bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a CNGB1 Frameshift Mutation in a Han Chinese Family with Retinitis Pigmentosa
Authors: Xiang Qin , Guo Yi , Cao Yanna , Xiong Wei , Deng Xiong , Xu Hongbo , Li Yu , Du Dongdong , Deng Hao
Published: November 2018

SIGNIFICANCE

Retinitis pigmentosa (RP) is a severe hereditary retinal disorder characterized by progressive degeneration of rod and cone photoreceptors. This study identified a novel frameshift mutation, c.385delC, p.(L129WfsTer148), in the cyclic nucleotide-gated channel beta 1 (CNGB1) gene of a consanguineous Han Chinese family with autosomal recessive RP (arRP). This expands the spectrum of CNGB1 gene variants in RP cases and possibly refines future genetic counseling.

PURPOSE

The present study sought to identify potential pathogenetic gene mutations in a five-generation consanguineous Han Chinese family with RP.

METHODS

Two members of a five-generation consanguineous Han Chinese pedigree with arRP and 100 normal individuals were enrolled in this study. Exome sequencing was performed on the 70-year-old male proband from a consanguineous family to screen potential pathogenic mutations according to the American College of Medical Genetics and Genomics for the interpretation of sequence variants. Sanger sequencing was performed on the proband, the proband's unaffected son, and 100 normal individuals to verify the disease-causing mutation.

RESULTS

A novel frameshift mutation, c.385delC, p.(L129WfsTer148), with homozygous status in the CNGB1 gene was identified in the proband of the family with arRP, and the mutation with heterozygous status was carried by the asymptomatic son.

CONCLUSIONS

The c.385delC (p.(L129WfsTer148)) mutation in the CNGB1 gene screened by exome sequencing is probably responsible for the RP phenotype in this family. The result expands the spectrum of CNGB1 gene variants in RP cases and possibly refines future genetic counseling.
Evidence of reduced viremia, pathogenicity and vector competence in a re-emerging European strain of bluetongue virus serotype 8 in sheep
Authors: Flannery John , Sanz-Bernardo Beatriz , Ashby Martin , Brown Hannah , Carpenter Simon , Cooke Lyndsay , Corla Amanda , Frost Lorraine , Gubbins Simon , Hicks Hayley , Qureshi Mehnaz , Rajko-Nenow Paulina , Sanders Christopher , Tully Matthew , Bréard Emmanuel , Sailleau Corinne , Zientara Stephan , Darpel Karin , Batten Carrie
Published: November 2018

The outbreak of bluetongue virus (BTV) serotype 8 (BTV-8) during 2006-2009 in Europe was the most costly epidemic of the virus in recorded history. In 2015, a BTV-8 strain re-emerged in France which has continued to circulate since then. To examine anecdotal reports of reduced pathogenicity and transmission efficiency, we investigated the infection kinetics of a 2007 UK BTV-8 strain alongside the re-emerging BTV-8 strain isolated from France in 2017. Two groups of eight BTV-naïve British mule sheep were inoculated with 5.75 log10TCID50 ml−1 of either BTV-8 strain. BTV RNA was detected by 2 dpi in both groups with peak viremia occurring between 5-9 dpi. A significantly greater amount of BTV RNA was detected in sheep infected with the 2007 strain (6.0-8.8 log10 genome copies mL−1) than the re-emerging BTV-8 strain (2.9-7.9 log10 genome copies mL−1). All infected sheep developed BTV-specific antibodies by 9 dpi. BTV was isolated from 2 dpi to 12 dpi for 2007 BTV-8-inoculated sheep and from 5 to 10 dpi for sheep inoculated with the remerging BTV-8. In Culicoides sonorensis feeding on the sheep over the period 7-12 dpi, vector competence was significantly higher for the 2007 strain than the re-emerging strain. Both the proportion of animals showing moderate (as opposed to mild or no) clinical disease (6/8 vs 1/8) and the overall clinical scores (median 5.25 vs 3) were significantly higher in sheep infected with the 2007 strain, compared to those infected with the re-emerging strain. However, one sheep infected with the re-emerging strain was euthanized at 16 dpi having developed severe lameness. This highlights the potential of the re-emerging BTV-8 to still cause illness in naïve ruminants with concurrent costs to the livestock industry.

The re-emerging Bluetongue virus serotype 8 still presents a threat to naïve ruminants in Europe despite reduced virulence
Lower hemoglobin levels associate with lower body mass index and healthier metabolic profile
Authors: Auvinen Juha , Tapio Joona , Karhunen Ville , Kettunen Johannes , Serpi Raisa , Dimova Elitsa Y. , Soininen Pasi , Tammelin Tuija , Mykkänen Juha , Puukka Katri , Kähönen Mika , Raitoharju Emma , Lehtimäki Terho , Ala-Korpela Mika , Raitakari Olli T. , Keinänen-Kiukaanniemi Sirkka , Järvelin Marjo-Riitta , Koivunen Peppi
Published: November 2018

Hemoglobin (Hb) is the main carrier of oxygen. In general, high-end Hb levels within the normal range are considered beneficial for health1. However, activation of the hypoxia response has been shown to protect mice against metabolic dysfunction2-4. We used Hb levels as an indicator for oxygenation status and studied its association with >170 anthropometric and metabolic parameters in two Finnish birth cohorts both in cross-sectional and longitudinal design (max n = 7,175). Here we show a positive linear association between Hb levels and body mass index (BMI). Subjects with the lower Hb levels had better glucose tolerance, lower cholesterol and blood pressure levels, less adverse metabolite profiles and lower inflammatory load. Notably, these associations were not only mediated by the lower BMI, and the effect size of many of them increased with age. Polygenic risk score (PRS) analyses indicated shared genetic determinants between Hb levels and BMI, insulin, triglyceride and HDL cholesterol levels. Mendelian randomization (MR) analyses could not demonstrate causal relationships between Hb and metabolic parameters. However, manipulation of Hb levels by venesection in mice showed evidence for causal associations with body weight and metabolic parameters. Our findings suggest that lower-end normal Hb levels may be favorable for systemic metabolism involving mild chronic activation of the hypoxia response. Therefore modulation of Hb levels could be a novel strategy towards maintenance of metabolic health.
Leveraging collective regulatory effects of long-range DNA methylations to predict gene expressions and estimate their effects on phenotypes in cancer
Authors: Kim Soyeon , Park Hyun Jung , Cui Xiangqin , Zhi Degui
Published: November 2018

DNA methylation of various genomic regions plays an important role in regulating gene expression in diverse biological contexts. However, most genome-wide studies have focused on the effect of 1) methylation in cis, not in trans and 2) a single CpG, not the collective effects of multiple CpGs, on gene expression. In this study, we developed a statistical machine learning model, geneEXPLORER (geneexpression prediction by long-range epigenetic regulation), that quantifies the collective effects of both cis- and trans- methylations on gene expression. By applying geneEXPLORER to The Cancer Genome Atlas (TCGA) breast and lung cancer data, we found that most genes are affected by methylations of as much as 10Mb from promoter regions or more, and the long-range methylation explains 50% of the variation in gene expression on average, far greater than cis-methylation. The highly predictive genes are related to breast cancer, especially oncogenes and suppressor genes. Further, the predicted gene expressions could predict clinical phenotypes such as breast tumor status and estrogen receptor status (AUC=0.999, 0.94 respectively) as accurately as the measured gene expression levels. These results suggest that geneEXPLORER provides a means for accurate imputation of gene expression, which can be further used to predict clinical phenotypes.
Variability of bacterial behavior in the mammalian gut captured using a growth-linked single-cell synthetic gene oscillator
Authors: Riglar David T , Richmond David L , Potvin-Trottier Laurent , Verdegaal Andrew A , Naydich Alexander D , Bakshi Somenath , Leoncini Emanuele , Paulsson Johan , Silver Pamela A
Published: November 2018

The dynamics of the bacterial population that comprises the gut microbiota plays key roles in overall mammalian health. However, a detailed understanding of bacterial growth within the gut is limited by the inherent complexity and inaccessibility of the gut environment. Here, we deploy an improved synthetic genetic oscillator to investigate dynamics of bacterial colonization and growth in the mammalian gut under both healthy and disease conditions. The synthetic oscillator, when introduced into both Escherichia coli and Salmonella Typhimurium maintains regular oscillations with a constant period in generations across growth conditions. We determine the phase of oscillation from individual bacteria using image analysis of resultant colonies and thereby infer the number of cell divisions elapsed. In doing so, we demonstrate robust functionality and controllability of the oscillator circuit’s activity during bacterial growth in vitro, in a simulated murine gut microfluidic environment, and in vivo within the mouse gut. We determine different dynamics of bacterial colonization and growth in the gut under normal and inflammatory conditions. Our results show that a precise genetic oscillator can function in a complex environment and reveal single cell behavior under diverse conditions where disease may create otherwise impossible-to-quantify variability in growth across the population.
SYNPLA: A synapse-specific method for identifying learning-induced synaptic plasticity loci
Authors: Dore Kim , Pao Yvonne , Lopez Jose Soria , Aronson Sage , Zhan Huiqing , Ghosh Sanchari , Merrill Sabina , Zador Anthony M. , Malinow Roberto , Kebschull Justus M.
Published: November 2018

Which neural circuits undergo synaptic changes when an animal learns? Although it is widely accepted that changes in synaptic strength underlie many forms of learning and memory, it remains challenging to connect changes in synaptic strength at specific neural pathways to specific behaviors and memories. Here we introduce SYNPLA (SYNaptic Proximity Ligation Assay), a synapse-specific, high-throughput and potentially brain-wide method capable of detecting circuit-specific learning-induced synaptic plasticity.
Cognitive and white-matter compartment models revealed the contribution of microstructural variability along sensorimotor tracts to simple reaction time
Authors: Karahan Esin , Costigan Alison G. , Graham Kim S. , Lawrence Andrew D. , Zhang Jiaxiang
Published: November 2018

The speed of voluntary reaction to an external stimulus varies substantially between individuals and is impaired in ageing. However, the neuroanatomical origins of inter-individual variability in reaction time (RT) remain largely unknown. Here, we combined a cognitive model of RT and a biophysical compartmental model of diffusion-weighted MRI (DWI) to characterize the relationship between RT and microstructure of the corticospinal tract (CST) and the optic radiation (OR), the primary motor output and visual input pathways associated with visual-motor responses.

We fitted an accumulator model of RT to 46 female participants’ behavioral performance in a simple reaction time task. The non-decision time parameter (Ter) derived from the model was used to account for the latencies of stimulus encoding and action initiation. From multi-shell DWI data, we quantified tissue microstructure of the CST and OR with the neurite orientation dispersion and density imaging (NODDI) model as well as the conventional diffusion tensor imaging (DTI) model.

Using novel skeletonization and segmentation approaches, we showed that DWI-based microstructure metrics varied substantially along CST and OR. The Ter of individual participants was negatively correlated with the NODDI measure of the neurite density in the bilateral superior CST. At an uncorrected threshold, the Ter positively correlated with the DTI measure of fractional anisotropy in an anterior segment of left OR. Further, we found no significant correlation between the microstructural measures and mean RT. Thus, our findings suggest a link between the inter-individual variability of sensorimotor speed and selective microstructural properties in white matter tracts.
APOBEC-mediated DNA alterations: a possible new mechanism of carcinogenesis in EBV-positive gastric cancer
Authors: Bobrovnitchaia Irina , Valieris Renan , Drummond Rodrigo , Lima João , Freitas Helano , Bartelli Thais , Amorin Maria , Nunes Diana , Dias-Neto Emmanuel , Silva Israel
Published: November 2018

Mechanisms of viral oncogenesis are diverse and include the off-target activity of enzymes expressed by the infected cells, which evolved to target viral genomes for controlling their infection. Among these enzymes, the single-strand DNA editing capability of APOBECs represent a well-conserved viral infection response that can also cause untoward mutations in host DNA. Here we show, after evaluating somatic single-nucleotide variations and transcriptome data in 240 gastric cancer samples, a positive correlation between APOBEC3s mRNA-expression and the APOBEC-mutation signature, both increased in EBV+ tumors. The correlation was reinforced by the observation of APOBEC-mutations preferentially occuring in transcriptionally-active loci. The EBV-infection and APOBEC3 mutation-signature axis was confirmed in a validation cohort of 112 gastric cancer patients. Our findings suggest that APOBEC3 upregulation in EBV+ cancer may boost the mutation load, providing further clues to the mechanisms of EBV-induced gastric carcinogenesis. After further validation, this EBV-APOBEC axis may prove to be a secondary driving force in the mutational evolution of EBV+ gastric tumors, whose consequences in terms of prognosis and treatment implications should be vetted.
Error sensitivity and optimization of steady-state kinetic parameters using multidimensional chemical kinetic analysis
Authors: Eskew Joseph S. , Connell Christopher G. , Cochran Jared C.
Published: November 2018

Enzyme behavior has been described using the Michaelis-Menten mechanism. The analysis of extended time domains provides a means to extract the Michaelis-Menten constants through direct fitting of raw data. We have developed a scheme for determining Michaelis-Menten rate constants by appropriate fitting of multidimensional experimental data sets to the closed form of the Michaelis-Menten model. We considered how varying parameters in experimental data affect the accuracy of the remaining parameter estimates. We determine how to improve experimental design to achieve a given accuracy, relative to the amount of intrinsic or external error. We analyze this scheme on data sets built around 20 hypothetical and 2 natural enzymes (kinesin and apyrase) to test error sensitivity in different parameter regimes. Overall, we provide evidence that our data fitting regime will tolerate significant experimental error in the raw data and still converge on the four Michaelis-Menten constants.
CDEK: Clinical Drug Experience Knowledgebase
Authors: Griesenauer Rebekah , Schillebeeckx Constantino , Kinch Michael S
Published: November 2018

The Clinical Drug Experience Knowledgebase (CDEK) is a database and web platform of active pharmaceutical ingredients with evidence of clinical testing as well as the organizations involved in their research and development. CDEK was curated by disambiguating intervention and organization names from ClinicalTrials.gov and cross-referencing these entries with other prominent drug databases. Approximately 43% of active pharmaceutical ingredients in the CDEK database were sourced from ClinicalTrials.gov and cannot be found in any other prominent compound-oriented database. The contents of CDEK are structured around three pillars: active pharmaceutical ingredients (n = 22,292), clinical trials (n = 127,223), and organizations (n = 24,728). The envisioned use of the CDEK is to support the investigation of many aspects of drug development, including discovery, repurposing opportunities, chemo- and bio-informatics, clinical and translational research, and regulatory sciences.
AICAR induces apoptosis and inhibits migration of prostate cancer cells through an AMPK/mTOR-dependent pathway
Authors: Su Chia-Cheng , Hsieh Kun-Lin , Wang Shu-Chi , Yeh Hsin-Chih , Huang Shu-Pin , Liu Po-Len , Fang Shih-Hua , Cheng Wei-Chung , Huang Kuan-Hua , Chiu Fang-Yen , Lin I-Ling , Huang Ming-Yii , Li Chia-Yang
Published: November 2018

AICAR (5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells, 22RV1 cells. Cell growth was performed by MTT assay and soft agar assay. Cell apoptosis was examined by Annexin V/PI staining and PARP cleavage Western blot. Cell migration was evaluated by wound-healing assay. The expression of EMT-related protein and the activity of the AMPK/ mTOR-dependent pathway were analyzed by Western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth, induces apoptosis, attenuates TGF-β-induced cell migration and EMT-related protein expression, and enhances the chemosensitivity to docetaxel through regulating the AMPK/mTOR-dependent pathway. Collectively, these findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.
Knockdown of DGKZ induces apoptosis and G2/M phase arrest in human acute myeloid leukemia HL-60 cells
Authors: Dong Changhu , Li Hong , Tian Yanning , Li Xiang , Wang Bing , Zhai Dongzhi , Bai Yingying , Chao Xu
Published: November 2018

Diacylglycerol kinase zeta (DGKZ) is associated with the pathogenesis of a variety of malignant diseases, but its biological function on acute myeloid leukemia (AML) has not been explored. This study was aimed to analyze apoptosis induced by Knockdown of DGKZ and its mechanism in human acute myeloid leukemia HL-60 cells.In the present study qRT-PCR was used to detect the expression of DGKZ in HL-60, THP-1, K562, H9, Jurkat and CD34 cell lines. DGKZ-shRNA lentiviral vector was established and used to infect acute myeloid leukemia HL-60 cells. Cell Counting Kit-8 (CCK-8) assay was used to determine the viability of HL-60 cells DGKZ knocked down. Apoptosis and cell cycle phase of HL-60 cells after DGKZ knockdown were evaluated by flow cytometry. Western blot analysis was performed to investigated the protein expression related to apoptosis and cell cycle. Results showed DGKZ expression were stable and higher in Jurkat, HL-60, THP-1,K562 leukemia cells than those of H9 and CD34 cells. Compared with cells of the shCtrl group, DGKZ was markedly knocked down in cells which were transfected with lentivirus encoding shRNA of DGKZ in HL-60 cells. DGKZ knockdown significantly inhibited the proliferation and induced cycle arrest at the G2/M phase in HL-60 cells. Western blot results indicated the expressions of caspase-3, caspase-8, and survivin markedly increased in HL-60 cells after knockdown of DGKZ. The results suggest Knockdown of DGKZ can inhibit proliferation of acute myeloid leukemia HL-60 cell caused cell cycle arrest at the G2/M phase through caspases pathway.
Street fighters: Bite force, injury rates, and density of urban Australian water dragons (Intellagama lesueurii)
Authors: Baxter‐Gilbert James H. , Whiting Martin J.
Published: November 2018

In an increasingly urbanized world it is imperative that we understand how wildlife responds to this novel anthropogenic landscape, both at the individual‐ and population‐level. Urbanization generally reduces biodiversity, but can also favour particular species and increase their abundance relative to wild populations. When population density increases, so too does the frequency and cost of social interactions. We studied Australian water dragons (Intellagama lesueurii), a species common in urban, semi‐natural and natural areas, to firstly test the prediction that urban populations occur at higher densities, and then determine the consequences of urbanization for combat rates (quantified using wounding) and bite force. We established that urban populations are denser than ones from semi‐natural and natural habitats. We also recorded significantly more wounds in females from urban populations than females from both natural and semi‐natural populations. Urban males also had significantly higher incidence of wounding than males from natural populations. We did not find a difference in male or female bite force among any populations across the urban‐natural gradient. Overall, we found evidence that urbanization results in a higher population density of water dragons and more frequent conspecific combat, but this was not associated with an increase in bite force. These finding suggests that there may be a physiological cost to living in urban habitats related to increased contest rates and wounding.
Cannibalism or congeneric predation? The African clawed frog, Xenopus laevis (Daudin), preferentially predates on larvae of Cape platannas, Xenopus gilli Rose & Hewitt
Authors: Thorp Corey J. , Vonesh James R. , Measey John
Published: November 2018

Predators are not limited to prey from other species as they can cannibalise vulnerable individuals within their own population. The African clawed frog, Xenopus laevis (Daudin), is a predator with a broad diet, known to consume multiple prey species, including congeners and conspecifics. African clawed frogs occur in sympatry with the Endangered Cape platanna, Xenopus gilli Rose & Hewitt, which are under threat through competition and predation from X. laevis. We investigated the threat of X. laevis predation on X. gilli using choice and no‐choice experiments to evaluate the relative vulnerability of X. laevis and X. gilli larvae. Results showed that large X. gilli larvae had a significantly higher vulnerability to X. laevis predation compared to small X. gilli larvae. However, the same discrimination was not discerned when offered large and small X. laevis larvae, or mixed larvae of the same size. We report ontogenic shifts in behaviour of X. gilli larvae that may be a factor in contributing to the vulnerability of large X. gilli larvae to adult X. leavis predation. Congeneric predation likely has negative implications for the population structure of the Endangered X. gilli. Our study underlines the call for the removal of X. laevis to conserve populations of X. gilli.
Autotaxin and vascular endothelial growth factor receptor‐2 and ‐3 are related to vascular development during the progression of chronic viral hepatitis C
Authors: Yokomori Hiroaki , Ando Wataru , Kaneko Fumihiko , Suzuki Hidekazu , Igarashi Koji , Oda Masaya
Published: November 2018

Vascular endothelial growth factor (VEGF) and autotaxin (ATX) play important roles in embryonic vasculogenesis and cancer progression. This study examines whether these two angiogenic factors cooperate in the mechanism that regulates vascular development during the progression of chronic viral hepatitis C (CVH‐C) (Inuyama classification, F1–F4). First, surgical wedge biopsy specimens and needle biopsy specimens were obtained. Immunohistochemical staining for ATX and vascular endothelial growth factor receptor was assessed in serial sections. Immunoelectron microscopy was conducted with a perfusion‐fixation method. In normal control liver tissue specimens, ATX was expressed at low levels within the branches of the hepatic artery and hepatic sinusoids. In F1 CVH‐C liver tissue specimens, ATX was expressed within the branches of the hepatic artery. Additionally, VEGFR‐2 was expressed within the branches of the hepatic artery and capillaries. In F3–F4 CVH‐C liver tissue specimens, positive staining for ATX and VEGFR‐2 or VEGFR‐3 was detected in the branches of the hepatic artery or microlymphatic vessels. ATX‐1 reaction products were specifically expressed on the plasma membrane of some microvascular endothelial cells (ECs) in the proliferative capillary artery. VEGFR‐2 was expressed on caveolae in ECs and vascular smooth muscle cells. VEGFR‐3 immunogold particles were also observed in lymphatic ECs. These results suggest functional interactions among ATX, VEGFR‐2, and VEGFR‐3 in the modulation of hemovascular and lymphovascular cell activation during vascular development.
Analysis of implant loss risk factors especially in maxillary molar location: A retrospective study of 6977 implants in Chinese individuals
Authors: Zhou Na , Dong Heng , Zhu Yanxiang , Liu Hui , Zhou Nan , Mou Yongbin
Published: November 2018

Background

The knowledge of the potential risk factors associated with implant loss is crucial for dental clinicians, but the opinions about the risk factors are still diverse and controversial.

Purpose

This retrospective study assessed the risk factors associated with implant loss, especially that in the maxillary molar location.

Materials and Methods

From January 2015 to March 2017, 4338 Chinese patients received 6977 implants at Nanjing Stomatological Hospital. Information on patient age, gender, bone grafting procedure, implant location, length and diameter, and the records of lost implants were obtained. The Kaplan‐Meier method and log‐rank test were used to conduct a survival function analysis. Chi‐square test and multivariate Cox regression analysis were used to identify risk factors related to implant loss.

Results

The cumulative survival rate (CSR) after 0‐32 months of observation period for all implants was 97.76%, and the CSR for maxillary molar implants was 97.00%. Maxillary molar implants showed a significantly lower CSR than the other implants (P < .05). Male sex, short implants (<10 mm) were considered as risk factors for implant loss. However, male sex and bone grafting procedure were regarded as risk factors for maxillary molar implant loss, which was slightly different from the result of all implants.

Conclusions

Male sex, short implants (<10 mm) and maxillary molar location were considered as potential risk factors for implant loss, whereas male sex and bone grafting procedure were significantly associated with implant loss in maxillary molar location.
Patients with extensive regional lymph node involvement (pN2) following potentially curative surgery for colorectal cancer are at increased risk for developing peritoneal metastases: a retrospective single‐institution study
Authors: Bhatt A. , Bhamre R. , Rohila J. , Kalikar V. , Desouza A. , Saklani A.
Published: November 2018

Aim

Our goal was to determine the incidence and clinical behaviour of peritoneal metastases (PM) in patients with colorectal cancer undergoing potentially curative surgery, comparing patients with extensive locoregional lymph node involvement (pN2) with those who have serosal involvement (pT4), a known risk factor for developing PM.

Method

A retrospective analysis of a prospectively maintained database was performed. All patients with pT4 and pN2 were included in the analysis. The diagnostic criteria were the finding of PM during surgery with biopsy confirmation as well as imaging features suggestive of PM, including ovarian metastases and omental deposits.

Results

Two hundred and fourteen patients treated between May 2010 and October 2015 were included. Of these, 110 (51.4%) had pT4 and 131 (61.2%) pN2 tumours: 17.2% of patients with pT4 tumours and 20.2% of patients with pN2 tumours developed PM (P = 0.53). The median time to detection of PM was 16.6 months and 11.8 months for pT4 and pN2 tumours, respectively. PM were isolated in 51.8% of patients with pN2 tumours. Nonperitoneal metastases developed in 37.5% of patients with pN2 tumours. In pN2 tumours, the incidence of PM was higher in signet ring cell and mucinous tumours (P < 0.01), positive surgical margins (P = 0.02), colonic versus rectal tumours (P = < 0.01) and right colon primary tumours (P = 0.01).

Conclusion

Patients with pN2 tumours are at an increased risk of developing PM, which is similar to the risk in pT4 tumours. pN2 tumours should be included in clinical trials evaluating preventive/proactive strategies. There is a need to identify predictive biomarkers for the development of PM versus other sites of metastasis.
Lipoprotein (a) and Low‐density lipoprotein apolipoprotein B metabolism following apheresis in patients with elevated lipoprotein(a) and coronary artery disease
Authors: Ma Louis , Waldmann Elisa , Ooi Esther M. M. , Chan Dick C. , Barrett Hugh P. R. , Watts Gerald F. , Parhofer Klaus G.
Published: November 2018

Background

Lipoprotein apheresis effectively lowers lipoprotein(a) [Lp(a)] and low‐density lipoprotein (LDL) by approximately 60%‐70%. The rebound of LDL and Lp(a) particle concentrations following lipoprotein apheresis allows the determination of fractional catabolic rate (FCR) and hence production rate (PR) during non‐steady state conditions. We aimed to investigate the kinetics of Lp(a) and LDL apolipoprotein B‐100 (apoB) particles in patients with elevated Lp(a) and coronary artery disease undergoing regular apheresis.

Patients and methods

A cross‐sectional study was carried out in 13 patients with elevated Lp(a) concentration (>500 mg/L) and coronary artery disease. Lp(a) and LDL‐apoB metabolic parameters, including FCR and PR were derived by the fit of a compartment model to the Lp(a) and LDL‐apoB concentration data following lipoprotein apheresis.

Results

The FCR of Lp(a) was significantly lower than that of LDL‐apoB (0.39 [0.31, 0.49] vs 0.57 [0.46, 0.71] pools/day, P = 0.03) with no significant differences in the corresponding PR (14.80 [11.34, 19.32] vs 15.73 [11.93, 20.75] mg/kg/day, P = 0.80). No significant associations were observed between the FCR and PR of Lp(a) and LDL‐apoB.

Conclusions

In patients with elevated Lp(a), the fractional catabolism of Lp(a) is slower than that of LDL‐apoB particles, implying that different metabolic pathways are involved in the catabolism of these lipoproteins. These findings have implications for new therapies for lowering apolipoprotein(a) and apoB to prevent atherosclerotic cardiovascular disease.
A genetic algorithm‐based stacking algorithm for predicting soil organic matter from vis–NIR spectral data
Authors: Tsakiridis Nikolaos L. , Tziolas Nikolaos V. , Theocharis John B. , Zalidis George C.
Published: November 2018

It has been demonstrated that diffuse reflectance spectroscopy in the visible and near‐infrared (vis–NIR) can be exploited to predict chemical and physical soil properties. Immense soil spectral libraries (SSL) are being developed; therefore, more elaborate tools that capitalize on contemporary knowledge and techniques need to be established to provide accurate predictions. In this paper, we propose a novel genetic algorithm‐based stacking model that makes synergetic use of multiple models developed from different preprocessed spectral sources (termed L1 models). This is a form of ensemble learning where multiple hypotheses are combined to create a more robust and more accurate ensemble hypothesis. The genetic algorithm automatically defines the configuration of the stacked model, by selecting the best cooperating subset of the initial models. Our methodology was tested on the newly developed GEO‐CRADLE SSL to predict soil organic matter (SOM). Results showed that the accuracy of prediction of the proposed method (
R2 = 0.76, and ratio of performance to interquartile range [RPIQ] = 2.22) was better than the one attained by the best L1 model (
R2 = 0.65, RPIQ = 1.93). This approach can thus be effectively utilized to enhance the predictions of soil properties in small and large soil spectral libraries alike.

Highlights

A novel model stacking algorithm is proposed, combining spectral models from different sources and algorithms.

Use of a genetic algorithm is examined, accounting for the large number of possible model permutations.

The methodology was applied to the GEO‐CRADLE vis–NIR soil spectral library.

Results indicate that model stacking creates more accurate and robust models.
Provincializing the history of speculation from colonial South Asia
Authors: Bhattacharyya Debjani
Published: November 2018

This article proposes that South Asia has produced rich histories of economic practices understood variously as hoarding, speculation, and extortion. This essay frames the discussion of speculation in South Asian history along these three axes. First, it puts the term speculation under scrutiny to look at its changing meanings within the colonial and metropolitan context in order to assess how the term enters the colonial archive of law and finance. Especially, it looks at how the colonial officials created and sustained (mis)translations between indigenous practices and Anglo‐European categories of economic crimes. Second, it looks at the early scholarship on 18th and 19th century indigenous commercial practices that were coded as hoarding, speculating, profiteering, hedging, and squeezing in an attempt to rescue the colonial bazaar and what has been called its “inside history” alongside the development of market practices. This body of scholarship remains primarily focused on trading activities under the Mughals and East India Company. In the third and final section, we turn to the recent histories that have returned to vernacular commercial practices and the historical roots of India's market society to raise critical questions about how speculation and calculation shaped late colonial capitalism and governmentality.
Sex‐related differences in response to zinc pyrithione shampoo vs. non‐anti‐dandruff shampoo
Authors: Collins L. Z. , Baines F. L. , Matheson J. R. , Turner G. A. , Diao Y. , Li Y. , Pi Y.
Published: November 2018

Objective

Sex‐related differences in skin properties may be expected to impact dandruff formation and treatment. A meta‐analysis approach was undertaken to investigate potential differences between males and females in response to zinc pyrithione (ZnPT) treatment vs. non‐anti‐dandruff (AD) shampoo. A separate pooled statistical analysis of ceramide and total protein loss endpoints was also undertaken to assess potential sex‐related differences in stratum corneum properties that might influence response to ZnPT vs. non‐AD shampoo in subjects with dandruff.

Methods

The meta‐analysis approach included data from 17 half‐head, double‐blind, randomized studies (N = 2088) undertaken in Asia to assess the effectiveness of 1% ZnPT shampoo and/or non‐AD shampoo in reducing dandruff severity, as assessed by Total Weighted Head Score Adherent Flake (TWHS‐AF) methodology. Treatment duration was 4 weeks, with TWHS‐AF measured at weekly intervals. Data from an additional three studies (N = 143) conducted in Asia were included in the pooled analysis of ceramide levels and protein loss from scalp skin of subjects with dandruff.

Results

Response to 1% ZnPT vs. non‐AD shampoo was greater in males than in females at all time points; after 4 weeks, the between‐treatment difference in TWHS‐AF was −17.5 (95% confidence interval [CI] −19.5, −15.5) in males and −11.1 (−13.2, −8.9) in females. Sex‐related differences were observed between males and females in response to both 1% ZnPT and non‐AD shampoos. Males had a stronger response than females to treatment with 1% ZnPT shampoo, while dandruff decreased to a greater extent in females than in males when using non‐AD shampoo. Statistically significant sex‐related differences in ceramide levels and total protein loss were observed (both P < 0.01). Ceramide levels were 0.76 times lower (95% CI 0.60, 0.97) in males than in females, while total protein loss was 1.4 times greater (95% CI 1.1, 1.9) in males than in females.

Conclusion

Males show a greater response than females to 1% ZnPT shampoo, while females show a greater response than males to non‐AD shampoo. These findings may in part be explained by the sex‐related differences observed in stratum corneum properties, which may make males more prone to dandruff than females.
Sampling, Embedding and Inference for CARMA Processes
Authors: Brockwell Peter J. , Lindner Alexander
Published: November 2018

A CARMA(p,q) process Y is a strictly stationary solution Y of the pth‐order formal stochastic differential equation a(D)Yt = b(D)DLt, where L is a two‐sided Lévy process, a(z) and b(z) are polynomials of degrees p and q respectively, with p > q, and D denotes differentiation with respect to t. Since estimation of the coefficients of a(z) and b(z) is frequently based on observations of the Δ‐sampled sequence , for some Δ > 0, it is crucial to understand the relation between Y and YΔ. If then YΔ is an ARMA sequence with coefficients depending on those of Y and the crucial problems for estimation are the determination of the coefficients of YΔ from those of Y (the sampling problem) and the determination of the coefficients of Y from those of YΔ (the embedding problem). In this article we consider both questions and use the results to determine the asymptotic distribution, as n→∞, with Δ fixed, of , where is the quasi‐maximum‐likelihood estimator of the vector of coefficients of a(z) and b(z), based on n consecutive observations of YΔ.
Influence of omega‐3 fatty acid on orthodontic tooth movement in rats: A biochemical, histological, immunohistochemical and gene expression study
Authors: Ogrenim Gozde , Cesur Mine G. , Onal Tuna , Kara Murat , Sirin Fevziye B. , Yalcin Gizem D. , Inan Sevinc
Published: November 2018

Structured Abstract

Objective

The aim of this study was to investigate the effects of omega‐3 fatty acids on orthodontic tooth movement.

Setting and Sample Population

For this study, 56 12‐week‐old adult male Wistar albino rats from the Animal Laboratory at Adnan Menderes University, Faculty of Medicine, were used.

Material and Methods

Rats were randomly divided into seven groups (n = 8 each): control group (without any treatment), tooth movement groups (three groups of animals with only tooth movement) and omega groups (three groups of animals with tooth movement and omega‐3 administration). Omega‐3 fatty acids were administered to the rats systemically during the tooth movement period. On the 3rd, 7th and 14th days after the orthodontic tooth movement, the rats were sacrificed and biochemical, histological, immunohistochemical andgene expression examinations were performed.

Results

On the 14th experimental day, the amount of tooth movement in the omega groups was significantly lower than the tooth movement groups (P = 0.012). Biochemical experimentsshowed that the omega groups had significantly lower total oxidant levels and higher total antioxidant levels compared to the tooth movement group on the 14th experimental day (P = 0.001). The levels of RANKL, IL‐6 and IL‐1β in the omega groups were significantly lower than the tooth movement groups on all experimental days (P < 0.05).

Conclusion

Systemic administration of omega‐3 fatty acids showed antioxidant and antiinflammatory effects and decelerate the orthodontic tooth movement.
The Role of Sleep Quality and Fatigue on the Benefits of an Interdisciplinary Treatment for Adults With Chronic Pain
Authors: de la Vega Rocío , Racine Melanie , Castarlenas Elena , Solé Ester , Roy Rubén , Jensen Mark P. , Miró Jordi , Cane Douglas
Published: November 2018

Background

Interdisciplinary chronic pain treatment is effective for reducing pain intensity and pain‐related disability, and for improving psychological function. However, the mechanisms that underlie these treatment‐related benefits are not yet well understood. Sleep problems and fatigue are modifiable factors often comorbid with chronic pain. The goal of this study was to evaluate the role that changes in sleep quality and fatigue might have on the benefits of an interdisciplinary chronic pain treatment.

Methods

A total of 125 adults with chronic pain participated in a 4‐week interdisciplinary pain management program. Measures of depression, sleep disturbance, fatigue, pain intensity, and physical function were administered at pre‐ and post‐treatment. Three regression analyses were conducted to evaluate the contribution of pre‐ to post‐treatment improvements in fatigue and sleep disturbance to the pre‐ to post‐treatment improvements in pain intensity, disability, and depression, while controlling for demographic characteristics (age and sex) and pain intensity.

Results

Changes in fatigue and sleep disturbance made independent and significant contributions to the prediction of treatment‐related benefits in pain intensity; improvements in depressive symptoms were predicted by improvements in fatigue, and improvements in disability were only predicted by pre‐treatment and pre‐ to post‐treatment decreases in pain intensity (one of the control variables).

Conclusions

In addition to sleep, fatigue emerged as a key potential mechanism of multidisciplinary chronic pain treatment‐related improvements, suggesting that interventions including elements that effectively target sleep and fatigue may enhance the efficacy of interdisciplinary chronic pain programs. This possibility should be evaluated in future research.
Should more donation after cardiac death livers be used in pediatric transplantation?
Authors: Hwang Christine S. , Levea Swee‐Ling , Parekh Justin R. , Liang Yun , Desai Dev M. , MacConmara Malcolm
Published: November 2018

Introduction

There is a mismatch that exists in donor liver organ supply and demand. DCD livers represents a potential source to increase the number of liver grafts available for use in pediatric recipients; however, there has been hesitancy to use such organs. We evaluated patient and allograft outcomes in pediatric liver transplant recipients of DCD livers.

Methods

The UNOS database was queried to examine outcomes in all liver transplant recipients from 1993 to 2017. Patients were then divided according to adult and pediatric status, DBD or DCD allograft status, and era of transplant. Donor and recipient demographic data were examined, and patient and allograft survival were calculated. A P‐value of <0.05 was considered to be significant.

Results

A total of 57 pediatric recipients received a DCD liver allograft. DCD recipients were older than DBD recipients. There was no difference in the final PELD score between the groups. There were no differences in causes of allograft failure between the DCD and DBD groups. Importantly, the overall allograft survival in the DCD and DBD groups was similar, as was allograft survival based on era.

Conclusion

Pediatric liver transplant recipients of DCD allografts have comparable patient and allograft survival when compared to DBD allograft recipients. Use of DCD allografts in the pediatric liver transplant population should be strongly considered to increase the donor organ pool.
Water‐Filtered Infrared Radiation Decreases the Generation of Photodermatoses Dependent on Ultraviolet and Visible Radiation
Authors: de Gálvez María V. , Aguilera José , Sánchez‐Roldán Cristina , Herrera‐Acosta Enrique , Herrera‐Ceballos Enrique
Published: November 2018

The potential role of infrared radiation in photodermatoses has received very little attention, even though the main sources of radiation used for photobiological studies (UVA, UVB and visible light) include infrared radiation. The objective of the work was to assess whether infrared radiation is involved in the development of skin lesions in patients with different types of photodermatoses. Twenty patients with different photodermatoses were exposed to UVA, UVB and visible radiation using a high‐pressure mercury UVA lamp, a fluorescent broadband UVB lamp, a tungsten bulb and a slide projector for visible radiation. Part of the radiation emitted by these lamps was water‐filtered to block infrared radiation above 1300 nm. All 20 patients developed lesions when exposed to different light sources used for phototest. When exposed to same sources without infrared radiation, 17 patients (85%) did not develop any lesions and the other three (15%) developed less severe lesions than in the area exposed to unfiltered light. Our results show that infrared radiation was necessary for the development of skin lesions in 85% of the patients with photodermatoses in our study. We believe that infrared radiation studies should be included in standard photobiology protocols.
Effect of Toxic Metal Ions on Photosensitized Singlet Oxygen Generation for Photodegradation of Polyaromatic Hydrocarbon Derivatives and Inactivation of Escherichia coli
Authors: Herschmann Jacob R. , Ali Aqeeb , Harris Michele , McClinton Matthew , Zamadar Matibur
Published: November 2018

Here, we report an experimental study of the effect of toxic metal ions on photosensitized singlet oxygen generation for photodegradation of PAH derivatives, Anthracene‐9,10‐dipropionic acid disodium salt (ADPA) and 1,5‐dihydroxynapthalene (DHN) and photoinactivation of Escherichia coli bacteria by using cationic meso‐tetra(N‐methyl‐4‐pyridyl)porphine tetrachloride (TMPyP) as a singlet oxygen photosensitizer. Three s‐block metals ions, such as Na+, K+ and Ca2+ and five toxic metals such as Cd2+, Cu2+, Hg2+, Zn2+ and Pb2+ were studied. The s‐block metal ions showed no change in the rate of photodegradation of ADPA or DHN by TMPyP, whereas a dramatic change in the photodegradation of ADPA and DHN was observed in the presence of toxic metals. The maximum photodegradation rate constants of ADPA and DHN were observed for Cd2+ ions [(3.91 ± 0.20) × 10−3 s−1 and (7.18 ± 0.35) × 10−4 s−1, respectively]. Strikingly, the photodegradation of ADPA and DHN was almost completely inhibited in the presence of Hg2+ ions and Cu2+ ions. A complete inhibition of growth of E. coli was observed upon visible light irradiation of E. coli solutions with TMPyP and toxic metal ions particularly, Cd2+, Hg2+, Zn2+ and Pb2+ ions, except for Cu2+ ions where a significantly slow inhibition of E. coli's growth was observed.
Prevalence of objectively measured sedentary behavior in early years: Systematic review and meta‐analysis
Authors: Pereira João Rafael , Cliff Dylan P. , Sousa‐Sá Eduarda , Zhang Zhiguang , Santos Rute
Published: November 2018

Background

The early years have been identified as a critical period during which sedentary habits may be established, as this behavior appears to track throughout life.

Objective

The purpose of this systematic review and meta‐analysis is to summarize the current literature on the prevalence of sedentary behavior in children aged 1‐5.99 years, reporting differences between boys and girls, weekdays and weekend days, childcare hours and nonchildcare hours, and between time spent indoors and outdoors while children attended childcare.

Methods

Five databases were searched until 26.10.2017 and meta‐analyses were conducted to estimate prevalence and calculate mean differences in prevalence between groups.

Results

Fifty studies representing 14 598 children (2‐5.99 years) were included. Children spent 51.4% of their waking time in sedentary behaviors. Boys spent less time being sedentary than girls (estimate difference = −1.4%; 95%CI = −2.0: −0.7; P < .001). No significant differences were found between weekdays/weekend days (estimate difference = −0.4; 95%CI = −2.0: 1.2; P = .61) nor between childcare hours/nonchildcare hours (estimate difference = %; 95%CI = −0.9: 6.6; P = .136). While attending childcare centers, children were more sedentary indoors than outdoors (estimate difference = 14.4%; 95%CI = 11.8: 16.9; P < .001).

Conclusions

Our results suggest that young children spend a significant portion of their waking hours in sedentary behaviors. While at childcare, young children accumulated more sedentary behavior indoors than outdoors. Girls were more likely to be more sedentary than boys. No significant differences were found between weekdays and weekends, or between childcare and nonchildcare hours. There is a need for higher‐quality studies with strong designs, using age and device appropriate cut‐off points, to improve evidence‐base and to better establish prevalence of sedentary behavior in young children.