was employed to alleviate the computational burden, resulting in at least three orders of magnitude of speed‐up. The applicability of the optimal experimental design framework was evaluated by both numerical and sandbox experimental cases. Results showed that the most informative locations centered in the transition zones among the main patterns of the hydraulic conductivity field, while the most informative times centered in a short period after the minimum/maximum temperature appeared. With the fixed number of measurements, extending the calibration period was more beneficial than increasing the monitoring frequency in improving the estimation results. To our best knowledge, this work is the first study on Bayesian monitoring design for streambed characterization with the heat tracing method. The method and results can provide guidance on selecting monitoring strategies under budget‐limited conditions.
Congenital coagulation factor X deficiency: Genetic analysis of five patients and functional characterization of mutant factor X proteins
Authors: Nagaya Satomi , Akiyama Masashi , Murakami Morika , Sekiya Akiko , Asakura Hidesaku , Morishita Eriko
Published: August 2018

Congenital factor X (FX) deficiency is a rare bleeding disorder that is inherited as an autosomal recessive trait. In this study, a genetic analysis of the FX gene was performed in five families with this disorder. Four heterozygous mutations [p.Gly154Arg, p.Val236Met, p.Gly263Val and p.Arg387Cys] and one pair of compound heterozygous FX gene mutations consisting of p.Gly406Ser and p.Val424Phe were identified. Mutant FX proteins containing the identified amino acid substitutions were also expressed in cultured cells. These proteins were analysed by enzyme‐linked immunosorbent assay and pulse‐chase experiments. The results demonstrated normal intracellular synthesis and extracellular secretion of mutant FX proteins carrying the p.Val236Met, p.Arg387Cys and p.Gly406Ser amino acid substitutions. However, the results also showed that the p.Gly154Arg, p.Gly263Val and p.Val424Phe proteins were secreted less efficiently than the wild‐type protein, although they were synthesized normally in the cell. Collectively, these observations suggest that the amino acid substitutions p.Gly154Arg, p.Gly263Val and p.Val424Phe induce protein misfolding, leading to the intracellular degradation of many FX proteins containing any of these mutations, and ultimately to the development of FX deficiency. On the other hand, for the p.Val236Met, p.Arg387Cys and p.Gly406Ser mutant proteins, we hypothesize that secreted FX proteins have impaired coagulant activities due to functional defects caused by these amino acid substitutions.
The implementation of the consensus on the management of Helicobacter pylori and barriers to consensus
Authors: Cheng Hsiu‐Chi , Liou Jyh‐Ming , Luo Jiing‐Chyuan , Chiu Cheng‐Tang , Wu Ming‐Shiang , Lee Yi‐Chia , Wu Chun‐Ying , Wu Deng‐Chyang , Hsu Ping‐I , Chang Chun‐Chao , Chang Wei‐Lun , Lin Jaw‐Town , Sheu Bor‐Shyang
Published: August 2018

Background

A consensus on the management of Helicobacter pylori has been developed. We aimed to assess whether dissemination through continuing medical education (CME) could enhance the adoption of this consensus among clinicians and to explore potential barriers to acceptance.

Materials and methods

Four CME courses were held to disseminate the consensus. Adoption surveys were performed to evaluate participants’ behavior in the past and their commitment to adopt the consensus in future clinical practice after CME. The gaps and barriers to adoption were also surveyed.

Results

A total of 240 physicians had attended the CME courses and received surveys with the 22 statements/substatements of the consensus. Before CME, adoption was good in six, fair in ten, and poor in six. After CME, 21 statements had either an initial >90% adoption or improvement to good or fair (P < 0.001), but one still had poor even though it showed improvement (P = 0.02). Although commitment was good or fair after CME, there was a >20% gap between “commitment” and “no barrier” to adoption for 11 statements, ten of which had a main barrier of financial incentives. Among the statements with fair or poor commitment after CME, less commitment to adoption and more barriers related to financial incentives were pronounced in clinicians serving in regional/district hospitals or clinics compared to those serving in medical centers.

Conclusions

Continuing medical education may improve the adoption of the H. pylori consensus. The financial incentives were shown to be a main barrier to adoption of the consensus and should be improved.
Concordance of biopsy and prostatectomy diagnosis of intraductal and cribriform carcinoma in a prospectively collected data set
Authors: Masoomian Mehdi , Downes Michelle R , Sweet Joan , Cheung Carol , Evans Andrew J , Fleshner Neil , Maganti Manjula , Van der Kwast Theodorus
Published: August 2018

Aims

Intraductal and cribriform carcinoma of the prostate are increasingly recognised as independent prognosticators of poor outcome, both in prostate biopsies and surgical specimens. We studied the concordance of biopsy and prostatectomy diagnosis for these two subpathologies in relationship with pathological stage.

Methods and results

Mandatory synoptic reporting of intraductal and cribriform carcinoma in prostate biopsies and prostatectomy specimens was adopted by two academic institutions in November 2015. Synoptic reports of 245 biopsy and corresponding prostatectomy specimens were interrogated to determine the prevalence of intraductal and cribriform carcinoma. Sensitivity and specificity were determined, with prostatectomy diagnosis as the gold standard. Associations with pathological stage as primary outcome parameter were determined using univariable and multivariable logistic regression analysis. Prevalence of the combination of intraductal and cribriform carcinoma was 26.9% in biopsies and 51.8% in prostatectomy specimens. Sensitivity and specificity at biopsy were 47.2% and 94.9%, respectively. Intraductal and cribriform carcinoma at biopsy were associated with advanced pathological stage independent of grade (P = 0.013). Among patients with grade group 2 prostate cancer at biopsy, the more advanced pathological stage distribution was similar for those with a false negative and a true positive biopsy diagnosis of intraductal and cribriform carcinoma (P = 0.29).

Conclusion

In spite of low sensitivity, intraductal and cribriform carcinoma at biopsy was associated strongly with advanced stage at radical prostatectomy. As a false negative biopsy diagnosis was equally associated with advanced pathological stage, efforts should be undertaken to improve the sensitivity of biopsy diagnosis for intraductal and cribriform carcinoma.
Associations among histological characteristics and patient outcomes in colorectal carcinoma with a mucinous component
Authors: Gonzalez Raul S , Cates Justin M M , Washington Kay
Published: August 2018

Aims

Colorectal carcinoma (CRC) often has a mucinous component, with more than 50% mucin by volume defining the mucinous subtype of CRC. The prognostic impact of the mucinous phenotype remains unclear.

Methods and results

We evaluated 224 CRC with at least 5% mucinous component (herein ‘mCRC’) for patient sex, age, race and outcome; tumour size, location, stage and microsatellite instability (MSI) status; percentage of glands producing mucin; percentage of tumour volume composed of mucin; whether tumoral epithelium floated in mucin pools; tumour budding; signet ring cells (SRCs); and peritumoural inflammation (PI). We related these features to disease‐specific survival and compared outcomes to 499 stage‐matched, conventional colorectal adenocarcinomas. Factors predicting worse prognosis in mCRC on univariable analysis included non‐MSI‐high status (P = 0.0008), SRC (P = 0.0017) and lack of PI (P = 0.0034). No parameters were independently associated with outcome after adjusting for tumour stage in multivariate analysis. The percentage of glands producing mucin and percentage tumour volume composed of mucin did not affect prognosis, including at the recommended 50% cut‐off for subtyping mCRC. Disease‐specific survival for mCRC and adenocarcinomas were similar after accounting for stage.

Conclusions

Stage‐matched mCRCs and adenocarcinomas have similar outcomes, with no prognostic significance to morphological subtyping. Histological characteristics of mCRC, including percentage of tumour volume comprised of mucin, were not predictive of outcome.
Microstructure and mechanical properties of TiN‐based cermet reinforced by Cr3C2 addition
Authors: Wu Yuxue , Xiong Huiwen , Gan Xueping , Li Zhiyou , Zhou Kechao
Published: August 2018

TiN‐based cermets with different Cr3C2 addition were prepared by conventional vacuum sintering. Effect of Cr3C2 on microstructure and properties of TiN‐based cermets were discussed. Owing to the formation of sound rims on TiN cores, ultrafine TiN‐based cermets with more uniform microstructure and finer grains were obtained with 1 wt% Cr3C2. When the added Cr3C2 content enhanced from 0 to 2 wt%, the transverse rupture strength (TRS) and fracture toughness increased firstly and then decreased, while the hardness increased monotonically. For the experimental conditions considered, the cermet with 1 wt% Cr3C2 addition had optimal combination of hardness (91HRA), fracture toughness (14.7 MPa m1/2) and TRS (2123 MPa).
Molecular pathogenesis of renal cell carcinoma: Impact of the anti‐tumor miR‐29 family on gene regulation
Authors: Yamada Yasutaka , Sugawara Sho , Arai Takayuki , Kojima Satoko , Kato Mayuko , Okato Atsushi , Yamazaki Kazuto , Naya Yukio , Ichikawa Tomohiko , Seki Naohiko
Published: August 2018

Objectives

To identify key oncogenes and proteins that are controlled by the microRNA miR‐29 family (miR‐29a, miR‐29b and miR‐29c) in renal cell carcinoma pathogenesis.

Methods

Genome‐wide gene expression and in silico database analyses were carried out. The Cancer Genome Atlas database was used to investigate the clinical significance of gene expression data in renal cell carcinoma patients. Loss‐of‐function assays were applied to investigate the function of target genes.

Results

We identified 47 possible target genes that might be regulated by the miR‐29 family in renal cell carcinoma cells. Among the targets of the miR‐29 family, high expression of 10 genes (ADAMTS14, TRIB13, SERPINH1, FCGR1B, COL1A1, LAIR2, WISP2, TREM1, TNKS1BP1 and GBP2) significantly predicted poor patient prognosis (P < 0.001). SERPINH1 was directly regulated by the miR‐29 family, and its overexpression was detected in renal cell carcinoma surgical specimens and tyrosine kinase inhibitor failure autopsy specimens. High expression of SERPINH1 was significantly associated with tumor stage, pathological grade and poor prognosis (P < 0.0001). Knockdown assays showed that its expression enhanced cancer cell migration and invasive abilities.

Conclusions

Genes regulated by the anti‐tumor miR‐29 family are closely involved in the molecular pathogenesis of renal cell carcinoma. Our approach based on anti‐tumor microRNAs might contribute to the development of new diagnostic markers and therapeutic strategies.
Linking Migration Intentions with Flows: Evidence and Potential Use
Authors: Tjaden Jasper , Auer Daniel , Laczko Frank
Published: August 2018

In the absence of reliable, internationally available migration flow data necessary for statistical forecasting, policymakers increasingly turn to survey data on emigration intentions to evaluate future migration trends. The important assumption – i.e. that there is a measurable and systematic relationship between the intention to migrate and actual migration – has not been firmly established at the international level. We examine the association between estimated population averages of emigration intentions and official migration flow data based on data for more than 160 countries. The results show a strong association between emigration intentions and recorded bilateral flows to industrialized countries, as well as between intentions and aggregated out‐migration. The results provide policymakers with a reliability assessment of survey data on emigration intentions and encourage future attempts to incorporate survey data in formal statistical migration forecasting models.
Secondary‐intention healing following Mohs micrographic surgery for squamous cell carcinoma of a finger
Authors: Magliano Julio , Rossi Virginia , Turra Nelson , Bazzano Carlos
Published: August 2018

Mohs micrographic surgery is the best therapeutical option for hand squamous cell carcinoma without bone involvement; however, the reconstruction of the surgical defect could be very difficult if the tumour is located in the distal phalanx of a finger. We present the case of a patient with a squamous cell carcinoma of the distal phalanx of a finger, which was treated with Mohs micrographic surgery, and its surgical defect was successfully resolved by secondary‐intention healing using hydrocolloid dressings.
Statistical size scaling of ceramic strength
Authors: Lei Wei‐Sheng
Published: August 2018

This work is based on the belief that the uniform spatial distribution of flaws underlying Weibull statistics is not necessarily always true for all ceramics. The weakest‐link statistics for a power‐law spatial distribution of flaws is adopted to synchronize the size dependence and random variation of ceramic strength. Three sets of published strength data of ceramics from different sized specimens are used for this purpose. The assumption of power‐law spatial distribution of flaws in ceramics is validated, with both uniform and nonuniform spatial distributions being showcased possible. For all the three case studies, there exists a master curve to correlate a compound parameter encompassing cumulative failure probability and size effect with the nominal fracture strength.
Response of isotopically tailored titanium diboride to neutron irradiation
Authors: Koyanagi Takaaki , Katoh Yutai , Ang Caen , King Derek , Hilmas Greg E. , Fahrenholtz William G.
Published: August 2018

The response of polycrystalline TiB2 to neutron irradiation was investigated. The material was fabricated using isotopically enriched 11B powders to minimize helium production via the 10B(n, α)7Li reaction. Neutron irradiation was conducted at temperatures of ~200°C and ~600°C to a fast fluence of 2.4 × 1025 n/m2 (>0.1 MeV). The material exhibited some swelling, but less swelling at the higher irradiation temperature. No macroscopic damage was observed in the irradiated material, although moderate irradiation‐induced micro‐cracking was found in the irradiated TiB2. This study demonstrated improved radiation resistance of isotopically tailored TiB2 compared with natural boron TiB2, which exhibited macroscopic fracture by irradiation.
Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo
Authors: Hu Chenxia , Zhao Lingfei , Peng Conggao , Li Lanjuan
Published: August 2018

Mesenchymal stem cells (MSCs) are broadly used in cell‐based regenerative medicine because of their self‐renewal and multilineage potencies in vitro and in vivo. To ensure sufficient amounts of MSCs for therapeutic purposes, cells are generally cultured in vitro for long‐term expansion or specific terminal differentiation until cell transplantation. Although physiologically up‐regulated reactive oxygen species (ROS) production is essential for maintenance of stem cell activities, abnormally high levels of ROS can harm MSCs both in vitro and in vivo. Overall, additional elucidation of the mechanisms by which physiological and pathological ROS are generated is necessary to better direct MSC fates and improve their therapeutic effects by controlling external ROS levels. In this review, we focus on the currently revealed ROS generation mechanisms and the regulatory routes for controlling their rates of proliferation, survival, senescence, apoptosis, and differentiation. A promising strategy in future regenerative medicine involves regulating ROS generation via various means to augment the therapeutic efficacy of MSCs, thus improving the prognosis of patients with terminal diseases.