bluuebunny/crossref_metadata_2025 huggingface dataset:
The Historical Presidency: A Theoretical Critique of the Unitary Executive Framework: Rethinking the First‐Mover Advantage, Collective‐Action Advantage, and Informational Advantage
Authors: O'Brien Patrick R.
Published: January 2017

The unitary executive framework assumes that all presidents hold the same structural advantages relative to Congress or the Court—a first‐mover advantage, a collective‐action advantage, and an informational advantage. Therefore, variation is sought in changes in peripheral institutional conditions such as party control of the presidency, congressional support, and public approval. In this article, I provide a theoretical critique of the unitary executive framework. I show that its foundational assumptions do not hold in practice, and I develop an argument based on the simple idea that systems of administration for individual policy domains change substantially from time to time. Specifically, I contend that when the president relies on the established collective‐action and informational arrangement, it often obstructs or compromises his first‐mover advantage. Conversely, the president's first‐mover advantage in a policy domain is strengthened when he restructures the established collective‐action and informational arrangement.
Retracted: Gonad histology and serum 11‐KT profile during the annual reproductive cycle in sterlet sturgeon adult males, Acipenser ruthenus
Authors: Golpour A , Broquard C , Milla S , Dadras H , Baloch AR , Saito T , Pšenička M
Published: January 2017

Contents

The aim of this study was to assess monthly testicular development in the cultured breeding stock of sterlet, Acipenser ruthenus, using histological and serum sex steroid changes. Testicular development in the adult male was examined monthly and showed four distinct phases including resting, pre‐spawning, spawning and post‐spawning. Also, seasonal changes of the testes were described according to its variations in gonadosomatic index (GSI) during different phases of testicular development. Using histology, we identified continuous spermatogenesis and asynchronous gonad development pattern in the testes of male sterlet, which shows that regulation of annual gonadal cycle is influenced by season. Results also showed variation in the GSI value and number of spermatogenic cells according to each season during annual cycle of gonad, as the highest value of GSI was recorded during spawning phase (spring; March‐May). Hormonal profiles of 11‐ketotestosterone (11‐KT) showed peak, which indicated a seasonal pattern of gonadal development. The 11‐KT concentration increased considerably during the spermatogenesis (pre‐spawning phase) and remained quite high throughout the pre‐spermiation period. In the final phase of testicular development (spawning phase), the 11‐KT markedly dropped. This study undertook an examination of complete reproductive development in cultured sterlet sturgeon to provide a valuable guide for the future sterlet studies, and allows comparison of reproductive development between sturgeon species.
Immune Regulation by T Regulatory Cells in Hepatitis B Virus‐Related Inflammation and Cancer
Authors: Trehanpati N. , Vyas A. K.
Published: January 2017

Hepatocellular carcinoma (HCC) is the leading cause of cancer death, and hepatitis B virus (HBV) infection is one of the commonest causes in Asian countries. India has the second largest pool after China for hepatitis B‐infected subjects.HBVclearance is T cell dependent, and one of the reasons for T cells hyporesponsiveness is due to mass production of regulatory T cells (Tregs) through activation of Notch signalling, which suppressCD4/CD8 T cells. Tregs are important to maintain cellular homoeostasis; however, during viral infection increase of Tregs is inversely proportional toHBV DNAtitres. Tregs exert their suppressive effect either via cell‐to‐cell contact or through release of interleukin (IL)‐2,IL‐10,TGF‐βandIL‐35. In Chronic hepatitis B virusCHBVinfection,PD‐1 pathway also gets activated and is involved in promoting tolerance. However, with Tregs induction, virus‐specific T cell responses also get decreased. Circulatory and intratumoural Tregs promote development ofHBV‐specificHCCmore by decreasing and impairing the effector functions ofCD8 T cells. Antiviral therapies andPD‐1 blockade strategy had shown the inhibition of Tregs and reduction inHBV DNA. However, inhibition ofHBV‐specific Tregs is major challenge for future therapies. New cytokine blockade therapies have emerged as potential therapeutic potentials.
Emplacement of Semail–Emirates ophiolite at ridge–trench collision
Authors: Nicolas Adolphe , Boudier Françoise
Published: January 2017

The Oman‐Emirates is the largest and best‐exposed ophiolite; consequently, it has attracted significant interest among scientists, together with serious conflicts. Most geologists regard this ophiolite as having formed in an intra‐oceanic subduction zone before being accreted to the Arabian continent. Here, we propose an alternative scenario, supported by detailed field observations and integrated geophysics. The smaller Emirates part of the ophiolite was forced into a nearby continent, in the pre‐collision stage of Tethyan closure. The contraction led to the exhumation of the mantle floor of segmented basins accreted in a rifted system similar to the present‐day Gulf of California. The implied high temperature–high pressure metamorphism and the range of geochemical signatures were introduced during the process of rifting, whereas the larger Oman ophiolite was emplaced by obduction onto and along the subducting continental shore. This Ridge–Trench–Transform system might call for a new process to obduct over continents in particular Tethyan ophiolites.
Measurements of Stretch Statistics at Flame Leading Points for High Hydrogen Content Fuels
Authors: Marshall Andrew , Lundrigan Julia , Venkateswaran Prabhakar , Seitzman Jerry , Lieuwen Tim
Published: January 2017

Fuel composition has a strong influence on the turbulent flame speed, even at very high turbulence intensities. An important implication of this result is that the turbulent flame speed cannot be extrapolated from one fuel to the next using only the laminar flame speed and turbulence intensity as scaling variables. This paper presents curvature and tangential strain rate statistics of premixed turbulent flames for high hydrogen content (HHC) fuels. Global (unconditioned) stretch statistics are presented as well as measurements conditioned on the leading points of the flame front. These measurements are motivated by previous experimental and theoretical work that suggests the turbulent flame speed is controlled by the flame front characteristics at these points. The data were acquired with high-speed particle image velocimetry (PIV) in a low-swirl burner (LSB). We attained measurements for several H2:CO mixtures over a range of mean flow velocities and turbulence intensities. The results show that fuel composition has a systematic, yet weak effect on curvatures and tangential strain rates at the leading points. Instead, stretch statistics at the leading points are more strongly influenced by mean flow velocity and turbulence level. It has been argued that the increased turbulent flame speeds seen with increasing hydrogen content are the result of increasing flame stretch rates, and therefore, SL,max values, at the flame leading points. However, the differences observed with changing fuel compositions are not significant enough to support this hypothesis. Additional analysis is needed to understand the physical mechanisms through which the turbulent flame speed is altered by fuel composition effects.
Papers of note in
Science
355 (6322)
Authors: VanHook Annalisa M.
Published: January 2017

This week's articles are about two pairs of plant peptides: One pair controls the formation of a waterproof barrier that protects roots, and another pair regulates the response to pathogens.
Antimicrobial Activities of Ceftazidime-Avibactam and Comparator Agents against Clinical Bacteria Isolated from Patients with Cancer
Authors: Hachem Ray , Reitzel Ruth , Rolston Kenneth , Chaftari Anne-Marie , Raad Issam
Published: January 2017

A total of 521 unique clinical isolates from cancer patients with primarily (>90%) bloodstream infections were tested for susceptibility to ceftazidime-avibactam and comparators using broth microdilution methods. Ceftazidime-avibactam inhibited 97.8% of all
Enterobacteriaceae
(
n
= 321) at the susceptibility breakpoint of ≤8/4 μg/ml (there were 7 nonsusceptible strains). It was also active against
Pseudomonas aeruginosa
(91.7% isolates susceptible,
n
= 121), including many isolates not susceptible to meropenem, cefepime, ceftazidime, piperacillin-tazobactam, or other comparators.
Cyclic Boronates Inhibit All Classes of β-Lactamases
Authors: Cahill Samuel T. , Cain Ricky , Wang David Y. , Lohans Christopher T. , Wareham David W. , Oswin Henry P. , Mohammed Jabril , Spencer James , Fishwick Colin W. G. , McDonough Michael A. , Schofield Christopher J. , Brem Jürgen
Published: January 2017

β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, and tazobactam and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistance via these enzymes. These molecules are, however, ineffective against the metallo-β-lactamases (MBLs), which catalyze their hydrolysis. To date, there are no clinically available metallo-β-lactamase inhibitors. Coproduction of MBLs and SBLs in resistant infections is thus of major clinical concern. The development of “dual-action” inhibitors, targeting both SBLs and MBLs, is of interest, but this is considered difficult to achieve due to the structural and mechanistic differences between the two enzyme classes. We recently reported evidence that cyclic boronates can inhibit both serine- and metallo-β-lactamases. Here we report that cyclic boronates are able to inhibit all four classes of β-lactamase, including the class A extended spectrum β-lactamase CTX-M-15, the class C enzyme AmpC from
Pseudomonas aeruginosa
, and class D OXA enzymes with carbapenem-hydrolyzing capabilities. We demonstrate that cyclic boronates can potentiate the use of β-lactams against Gram-negative clinical isolates expressing a variety of β-lactamases. Comparison of a crystal structure of a CTX-M-15:cyclic boronate complex with structures of cyclic boronates complexed with other β-lactamases reveals remarkable conservation of the small-molecule binding mode, supporting our proposal that these molecules work by mimicking the common tetrahedral anionic intermediate present in both serine- and metallo-β-lactamase catalysis.
Synthesis, Antifungal Activity, and Biocompatibility of Novel 1,4-Diazabicyclo[2.2.2]Octane (DABCO) Compounds and DABCO-Containing Denture Base Resins
Authors: Herman Jenny L. , Wang Yapin , Lilly Elizabeth A. , Lallier Thomas E. , Peters Brian M. , Hamdan Suleiman , Xu Xiaoming , Fidel Paul L. , Noverr Mairi C.
Published: January 2017

The fungal pathogen
Candida albicans
causes a variety of oral infections, including denture stomatitis, which is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. While antifungal treatment reduces symptoms, infections are often recurrent. One strategy to address this problem is to incorporate compounds with fungicidal activities into denture materials to prevent colonization. Our laboratory synthesized novel derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO), which is an organic compound typically used as a catalyst in polymerization reactions. DABCO derivatives with different aliphatic chain lengths (DC16, DC16F, DC18, and C6DC16), as well as methacrylate monomers conjugated to DABCO compounds (DC11MAF and C2DC11MAF), were synthesized and tested for antimicrobial activity. All the compounds exhibited fungicidal activity against several
Candida
species at concentrations ranging between 2 and 4 μg/ml. Moreover, acrylic denture base resins fabricated to contain 1, 2, or 4 wt% DABCO compounds inhibited surface
C. albicans
biofilm formation, as well as fungal growth, in disc diffusion assays. Remarkably, discs (4 wt%) aged for 2 months also exhibited approximately 100% growth-inhibitory activity. While some DABCO compounds exerted intermediate to high cytotoxicity against mammalian oral cell types, DC11MAF and denture base resin discs containing 2 or 4 wt% C2DC11MAF exhibited relatively low cytotoxicity against periodontal ligament (PDL) cell and gingival fibroblast (GF) lines, as well as primary oral epithelial cells. These studies demonstrate that DABCO derivatives can be incorporated into denture materials and exert fungicidal activity with minimal cytotoxicity to mammalian cells. DC11MAF and C2DC11MAF are considered strong candidates as therapeutic or preventive alternatives against
Candida
-associated denture stomatitis.
Mechanistic Study of Utilization of Water-Insoluble Saccharomyces cerevisiae Glucans by Bifidobacterium breve Strain JCM1192
Authors: Keung Hoi Yee , Li Tsz Kai , Sham Lok To , Cheung Man Kit , Cheung Peter Chi Keung , Kwan Hoi Shan
Published: January 2017

Bifidobacteria exert beneficial effects on hosts and are extensively used as probiotics. However, due to the genetic inaccessibility of these bacteria, little is known about their mechanisms of carbohydrate utilization and regulation.
Bifidobacterium breve
strain JCM1192 can grow on water-insoluble yeast (
Saccharomyces cerevisiae
) cell wall glucans (YCWG), which were recently considered as potential prebiotics. According to the results of
1
H nuclear magnetic resonance (NMR) spectrometry, the YCWG were composed of highly branched (1→3,1→6)-β-glucans and (1→4,1→6)-α-glucans. Although the YCWG were composed of 78.3% β-glucans and 21.7% α-glucans, only α-glucans were consumed by the
B. breve
strain. The ABC transporter (
malEFG1
) and pullulanase (
aapA
) genes were transcriptionally upregulated in the metabolism of insoluble yeast glucans, suggesting their potential involvement in the process. A nonsense mutation identified in the gene encoding an ABC transporter ATP-binding protein (MalK) led to growth failure of an ethyl methanesulfonate-generated mutant with yeast glucans. Coculture of the wild-type strain and the mutant showed that this protein was responsible for the import of yeast glucans or their breakdown products, rather than the export of α-glucan-catabolizing enzymes. Further characterization of the carbohydrate utilization of the mutant and three of its revertants indicated that this mutation was pleiotropic: the mutant could not grow with maltose, glycogen, dextrin, raffinose, cellobiose, melibiose, or turanose. We propose that insoluble yeast α-glucans are hydrolyzed by extracellular pullulanase into maltose and/or maltooligosaccharides, which are then transported into the cell by the ABC transport system composed of MalEFG1 and MalK. The mechanism elucidated here will facilitate the development of
B. breve
and water-insoluble yeast glucans as novel synbiotics.

IMPORTANCE
In general,
Bifidobacterium
strains are genetically intractable. Coupling classic forward genetics with next-generation sequencing, here we identified an ABC transporter ATP-binding protein (MalK) responsible for the import of insoluble yeast glucan breakdown products by
B. breve
JCM1192. We demonstrated the pleiotropic effects of the ABC transporter ATP-binding protein in maltose/maltooligosaccharide, raffinose, cellobiose, melibiose, and turanose transport. With the addition of transcriptional analysis, we propose that insoluble yeast glucans are broken down by extracellular pullulanase into maltose and/or maltooligosaccharides, which are then transported into the cell by the ABC transport system composed of MalEFG1 and MalK. The mechanism elucidated here will facilitate the development of
B. breve
and water-insoluble yeast glucans as novel synbiotics.
The changing landscape of diabetes prevalence among first-generation Asian immigrants in California from 2003 to 2013
Authors: Fan Wenjun , Lee Debora H , Billimek John , Choi Sarah , Wang Ping H
Published: January 2017

Objective

The prevalence of diabetes mellitus (DM) is increasing rapidly, particularly in Asia. Asian immigrants in Western countries are a fast-growing population who carry both intrinsic risks due to their genetic background and extrinsic risks associated with Western lifestyles. However, recent trends in diabetes prevalence and associated risk factors among Asian immigrants in the USA are not well understood.

Research design and methods

We examined adults aged 18 and older from the recent California Health Interview Survey data sets from 2003 to 2013 to determine prevalence of known DM among first-generation Asian immigrants and whites. The impact of various DM risk factors in Asian immigrants relative to whites was analyzed and multivariable regression models were constructed to obtain adjusted DM risk in Asian immigrants versus in whites.

Results

Across the study span, we identified 2007 first-generation Asian immigrants and 14 668 whites as having known DM or prediabetes mellitus (pre-DM). From 2003 to 2013, the prevalence of DM and pre-DM combined rose from 6.8% to 12.4% in Asian immigrants and 5.5% to 6.9% in whites. Much of the increase could be attributed to pre-DM, which rose from 0.7% to 3.2% in Asian immigrants during the study period. The impacts of age and body mass index on DM risk were consistently greater in Asian immigrants than in whites. Non-DM Asian immigrants were found less likely to engage in physical activity than were non-DM whites. After adjustment of various associated factors, Asian immigrants were more likely than whites to have DM and this relative risk for DM gradually increased across the study period.

Conclusions

A rising prevalence of known DM and particularly pre-DM among Asian immigrants in California was observed during the previous decade. To reduce the burden of diabetes and its complications, future strategies should consider specific risk factors for this ethnic group, including encouraging physical activity.
Association between soil heavy metals and fatty liver disease in men in Taiwan: a cross sectional study
Authors: Lin Yen-Chih , Lian Ie-Bin , Kor Chew-Teng , Chang Chia-Chu , Su Pei-Yuan , Chang Wan-Tzu , Liang Yu-Fen , Su Wei-Wen , Soon Maw-Soan
Published: January 2017

Objectives

Metabolic factors are major risk factors for non-alcoholic fatty liver disease although other factors may also contribute to development of fatty liver disease. We explored the association between exposure to soil heavy metals and prevalence of fatty liver disease.

Methods

We retrospectively analysed data from patients diagnosed with fatty liver disease in 2014 at the Health Evaluation Centre of Chang-Hua Christian Hospital (n=1137). We used residency data provided in the records of the Health Evaluation Centre and data for soil metal concentrations from a nationwide survey conducted by the Environmental Protection Administration of Taiwan. We studied the correlations between the severity of fatty liver disease and concentrations of soil heavy metals (arsenic, mercury, cadmium, chromium, copper, nickel, lead and zinc).

Results

The prevalence of moderate to severe fatty liver disease in our study was 26.5%. Using univariate and multivariate analysis, we demonstrated that the presence of soil heavy metals was a significant risk factor for fatty liver disease in men (OR 1.83, 95% CI 1.161 to 2.899, p=0.009). With stratification by body mass index (BMI) and gender, lean men with a BMI <24 kg/m2were the most susceptible to soil heavy metals (OR 5.059, 95% CI 1.628 to 15.728, p<0.05).

Conclusions

Our study suggested a significant association between exposure to soil heavy metals and fatty liver disease in lean men.
Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis
Authors: Mayerle Julia , Kalthoff Holger , Reszka Regina , Kamlage Beate , Peter Erik , Schniewind Bodo , González Maldonado Sandra , Pilarsky Christian , Heidecke Claus-Dieter , Schatz Philipp , Distler Marius , Scheiber Jonas A , Mahajan Ujjwal M , Weiss F Ulrich , Grützmann Robert , Lerch Markus M
Published: January 2017

Objective

Current non-invasive diagnostic tests can distinguish between pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC)) and chronic pancreatitis (CP) in only about two thirds of patients. We have searched for blood-derived metabolite biomarkers for this diagnostic purpose.

Design

For a case–control study in three tertiary referral centres, 914 subjects were prospectively recruited with PDAC (n=271), CP (n=282), liver cirrhosis (n=100) or healthy as well as non-pancreatic disease controls (n=261) in three consecutive studies. Metabolomic profiles of plasma and serum samples were generated from 477 metabolites identified by gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry.

Results

A biomarker signature (nine metabolites and additionally CA19-9) was identified for the differential diagnosis between PDAC and CP. The biomarker signature distinguished PDAC from CP in the training set with an area under the curve (AUC) of 0.96 (95% CI 0.93–0.98). The biomarker signature cut-off of 0.384 at 85% fixed specificity showed a sensitivity of 94.9% (95% CI 87.0%–97.0%). In the test set, an AUC of 0.94 (95% CI 0.91–0.97) and, using the same cut-off, a sensitivity of 89.9% (95% CI 81.0%–95.5%) and a specificity of 91.3% (95% CI 82.8%–96.4%) were achieved, successfully validating the biomarker signature.

Conclusions

In patients with CP with an increased risk for pancreatic cancer (cumulative incidence 1.95%), the performance of this biomarker signature results in a negative predictive value of 99.9% (95% CI 99.7%–99.9%) (training set) and 99.8% (95% CI 99.6%–99.9%) (test set). In one third of our patients, the clinical use of this biomarker signature would have improved diagnosis and treatment stratification in comparison to CA19-9.
YouTube and the single-rod contraceptive implant: a content analysis
Authors: Paul Jennifer , Boraas Christy M , Duvet Mildred , Chang Judy C
Published: January 2017

Background

Since the internet has become an important source of contraceptive information with YouTube.com as the second most visited site, we analysed contraceptive implant YouTube videos for content and clinical accuracy.

Methods

Using the terms ‘contraceptive implant’, ‘Nexplanon’ and ‘Implanon’, the top 20 results on YouTube by relevance and view count were identified. After excluding duplicates, single-rod implant videos in English were included. Videos were classified as providing a professional or patient perspective. Views, duration and comments were noted. Videos were rated for reliability, global quality scale and whether they were positive or negative about the implant. Inter-rater agreement was measured.

Results

A total of 120 videos were retrieved; 52 were eligible for review. Less than 23% were professional videos; the majority reported patient experience (46% testimonials, 27% real-time procedure videos, 4% other). Patient videos had been posted a significantly longer duration of time than professional videos (364 vs 188 days,p=0.02), were less reliable (p≤0.0001) and were of lower global quality (p<0.0001). Some 61% of implant testimonial videos were rated as ‘positive experiences’ and inter-rater agreement was very good (κ=0.81). All testimonials mentioned side effects, commonly irregular bleeding and discomfort with insertion. A minority (26%) reported misinformation.

Conclusions

This study found that most of the information on YouTube pertaining to contraceptive implants is accurate, is presented from the patient's perspective, and promotes the method's use.
Investigating human skeletal muscle physiology with unilateral exercise models: when one limb is more powerful than two
Authors: MacInnis Martin J. , McGlory Chris , Gibala Martin J. , Phillips Stuart M.
Published: January 2017

Direct sampling of human skeletal muscle using the needle biopsy technique can facilitate insight into the biochemical and histological responses resulting from changes in exercise or feeding. However, the muscle biopsy procedure is invasive, and analyses are often expensive, which places pragmatic restraints on sample sizes. The unilateral exercise model can serve to increase statistical power and reduce the time and cost of a study. With this approach, 2 limbs of a participant are randomized to 1 of 2 treatments that can be applied almost concurrently or sequentially depending on the nature of the intervention. Similar to a typical repeated measures design, comparisons are made within participants, which increases statistical power by reducing the amount of between-person variability. A washout period is often unnecessary, reducing the time needed to complete the experiment and the influence of potential confounding variables such as habitual diet, activity, and sleep. Variations of the unilateral exercise model have been employed to investigate the influence of exercise, diet, and the interaction between the 2, on a wide range of variables including mitochondrial content, capillary density, and skeletal muscle hypertrophy. Like any model, unilateral exercise has some limitations: it cannot be used to study variables that potentially transfer across limbs, and it is generally limited to exercises that can be performed in pairs of treatments. Where appropriate, however, the unilateral exercise model can yield robust, well-controlled investigations of skeletal muscle responses to a wide range of interventions and conditions including exercise, dietary manipulation, and disuse or immobilization.
Estimation of Lattice Stress and Strain in Zinc and Manganese Ferrite Nanoparticles by Williamson–Hall and Size-Strain Plot Methods
Authors: Augustin M. , Balu T.
Published: January 2017

The Williamson–Hall (W–H) analysis and size-strain plot method (SSP) were used to study the lattice stress, strain and crystalline size of zinc (ZnFe2O4) and manganese (MnFe2O4) ferrite nanoparticles. These nanoparticles were synthesized by chemical co-precipitation method and characterized by powder X-ray diffraction analysis (PXRD). The PXRD results revealed that the sample product was crystalline with mixed type spinel with cubic structure. The crystalline development in the ZnFe2O4 and MnFe2O4 was investigated by X-ray peak broadening. The physical parameters such as strain, stress and energy density values were calculated more precisely for all the reflection peaks of PXRD using the W–H plots and SSP method. The variation in particle size, lattice strain, stress and energy density calculated from W–H analysis and SSP method reveals a nonuniform strain in the particles. This nonuniform strain was increased when the particle sizes were increased.
Utilizing Selected Di- and Trinucleotides of siRNA to Predict RNAi Activity
Authors: Han Ye , Liu Yuanning , Zhang Hao , He Fei , Shu Chonghe , Dong Liyan
Published: January 2017

Small interfering RNAs (siRNAs) induce posttranscriptional gene silencing in various organisms. siRNAs targeted to different positions of the same gene show different effectiveness; hence, predicting siRNA activity is a crucial step. In this paper, we developed and evaluated a powerful tool named “siRNApred” with a new mixed feature set to predict siRNA activity. To improve the prediction accuracy, we proposed 2-3NTs as our new features. A Random Forest siRNA activity prediction model was constructed using the feature set selected by our proposed Binary Search Feature Selection (BSFS) algorithm. Experimental data demonstrated that the binding site of the Argonaute protein correlates with siRNA activity. “siRNApred” is effective for selecting active siRNAs, and the prediction results demonstrate that our method can outperform other current siRNA activity prediction methods in terms of prediction accuracy.
Evaluation of Anti‐Inflammatory Properties of Isoorientin Isolated from Tubers of Pueraria tuberosa
Authors: Anilkumar Kotha , Reddy Gorla V. , Azad Rajaram , Yarla Nagendra Sastry , Dharmapuri Gangappa , Srivastava Anand , Kamal Mohammad A. , Pallu Reddanna
Published: January 2017

Inflammation is the major causative factor of different diseases such as cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, and cancer. Anti‐inflammatory drugs are often the first step of treatment in many of these diseases. The present study is aimed at evaluating the anti‐inflammatory properties of isoorientin, a selective cyclooxygenase‐2 (COX‐2) inhibitor isolated from the tubers of Pueraria tuberosa, in vitro on mouse macrophage cell line (RAW 264.7) and in vivo on mouse paw edema and air pouch models of inflammation. Isoorientin reduced inflammation in RAW 264.7 cell line in vitro and carrageenan induced inflammatory animal model systems in vivo. Cellular infiltration into pouch tissue was reduced in isoorientin treated mice compared to carrageenan treated mice. Isoorientin treated RAW 264.7 cells and animals showed reduced expression of inflammatory proteins like COX‐2, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), 5‐lipoxygenase (5‐LOX), and interleukin 1‐β (IL‐1‐β) both in vitro and in vivo. The antioxidant enzyme levels of catalase and GST were markedly increased in isoorientin treated mice compared to carrageenan treated mice. These results suggest that isoorientin, a selective inhibitor of COX‐2, not only exerts anti‐inflammatory effects in LPS induced RAW cells and carrageenan induced inflammatory model systems but also exhibits potent antioxidant properties.
Robotic Assisted Laparoscopic Prostatectomy after High Intensity Focused Ultrasound Failure
Authors: Telis Leon , Jazayeri Seyed Behzad , Samadi David B.
Published: January 2017

Background. Prostate cancer is the most common cancer diagnosed in men. As new focal therapies become more popular in treatment of prostate cancer, failure cases requiring salvage therapy with either surgical or other techniques are being reported. Objective. To report the options in treatment of prostate cancer after recurrence or failure of the primary treatment modality. Methods. We report a salvage robotic assisted laparoscopic radical prostatectomy (RALP) for prostate cancer recurrence following high intensity focused ultrasound treatment (HIFU) in the United States. Results. A 67-year-old man who underwent HIFU treatment for prostate adenocarcinoma 2 years prior was presented with a rising prostate specific antigen of 6.1 ng/mL to our clinic. A biopsy proven recurrent disease in the area of previous treatment documented the failure of treatment. The patient elected to undergo a salvage RALP. The operation time was 159 minutes. The patient was discharged from the hospital on postoperative day 1 with no complications. The catheter was removed on post-op day 10. The patient reserved sexual function and urinary continence. The PSA levels on 6 months’ follow-up are undetectable. Conclusions. Salvage RALP is an effective and safe treatment choice for recurrent prostate adenocarcinoma following failed HIFU treatment if operated by an experienced surgeon.
Enhancement of Bone-Marrow-Derived Mesenchymal Stem Cell Angiogenic Capacity by NPWT for a Combinatorial Therapy to Promote Wound Healing with Large Defect
Authors: Shou Kangquan , Niu Yahui , Zheng Xun , Ma Zhanjun , Jian Chao , Qi Baiwen , Hu Xiang , Yu Aixi
Published: January 2017

Poor viability of engrafted bone marrow mesenchymal stem cells (BMSCs) often hinders their application for wound healing, and the strategy of how to take full advantage of their angiogenic capacity within wounds still remains unclear. Negative pressure wound therapy (NPWT) has been demonstrated to be effective for enhancing wound healing, especially for the promotion of angiogenesis within wounds. Here we utilized combinatory strategy using the transplantation of BMSCs and NPWT to investigate whether this combinatory therapy could accelerate angiogenesis in wounds. In vitro, after 9-day culture, BMSCs proliferation significantly increased in NPWT group. Furthermore, NPWT induced their differentiation into the angiogenic related cells, which are indispensable for wound angiogenesis. In vivo, rat full-thickness cutaneous wounds treated with BMSCs combined with NPWT exhibited better viability of the cells and enhanced angiogenesis and maturation of functional blood vessels than did local BMSC injection or NPWT alone. Expression of angiogenesis markers (NG2, VEGF, CD31, and α-SMA) was upregulated in wounds treated with combined BMSCs with NPWT. Our data suggest that NPWT may act as an inductive role to enhance BMSCs angiogenic capacity and this combinatorial therapy may serve as a simple but efficient clinical solution for complex wounds with large defects.
Miniature Dielectric Barrier Discharge Nonthermal Plasma Induces Apoptosis in Lung Cancer Cells and Inhibits Cell Migration
Authors: Karki Surya B. , Yildirim-Ayan Eda , Eisenmann Kathryn M. , Ayan Halim
Published: January 2017

Traditional cancer treatments like radiotherapy and chemotherapy have drawbacks and are not selective for killing only cancer cells. Nonthermal atmospheric pressure plasmas with dielectric barrier discharge (DBD) can be applied to living cells and tissues and have emerged as novel tools for localized cancer therapy. The purpose of this study was to investigate the different effects caused by miniature DBD (mDBD) plasma to A549 lung cancer cells. In this study, A549 lung cancer cells cultured in 12 well plates were treated with mDBD plasma for specified treatment times to assess the changes in the size of the area of cell detachment, the viability of attached or detached cells, and cell migration. Furthermore, we investigated an innovative mDBD plasma-based therapy for localized treatment of lung cancer cells through apoptotic induction. Our results indicate that plasma treatment for 120 sec causes apoptotic cell death in 35.8% of cells, while mDBD plasma treatment for 60 sec, 30 sec, or 15 sec causes apoptotic cell death in 20.5%, 14.1%, and 6.3% of the cell population, respectively. Additionally, we observed reduced A549 cell migration in response to mDBD plasma treatment. Thus, mDBD plasma system can be a viable platform for localized lung cancer therapy.
Are Health Videos from Hospitals, Health Organizations, and Active Users Available to Health Consumers? An Analysis of Diabetes Health Video Ranking in YouTube
Authors: Fernandez-Llatas Carlos , Traver Vicente , Borras-Morell Jose-Enrique , Martinez-Millana Antonio , Karlsen Randi
Published: January 2017

Health consumers are increasingly using the Internet to search for health information. The existence of overloaded, inaccurate, obsolete, or simply incorrect health information available on the Internet is a serious obstacle for finding relevant and good-quality data that actually helps patients. Search engines of multimedia Internet platforms are thought to help users to find relevant information according to their search. But, is the information recovered by those search engines from quality sources? Is the health information uploaded from reliable sources, such as hospitals and health organizations, easily available to patients? The availability of videos is directly related to the ranking position in YouTube search. The higher the ranking of the information is, the more accessible it is. The aim of this study is to analyze the ranking evolution of diabetes health videos on YouTube in order to discover how videos from reliable channels, such as hospitals and health organizations, are evolving in the ranking. The analysis was done by tracking the ranking of 2372 videos on a daily basis during a 30-day period using 20 diabetes-related queries. Our conclusions are that the current YouTube algorithm favors the presence of reliable videos in upper rank positions in diabetes-related searches.
Enamel Thickness before and after Orthodontic Treatment Analysed in Optical Coherence Tomography
Authors: Seeliger Julia , Machoy Monika , Koprowski Robert , Safranow Krzysztof , Gedrange Tomasz , Woźniak Krzysztof
Published: January 2017

Despite the continuous development of materials and techniques of adhesive bonding, the basic procedure remains relatively constant. The technique is based on three components: etching substance, adhesive system, and composite material. The use of etchants during bonding orthodontic brackets carries the risk of damage to the enamel. Therefore, the article examines the effect of the manner of enamel etching on its thickness before and after orthodontic treatment. The study was carried out in vitro on a group of 80 teeth. It was divided into two subgroups of 40 teeth each. The procedure of enamel etching was performed under laboratory conditions. In the first subgroup, the classic method of enamel etching and the fifth-generation bonding system were used. In the second subgroup, the seventh-generation (self-etching) bonding system was used. In both groups, metal orthodontic brackets were fixed and the enamel was cleaned with a cutter fixed on the micromotor after their removal. Before and after the treatment, two-dimensional optical coherence tomography scans were performed. The enamel thickness was assessed on the two-dimensional scans. The average enamel thickness in both subgroups was not statistically significant.
Immune Profile of Obese People and In Vitro Effects of Red Grape Polyphenols on Peripheral Blood Mononuclear Cells
Authors: Magrone Thea , Jirillo Emilio , Spagnoletta Anna , Magrone Manrico , Russo Matteo Antonio , Fontana Sergio , Laforgia Flavia , Donvito Ilaria , Campanella Angelo , Silvestris Franco , De Pergola Giovanni
Published: January 2017

The in vitro ability of polyphenols, extracted from red grape, to modulate peripheral blood mononuclear cell responses has been evaluated in 20 obese (Ob) people. With regard to cytokine release in response to phorbol myristate acetate (PMA), levels of interleukin‐2 (IL‐2), interferon‐γ (IFN‐γ), IL‐4, IL‐10, and IL‐17 were higher in the Ob than in healthy (H) subjects. Vice versa, IL‐21 concentrations were detected only in H people but they were undetectable in the Ob counterpart. In general terms, levels of IL‐1β, IL‐6, IL‐8, and tumor necrosis factor‐α were higher in Ob people when compared to H controls. On the other hand, polyphenols did not modify IFN‐γ, IL‐4, and IL‐17 levels. However, an increase in IL‐2 was observed in H individuals, whereas its levels were decreased in the Ob counterpart. Polyphenols significantly increased IL‐10 release from H donors, whereas a trend to increase was observed in Ob people. In addition, polyphenols were able to significantly increase levels of H IL‐21, while this was not the case in Ob people. Since IL‐21 is an inducer of Th17 cells, it is likely that polyphenols may suppress the sources of this cytokine via production of IL‐10. Accordingly, polyphenols decreased IL‐1β and IL‐6 release in comparison to H controls.
Bone Metastasis of Prostate Cancer Can Be Therapeutically Targeted at the TBX2–WNT Signaling Axis
Authors: Nandana Srinivas , Tripathi Manisha , Duan Peng , Chu Chia-Yi , Mishra Rajeev , Liu Chunyan , Jin Renjie , Yamashita Hironobu , Zayzafoon Majd , Bhowmick Neil A. , Zhau Haiyen E. , Matusik Robert J. , Chung Leland W.K.
Published: January 2017

Identification of factors that mediate visceral and bone metastatic spread and subsequent bone remodeling events is highly relevant to successful therapeutic intervention in advanced human prostate cancer. TBX2, a T-box family transcription factor that negatively regulates cell-cycle inhibitor p21, plays critical roles during embryonic development, and recent studies have highlighted its role in cancer. Here, we report that TBX2 is overexpressed in human prostate cancer specimens and bone metastases from xenograft mouse models of human prostate cancer. Blocking endogenous TBX2 expression in PC3 and ARCaPM prostate cancer cell models using a dominant-negative construct resulted in decreased tumor cell proliferation, colony formation, and invasion in vitro. Blocking endogenous TBX2 in human prostate cancer mouse xenografts decreased invasion and abrogation of bone and soft tissue metastasis. Furthermore, blocking endogenous TBX2 in prostate cancer cells dramatically reduced bone-colonizing capability through reduced tumor cell growth and bone remodeling in an intratibial mouse model. TBX2 acted in trans by promoting transcription of the canonical WNT (WNT3A) promoter. Genetically rescuing WNT3A levels in prostate cancer cells with endogenously blocked TBX2 partially restored the TBX2-induced prostate cancer metastatic capability in mice. Conversely, WNT3A-neutralizing antibodies or WNT antagonist SFRP-2 blocked TBX2-induced invasion. Our findings highlight TBX2 as a novel therapeutic target upstream of WNT3A, where WNT3A antagonists could be novel agents for the treatment of metastasis and for skeletal complications in prostate cancer patients. Cancer Res; 77(6); 1331–44. ©2017 AACR.
Two-Pore Channel Function Is Crucial for the Migration of Invasive Cancer Cells
Authors: Nguyen Ong Nam Phuong , Grimm Christian , Schneider Lina S. , Chao Yu-Kai , Atzberger Carina , Bartel Karin , Watermann Anna , Ulrich Melanie , Mayr Doris , Wahl-Schott Christian , Biel Martin , Vollmar Angelika M.
Published: January 2017

Metastatic invasion is the major cause of cancer-related deaths. In this study, we introduce two-pore channels (TPC), a recently described class of NAADP- and PI(3,5)P2–sensitive Ca2+-permeable cation channels in the endolysosomal system of cells, as candidate targets for the treatment of invasive cancers. Inhibition of the channel abrogated migration of metastatic cancer cells in vitro. Silencing or pharmacologic inhibition of the two-pore channel TPC2 reduced lung metastasis of mammary mouse cancer cells. Disrupting TPC function halted trafficking of β1-integrin, leading to its accumulation in EEA1-positive early endosomes. As a consequence, invasive cancer cells were no longer able to form leading edges, which are required for adequate migration. Our findings link TPC to cancer cell migration and provide a preclinical proof of concept for their candidacy as targets to treat metastatic cancers. Cancer Res; 77(6); 1427–38. ©2017 AACR.
Constitutive NOTCH3 Signaling Promotes the Growth of Basal Breast Cancers
Authors: Choy Lisa , Hagenbeek Thijs J. , Solon Margaret , French Dorothy , Finkle David , Shelton Amy , Venook Rayna , Brauer Matthew J. , Siebel Christian W.
Published: January 2017

Notch ligands signal through one of four receptors on neighboring cells to mediate cell–cell communication and control cell fate, proliferation, and survival. Although aberrant Notch activation has been implicated in numerous malignancies, including breast cancer, the importance of individual receptors in distinct breast cancer subtypes and the mechanisms of receptor activation remain unclear. Using a novel antibody to detect active NOTCH3, we report here that NOTCH3 signals constitutively in a panel of basal breast cancer cell lines and in more than one third of basal tumors. Selective inhibition of individual ligands revealed that this signal does not require canonical ligand induction. A NOTCH3 antagonist antibody inhibited growth of basal lines, whereas a NOTCH3 agonist antibody enhanced the transformed phenotype in vitro and in tumor xenografts. Transcriptomic analyses generated a Notch gene signature that included Notch pathway components, the oncogene c-Myc, and the mammary stem cell regulator Id4. This signature drove clustering of breast cancer cell lines and tumors into the common subtypes and correlated with the basal classification. Our results highlight an unexpected ligand-independent induction mechanism and suggest that constitutive NOTCH3 signaling can drive an oncogenic program in a subset of basal breast cancers. Cancer Res; 77(6); 1439–52. ©2017 AACR.
A Transposon-based Analysis Reveals RASA1 Is Involved in Triple-Negative Breast Cancer
Authors: Suárez-Cabrera Cristian , Quintana Rita M. , Bravo Ana , Casanova M. Llanos , Page Angustias , Alameda Josefa P. , Paramio Jesús M. , Maroto Alicia , Salamanca Javier , Dupuy Adam J. , Ramírez Angel , Navarro Manuel
Published: January 2017

RAS genes are mutated in 20% of human tumors, but these mutations are very rare in breast cancer. Here, we used a mouse model to generate tumors upon activation of a mutagenic T2Onc2 transposon via expression of a transposase driven by the keratin K5 promoter in a p53+/− background. These animals mainly developed mammary tumors, most of which had transposon insertions in one of two RASGAP genes, neurofibromin1 (Nf1) and RAS p21 protein activator (Rasa1). Immunohistochemical analysis of a collection of human breast tumors confirmed that low expression of RASA1 is frequent in basal (triple-negative) and estrogen receptor negative tumors. Bioinformatic analysis of human breast tumors in The Cancer Genome Atlas database showed that although RASA1 mutations are rare, allelic loss is frequent, particularly in basal tumors (80%) and in association with TP53 mutation. Inactivation of RASA1 in MCF10A cells resulted in the appearance of a malignant phenotype in the context of mutated p53. Our results suggest that alterations in the Ras pathway due to the loss of negative regulators of RAS may be a common event in basal breast cancer. Cancer Res; 77(6); 1357–68. ©2017 AACR.
Fibrinolytic Enzyme Cotherapy Improves Tumor Perfusion and Therapeutic Efficacy of Anticancer Nanomedicine
Authors: Kirtane Ameya R. , Sadhukha Tanmoy , Kim Hyunjoon , Khanna Vidhi , Koniar Brenda , Panyam Jayanth
Published: January 2017

Elevated interstitial fluid pressure and solid stress within tumors contribute to poor intratumoral distribution of nanomedicine. In this study, we hypothesized that the presence of fibrin in tumor extracellular matrix contributes to hindered intratumoral distribution of nanocarriers and that this can be overcome through the use of a fibrinolytic enzyme such as tissue plasminogen activator (tPA). Analysis of fibrin expression in human tumor biopsies showed significant fibrin staining in nearly all tumor types evaluated. However, staining was heterogeneous across and within tumor types. We determined the effect of fibrin on the diffusion, intratumoral distribution, and therapeutic efficacy of nanocarriers. Diffusivity of nanocarriers in fibrin matrices was limited and could be improved significantly by coincubation with tPA. In vivo, coadministration of tPA improved the anticancer efficacy of nanoparticle-encapsulated paclitaxel in subcutaneous syngeneic mouse melanoma and orthotopic xenograft lung cancer models. Furthermore, treatment with tPA led to decompression of blood vessels and improved tumor perfusion. Cotreatment with tPA resulted in greater intratumoral penetration of a model nanocarrier (Doxil), leading to enhanced availability of the drug in the tumor core. Fibrinolytics such as tPA are already approved for other indications. Fibrinolytic cotherapy is therefore a rapidly translatable strategy for improving therapeutic effectiveness of anticancer nanomedicine. Cancer Res; 77(6); 1465–75. ©2017 AACR.