bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers to Diet and Exercise among Nepalese Type 2 Diabetic Patients
Authors: Ghimire Saruna
Published: November 2017

This study aims to identify the modifiable barriers encountered by type 2 diabetic patients in Nepal to achieving their recommended dietary and exercise advice. A cross-sectional study was conducted among 197 type 2 diabetic patients, attending a diabetic clinic. Binary logistic regression models were used to identify perceived barriers. About 41% and 46% of the participants were noncompliant to diet and exercise advice, respectively; only 35.5% the participants were compliant to both. Perceived social acceptability (OR = 0.14; 95% CI: 0.03–0.58) and reminder to action (OR = 2.77; 95% CI: 1.38–5.53) were associated with noncompliance to diet. Most of the barriers to diet were related to taste, feast and festivals, lack of knowledge, and availability of healthy options. Self-efficacy (OR = 0.09; 95% CI: 0.02–0.34) and social acceptability (OR = 0.12; 95% CI: 0.04–0.34) were significant predictors of noncompliance to exercise. The supportive role of children and spouse and the opposing role of friends and relatives were important for compliance to both. A misconception on diabetes severity, effectiveness of healthy lifestyle, and exercise timing was prevalent among the study participants. Addressing the modifiable barriers identified in this study is essential for successful diabetes management in Nepal.
TheIn VivoDynamics of HIV Infection with the Influence of Cytotoxic T Lymphocyte Cells
Authors: Ngina Purity , Mbogo Rachel Waema , Luboobi Livingstone S.
Published: November 2017

Thein vivodynamics of HIV infection, the infection mechanism, the cell types infected, and the role played by the cytotoxic cells are poorly understood. This paper uses mathematical modelling as a tool to investigate and analyze the immune system dynamics in the presence of HIV infection. We formulate a six-dimensional model of nonlinear ordinary differential equations derived from known biological interaction mechanisms between the immune cells and the HIV virions. The existence and uniqueness as well as positivity and boundedness of the solutions to the differential equations are proved. Furthermore, the disease-free reproduction number is derived and the local asymptotic stability of the model investigated. In addition, numerical analysis is carried out to illustrate the importance of havingR0<1. Lastly, the biological dynamics of HIVin vivoinfection are graphically represented. The results indicate that, at acute infection, the cytotoxic T-cells play a paramount role in reducing HIV viral replication. In addition, the results emphasize the importance of developing controls, interventions, and management policies that when implemented would lead to viral suppression during acute infection.
Efficient Simulation for Pricing Barrier Options with Two‐Factor Stochastic Volatility and Stochastic Interest Rate
Authors: Sumei Zhang , Jieqiong Zhao
Published: November 2017

This paper presents an extension of the double Heston stochastic volatility model by combining Hull‐White stochastic interest rates. By the change of numeraire and quadratic exponential scheme, this paper develops a new simulation scheme for the extended model. By combining control variates and antithetic variates, this paper provides an efficient Monte Carlo simulation algorithm for pricing barrier options. Based on the differential evolution algorithm the extended model is calibrated to S&P 500 index options to obtain the model parameter values. Numerical results show that the proposed simulation scheme outperforms the Euler scheme, the proposed simulation algorithm is efficient for pricing barrier options, and the extended model is flexible to fit the implied volatility surface.
SnO2 Nanoparticles Decorated 2D Wavy Hierarchical Carbon Nanowalls with Enhanced Photoelectrochemical Performance
Authors: Khanis Noor Hamizah , Ritikos Richard , Chiu Wee Siong , Haw Choon Yian , Abdul Rashid Nur Maisarah , Chia Mei Yuen , Khiew Poi Sim , Abdul Rahman Saadah
Published: November 2017

Two-dimensional carbon nanowall (2D-CNW) structures were prepared by hot wire assisted plasma enhanced chemical vapor deposition (hw-PECVD) system on silicon substrates. Controlled variations in the film structure were observed with increase in applied rf power during deposition which has been established to increase the rate of dissociation of precursor gases. The structural changes resulted in the formation of wavy-like features on the 2D-CNW, thus further enhancing the surface area of the nanostructures. The FESEM results confirmed the morphology transformation and conclusively showed the evolution of the 2D-CNW novel structures while Raman results revealed increase in ID/IG ratio indicating increase in the presence of disordered domains due to the presence of open edges on the 2D-CNW structures. Subsequently, the best 2D-CNW based on the morphology and structural properties was functionalized with tin oxide (SnO2) nanoparticles and used as a working electrode in a photoelectrochemical (PEC) measurement system. Intriguingly, the SnO2 functionalized 2D-CNW showed enhancement in both Mott-Schottky profiles and LSV properties which suggested that these hierarchical networks showed promising potential application as effective charge-trapping medium in PEC systems.
HMMBinder: DNA-Binding Protein Prediction Using HMM Profile Based Features
Authors: Zaman Rianon , Chowdhury Shahana Yasmin , Rashid Mahmood A. , Sharma Alok , Dehzangi Abdollah , Shatabda Swakkhar
Published: November 2017

DNA-binding proteins often play important role in various processes within the cell. Over the last decade, a wide range of classification algorithms and feature extraction techniques have been used to solve this problem. In this paper, we propose a novel DNA-binding protein prediction method called HMMBinder. HMMBinder uses monogram and bigram features extracted from the HMM profiles of the protein sequences. To the best of our knowledge, this is the first application of HMM profile based features for the DNA-binding protein prediction problem. We applied Support Vector Machines (SVM) as a classification technique in HMMBinder. Our method was tested on standard benchmark datasets. We experimentally show that our method outperforms the state-of-the-art methods found in the literature.
Algebro-Geometric Solutions for a Discrete Integrable Equation
Authors: Tao Mengshuang , Dong Huanhe
Published: November 2017

With the assistance of a Lie algebra whose element is a matrix, we introduce a discrete spectral problem. By means of discrete zero curvature equation, we obtain a discrete integrable hierarchy. According to decomposition of the discrete systems, the new differential-difference integrable systems with two-potential functions are derived. By constructing the Abel-Jacobi coordinates to straighten the continuous and discrete flows, the Riemann theta functions are proposed. Based on the Riemann theta functions, the algebro-geometric solutions for the discrete integrable systems are obtained.
Nodular Lymphocyte-Predominant Hodgkin Lymphoma in Progressive Transformation of Germinal Centers
Authors: Bailey C. Eric , Jung Francesca , Addicks Benjamin , Esan Olukemi A. , Kellermeyer Brian
Published: November 2017

Nodular lymphocyte-predominant Hodgkin lymphoma is an uncommon variant of Hodgkin lymphoma. Progressive transformation of germinal centers has been associated with and can develop prior to, concurrent with, or after the diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma. We present a patient with a history of progressive transformation of germinal centers of the right parotid who presented 4 years later with ipsilateral parotid mass and cervical adenopathy. Knowledge of her previous diagnosis raised our concern for lymphoma, influenced our surgical management, and spared the patient additional surgery with risk of facial nerve injury inherent in revision parotidectomy.
Mucin-Poor Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Presented with Multiple Metastases Two Years after Nephrectomy: An Atypical Behaviour of a Rare, Indolent Tumour
Authors: Sokolakis I. , Kalogirou C. , Frey L. , Oelschläger M. , Krebs M. , Riedmiller H. , Kübler H. , Vergho D.
Published: November 2017

Background. Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of renal cell carcinoma, whose clinical behaviour and metastatic potential have not been fully elucidated to date. There are only a few metastatic cases in the literature, which all either featured sarcomatoid differentiation or were synchronously metastasised at diagnosis. Case Presentation. We report a case of a 49-year-old male with end-stage kidney disease on dialysis, presenting with multiple osseous metastases of a mucin-poor variant of MTSCC of the kidney, without sarcomatoid differentiation, two years after bilateral nephrectomy for papillary renal cell carcinoma (RCC) at a curable stage. After retrospectively reexamining the initial nephrectomy specimens, the tumour of the right kidney was also diagnosed as a mucin-poor variant of MTSCC, while the tumour of the left kidney was confirmed as a papillary RCC. Conclusions. It is proposed that MTSCC can be associated with end-stage renal disease and that particularly the mucin-poor variant is easily confused with papillary renal cell carcinoma, as happened in this case. Although it is considered as a relatively indolent malign entity, it can metastasise even years after successful primary surgical treatment. This implies, besides accurate diagnosis, that MTSCC patients should be monitored closely in the follow-up period.
Managing an Acute and Chronic Periprosthetic Infection
Authors: Barrientos Cristian , Barahona Maximiliano , Olivares Rodrigo
Published: November 2017

A case report of a 65-year-old female with a history of right total hip arthroplasty (THA) in 2007 and left THA in 2009 was presented. She consulted with our institution for the first time, on December 2013, for right hip pain and fistula on the THA incision. It was managed as a chronic infection, so a two-stage revision was performed. First-time intraoperative cultures were positive for Staphylococcus aureus (3/5) and Proteus mirabilis (2/5). Three weeks after the second half of the review, it evolved with acute fever and pain in relation to right hip. No antibiotics were used, arthrocentesis was performed, and a coagulase-negative staphylococci multisensible was isolated at the 5th day. Since the germ was different from the first revision, it was decided to perform a one-stage revision. One year after the first review, the patient has no local signs of infection and presents ESV and RPC in normal limits. The indication and management of periprosthetic infections are discussed.
Seronegative Myasthenia Gravis, as a Rare Autoimmune Condition in Turner Syndrome
Authors: Sharief Rimah , Miodovnik Amir , Motaghedi Roja
Published: November 2017

Girls with Turner syndrome (TS), especially with isochromosome 46,X,i(X)(q10), are prone to develop autoimmunity. Associations of several autoimmune conditions with TS have been frequently described in the past. However, the unique combination of TS and myasthenia gravis (MG) has been reported only once before in a girl with mosaic monosomy 45,X/46,XX. Here, we present the second case of a girl affected with seronegative MG but with mosaic isochromosome TS. This is a child with developmental delay presented with muscle weakness, frequent fall, and bilateral ptosis. Diagnosis of MG was made based on positive Tensilon and electromyography tests and excellent response to intravenous immunoglobulin. At the age of 11 years due to short stature and developmental delay, a karyotype was done and revealed the mosaic isochromosome 45,X/46,X,i(X)(q10). Overall, clinicians should be aware of the vulnerability of girls with TS to autoimmunity, especially if the isochromosome 46,X,i(X)(q10) karyotype is identified. Furthermore, if a child with TS develops muscle weakness, ptosis, or ophthalmoplegia, MG should also be included in the differential diagnosis, particularly if other concurrent autoimmune conditions are present.
Genome-Wide Analysis of mRNA and Long Noncoding RNA Profiles in Chronic Actinic Dermatitis
Authors: Lei Dongyun , Lv Lechun , Yang Li , Wu Wenjuan , Liu Yong , Tu Ying , Xu Dan , Jin Yumei , Nong Xiang , He Li
Published: November 2017

Chronic actinic dermatitis (CAD), a photosensitive dermatosis, is characterized by inflammatory lesions, especially on sun-exposed skin. However, its pathogenesis remains unclear. In this study, second-generation RNA sequencing and comprehensive bioinformatics analyses of mRNAs and long noncoding RNAs (lncRNAs) were performed to determine the transcriptome profiles of patients with CAD. A total 6889 annotated lncRNAs, 341 novel lncRNAs, and 65091 mRNAs were identified. Interestingly, patients with CAD and healthy controls showed distinct transcriptome profiles. Indeed, 198 annotated (81.48%) and 45 novel (18.52%) lncRNAs were differentially expressed between the two groups. GO, KEGG, and RGSEA analyses of lncRNAs showed that inflammatory and immune response related pathways played crucial roles in the pathogenetic mechanism of CAD. In addition, we unveiled key differentially expressed lncRNAs, including lncRNA RP11-356I2.4 which plays a role probably by regulating TNFAIP3 and inflammation. qRT-PCR data validated the differentially expressed genes. The newly identified lncRNAs may have potential roles in the development of CAD; these findings lay a solid foundation for subsequent functional exploration of lncRNAs and mRNAs as therapeutic targets for CAD.
Stability and Convergence Analysis of Direct Adaptive Inverse Control
Authors: Shafiq Muhammad , Shafiq Muhammad A. , Yousef Hassan A.
Published: November 2017

In adaptive inverse control (AIC), adaptive inverse of the plant is used as a feed-forward controller. Majority of AIC schemes estimate controller parameters using the indirect method. Direct adaptive inverse control (DAIC) alleviates the adhocism in adaptive loop. In this paper, we discuss the stability and convergence of DAIC algorithm. The computer simulation results are presented to demonstrate the performance of the DAIC. Laboratory scale experimental results are included in the paper to study the efficiency of DAIC for physical plants.
Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice with Oxazolone‐Induced Atopic Dermatitis through Regulation of Calcium Channels, Orai‐1 and TRPV3, and Mast Cell Activation
Authors: Kang Seok Yong , Jung Hyo Won , Nam Joo Hyun , Kim Woo Kyung , Kang Jong-Seong , Kim Young-Ho , Cho Cheong-Weon , Cho Chong Woon , Park Yong-Ki , Bae Hyo Sang
Published: November 2017

Ethnopharmacological Relevance. In this study, we investigated the effects of Tribulus terrestris fruit (Leguminosae, Tribuli Fructus, TF) extract on oxazolone‐induced atopic dermatitis in mice. Materials and Methods. TF extract was prepared with 30% ethanol as solvent. The 1% TF extract with or without 0.1% HC was applied to the back skin daily for 24 days. Results. 1% TF extract with 0.1% HC improved AD symptoms and reduced TEWL and symptom scores in AD mice. 1% TF extract with 0.1% HC inhibited skin inflammation through decrease in inflammatory cells infiltration as well as inhibition of Orai‐1 expression in skin tissues. TF extract inhibited Orai‐1 activity in Orai‐1‐STIM1 cooverexpressing HEK293T cells but increased TRPV3 activity in TRPV3‐overexpressing HEK293T cells. TF extract decreased β‐hexosaminidase release in RBL‐2H3 cells. Conclusions. The present study demonstrates that the topical application of TF extract improves skin inflammation in AD mice, and the mechanism for this effect appears to be related to the modulation of calcium channels and mast cell activation. This outcome suggests that the combination of TF and steroids could be a more effective and safe approach for AD treatment.
Preimplantation Genetic Diagnosis for Myotonic Dystrophy Type 1 and Analysis of the Effect of the Disease on the Reproductive Outcome of the Affected Female Patients
Authors: Fernández Raquel María , Lozano-Arana María Dolores , Sánchez Beatriz , Peciña Ana , García-Lozano Juan Carlos , Borrego Salud , Antiñolo Guillermo
Published: November 2017

Myotonic dystrophy type 1 (DM1) is the most common adult muscular dystrophy and presents an autosomal dominant inheritance. A reproductive option for the families affected is preimplantation genetic diagnosis (PGD). One limitation of this option is the nonoptimal response to ovarian stimulation of the women with DM1, although controversial results exist regarding this subject. In this study, we have analyzed the results of the PGD program applied to DM1 at our institution. A total of 35 couples have been included in our program since 2010, and 59 cycles have been performed. The percentage of transfers per cycle was 64.4% and the live birth rate per cycle was 18.6%. Interestingly, statistically significant differences were observed for the clinical results in the group of couples with an affected female versus the group with an affected male or versus a group of couples with different referral reasons. Specifically, both the percentage of mature oocytes out of the total oocytes retrieved and the percentage of fertilization were considerably lower in the group of DM1 females. Our findings would suggest the possibility of achieving less favourable PGD outcomes in women with DM1 in comparison with other pathologies, although the underlying mechanism remains unknown.
Targeting the MYCN–PARP–DNA Damage Response Pathway in Neuroendocrine Prostate Cancer
Authors: Zhang Wei , Liu Bo , Wu Wenhui , Li Likun , Broom Bradley M. , Basourakos Spyridon P. , Korentzelos Dimitrios , Luan Yang , Wang Jianxiang , Yang Guang , Park Sanghee , Azad Abul Kalam , Cao Xuhong , Kim Jeri , Corn Paul G. , Logothetis Christopher J. , Aparicio Ana M. , Chinnaiyan Arul M. , Navone Nora , Troncoso Patricia , Thompson Timothy C.
Published: November 2017

Purpose: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC).

Experimental Design and Results: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public data sets and a panel of 28 PDX models, we identified a MYCN–PARP–DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro. ChIP-PCR assay revealed that N-MYC transcriptionally activates PARP1, PARP2, BRCA1, RMI2, and TOPBP1 through binding to the promoters of these genes. MYCN or PARP1 gene knockdown significantly reduced the expression of MYCN–PARP–DDR pathway genes and NED markers, and inhibition with MYCNsi and/or PARPsi, BRCA1si, or RMI2si significantly suppressed malignant activities, including cell viability, colony formation, and cell migration, in C4-2b4 and NCI-H660 cells. Targeting this pathway with AURKA inhibitor PHA739358 and PARP inhibitor olaparib generated therapeutic effects similar to those of gene knockdown in vitro and significantly suppressed tumor growth in both C4-2b4 and MDACC PDX144-13C subcutaneous models in vivo.

Conclusions: Our results identify a novel MYCN–PARP–DDR pathway that is driven by N-MYC in a subset of CRPC-Adeno and in NEPC. Targeting this pathway using in vitro and in vivo CRPC-Adeno and CRPC-Neuro models demonstrated a novel therapeutic strategy for NEPC. Further investigation of N-MYC–regulated DDR gene targets and the biological and clinical significance of MYCN–PARP–DDR signaling will more fully elucidate the importance of the MYCN–PARP–DDR signaling pathway in the development and maintenance of NEPC. Clin Cancer Res; 24(3); 696–707. ©2017 AACR.
Ceritinib Enhances the Efficacy of Trametinib inBRAF/NRAS-Wild-Type Melanoma Cell Lines
Authors: Verduzco Daniel , Kuenzi Brent M. , Kinose Fumi , Sondak Vernon K. , Eroglu Zeynep , Rix Uwe , Smalley Keiran S.M.
Published: November 2017

Targeted therapy options are currently lacking for the heterogeneous population of patients whose melanomas lack BRAF or NRAS mutations (∼35% of cases). We undertook a chemical biology screen to identify potential novel drug targets for this understudied group of tumors. Screening a panel of 8 BRAF/NRAS-WT melanoma cell lines against 240 targeted drugs identified ceritinib and trametinib as potential hits with single-agent activity. Ceritinib enhanced the efficacy of trametinib across the majority of the BRAF/NRAS-WT cell lines, and the combination showed increased cytotoxicity in both three-dimensional spheroid culture and long-term colony formation experiments. Coadministration of ceritinib and trametinib led to robust inhibition of tumor growth in an in vivo xenograft BRAF/NRAS-WT melanoma model; this was not due to ALK inhibition by ceritinib. Mechanistic studies showed the ceritinib–trametinib combination to increase suppression of MAPK and TORC1 signaling. Similar results were seen when BRAF/NRAS-WT melanoma cells were treated with a combination of trametinib and the TORC1/2 inhibitor INK128. We next used mass spectrometry–based chemical proteomics and identified known and new ceritinib targets, such as IGF1R and ACK1, respectively. Validation studies suggested that ceritinib could suppress mTORC1 signaling in the presence of trametinib through inhibition of IGF1R and/or ACK1 in a cell line–dependent manner. Together, our studies demonstrated that combining a specific inhibitor (trametinib) with a more broadly targeted agent (ceritinib) has efficacy against tumors with heterogeneous mutational profiles. Mol Cancer Ther; 17(1); 73–83. ©2017 AACR.
Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas In Vivo and Ex Vivo
Authors: Hartsough Edward J. , Kugel Curtis H. , Vido Michael J. , Berger Adam C. , Purwin Timothy J. , Goldberg Allison , Davies Michael A. , Schiewer Matthew J. , Knudsen Karen E. , Bollag Gideon , Aplin Andrew E.
Published: November 2017

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K–mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenib-resistant BRAF splice variant–expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. Mol Cancer Ther; 17(1); 84–95. ©2017 AACR.
Chemokine Signaling Facilitates Early-Stage Breast Cancer Survival and Invasion through Fibroblast-Dependent Mechanisms
Authors: Brummer Gage , Acevedo Diana S. , Hu Qingting , Portsche Mike , Fang Wei Bin , Yao Min , Zinda Brandon , Myers Megan , Alvarez Nehemiah , Fields Patrick , Hong Yan , Behbod Fariba , Cheng Nikki
Published: November 2017

Ductal carcinoma in situ (DCIS) is the most common form of breast cancer, with 50,000 cases diagnosed every year in the United States. Overtreatment and undertreatment remain significant clinical challenges in patient care. Identifying key mechanisms associated with DCIS progression could uncover new biomarkers to better predict patient prognosis and improve guided treatment. Chemokines are small soluble molecules that regulate cellular homing through molecular gradients. CCL2-mediated recruitment of CCR2+ macrophages are a well-established mechanism for metastatic progression. Although the CCL2/CCR2 pathway is a therapeutic target of interest, little is known about the role of CCR2 expression in breast cancer. Here, using a mammary intraductal injection (MIND) model to mimic DCIS formation, the role of CCR2 was explored in minimally invasive SUM225 and highly invasive DCIS.com breast cancer cells. CCR2 overexpression increased SUM225 breast cancer survival and invasion associated with accumulation of CCL2 expressing fibroblasts. CCR2-deficient DCIS.com breast cancer cells formed fewer invasive lesions with fewer CCL2+ fibroblasts. Cografting CCL2-deficient fibroblasts with DCIS.com breast cancer cells in the subrenal capsule model inhibited tumor invasion and survival associated with decreased expression of aldehyde dehydrogenase (ALDH1), a proinvasive factor, and decreased expression of HTRA2, a proapoptotic serine protease. Through data mining analysis, high expression of CCR2 and ALDH1 and low HTRA2 expression were correlated with poor prognosis of breast cancer patients.

Implications: This study demonstrates that CCR2 overexpression in breast cancer drives early-stage breast cancer progression through stromal-dependent expression of CCL2 with important insight into prognosis and treatment of DCIS. Mol Cancer Res; 16(2); 296–308. ©2017 AACR.
Genotoxic Damage Activates the AMPK-α1 Isoform in the Nucleus via Ca2+/CaMKK2 Signaling to Enhance Tumor Cell Survival
Authors: Vara-Ciruelos Diana , Dandapani Madhumita , Gray Alexander , Egbani Ejaife O. , Evans A. Mark , Hardie D. Grahame
Published: November 2017

Many genotoxic cancer treatments activate AMP-activated protein kinase (AMPK), but the mechanisms of AMPK activation in response to DNA damage, and its downstream consequences, have been unclear. In this study, etoposide activates the α1 but not the α2 isoform of AMPK, primarily within the nucleus. AMPK activation is independent of ataxia-telangiectasia mutated (ATM), a DNA damage-activated kinase, and the principal upstream kinase for AMPK, LKB1, but correlates with increased nuclear Ca2+ and requires the Ca2+/calmodulin-dependent kinase, CaMKK2. Intriguingly, Ca2+-dependent activation of AMPK in two different LKB1-null cancer cell lines caused G1-phase cell-cycle arrest, and enhanced cell viability/survival after etoposide treatment, with both effects being abolished by knockout of AMPK-α1 and α2. The CDK4/6 inhibitor palbociclib also caused G1 arrest in G361 but not HeLa cells and, consistent with this, enhanced cell survival after etoposide treatment only in G361 cells. These results suggest that AMPK activation protects cells against etoposide by limiting entry into S-phase, where cells would be more vulnerable to genotoxic stress.

Implications: These results reveal that the α1 isoform of AMPK promotes tumorigenesis by protecting cells against genotoxic stress, which may explain findings that the gene encoding AMPK-α1 (but not -α2) is amplified in some human cancers. Furthermore, α1-selective inhibitors might enhance the anticancer effects of genotoxic-based therapies. Mol Cancer Res; 16(2); 345–57. ©2017 AACR.
Precision Oncology beyond Targeted Therapy: Combining Omics Data with Machine Learning Matches the Majority of Cancer Cells to Effective Therapeutics
Authors: Ding Michael Q. , Chen Lujia , Cooper Gregory F. , Young Jonathan D. , Lu Xinghua
Published: November 2017

Precision oncology involves identifying drugs that will effectively treat a tumor and then prescribing an optimal clinical treatment regimen. However, most first-line chemotherapy drugs do not have biomarkers to guide their application. For molecularly targeted drugs, using the genomic status of a drug target as a therapeutic indicator has limitations. In this study, machine learning methods (e.g., deep learning) were used to identify informative features from genome-scale omics data and to train classifiers for predicting the effectiveness of drugs in cancer cell lines. The methodology introduced here can accurately predict the efficacy of drugs, regardless of whether they are molecularly targeted or nonspecific chemotherapy drugs. This approach, on a per-drug basis, can identify sensitive cancer cells with an average sensitivity of 0.82 and specificity of 0.82; on a per-cell line basis, it can identify effective drugs with an average sensitivity of 0.80 and specificity of 0.82. This report describes a data-driven precision medicine approach that is not only generalizable but also optimizes therapeutic efficacy. The framework detailed herein, when successfully translated to clinical environments, could significantly broaden the scope of precision oncology beyond targeted therapies, benefiting an expanded proportion of cancer patients. Mol Cancer Res; 16(2); 269–78. ©2017 AACR.
Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms
Authors: Zhang Bo , Li Qin , Shi Chenyang , Zhang Xinyue
Published: November 2017

Adverse drug reactions occur frequently and can trigger pseudoallergy, which has become a serious threat to public health. Pseudoallergy is a typical non-immune anaphylactic reaction characterized by the independence of antigen-specific immune responses. In the clinic, pseudoallergy is often elicited by the first dose of medication, and here lies its unpredictability and occasional lethal outcome. However, the mechanisms of pseudoallergy are not well understood. This review focusses on the causes and mechanisms of pseudoallergy induced by drugs. Two categories of mechanisms will be considered, namely, (1) complement activation-related pseudoallergy and (2) mast cell activation-related pseudoallergy. The factors that induce pseudoallergy include opioid drugs, complement activation-related pseudoallergenic drugs, nonsteroidal anti-inflammatory drugs and traditional Chinese medicine injections.
Caries-Preventive Effect of Salt Fluoridation in Preschool Children in The Gambia: A Prospective, Controlled, Interventional Study
Authors: Jordan Rainer A. , Schulte Andreas , Bockelbrink Alexander C. , Puetz Sarah , Naumova Ella , Wärn Lars G. , Zimmer Stefan
Published: November 2017

The aim of this study was to investigate the anticaries effect of fluoridated salt in a communal feeding program for preschool children. In the Gambian city of Brikama, drinking water had a low fluoride content (0.1 mg F-/L) and young children did not use toothpaste for oral hygiene. Its 2 preschools served as clusters for the trial. Random allocation of the kindergartens was performed by one person not involved in the study, and the clinical examinations were carried out using the envelope method. Meals were prepared with fluoridated salt (250 mg F-/kg salt) in the intervention group but not in the control group. According to the inclusion criteria (complete primary dentition and informed consent from legal guardian), 441 children aged 3-5 years were enrolled. The children were examined by calibrated persons according to WHO criteria, allowing the calculation of d3mft scores. The primary end point was the mean difference in the incidence of caries cavities (Δd3/4mft) after 12 months. After 12 months, the mean caries incidence per person was 1.29 d3/4mf teeth (95% CI: 0.96; 1.62) in the test group (n = 304 children) and 3.83 d3/4mf teeth (95% CI: 2.94; 4.72) in the control group (n = 137 children). Thus, the caries-prevented fraction was 66.3%. No signs of harm due to the intervention were observed. The use of fluoridated salt in a communal feeding program and in an environment with negligible availability of fluoride from other sources yields a considerable caries-preventive effect.
Toll-Like Receptor 4 Reduces Occludin and Zonula Occludens 1 to Increase Retinal Permeability Both in vitro and in vivo
Authors: Liu Li , Jiang Youde , Steinle Jena J.
Published: November 2017

We reported that β-adrenergic receptors regulate toll-like receptor 4 (TLR4) signaling in the retina of diabetic mice and in retinal endothelial cells (REC) and Müller cells. We hypothesized that TLR4 regulates retinal permeability both in vitro and in vivo in the retinal vasculature. We used REC cultured in normal and high-glucose conditions and TLR4 siRNA treatments for cell culture studies of permeability and protein analyses of tumor necrosis factor α, occludin, and zonula occludens 1 (ZO-1). We used endothelial cell (EC)-specific Cre-Lox TLR4 knockout mice to study retinal permeability and neuronal and vascular changes following exposure to ocular ischemia/reperfusion (I/R) used as a retinal stressor. We found that the loss of TLR4 in the EC led to the reduced permeability following I/R and fewer degenerate capillaries. Retinal permeability was increased in REC grown in high-glucose conditions but was inhibited by TLR4 siRNA treatment. High-glucose culture conditions significantly reduced occludin and ZO-1 levels in REC, and TLR4 siRNA treatment restored levels to baseline. In conclusion, these studies demonstrate that TLR4 in EC strongly regulates retinal permeability and neuronal and vascular changes following exposure to stressors such as I/R.
Hepcidin in Iron Homeostasis: Diagnostic and Therapeutic Implications in Type 2 Diabetes Mellitus Patients
Authors: Ambachew Sintayehu , Biadgo Belete
Published: November 2017

The prevalence of type 2 diabetes is increasing in epidemic proportions worldwide. Evidence suggests body iron overload is frequently linked and observed in patients with type 2 diabetes. Body iron metabolism is based on iron conservation and recycling by which only a part of the daily need is replaced by duodenal absorption. The principal liver-produced peptide called hepcidin plays a fundamental role in iron metabolism. It directly binds to ferroportin, the sole iron exporter, resulting in the internalization and degradation of ferroportin. However, inappropriate production of hepcidin has been shown to play a role in the pathogenesis of type 2 diabetes mellitus and its complications, based on the regulation and expression in iron-abundant cells. Underexpression of hepcidin results in body iron overload, which triggers the production of reactive oxygen species simultaneously thought to play a major role in diabetes pathogenesis mediated both by β-cell failure and insulin resistance. Increased hepcidin expression results in increased intracellular sequestration of iron, and is associated with the complications of type 2 diabetes. Besides, hepcidin concentrations have been linked to inflammatory cytokines, matriptase 2, and chronic hepatitis C infection, which have in turn been reported to be associated with diabetes by several approaches. Either hepcidin-targeted therapy alone or as adjunctive therapy with phlebotomy, iron chelators, or dietary iron restriction may be able to alter iron parameters in diabetic patients. Therefore, measuring hepcidin may improve differential diagnosis and the monitoring of disorders of iron metabolism.
Screening of Skin Lesion-Associated Genes in Patients with Psoriasis by Meta-Integration Analysis
Authors: Mei Rong , Mei Xiaofeng
Published: November 2017

Aim: Psoriasis is an inflammatory skin disease, and approximately one quarter of individuals with psoriasis develop painful and debilitating arthritis. As a complex and polygenetic hereditary disease, it is significant to investigate skin lesion-associated genes of psoriasis. Method: In the present study, a total of 3,047 differentially expressed genes between lesional and nonlesional skin of psoriasis patients were screened based on 4 data sets in GEO DataSets. In the following, network module analyses were performed. Result: After calculating the correlation coefficients between eigenvalues of each module and disease status (psoriatic lesion and nonlesion), it was observed that the genes in black and green modules showed a significant correlation in each data set. Consequently, 58 significant characteristic genes of black modules and 74 of green modules were chosen for further analysis. The interaction network of the candidate feature genes was constructed based on the BioGRID, HPRD, and BIND databases, which contained 310 nodes. The mutual relationships of 70 genes, including 28 genes in the black module and 42 genes in the green module, were summarized, and 5 drug molecules related to these 70 factors were detected. Mepacrine and camptothecin were indicated as 2 drugs negatively related to psoriasis. Conclusion: The results suggested a pathogenesis mechanism of psoriasis and indicated novel therapeutic targets for psoriasis.
Impaired Enterohormone Response Following a Liquid Test Meal in Gastrectomized Patients
Authors: Santarpia Lidia , Pagano Maria Carmen , Cioffi Iolanda , Alfonsi Lucia , Cuomo Rosario , Labruna Giuseppe , Sacchetti Lucia , Contaldo Franco , Pasanisi Fabrizio
Published: November 2017

Background: Total gastrectomy (TG) is responsible for symptoms or disturbance of alimentary status (changes in body weight, food intake per meal and frequency of meal per day) which, in turn are responsible for weight loss and malnutrition. The study evaluates the gut hormone responses in totally gastrectomized (TG) patients after a liquid meal test. Methods: Twenty total gastrectomized cancer-free patients (12 M, 8 F, 56.4 ± 10.2 years, BMI 21.4 ± 2.2 kg/m2) and 10 healthy volunteers (4 M, 6 F, 48.0 ± 12.7 years, BMI 26.7 ± 3.0 kg/m2 ) drank a liquid meal (1.25 kcal/mL) at the rate of 50 mL/5′ min for a maximum of 30 min. Satiety score was assessed and blood sample was taken at different time points. Results: The time response course, particularly for insulin, glucose-like pepetide-1, and cholecystokinin, significantly differed between TG patients and controls. Conclusions: Our results may help to better understand hormone responses triggered by the faster arrival of nutrients in the small bowel and to explain some post-TG symptoms.
Evaluation of Nickel Release from Endobronchial Valves as a Possible Cause of Hypersensitivity Pneumonitis in a Patient Treated with Bronchoscopic Lung Volume Reduction
Authors: Franzen Daniel P. , Lang Claudia , Agorastos Nikos , Freitag Lutz , Kohler Malcolm , Schmid-Grendelmeier Peter
Published: November 2017

Background: Endobronchial valve (EBV) placement is an established lung volume reduction procedure aiming to improve lung function and exercise capacity in patients with severe emphysema. As EBVs consist of silicone and nitinol (a metal alloy of nickel and titanium), there are concerns that nickel ions might be released and could have a clinical impact in patients with a contact allergy to nickel. Based on a case with hypersensitivity pneumonitis (HP) after treatment with EBVs, we aimed to evaluate the in vitro nickel release from EBVs using inductively coupled plasma mass spectrometry (ICP-MS) and scanning electron microscopy (SEM). Methods: Six EBVs were immersed in artificial saliva for a period of 7 days. At 24-h intervals, the nickel ion concentration was measured using ICP-MS. Results: There was evidence of a significant nickel release from EBV during the first 48 h, which is possibly due to an incomplete silicone layer detected by SEM. The concentration of released nickel was below the toxic limit. Conclusions: To the best of our knowledge, we report the first case of HP after EBV treatment. Our finding of in vitro release of nickel ions from EBVs may contribute to the current understanding on hypersensitivity reactions after nitinol implants in patients with nickel contact allergy. However, it did not confirm a causative relationship.
One-to-One Correspondence Locations of Resected Polyps after Endoscopic Resection Using Catcher Tagged Method: A Randomized Prospective Study
Authors: Mori Hirohito , Kobara Hideki , Kobayashi Nobuya  , Nishiyama Noriko , Kobayashi Seiki , Yagi Takaharu , Masaki Tsutomu
Published: November 2017

Background/Aims: Multiple colorectal polyps with a diameter in the range of 10–19 mm are unable to be retrieved through a 3-mm endoscopic channel by the aspiration method. This study aims to assess the usefulness of Catcher Tag retrieval, which not only allows the accurate identification of the resected location but also enables the easiest retrieval in a short time without any special device. Methods: One hundred thirty five patients (483 polyps) were diagnosed with colorectal neoplasm, and 64 patients (225 polyps) were enrolled and randomly allocated into the Net forceps group (NET) and the Catcher Tagged group (TAG). In TAG, 3 types of colored ring-threads were used to retrieve resected polyps. After local injection of natural saline, ring-threads were placed close to polyps. The primary outcome was the number of one-to-one correspondence locations (UMIN000020826). Results: There was significant difference in one-to-one correspondence (p = 0.004). The average retrieval procedure time was 13.56 ± 3.47 (min) in NET and 3.55 ± 1.68 in TAG (p = 0.006). In NET, 1 polyp in each of 4 cases was lost during endoscopic mucosal resection and 2 polyps were lost in 1 case. In TAG, no polyp was lost (p = 0.016). Conclusion: The Catcher Tagged method is very useful for accurate one-to-one correspondence locations and pathological evaluation, and easy-to-retrieve multiple resected specimens.
Increasing Incidence and Prevalence of Multiple Sclerosis in Puerto Rico (2013–2016)
Authors: Chinea Angel , Ríos-Bedoya Carlos F. , Vicente Ivonne , Rubí Cristina , García Guillermo , Rivera Ana , Díaz Astrid , Romero Eduardo Estades , Hernández Silvestrini Yatzka , Díaz Yaritza ,   Grupo de Estudios Colaborativos de Puerto Rico en Esclerosis Múltiple (GECPREM)
Published: November 2017

Background: The incidence of multiple sclerosis (MS) has been increasing worldwide over the past decades. However, this upward trend has not been examined at the country level in Latin America and the Caribbean (LAC). The aims of this study are to examine trends of MS incidence over 4 years and to provide age- and gender-standardized incidence rate estimates for a Caribbean island. Methods: Data from the Puerto Rico (PR) MS Foundation’s registry was used to identify all newly diagnosed MS cases between 2013 and 2016. MS patients were 18 years and older and met the 2010 revised McDonald criteria. Age- and gender-standardized incidence rates were estimated. Results: A total of 583 new MS cases were diagnosed in PR from 2013 to 2016. The age- and gender-standardized MS incidence rate for PR increased from 6.1/100,000 in 2013 to 6.7/100,000 in 2016. The annual age-standardized MS incidence rates for females rose from 8.4/100,000 in 2013 to 9.8/100,000 in 2016 and were higher than males, which remained around 3.7/100,000. Conclusion: Incidence estimates for PR were higher than other LAC countries but consistent with MS increases in other world regions. Our findings tend to rule out several prior potential environmental explanations for high MS incidence rates.
Modified Alcohol-Formalin Cell Block Technique in Head and Neck Pathology Diagnosis
Authors: Desai Karishma M. , Angadi Punnya V. , Kale Alka D. , Hallikerimath Seema
Published: November 2017

Objectives: Cell block preparation is a recognized technique in histopathological diagnosis. This technique aids in maintaining an intact architecture and reducing the diagnostic errors associated with fine-needle aspiration cytology. Numerous techniques have been put forth, but the need for an optimal technique for routine use in the laboratory still persists. The aim of our study was to establish a cell block technique which aids in the accurate diagnosis of head and neck pathology. Methodology: A modified cell block technique was developed using alcohol-formalin as a fixative. Forty fine-needle aspiration fluids from clinically and radiologically diagnosed cases of head and neck pathology were used as samples. The cell block sections were compared with the cytology smears to determine the utility of the technique. Results: The cell blocks presented with better preservation of the architectural framework and enabled a quick diagnosis. Cellular clumping was negligible, and nuclear as well as cellular details were maintained similar to tissue sections. It led to the integration of conventional techniques using 10% neutral buffered formalin with that of the 10% alcohol-formalin technique. Conclusion: Modified cell block technique can be used as a simple and effective tool in the routine diagnosis of head and neck pathology.
Biochemical, Anthropometric and Lifestyle Factors Related with Weight Maintenance after Weight Loss Secondary to a Hypocaloric Mediterranean Diet
Authors: de Luis Daniel Antonio , Izaola Olatz , Primo David , Ovalle Hilda F. , Lopez Juan Jose , Gomez Emilia , Ortola Ana , Aller Rocio
Published: November 2017

Background/Aims: The aim of our study was to evaluate the influence of lifestyle factors and molecular biomarkers on the maintenance of the weight lost after a hypocaloric Mediterranean diet. Design: After 3 months on a diet, patients (n = 335) remained with no controlled diet during 3 years and they were revaluated. Results: Using linear regression, in the group of responders, we detected that a positive weight loss at 3 months, serum levels of leptin at 3 months, and each 30 min per week of physical activity were associated with weight loss maintenance. In the model with reduced weight (RW) as dependent variable, a positive weight loss at 3 months was associated with 2.4% RW (95% CI 1.31–8.11; p = 0.015), each unit of serum leptin levels at 3 months with –0.44% RW (95% CI –0.59 to –0.020; p = 0.007), each basal unit homeostasis model assessment for insulin resistance (HOMA-IR) level with –2.32% (95% CI –13.01 to –0.17; p = 0.040), and each 30 min per week of physical activity with 1.58% RW (95% CI 1.08–2.94; p = 0.020). Conclusion: Obese subjects who are on maintenance weight loss after a dietary intervention appear to have a better initial response during the 3 months intervention, more physical activity at 3 years, and lower basal HOMA-IR and leptin after weight loss than those who regain weight.
Dez mandamentos para preservar a saúde pela atividade física
Authors: Silva Antônio Boa Ventura da
Published: November 2017

O autor pretende alertar, orientar e encorajar o indivíduo de qualquer idade a se tornar fisicamente mais ativo, compreendendo a prática da atividade física como um hábito indispensável para uma vida mais sadia
Aproveitamento dos jogos folclóricos na educação física
Authors: Navarro Maria Alice Magalhães
Published: November 2017

A pesquisa consistiu em entrevistar estudantes do primeiro e segundo graus e universitários, sobre suas preferências por certos jogos folclóricos; analisar a influência da idade (e, conseqüentemente, do grau de escolaridade) e do sexo a esse respeito; compilar as descrições feitas pelos entrevistados sobre os jogos e classificá-los, segundo o interesse em Educação Física
Lactato em teses de endurance e de velocidade
Authors: Kiss M. A. P. D. M , Machida J , Dirani I. , Zucas S. M
Published: November 2017

O objetivo do trabalho é analisar o comportamento do lactato sanguíneo em testes repetidos de velocidade, os quais procuram simular as atividades intensas e intermitentes durante jogo de voleibol. Foram examinados 10 jogadores da TELESP, antes da fase de treinamento de base e 2 meses após; os testes de laboratório seguiram os protocolos de Astrand no cicloergomêtro e de Mader em esteira. Em campo cada atleta correu 5 vezes a distância de 30ma velocidade máxima (5 "tiros"), com coleta de sangue entre os mesmos. Houve diminuição do lactato no teste de esteira com o treinamento, para o subgrupo em piores condições de endurance; a diminuição da produ­ ção de lactato nos tiros ocorreu apenas a partir do 2Ç tiro; não houve correlação entre a evolução do teste de esteira e de campo. Concluímos que existe aumento de lactato já a partir do 19 tiro e que há necessdade de aplicarmos dois diferentes tipos de testes para acompanhamento da intensidade de treinamento em voleibol