bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Instantaneous Dynamic Displacements of Masonry Walls in Seismic Oscillation Outdoors by Monocular Digital Photography
Authors: Zhang Guojian , Guo Guangli , Yu Chengxin , Li Long , Hu Sai , Wang Xue
Published: August 2018

Understanding the development of cracks in masonry walls can provide insight into their capability for earthquake resistance. The crack development is characterized by the displacement difference of the adjacent positions on masonry walls. In seismic oscillation, the instantaneous dynamic displacements of multiple positions on masonry walls can warn of crack development and reflect the propagation of the seismic waves. For this reason, we proposed a monocular digital photography technique based on the PST-TBP (photographing scale transformation-time baseline parallax) method to monitor the instantaneous dynamic displacements of a masonry wall in seismic oscillation outdoors. The seismic oscillation was simulated by impacting a suspended steel plate with a hammer and by simulation software ANSYS (analysis system), for comparative analysis. The results show that it is feasible to use a hammer to impact a suspended steel plate to simulate the seismic oscillation as the stress concentration zones of the masonry wall model in ANSYS are consistent with the positions of destruction on the masonry wall, and that the crack development of the masonry wall in the X-direction could be characterized by a sinusoid-like curve, which is consistent with previous studies. The PST-TBP method can improve the measurement accuracy as it corrects the parallax errors caused by the change of intrinsic and extrinsic parameters of a digital camera. South of the test masonry wall, the measurement errors of the PST-TBP method were shown to be 0.83mm and 0.84mm in the X- and Z-directions, respectively, and in the west, the measurement errors in the X- and Z-directions were 0.49mm and 0.44mm, respectively. This study provides a technical basis for monitoring the crack development of the real masonry structures in seismic oscillation outdoors to assess their safety and has significant implications for improving the construction of masonry structures in earthquake-prone areas.
Some Properties of the Strong Primitivity of Nonnegative Tensors
Authors: You Lihua , Chen Yafei , Yuan Pingzhi
Published: August 2018

We show that an order m dimension 2 tensor is primitive if and only if its majorization matrix is primitive, and then we obtain the characterization of order m dimension 2 strongly primitive tensors and the bound of the strongly primitive degree. Furthermore, we study the properties of strongly primitive tensors with n≥3 and propose some problems for further research.
Renal Outcomes in Children with Operated Spina Bifida in Uganda
Authors: Sims-Williams Helen J. , Sims-Williams Hugh P. , Mbabazi Kabachelor Edith , Warf Benjamin C.
Published: August 2018

Background. To describe the extent of renal disease in Ugandan children surviving at least ten years after spina bifida repair and to investigate risk factors for renal deterioration in this cohort.Patients and Methods. Children who had undergone spina bifida repair at CURE Children’s Hospital of Uganda between 2000 and 2004 were invited to attend interview, physical examination, renal tract ultrasound, and a blood test (creatinine). Medical records were retrospectively reviewed. The following were considered evidence of renal damage: elevated creatinine, hypertension, and ultrasound findings of hydronephrosis, scarring, and discrepancy in renal size >1cm. Female sex, previous UTI, neurological level, mobility, detrusor leak point pressure, and adherence with clean intermittent catheterisation (CIC) were investigated for association with evidence of renal damage.Results. 65 of 68 children aged 10–14 completed the assessment. The majority (83%) reported incontinence. 17 children (26%) were performing CIC. One child had elevated creatinine. 25 children (38%) were hypertensive. There was a high prevalence of ultrasound abnormalities: hydronephrosis in 10 children (15%), scarring in 42 (64%), and >1cm size discrepancy in 28 (43%). No children with lesions at S1 or below had hydronephrosis (p = 0.025), but this group had comparable prevalence of renal size discrepancy, scarring, and hypertension to those children with higher lesions.Conclusions. Incontinence, ultrasound abnormalities, and hypertension are highly prevalent in a cohort of Ugandan children with spina bifida, including those with low neurological lesions. These findings support the early and universal initiation of CIC with anticholinergic therapy in a low-income setting.
Meta-Analysis of Genome-Wide Association Studies Identifies Novel Functional CpG-SNPs Associated with Bone Mineral Density at Lumbar Spine
Authors: Qiu Chuan , Shen Hui , Fu Xiaoying , Xu Chao , Deng Hongwen
Published: August 2018

Osteoporosis is a serious public health issue, which is mostly characterized by low bone mineral density (BMD). To search for additional genetic susceptibility loci underlying BMD variation, an effective strategy is to focus on testing of specific variants with high potential of functional effects. Single nucleotide polymorphisms (SNPs) that introduce or disrupt CpG dinucleotides (CpG-SNPs) may alter DNA methylation levels and thus represent strong candidate functional variants. Here, we performed a targeted GWAS for 63,627 potential functional CpG-SNPs that may affect DNA methylation in bone-related cells, in five independent cohorts (n=5905). By meta-analysis, 9 CpG-SNPs achieved a genome-wide significance level (p<7.86×10−7) for association with lumbar spine BMD and additional 15 CpG-SNPs showed suggestive significant (p<5.00×10−5) association, of which 2 novel SNPs rs7231498 (NFATC1) and rs7455028 (ESR1) also reached a genome-wide significance level in the joint analysis. Several identified CpG-SNPs were mapped to genes that have not been reported for association with BMD in previous GWAS, such as NEK3 and NFATC1 genes, highlighting the enhanced power of targeted association analysis for identification of novel associations that were missed by traditional GWAS. Interestingly, several genomic regions, such as NEK3 and LRP5 regions, contained multiple significant/suggestive CpG-SNPs for lumbar spine BMD, suggesting that multiple neighboring CpG-SNPs may synergistically mediate the DNA methylation level and gene expression pattern of target genes. Furthermore, functional annotation analyses suggested a strong regulatory potential of the identified BMD-associated CpG-SNPs and a significant enrichment in biological processes associated with protein localization and protein signal transduction. Our results provided novel insights into the genetic basis of BMD variation and highlighted the close connections between genetic and epigenetic mechanisms of complex disease.
Dapagliflozin-Associated Euglycemic Diabetic Ketoacidosis in a Patient Presenting with Acute Pancreatitis
Authors: Badwal Karun , Tariq Tooba , Peirce Diane
Published: August 2018

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a class of medications used for glycemic control in type II diabetes mellitus. Their mechanism of action involves preventing resorption of glucose at the proximal kidney, thereby promoting glucosuria and weight loss. However, they have also been found to be associated with euglycemic diabetic ketoacidosis (euDKA). This case describes a 25-year-old male with a history of type II diabetes on metformin, sitagliptin, and dapagliflozin who was admitted with his third episode of pancreatitis secondary to hypertriglyceridemia. His home oral glycemic agents were continued as inpatient. Despite tight euglycemic control, the patient developed profound metabolic acidosis and was found to have an elevated beta-hydroxybutyrate level and normal lactic acid level. He was admitted into the intensive care unit and started on an insulin drip, and after resolution of his acidosis he was transitioned to basal insulin successfully. He was discharged with an insulin regimen while his oral glycemic agents were discontinued indefinitely. SGLT-2 inhibitors are associated with euDKA, most likely as a result of their non-insulin-dependent glucose clearance, hyperglucagonemia, and decreased ketone clearance. The aim of this case report is to inform the physician about the possibility of euDKA in a patient with type II diabetes on a SGLT-2 inhibitor presenting with an acute illness.
Political Risk Paths in International Construction Projects: Case Study from Chinese Construction Enterprises
Authors: Chang Tengyuan , Deng Xiaopeng , Hwang Bon-Gang , Zhao Xiaojing
Published: August 2018

International construction enterprises (ICEs) have been plagued with political risks in the global market. To ensure the success of political risk management, it is necessary to comprehend the political risks in international construction projects. This study aims at exploring the political risk paths in international construction projects. The preliminary political risk factors and paths were proposed from the literature review. A survey questionnaire was developed to collect political risk cases faced by Chinese construction enterprises (CCEs) performing international construction projects, and 264 valid cases were received and analyzed for this study. Adopting the confirmatory factor analysis (CFA) method, 6 macrofactors (“sociopolitical stability” (A), “legal and regulatory” (B), “social safety” (C), “economy performance” (D), “attitude towards foreigners” (E), and “international environment” (F)) and 2 microfactors (“low exposure” (G) and “capability of enterprises” (H)) were identified. Moreover, the results of path analysis illustrated that 7 factors (A, B, C, D, E, G, and H) had the significant direct negative effect on “risk consequences” and 3 factors (A, D, and F) had the indirect negative effect on “risk consequences.” The findings from this study help practitioners gain an in‐depth understanding of political risks in international construction projects and provide a useful reference for ICEs to manage political risks when venturing outside their home countries.
A Comparison of the Prevalence of the Metabolic Syndrome among Sri Lankan Patients with Type 2 Diabetes Mellitus Using WHO, NCEP-ATP III, and IDF Definitions
Authors: Herath H. M. M. , Weerasinghe N. P. , Weerarathna T. P. , Amarathunga A.
Published: August 2018

Background. Presence of metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (type 2 DM) increases the risk of cardiovascular morbidity and mortality. Therefore, recognition of MetS in type 2 DM is important in initiating the appropriate preventive and therapeutic measures. The commonly used definitions have similarities and discrepancies. Aims of this study was to investigate the prevalence of MetS among patients with type 2DM using all three well known (WHO, IDF, and NCEP-ATP III) definitions and to identify the concordance and the difference of these three definitions. Methods. This cross-sectional study included patients with type 2 DM who were followed up at the regional diabetes centre in Galle, Sri Lanka. A total of 2913 type 2 DM patients were recruited by convenient sampling method, and their clinical and biochemical data were collected. Results. The mean age (SD) of the sample was 49.9 (10.2) years and the mean duration of diabetes was 5.04 (5.71). Prevalence of MetS was highest by WHO (70%) followed by IDF (44%) and NCEP-ATP III (29%) definitions. The prevalence was significantly higher in women according to all three definitions, and the difference was most marked with NCEP-ATP III and IDF definitions. Around 25% were identified as having MetS by all three definitions whereas around 45% were recognized with MetS by two definitions. While concordances between WHO with IDF (0.37, p < 0.001) and NCEP-ATP III (0.24, p < 0.001) criteria were poor, they were average (0.53, p < 0.001) between NCEP-ATP III and IDF criteria. Conclusions. The prevalence of MetS among patients with type 2 DM can significantly be varied based on the definition used and the three definitions of MetS recognized different set of individuals. The highest prevalence of MetS was observed with WHO (70.6%) whereas lowest was observed with NCEP-ATP III definition.
Anti‐Inflammatory Effect of a Polyphenol‐Enriched Fraction from Acalypha wilkesiana on Lipopolysaccharide‐Stimulated RAW 264.7 Macrophages and Acetaminophen‐Induced Liver Injury in Mice
Authors: Wu Hongtan , Pang Haiyue , Chen Yupei , Huang Lisen , Liu Huaxin , Zheng Yongbiao , Sun Cuiling , Zhang Gang , Wang Gueyhorng
Published: August 2018

A polyphenol‐enriched fraction (PEF) from Acalypha wilkesiana, whose leaves have been traditionally utilized for the treatment of diverse medical ailments, was investigated for the anti‐inflammatory effect and molecular mechanisms by using lipopolysaccharide‐ (LPS‐) stimulated RAW 264.7 macrophages and acetaminophen‐ (APAP‐) induced liver injury mouse model. Results showed that PEF significantly attenuated LPS‐induced nitric oxide (NO) and prostaglandin E2 (PGE2) production and suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX‐2) in RAW 264.7 macrophages. PEF also reduced the secretion of proinflammatory cytokines including tumor necrosis factor‐α (TNF‐α), interleukin‐ (IL‐) 1β, and IL‐6 in LPS‐stimulated RAW 264.7 macrophages. Moreover, PEF potently inhibited LPS‐induced phosphorylation of mitogen‐activated protein kinases (MAPKs) as well as the activation of nuclear factor‐κB (NF‐κB) by preventing the degradation of inhibitor κB‐α (IκB‐α). In vivo, PEF pretreatment ameliorated APAP‐induced liver injury and hepatic inflammation, as presented by decreased hepatic damage indicators and proinflammatory factors at both plasma and gene levels. Additionally, PEF pretreatment remarkably diminished Toll‐like receptor 3 (TLR3) and TLR4 expression and the subsequent MAPKs and NF‐κB activation. HPLC analysis revealed that two predominantly polyphenolic compounds present in PEF were geraniin and corilagin. These results indicated that PEF has an anti‐inflammatory effect, and its molecular mechanisms may be involved in the inactivation of the TLR/MAPK/NF‐κB signaling pathway, suggesting the therapeutic potential of PEF for inflammatory diseases.
Synthesis and Characterization of Semicrystalline Polyimides Containing Bridged Linkages
Authors: Chao Min
Published: August 2018

A series of polyimides (PI) containing bridged linkages were prepared successfully through a three-step technique. The results indicated that the glass transition temperature (Tg) of polyimides was affected by flexibility of polymer chain and the intermolecular interactions. ODPA-TPER-based polyimide possesses the lowest Tg, which was 214°C. All polyimides had semicrystalline characteristics, and ODPA-TPER-based PI exhibited the lowest melting temperature (Tm) at 316°C. The polyimides had high weight loss temperatures, which indicated that bridged linkages can reduce the softening temperature, meanwhile keeping excellent thermal stability.
A Concurrent Cognitive Task Does Not Perturb Quiet Standing in Fibromyalgia and Chronic Fatigue Syndrome
Authors: Rasouli Omid , Fors Egil A. , Vasseljen Ottar , Stensdotter Ann-Katrin
Published: August 2018

Background and Objectives. Cognitive complaints are common in fibromyalgia (FM) and chronic fatigue syndrome (CFS). Fatigue as well as pain may require greater effort to perform cognitive tasks, thereby increasing the load on processing in the central nervous system and interfering with motor control.Methods. The effect of a concurrent arithmetic cognitive task on postural control during quiet standing was investigated in 75 women (aged 19–49 years) and compared between FM, CFS, and matched controls (n=25/group). Quiet standing on a force plate was performed for 60 s/condition, with and without a concurrent cognitive task. The center of pressure data was decomposed into a slow component and a fast component representing postural sway and adjusting ankle torque.Results. Compared to controls, CFS and FM displayed lower frequency in the slow component (p<0.001), and CFS displayed greater amplitude in the slow (p=0.038andp=0.018) and fast (p=0.045) components. There were no interactions indicating different responses to the added cognitive task between any of the three groups.Conclusion. Patients displayed insufficient postural control across both conditions, while the concurrent cognitive task did not perturb quiet standing. Fatigue but not pain correlated with postural control variables.
Positive Solutions for a Fractional Boundary Value Problem with a Perturbation Term
Authors: Zou Yumei
Published: August 2018

We obtain some new upper and lower estimates for the Green’s function associated with a fractional boundary value problem with a perturbation term. Criteria for the existence of positive solutions of the problem are then obtained based on it.
A Comparison of Percutaneous Endoscopic Lumbar Discectomy and Open Lumbar Microdiscectomy for Lumbar Disc Herniation in the Korean: A Meta-Analysis
Authors: Kim Manyoung , Lee Sol , Kim Hyeun-Sung , Park Sangyoon , Shim Sang-Yeup , Lim Dong-Ju
Published: August 2018

Background. Among the surgical methods for lumbar disc herniation, open lumbar microdiscectomy is considered the gold standard. Recently, percutaneous endoscopic lumbar discectomy is also commonly performed for lumbar disc herniation for its various strong points. Objectives. The present study aims to examine whether percutaneous endoscopic lumbar discectomy and open lumbar microdiscectomy show better results as surgical treatments for lumbar disc herniation in the Korean population. Methods. In the present meta-analysis, papers on Korean patients who underwent open lumbar microdiscectomy and percutaneous endoscopic lumbar discectomy were searched, both of which are surgical methods to treat lumbar disc herniation. The papers from 1973, when percutaneous endoscopic lumbar discectomy was first introduced, to March 2018 were searched at the databases of MEDLINE, EMBASE, PubMed, and Cochrane Library. Results. Seven papers with 1254 patients were selected. A comparison study revealed that percutaneous endoscopic lumbar discectomy had significantly better results than open lumbar microdiscectomy in the visual analogue pain scale at the final follow-up (leg: mean difference [MD]=-0.35; 95% confidence interval [CI]=-0.61, -0.09; p=0.009; back: MD=-0.79; 95% confidence interval [CI]=-1.42, -0.17; p=0.01), Oswestry Disability Index (MD=-2.12; 95% CI=-4.25, 0.01; p=0.05), operation time (MD=-23.06; 95% CI=-32.42, -13.70; p<0.00001), and hospital stay (MD=-4.64; 95% CI=-6.37, -2.90; p<0.00001). There were no statistical differences in the MacNab classification (odds ratio [OR]=1.02; 95% CI=0.71, 1.49; p=0.90), complication rate (OR=0.72; 95% CI=0.20, 2.62; p=0.62), recurrence rate (OR=0.83; 95% CI=0.50, 1.38; p=0.47), and reoperation rate (OR=1.45; 95% CI=0.89, 2.35; p=0.13). Limitations. All 7 papers used for the meta-analysis were non-RCTs. Some differences (type of surgery (primary or revisional), treatment options before the operation, follow-up period, etc.) existed depending on the selected paper, and the sample size was small as well. Conclusion. While percutaneous endoscopic lumbar discectomy showed better results than open lumbar microdiscectomy in some items, open lumbar microdiscectomy still showed good clinical results, and it is therefore reckoned that a randomized controlled trial with a large sample size would be required in the future to compare these two surgical methods.
Phylogenetic Groups and Antimicrobial Susceptibility Patterns of Escherichia coli from Healthy Chicken in Eastern and Central Uganda
Authors: Kabiswa Winston , Nanteza Ann , Tumwine Gabriel , Majalija Samuel
Published: August 2018

Antimicrobial resistance is an emerging problem in both humans and animals due to misuse and excessive use of drugs. Resistance in commensal E. coli isolates can be used to predict emergence of resistance in other gut microflora. The aim of this study is to determine the phylogenetic groups and antimicrobial resistance patterns of E. coli from healthy chickens in Uganda. The phylogenetic grouping of 120 fecal E. coli isolates from eastern and central Uganda was derived using the triplex PCR assay and their susceptibility patterns determined by agar disc diffusion method to 5 antimicrobial drugs. Most E. coli is segregated into phylogenetic group A comprising 84%, while 12% and 4% were in groups D and B1, respectively. Similarly most E. coli from central (87%) and eastern Uganda (82%) belonged to group A. Overall, 85 (70%) of E. coli were resistant to antimicrobial drugs, of which 72/101 (70%) are in PG A, 10 of 14 (71.4%) in PG D, and 3 of 5 (60%) in PG B1. Significantly, most of the isolates in PG A from both central (66.7%) and (60.6%) eastern Uganda were resistant to one antimicrobial. Resistance to tetracycline alone or in combination with other drugs for central and eastern Uganda in PG A is 51% and 55%, respectively. Multidrug resistance to tetracycline and ciprofloxacin or nalidixic acid was 10% and 18% in isolates from central and 10% and 12% in isolates from eastern region, respectively. Phylogenetic group A accounts for most of the E. coli in chicken from Uganda. No difference in the resistance rates between the phylogenetic groups of E. coli has been observed. The high prevalence of resistant E. coli strains from different phylogenetic groups in healthy chickens suggests antimicrobial drug selection pressure due to excessive drug in the rearing layer chickens.
Dynamic Contagion of Systemic Risks on Global Main Equity Markets Based on Granger Causality Networks
Authors: Zheng Qiuhong , Song Liangrong
Published: August 2018

A total of 156 Granger causal networks of stock markets are constructed by using the Granger causality test and time series sliding window based on stock index data of 34 major stock markets in the world from 2004 to 2017. The topological structures and evolution characteristics of the Granger causal networks are analyzed from the perspective of complex network theory. Empirical results demonstrate that the network topology has a significant difference during the global financial crisis and other periods. The causal relationships among different global stock markets exhibit a jump growth when each major crisis occurs. The contagion path is also short. A causal relationship between any two stock markets can usually be established with one stock market on average, not by using more than five stock markets. For risk contagion, the American stock markets exerted the largest influence in 12 years, followed by the European stock markets. Stock markets with high intermediate contagion ability play an important role in systemic risk contagion. Despite the crucial markets in Europe and America (e.g., USA, Brazil, and Mexico), stock markets with weak network correlation and strong media ability (e.g., the markets of Japan, Korea, Australia, and New Zealand) play a critical role in risk contagion.
Knowledge of Periodontal Diseases, Oral Hygiene Practices, and Self-Reported Periodontal Problems among Pregnant Women and Postnatal Mothers Attending Reproductive and Child Health Clinics in Rural Zambia
Authors: Kabali T. M. , Mumghamba E. G.
Published: August 2018

Aim. To determine the level of knowledge of periodontal diseases, practices regarding oral hygiene, and self-perceived periodontal problems among pregnant and postnatal women attending reproductive and child health clinics in rural districts of Zambia.Methodology.This was a quantitative, questionnaire-based, descriptive, and cross-sectional study that recruited 410 women aged 15 to 43 years. Data were analyzed using SPSS v19.0 computer program.Results. Participants knowledgeable of periodontal diseases were 62%; gingivitis signs included gum swelling (87.4%) and bleeding (93.3%). Of all participants, 95.6% practiced tooth brushing: twice/day (38.5%), using plastic toothbrush (95.6%), chewing stick (12.2%), toothpick (10.7%), dental floss (2.0%), and tongue cleaning (55.4%). Self-reported periodontal problems were bleeding gums (23.2%), gums that were reddish (10.5%), swollen (11.0%), painful (15.9%), and mobile teeth (3.4%). In logistic regression analysis, painful gums, reddish gums, and toothpick use were 21.9, 4.7, and 4.3 respectively, significantly more likely to cause gum bleeding on tooth brushing.Conclusions. Most studied women had general knowledge of periodontal diseases but only few knew the cause. All participants performed tooth cleaning; however, majority did not know appropriate practices, and only few had periodontal problems. Integration of oral health to general health promotion and periodontal therapy to pregnant women at high risk is recommended.
Subjugation of TGFβ Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End Joining
Authors: Liu Qi , Ma Lin , Jones Trevor , Palomero Luis , Pujana Miquel Angel , Martinez-Ruiz Haydeliz , Ha Patrick K. , Murnane John , Cuartas Isabel , Seoane Joan , Baumann Michael , Linge Annett , Barcellos-Hoff Mary Helen
Published: August 2018

Purpose:

Following cytotoxic therapy, 70% of patients with human papillomavirus (HPV)-positive oropharyngeal head and neck squamous cell carcinoma (HNSCC) are alive at 5 years compared with 30% of those with similar HPV-negative cancer. Loss of TGFβ signaling is a poorly studied consequence of HPV that could contribute to patient outcome by compromising DNA repair.

Experimental Design:

Human HNSCC cell lines (n = 9), patient-derived xenografts (n = 9), tissue microarray (n = 194), TCGA expression data (n = 279), and primary tumor specimens (n = 10) were used to define the relationship between TGFβ competency, response to DNA damage, and type of DNA repair.

Results:

Analysis of HNSCC specimens in situ and in vitro showed that HPV associated with loss of TGFβ signaling that increased response to radiation or cisplatin. TGFβ suppressed miR-182, which inhibited both BRCA1, necessary for homologous recombination repair (HRR), and FOXO3, required for ATM kinase activity. TGFβ signaling blockade by either HPV or inhibitors released miR182 control, compromised HRR and increased response to PARP inhibition. Antagonizing miR-182 rescued the HRR deficit in HPV-positive cells. Loss of TGFβ signaling unexpectedly increased repair by error prone, alternative end-joining (alt-EJ).

Conclusions:

HPV-positive HNSCC cells are unresponsive to TGFβ. Abrogated TGFβ signaling compromises repair by HRR and increases reliance on alt-EJ, which provides a mechanistic basis for sensitivity to PARP inhibitors. The effect of HPV in HNSCC provides critical validation of TGFβ’s role in DNA repair proficiency and further raises the translational potential of TGFβ inhibitors in cancer therapy.
BMI1 Drives Metastasis of Prostate Cancer in Caucasian and African-American Men and Is A Potential Therapeutic Target: Hypothesis Tested in Race-specific Models
Authors: Ganaie Arsheed A. , Beigh Firdous H. , Astone Matteo , Ferrari Marina G. , Maqbool Raihana , Umbreen Syed , Parray Aijaz S. , Siddique Hifzur R. , Hussain Tabish , Murugan Paari , Morrissey Colm , Koochekpour Shahriar , Deng Yibin , Konety Badrinath R. , Hoeppner Luke H. , Saleem Mohammad
Published: August 2018

Purpose:

Metastasis is the major cause of mortality in prostate cancer patients. Factors such as genetic makeup and race play critical role in the outcome of therapies. This study was conducted to investigate the relevance of BMI1 in metastatic prostate cancer disease in Caucasian and African-Americans.

Experimental Design:

We employed race-specific prostate cancer models, clinical specimens, clinical data mining, gene-microarray, transcription-reporter assay, chromatin-immunoprecipitation (ChIP), IHC, transgenic-(tgfl/fl) zebrafish, and mouse metastasis models.

Results:

BMI1 expression was observed to be elevated in metastatic tumors (lymph nodes, lungs, bones, liver) of Caucasian and African-American prostate cancer patients. The comparative analysis of stage III/IV tumors showed an increased BMI1 expression in African-Americans than Caucasians. TCGA and NIH/GEO clinical data corroborated to our findings. We show that BMI1 expression (i) positively correlates to metastatic (MYC, VEGF, cyclin D1) and (ii) negative correlates to tumor suppressor (INKF4A/p16, PTEN) levels in tumors. The correlation was prominent in African-American tumors. We show that BMI1 regulates the transcriptional activation of MYC, VEGF, INKF4A/p16, and PTEN. We show the effect of pharmacological inhibition of BMI1 on the metastatic genome and invasiveness of tumor cells. Next, we show the anti-metastatic efficacy of BMI1-inhibitor in transgenic zebrafish and mouse metastasis models. Docetaxel as monotherapy has poor outcome on the growth of metastatic tumors. BMI1 inhibitor as an adjuvant improved the taxane therapy in race-based in vitro and in vivo models.

Conclusions:

BMI1, a major driver of metastasis, represents a promising therapeutic target for treating advanced prostate cancer in patients (including those belonging to high-risk group).
BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in Kras-Mutant Non–Small Cell Lung Cancer
Authors: Adeegbe Dennis O. , Liu Shengwu , Hattersley Maureen M. , Bowden Michaela , Zhou Chensheng W. , Li Shuai , Vlahos Raven , Grondine Michael , Dolgalev Igor , Ivanova Elena V. , Quinn Max M. , Gao Peng , Hammerman Peter S. , Bradner James E. , Diehl J. Alan , Rustgi Anil K. , Bass Adam J. , Tsirigos Aristotelis , Freeman Gordon J. , Chen Huawei , Wong Kwok-Kin
Published: August 2018

KRAS mutation is present in approximately 30% of human lung adenocarcinomas. Although recent advances in targeted therapy have shown great promise, effective targeting of KRAS remains elusive, and concurrent alterations in tumor suppressors render KRAS-mutant tumors even more resistant to existing therapies. Contributing to the refractoriness of KRAS-mutant tumors are immunosuppressive mechanisms, such as increased presence of suppressive regulatory T cells (Treg) in tumors and elevated expression of the inhibitory receptor PD-1 on tumor-infiltrating T cells. Treatment with BET bromodomain inhibitors is beneficial for hematologic malignancies, and they have Treg-disruptive effects in a non–small cell lung cancer (NSCLC) model. Targeting PD-1–inhibitory signals through PD-1 antibody blockade also has substantial therapeutic impact in lung cancer, although these outcomes are limited to a minority of patients. We hypothesized that the BET bromodomain inhibitor JQ1 would synergize with PD-1 blockade to promote a robust antitumor response in lung cancer. In the present study, using Kras+/LSL-G12D; Trp53L/L (KP) mouse models of NSCLC, we identified cooperative effects between JQ1 and PD-1 antibody. The numbers of tumor-infiltrating Tregs were reduced and activation of tumor-infiltrating T cells, which had a T-helper type 1 (Th1) cytokine profile, was enhanced, underlying their improved effector function. Furthermore, lung tumor–bearing mice treated with this combination showed robust and long-lasting antitumor responses compared with either agent alone, culminating in substantial improvement in the overall survival of treated mice. Thus, combining BET bromodomain inhibition with immune checkpoint blockade offers a promising therapeutic approach for solid malignancies such as lung adenocarcinoma. Cancer Immunol Res; 6(10); 1234–45. ©2018 AACR.
Vowel Reduction in Coratino (South Italy): Phonological and Phonetic Perspectives
Authors: Bucci Jonathan , Perrier Pascal , Gerber Silvain , Schwartz Jean-Luc
Published: August 2018

Vowel reduction may involve phonetic reduction processes, with nonreached targets, and/or phonological processes in which a vowel target is changed for another target, possibly schwa. Coratino, a dialect of southern Italy, displays complex vowel reduction processes assumed to be phonological. We analyzed a corpus representative of vowel reduction in Coratino, based on a set of a hundred pairs of words contrasting a stressed and an unstressed version of a given vowel in a given consonant environment, produced by 10 speakers. We report vowelformants together with consonant-to-vowel formant trajectories and durations, and show that these data are rather in agreement with a change in vowel target from /i e ɛ·ɔ u/ to schwa when the vowel is a non-word-initial unstressed utterance, unless the vowel shares a place-of-articulation feature with the preceding or following consonant. Interestingly, it also appears that there are 2 targets for phonological reduction, differing in F1 values. A “higher schwa” - which could be considered as /ɨ/ - corresponds to reduction for high vowels /i u/ while a “lower schwa” - which could be considered as /ə/ - corresponds to reduction for midhigh
Intensive Care Therapy for Patients with Advanced Liver Diseases
Authors: Katsounas Antonios , Canbay Ali
Published: August 2018

Decompensated cirrhosis is characterized by high hospitalization rates and costs, frequent readmissions, and poor short-term survival. Patients admitted to the hospital with acute variceal bleeding and/or hepatic encephalopathy and/or renal dysfunction are at serious risk for developing infection and/or sepsis; in turn, this renders them highly susceptible to the development of multi-system organ failure. The lack of standardized intensive care unit management protocols in patients with cirrhosis along with only few data reports from longitudinal clinical trials makes it difficult for hepatologists and critical care specialists to provide uniform evidence for clinical practice that could safely consolidate favorable outcomes such as lower hospitalization rates and/or mortality. Based on a rigorous online search of the scientific literature as well as a longtime clinical experience of the authors in the field of hepatology and critical care medicine, this work represents a focused effort to elucidate the specific bio-morbidity of advanced liver diseases in relation to the aforementioned challenges in clinical management. Further meta-analyses and/or systematic reviews are needed to enable clinicians to develop more effective strategies to bridge patients with decompensated liver disease to recompensation or liver transplantation.
Assessing the Effectiveness of Coroners’ Inquests in Relation to Child Maltreatment Fatalities: A Human Rights Perspective
Authors: Martino Joseph
Published: August 2018

The potential of the coroner’s office in Ontario to reduce the incidents of child maltreatment-related fatalities is assessed through an examination of the four inquests completed between 2000 and 2015 involving the deaths of children connected with the child welfare system. Applying a human rights perspective rooted in the United Nations Convention on the Rights of the Child, it is argued that a concern for the fundamental legal entitlements of children has been little in evidence at the inquests of child fatalities, detracting from the ability of these proceedings to contribute to the prevention of maltreatment-related child deaths. Data derived from the juries’ verdicts at these inquests are compared with the rights and principles prescribed in the Convention with a view to assessing the extent to which the latter are implicated in the former. Findings of note include the absence of a simple instance in which the Convention or its provisions were explicitly referenced in the inquest verdicts, a startling fact given Canada’s obligations under international law to a treaty dedicated to the preservation of the life and wellbeing of children.
Does the Thunder Roll? Mandarin Chinese Meteorological Expressions and Their Iconicity
Authors: Van Hoey Thomas
Published: August 2018

From a typological perspective, Chinese meteorological expressions are argument-oriented. However, using a lexical semantic approach, based on corpus data as well as dictionaries and Chinese WordNet, a taxonomical lexical field can be established to further analyze the basic level items. Five main clusters of meteorological expressions are identified: precipitation, wind, thunder, sunshine and cloud. A comparison of these clusters with frames derived from the English FrameNet shows that Chinese has a narrower conception of weather phenomena than English. There is significant influence from the script on the linguistic system, at least in relation to meteorological expressions. It is shown that Chinese uses iconicity in its writing system where it is lacking in its phonology. A special case study are weather-related ideophones, where two strata are found: those that are phonologically and semantically motivated and receive iconic support from the writing system vs. those that do not receive this support.
Impact of Dynamically Downscaling Two CMIP5 Models on the Historical and Future Changes in Winter Extratropical Cyclones along the East Coast of North America
Authors: Zhang Zhenhai , Colle Brian A.
Published: August 2018

This study investigates the impact of dynamical downscaling on historical and future projections of winter extratropical cyclones over eastern North America and the western Atlantic Ocean. Six-hourly output from two global circulation models (GCMs), CCSM4 and GFDL-ESM2M, from phase 5 of the Coupled Model Intercomparison Project (CMIP5) are used to create the initial and boundary conditions for 20 historical (1986–2005) and 20 future (2080–99) winter simulations using the Weather Research and Forecasting (WRF) Model. Two sets of WRF grid spacing (1.0° and 0.2°) are examined to determine the impact of model resolution. Although the cyclone frequency in the WRF runs is largely determined by the GCM predictions, the higher-resolution WRF reduces the underprediction in cyclone intensity. There is an increase in late-twenty-first-century cyclone activity over the east coast of North America in CCSM4 and its WRF, whereas there is little change in GFDL-ESM2M and WRF given that there is a larger decrease in the temperature gradient in this region. There is a future increase in relatively deep cyclones over the East Coast in the high-resolution WRF forced by CCSM4. These storms are weaker than the historical cases early in their life cycle, but then because of latent heating they rapidly develop and become stronger than the historical events. This increase does not occur in the low-resolution WRF or the high-resolution WRF forced by GFDL since the latent heat increase is relatively small. This implies that the diabatic processes during cyclogenesis may become more important in a warmer climate, and these processes may be too weak in existing coarse-resolution GCMs.
Assessing the Skill of Medium-Range Ensemble Precipitation and Streamflow Forecasts from the Hydrologic Ensemble Forecast Service (HEFS) for the Upper Trinity River Basin in North Texas
Authors: Kim Sunghee , Sadeghi Hossein , Limon Reza Ahmad , Saharia Manabendra , Seo Dong-Jun , Philpott Andrew , Bell Frank , Brown James , He Minxue
Published: August 2018

To issue early warnings for the public to act, for emergency managers to take preventive actions, and for water managers to operate their systems cost-effectively, it is necessary to maximize the time horizon over which streamflow forecasts are skillful. In this work, we assess the value of medium-range ensemble precipitation forecasts generated with the Hydrologic Ensemble Forecast Service (HEFS) of the U.S. National Weather Service (NWS) in increasing the lead time and skill of streamflow forecasts for five headwater basins in the upper Trinity River basin in north-central Texas. The HEFS uses ensemble mean precipitation forecasts from the Global Ensemble Forecast System (GEFS) of the National Centers for Environment Prediction (NCEP). For comparative evaluation, we verify ensemble streamflow forecasts generated with the HEFS forced by the GEFS forecast with those forced by the short-range quantitative precipitation forecasts (QPFs) from the NWS West Gulf River Forecast Center (WGRFC) based on guidance from the NCEP’s Weather Prediction Center. We also assess the benefits of postprocessing the raw ensemble streamflow forecasts and evaluate the impact of selected parameters within the HEFS on forecast quality. The results show that the use of medium-range precipitation forecasts from the GEFS with the HEFS extends the time horizon for skillful forecasting of mean daily streamflow by 1–3 days for significant events when compared with using only the 72-h River Forecast Center (RFC) QPF with the HEFS. The HEFS forced by the GEFS also improves the skill of two-week-ahead biweekly streamflow forecast by about 20% over climatological forecast for the largest 1% of the observed biweekly flow.
Instability-Driven Benthic Storms below the Separated Gulf Stream and the North Atlantic Current in a High-Resolution Ocean Model
Authors: Schubert René , Biastoch Arne , Cronin Meghan F. , Greatbatch Richard J.
Published: August 2018

Benthic storms are important for both the energy budget of the ocean and for sediment resuspension and transport. Using 30 years of output from a high-resolution model of the North Atlantic, it is found that most of the benthic storms in the model occur near the western boundary in association with the Gulf Stream and the North Atlantic Current, in regions that are generally collocated with the peak near-bottom eddy kinetic energy. A common feature is meander troughs in the near-surface jets that are accompanied by deep low pressure anomalies spinning up deep cyclones with near-bottom velocities of up to more than 0.5 m s−1. A case study of one of these events shows the importance of both baroclinic and barotropic instability of the jet, with energy being extracted from the jet in the upstream part of the meander trough and partly returned to the jet in the downstream part of the meander trough. This motivates examining the 30-yr time mean of the energy transfer from the (annual mean) background flow into the eddy kinetic energy. This quantity is shown to be collocated well with the region in which benthic storms and large increases in deep cyclonic relative vorticity occur most frequently, suggesting an important role for mixed barotropic–baroclinic instability-driven cyclogenesis in generating benthic storms throughout the model simulation. Regions of the largest energy transfer and most frequent benthic storms are found to be the Gulf Stream west of the New England Seamounts and the North Atlantic Current near Flemish Cap.
Determining Ergonomic Smartphone Forms With High Grip Comfort and Attractive Design
Authors: Lee Songil , Kyung Gyouhyung , Yi Jihhyeon , Choi Donghee , Park Sungryul , Choi Byeonghwa , Lee Seungbae
Published: August 2018

Objective:

The authors aimed to identify ergonomic smartphone forms by investigating the effects of hand length, four major smartphone dimensions (height, width, thickness, and edge roundness), and smartphone mass on grip comfort and design attractiveness.

Background:

Despite their potential effect on grip comfort and design attractiveness, the dimensions specified above have never been simultaneously considered in a study investigating smartphone gripping.

Method:

Seventy-two young individuals participated in a three-stage study. Stage 1 determined the ranges of the four smartphone dimensions suitable for grip comfort and identified the strengths of their influences. Stage 2 investigated the effects of width and thickness (determined to have the greatest influence) on grip comfort and design attractiveness. Mock-ups of varying masses were fabricated using the dimensions determined during the first two stages to investigate the effect of mass on grip comfort and design attractiveness in Stage 3.

Results:

Phone width was found to significantly influence grip comfort and design attractiveness, and the dimensions of 140 × 65 (or 70) × 8 × 2.5 mm (height × width × thickness × edge roundness) provided high grip comfort and design attractiveness. The selected dimensions were fit with a mass of 122 g, with masses in the range of 106–137 g being comparable.

Conclusion:

The findings of this study contribute to ergonomic smartphone design developments by specifying dimensions and mass that provide high grip comfort and design attractiveness.

Application:

The dimensions and mass determined in this study should be considered for improving smartphone design grip comfort and attractiveness.
Association between socioeconomic attainments and suicidal ideation by age groups in Korea
Authors: Kim Joongbaeck , Yoon Soo-Yeon
Published: August 2018

Background:

Suicidal ideation is a strong antecedent of suicidal behavior, associated with increased likelihood of suicide. Thus, suicidal ideation serves to identify which groups are at more risk of suicide and has policy implications for targeting groups to prevent suicide.

Aims:

A substantial body of research has addressed potential determinants of suicide ideation in Korea. Little attention has been paid, however, to analyzing the extent to which socioeconomic attainments (education, household income, and employment status) are associated with risk of suicidal ideation, drawing on nationally representative data.

Methods:

Data were drawn from the 2012 Korea Welfare Panel Study (KOWEPS). Among the 12,606 respondents, the findings are based on 1,500 young adults (age 18–35) and 3,469 middle-aged adults (age 36–55) who answered a question about suicidal ideation.

Results:

For young adults, respondents from 2-year and 4-year colleges and higher had lower probabilities of suicidal ideation compared with respondents from high school. People out of the labor force also exhibited an elevated risk of suicidal ideation compared with those in waged employment. Middle-aged adults displayed different patterns. Middle-aged respondents from 4-year colleges or higher had an increased likelihood of suicidal ideation. The likelihood of reporting suicidal ideation was predicted to decrease as household income increased only for middle-aged adults.

Conclusions:

The information about suicidal ideation was obtained from only one question of self-response, which limits the validity of the suicidal ideation measurement. The cross-sectional setting of the data prevents us from estimating causal relationships. Nevertheless, the findings imply that age-specific policy should be implemented to ameliorate differential risk for suicidal ideation and benefit public mental health in the long run.
Cannabis Use and Supply Patterns Among Belgian Cannabis Social Club Members
Authors: Pardal Mafalda , Decorte Tom
Published: August 2018

Cannabis Social Clubs (CSCs) constitute a noncommercial model for the supply of cannabis among registered, adults users, which is present in several countries—including in Belgium. This analysis provides a first descriptive examination of a sample of Belgian CSC members’ patterns of use and supply, as well as their sociodemographic features. According to a new voluntary survey of 190 Belgian CSC members, more than three quarters are male, Belgian, and more than half work full- or part-time. About 44% of respondents have completed university studies. Securing cannabis was the primary reason to adhere to a CSC, and most are (near-)daily users. Our results revealed that the CSC was the sole supplier for most respondents of cannabis-producing CSCs, who obtained almost exclusively (dried) herbal cannabis. The presence of (self-declared) medical users in our sample is noteworthy. This analysis advances our knowledge of the segment of the market served by this noncommercial model.