bluuebunny/crossref_metadata_2025 huggingface dataset:
Next-Generation Sequence Analysis Reveals Transfer of Methicillin Resistance to a Methicillin-Susceptible Staphylococcus aureus Strain That Subsequently Caused a Methicillin-Resistant Staphylococcus aureus Outbreak: a Descriptive Study
Authors: Weterings Veronica , Bosch Thijs , Witteveen Sandra , Landman Fabian , Schouls Leo , Kluytmans Jan
Published: July 2017

Resistance to methicillin in
Staphylococcus aureus
is caused primarily by the
mecA
gene, which is carried on a mobile genetic element, the staphylococcal cassette chromosome
mec
(SCC
mec
). Horizontal transfer of this element is supposed to be an important factor in the emergence of new clones of methicillin-resistant
Staphylococcus aureus
(MRSA) but has been rarely observed in real time. In 2012, an outbreak occurred involving a health care worker (HCW) and three patients, all carrying a fusidic acid-resistant MRSA strain. The husband of the HCW was screened for MRSA carriage, but only a methicillin-susceptible
S. aureus
(MSSA) strain, which was also resistant to fusidic acid, was detected. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing showed that both the MSSA and MRSA isolates were MT4053-MC0005. This finding led to the hypothesis that the MSSA strain acquired the SCC
mec
and subsequently caused an outbreak. To support this hypothesis, next-generation sequencing of the MSSA and MRSA isolates was performed. This study showed that the MSSA isolate clustered closely with the outbreak isolates based on whole-genome multilocus sequence typing and single-nucleotide polymorphism (SNP) analysis, with a genetic distance of 17 genes and 44 SNPs, respectively. Remarkably, there were relatively large differences in the mobile genetic elements in strains within and between individuals. The limited genetic distance between the MSSA and MRSA isolates in combination with a clear epidemiologic link supports the hypothesis that the MSSA isolate acquired a SCC
mec
and that the resulting MRSA strain caused an outbreak.
Behavioral Effects of a Chemorepellent Receptor Knockout Mutation in Tetrahymena thermophila
Authors: Zou Dianxiong , Hennessey Todd M.
Published: July 2017

Although many single-cell eukaryotes have served as classical model systems for chemosensory studies for decades, the major emphasis has been on chemoattraction and no chemorepellent receptor gene has been identified in any unicellular eukaryote. This is the first description of a gene that codes for a chemorepellent receptor in any protozoan. Integration of both depolarizing chemorepellent pathways and hyperpolarizing chemoattractant pathways is as important to chemoresponses of motile unicells as excitatory and inhibitory neurotransmitter pathways are to neurons. Therefore, both chemoattractant and chemorepellent pathways should be represented in a useful unicellular model system.
Tetrahymena
cells provide such a model system because simple behavioral bioassays, gene knockouts, biochemical analysis, and other approaches can be used with these eukaryotic model cells. This work can contribute to the basic understanding of unicellular sensory responses and provide insights into the evolution of chemoreceptors and possible chemorepellent approaches for preventing infections by some pathogenic protozoa.
Sulfide Generation by Dominant
Halanaerobium
Microorganisms in Hydraulically Fractured Shales
Authors: Booker Anne E. , Borton Mikayla A. , Daly Rebecca A. , Welch Susan A. , Nicora Carrie D. , Hoyt David W. , Wilson Travis , Purvine Samuel O. , Wolfe Richard A. , Sharma Shikha , Mouser Paula J. , Cole David R. , Lipton Mary S. , Wrighton Kelly C. , Wilkins Michael J.
Published: July 2017

Although thousands of wells in deep shale formations across the United States have been hydraulically fractured for oil and gas recovery, the impact of microbial metabolism within these environments is poorly understood. Our research demonstrates that dominant microbial populations in these subsurface ecosystems contain the conserved capacity for the reduction of thiosulfate to sulfide and that this process is likely occurring in the environment. Sulfide generation (also known as “souring”) is considered deleterious in the oil and gas industry because of both toxicity issues and impacts on corrosion of the subsurface infrastructure. Critically, the capacity for sulfide generation via reduction of sulfate was not detected in our data sets. Given that current industry wellhead tests for sulfidogenesis target canonical sulfate-reducing microorganisms, these data suggest that new approaches to the detection of sulfide-producing microorganisms may be necessary.
Idiopathic abdominal cocoon: a rare presentation of small bowel obstruction in a virgin abdomen. How much do we know?
Authors: Al-Azzawi Marwa , Al-Alawi Rashid
Published: July 2017

Abdominal cocoon is an extremely rare condition that has been mainly associated with young adolescent women. It was first described in 1978 by Fooet al. We present here a case that describes an otherwise healthy adult man who presented with intestinal obstruction and was found to have an abdominal cocoon, also known as a peritoneal sac. The patient was taken for a laparotomy and the sac was released through blunt dissection along the avascular planes. He was discharged in good condition 3 days postoperatively. We discuss some of the current literature and previously reported cases on this condition.
Risk of dementia in patients with non-haemorrhagic stroke receiving acupuncture treatment: a nationwide matched cohort study from Taiwan’s National Health Insurance Research Database
Authors: Shih Chun-Chuan , Yeh Chun-Chieh , Hu Chaur-Jong , Lane Hsin-Long , Tsai Chin-Chuan , Chen Ta-Liang , Liao Chien-Chang
Published: July 2017

Objective

To investigate the risk of dementia in patients with stroke who did and did not receive acupuncture treatment.

Design

Retrospective cohort study.

Setting

This study was based on Taiwan’s National Health Insurance Research Database that included patients with stroke hospitalised between 1 January 2000 and 31 December 2004.

Participants

We identified 11 220 patients aged 50 years and older with newly diagnosed stroke hospitalisation.

Primary and secondary outcome measures

We compared the incident dementia during the follow-up period until the end of 2009 in patients with stroke who did and did not receive acupuncture. The adjusted HRs and 95% CIs of dementia associated with acupuncture were calculated in multivariate Cox proportional hazard regressions.

Results

Acupuncture treatment was associated with a decreased risk of dementia with multivariate adjustment (HR, 0.73; 95% CI 0.66 to 0.80), and the association was significant in both sexes and every age group, as well as in groups with ischaemic stroke, with fewer medical conditions and those hospitalised after stroke. Patients with stroke received acupuncture treatment, and conventional rehabilitation was associated with a significantly reduced risk of poststroke dementia (HR, 0.64; 95% CI 0.56 to 0.74).

Conclusions

This study raises the possibility that patients with non-haemorrhagic stroke who received acupuncture had a reduced risk of dementia. The results suggest the need for prospective sham-controlled and randomised trials to establish the efficacy of acupuncture in preventing dementia.
Prevalence and injury patterns among electronic waste workers in the informal sector in Nigeria
Authors: Ohajinwa Chimere May , van Bodegom Peter M , Vijver Martina G , Olumide Adesola O , Osibanjo Oladele , Peijnenburg Willie J G M
Published: July 2017

Background

Despite the large volume of e-waste recycled informally, the prevalence of work-related injuries among e-waste workers is unknown. Therefore, this study assessed the prevalence, patterns and factors associated with occupational injuries among e-waste workers in the informal sector in Nigeria.

Methods

This cross-sectional study adopted a multistage sampling method to select 279 respondents from three cities (Ibadan, Lagos and Aba) in Nigeria. A questionnaire was used to obtain information on sociodemographics, work practices and injury occurrences from the respondents in 2015. The data were analysed using descriptive statistics and standard logistic regression.

Results

We found high injury prevalence of 38% and 68% in 1–2 weeks and 6 months preceding the study, respectively. The most common injuries were cuts (59%). Injuries were mainly caused by sharp objects (77%). The majority (82%) of the injuries occurred on the hands/fingers. Despite the high occurrence of injury, only 18% of the workers use personal protective equipment (PPE) and 51% of those that use PPE got at least an injury in 1–2 weeks and 88% got at least an injury in 6 months preceding the study. The factors associated with injury in 1–2 weeks were job designation and the geographical location, while the factors associated with injury in 6 months were job designation, geographical location and age.

Conclusions

There is a high prevalence of injury and low use of PPE among the e-waste workers in Nigeria. Occupational injury can be reduced through health education and safety promotion programmes for e-waste workers.
CHINA’S INDUSTRIAL STRUCTURE UPGRADE IN THE “NEW NORMAL”: EMPIRICAL TEST AND DETERMINANTS
Authors: XIAO WEN , PAN JIA-DONG , LIU LI-YUN
Published: July 2017

This paper measures the index of industrial structure upgrade nationally, regionally and provincially by employing angle cosine method. The results show that China’s industrial structure has upgraded and the East is higher than the Northeast and the Midwest. The paper presents an empirical study to examine the effect of variables including demand-side factors, New Normal as a dummy variable and supply-side factors on industrial structure upgrading. It implies that New Normal is not significant, while consumption, investment, technology improvement and labor supply significantly facilitate the upgrade. It highlights policy suggestions designed to adopt innovation-driven strategy and regional economy development strategy.
The analytical transfer matrix method for PT-symmetric complex potential
Authors: Naceri Leila , Hammou Amine B.
Published: July 2017

We have extended the analytical transfer matrix (ATM) method to solve quantum mechanical bound state problems with complex PT-symmetric potentials. Our work focuses on a class of models studied by Bender and Jones, we calculate the energy eigenvalues, discuss the critical values of g and compare the results with those obtained from other methods such as exact numerical computation and WKB approximation method.
A New Optimization Strategy for Solving the Fall-Off Boundary Value Problem in Pixel-Value Differencing Steganography
Authors: Grajeda-Marín Ismael R. , Montes-Venegas Héctor A. , Marcial-Romero J. Raymundo , Hernández-Servín J. A. , Muñoz-Jiménez Vianney , Luna Guillermo De Ita
Published: July 2017

In Digital Image Steganography, Pixel-Value Differencing (PVD) methods use the difference between neighboring pixel values to determine the amount of data bits to be inserted. The main advantage of these methods is the size of input data that an image can hold. However, the fall-off boundary problem and the fall in error problem are persistent in many PVD steganographic methods. This results in an incorrect output image. To fix these issues, usually the pixel values are either somehow adjusted or simply not considered to carry part of the input data. In this paper, we enhance the Tri-way Pixel-Value Differencing method by finding an optimal pixel value for each pixel pair such that it carries the maximum input data possible without ignoring any pair and without yielding incorrect pixel values.
Minimal Heegaard genus of amalgamated 3-manifolds
Authors: Du Kun , Qiu Ruifeng
Published: July 2017

Let [Formula: see text] [Formula: see text] be a perfect [Formula: see text]-manifold, [Formula: see text] be a component of [Formula: see text], [Formula: see text] be a homeomorphic map, [Formula: see text] and [Formula: see text]. In this paper, we show that if [Formula: see text] [Formula: see text] and [Formula: see text], then [Formula: see text]. As a corollary, if [Formula: see text] [Formula: see text] is a component of [Formula: see text], [Formula: see text] is a homeomorphic map, [Formula: see text], [Formula: see text], [Formula: see text] [Formula: see text] and [Formula: see text] [Formula: see text], then [Formula: see text].
Solvable normal subgroups of 2-knot groups
Authors: Hillman J. A.
Published: July 2017

If [Formula: see text] is an orientable, strongly minimal [Formula: see text]-complex and [Formula: see text] has one end, then it has no nontrivial locally finite normal subgroup. Hence, if [Formula: see text] is a 2-knot group, then (a) if [Formula: see text] is virtually solvable, then either [Formula: see text] has two ends or [Formula: see text], with presentation [Formula: see text], or [Formula: see text] is torsion-free and polycyclic of Hirsch length 4 (b) either [Formula: see text] has two ends, or [Formula: see text] has one end and the center [Formula: see text] is torsion-free, or [Formula: see text] has infinitely many ends and [Formula: see text] is finite, and (c) the Hirsch–Plotkin radical [Formula: see text] is nilpotent.
On 2-strongly transitive geometric spaces
Authors: Jafarpour Morteza , Mousavi Seyed Shahin , Leoreanu Violeta , Jantani Fatemeh
Published: July 2017

In this paper, we introduce and analyze the concept of “2-geometric space” [Formula: see text] and the notion of [Formula: see text]-part in [Formula: see text]. Then we define 2-strongly transitive geometric spaces and analyze some examples.
Quantum Entropy and Complexity
Authors: Benatti F. , Oskouei S. Khabbazi , Abad A. Shafiei Deh
Published: July 2017

We study the relations between the recently proposed machine-independent quantum complexity of P. Gacs [1] and the entropy of classical and quantum systems. On one hand, by restricting Gacs complexity to ergodic classical dynamical systems, we retrieve the equality between the Kolmogorov complexity rate and the Shannon entropy rate derived by A. A. Brudno [2]. On the other hand, using the quantum Shannon-McMillan theorem [3], we show that such an equality holds densely in the case of ergodic quantum spin chains.
Quantum Behavior Arises Because Our Universe is a Fractal
Authors: Tao Yong
Published: July 2017

To explain the origin of quantum behavior, we propose a fractal calculus to describe the non-local property of the fractal curve [Y. Tao, J. Appl. Math. 2013 (2013) 308691]. This study demonstrates that if the dimension of time axis is slightly less than 1, then Planck’s energy quantum formula will naturally emerge. In this paper, we further show that if the dimension of time axis is less than 1, Heisenberg’s Principle of Uncertainty will emerge as well. Our finding implies that fractal calculus may be an intrinsic way of describing quantum behavior. To test our theory, we also provide an experimental proposal for measuring the dimension of time axis.
A student guide to proofreading and writing in science
Authors: Hyatt Jon-Philippe K. , Bienenstock Elisa Jayne , Tilan Jason U.
Published: July 2017

Scientific writing requires a distinct style and tone, whether the writing is intended for an undergraduate assignment or publication in a peer-reviewed journal. From the first to the final draft, scientific writing is an iterative process requiring practice, substantial feedback from peers and instructors, and comprehensive proofreading on the part of the writer. Teaching writing or proofreading is not common in university settings. Here, we present a collection of common undergraduate student writing mistakes and put forth suggestions for corrections as a first step toward proofreading and enhancing readability in subsequent draft versions. Additionally, we propose specific strategies pertaining to word choice, structure, and approach to make products more fluid and focused for an appropriate target audience.
Abdominal surgery induced gastric ileus and activation of M1-like macrophages in the gastric myenteric plexus: prevention by central vagal activation in rats
Authors: Yuan Pu-Qing , Taché Yvette
Published: July 2017

Inflammation plays a role in abdominal surgery (AS)-induced intestinal ileus that is alleviated by electrical vagal stimulation. Intracisternal injection of RX-77368, the stable thyrotropin-releasing hormone agonist, activates dorsal motor nucleus neurons and gastric vagal efferent discharges. We investigated the gastric inflammation induced by AS and the modulation by intracisternal RX-77368 in rats. RX-77368 (50 ng/rat) or saline was injected followed, 1 h later, by laparotomy and small intestinal/cecal manipulation. The sham group had anesthesia alone. After 6 h, gastric emptying (GE) and the inflammation in gastric corpus were determined. AS inhibited GE by 72% vs. control and doubled the number of M1-like macrophage immunoreactive for major histocompatibility complex class II (MHCII; M1 marker) but not for cluster of differentiation 206 (CD206; M2 marker) (MHCII+/CD206−) while there was no change in M2-like macrophages (MHCII−/CD206+). AS increased mRNA levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) by 1.7- and 1.5-fold, respectively, in the gastric submucosa plus muscle layers and the infiltration of neutrophils labeled by myeloperoxidase by 9.5-fold in the muscularis externa. RX-77368 inhibited AS-related gastric changes while not altering these parameters in the sham group. There was a significant negative correlation between GE and IL-1β ( r = −0.46), TNF-α ( r = −0.44), M1 macrophage ( r = −0.82), and neutrophils ( r = −0.91). The M2-like macrophages and IL-10 expression were unchanged by AS with intracisternal saline or RX-77368. These data indicate that AS activates gastric M1 macrophages and increases proinflammatory cytokines expression, which are prevented by central vagal activation and may contribute to the correlated dampening of postoperative gastric ileus.

NEW & NOTEWORTHY MHCII+/CD206− (M1) and MHCII−/CD206+ (M2) constitute two distinct populations of macrophages that are in close apposition to the cholinergic neurons in the rat gastric myenteric plexus (MP). Abdominal surgery (6 h) activates M1 macrophage leading to inflammation in the gastric MP correlated with the delayed gastric emptying, which was abolished by central vagal stimulation via intracisternal injection of RX-77368. Vagal stimulation linked with the cephalic phase may have potential beneficial effects to curtail postoperative gastric ileus.
Normobaric hypoxic conditioning to maximize weight loss and ameliorate cardio-metabolic health in obese populations: a systematic review
Authors: Hobbins L. , Hunter S. , Gaoua N. , Girard O.
Published: July 2017

Normobaric hypoxic conditioning (HC) is defined as exposure to systemic and/or local hypoxia at rest (passive) or combined with exercise training (active). HC has been previously used by healthy and athletic populations to enhance their physical capacity and improve performance in the lead up to competition. Recently, HC has also been applied acutely (single exposure) and chronically (repeated exposure over several weeks) to overweight and obese populations with the intention of managing and potentially increasing cardio-metabolic health and weight loss. At present, it is unclear what the cardio-metabolic health and weight loss responses of obese populations are in response to passive and active HC. Exploration of potential benefits of exposure to both passive and active HC may provide pivotal findings for improving health and well being in these individuals. A systematic literature search for articles published between 2000 and 2017 was carried out. Studies investigating the effects of normobaric HC as a novel therapeutic approach to elicit improvements in the cardio-metabolic health and weight loss of obese populations were included. Studies investigated passive ( n = 7; 5 animals, 2 humans), active ( n = 4; all humans) and a combination of passive and active ( n = 4; 3 animals, 1 human) HC to an inspired oxygen fraction ([Formula: see text]) between 4.8 and 15.0%, ranging between a single session and daily sessions per week, lasting from 5 days up to 8 mo. Passive HC led to reduced insulin concentrations (−37 to −22%) in obese animals and increased energy expenditure (+12 to +16%) in obese humans, whereas active HC lead to reductions in body weight (−4 to −2%) in obese animals and humans, and blood pressure (−8 to −3%) in obese humans compared with a matched workload in normoxic conditions. Inconclusive findings, however, exist in determining the impact of acute and chronic HC on markers such as triglycerides, cholesterol levels, and fitness capacity. Importantly, most of the studies that included animal models involved exposure to severe levels of hypoxia ([Formula: see text] = 5.0%; simulated altitude >10,000 m) that are not suitable for human populations. Overall, normobaric HC demonstrated observable positive findings in relation to insulin and energy expenditure (passive), and body weight and blood pressure (active), which may improve the cardio-metabolic health and body weight management of obese populations. However, further evidence on responses of circulating biomarkers to both passive and active HC in humans is warranted.
ADAM-Mediated Shedding and Adhesion: a Vascular Perspective
Authors: Herren Barbara
Published: July 2017

Proteolytic conversion (shedding) of membrane-bound proteins to soluble forms is a novel regulatory mechanism mediated by enzymes called a disintegrin and metalloproteases (ADAMs). In this review, the potential importance of ADAMs in vascular physiology and disease, especially in relation to atherosclerosis, will be highlighted.
Factors Affecting Energy‐Related Carbon Emissions in Beijing‐Tianjin‐Hebei Region
Authors: Wang Jing-min , Shi Yu-fang , Zhao Xue , Zhang Xue-ting
Published: July 2017

Beijing‐Tianjin‐Hebei is a typical developed region in China. The development of economy has brought lots of carbon emissions. To explore an effective way to reduce carbon emissions, we applied the Logarithmic Mean Divisia Index (LMDI) model to find drivers behind carbon emission from 2003 to 2013. Results showed that, in Beijing, Tianjin, and Hebei, economic output was main contributor to carbon emissions. Then we utilized the decoupling model to comprehensively analyze the relationship between economic output and carbon emission. Based on the two‐level model, results indicated the following: (1) Industry sector accounted for almost 80% of energy consumption in whole region. The reduced proportion of industrial GDP will directly reduce the carbon emissions. (2) The carbon factor for CO2/energy in whole region was higher than that of Beijing and Tianjin but lower than that of Hebei. The impact of energy structure on carbon emission depends largely on the proportion of coal in industry. (3) The energy intensity in whole region decreased from 0.79 in 2003 to 0.40 in 2013 (unit: tons of standard coal/ten thousand yuan), which was lower than national average. (4) The cumulative effects of industrial structure, energy structure, and energy intensity were negative, positive, and negative, respectively.
Characteristics of Human Endometrium-Derived Mesenchymal Stem Cells and Their Tropism to Endometriosis
Authors: Cheng Yan , Li Liru , Wang Dejun , Guo Qiuyan , He Yanan , Liang Tian , Sun Liyuan , Wang Xiaojun , Cheng Yulei , Zhang Guangmei
Published: July 2017

Human endometrial tissue has become an attractive source of mesenchymal stem cells (MSCs) for cell-based therapies because these MSCs can be easily harvested and have tumour tropism as well as reduced immunogenic and inflammatory properties. Our study aimed to obtain and characterise human endometrial mesenchymal stem cells (EMSCs) and assess their endometriosis tropism. EMSCs were successfully isolated from the endometrium of women undergoing laparoscopy for idiopathic infertility. The EMSCs presented a fibroblast-like morphology during culture. Flow cytometry analyses showed that the cells were positive for the specific stem cell markers CD73, CD90, CD105, CD166, and HLA-ABC (major histocompatibility complex class I (MHC I)) but negative for CD14, CD34, CD45, and HLA-DR (MHC II). Reverse transcription polymerase chain reaction results showed that the EMSCs expressed the stem cell marker OCT4. The EMSCs could differentiate into osteocytes, adipocytes, and chondrocytes under certain conditions. The EMSCs had a high tropism to endometriosis without tumourigenicity. This study enhances the possibility of using EMSCs as drug carriers in human cell-based therapies. Meanwhile, future research could also focus on developing targeted therapies for endometriosis.
Nonuniform Granularity‐Based Classification in Social Interest Detection
Authors: Shao Wenjuan , Shen Qingguo , Jin Xianli , Huang Liaoruo , Chen Jingjing
Published: July 2017

Social interest detection is a new computing paradigm which processes a great variety of large scale resources. Effective classification of these resources is necessary for the social interest detection. In this paper, we describe some concepts and principles about classification and present a novel classification algorithm based on nonuniform granularity. Clustering algorithm is used to generate a clustering pedigree chart. By using suitable classification cutting values to cut the chart, we can get different branches which are used as categories. The size of cutting value is vital to the performance and can be dynamically adapted in the proposed algorithm. Experiments results carried on the blog posts illustrate the effectiveness of the proposed algorithm. Furthermore, the results for comparing with Naive Bayes, k‐nearest neighbor, and so forth validate the better classification performance of the proposed algorithm for large scale resources.
PD-1+ Polyfunctional T Cells Dominate the Periphery after Tumor-Infiltrating Lymphocyte Therapy for Cancer
Authors: Donia Marco , Kjeldsen Julie Westerlin , Andersen Rikke , Westergaard Marie Christine Wulff , Bianchi Valentina , Legut Mateusz , Attaf Meriem , Szomolay Barbara , Ott Sascha , Dolton Garry , Lyngaa Rikke , Hadrup Sine Reker , Sewell Andrew K. , Svane Inge Marie
Published: July 2017

Purpose: Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TIL) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs 1 month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here, we studied the dynamics of bulk tumor-reactive CD8+ T-cell populations in patients with metastatic melanoma following treatment with TILs.

Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8+ T cells contained in serial blood samples of 16 patients treated with TILs.

Results: Polyfunctional tumor-reactive CD8+ T cells accumulated over time in the peripheral lymphocyte pool. Combinatorial analysis of multiple surface markers (CD57, CD27, CD45RO, PD-1, and LAG-3) showed a unique differentiation pattern of polyfunctional tumor-reactive CD8+ T cells, with highly specific PD-1 upregulation early after infusion. The differentiation and functional status appeared largely stable for up to 1 year after infusion. Despite some degree of clonal diversification occurring in vivo within the bulk tumor-reactive CD8+ T cells, further analyses showed that CD8+ T cells specific for defined tumor antigens had similar differentiation status.

Conclusions: We demonstrated that tumor-reactive CD8+ T-cell subsets that persist after TIL therapy are mostly polyfunctional, display a stable partially differentiated phenotype, and express high levels of PD-1. These partially differentiated PD-1+ polyfunctional TILs have a high capacity for persistence and may be susceptible to PD-L1/PD-L2–mediated inhibition. Clin Cancer Res; 23(19); 5779–88. ©2017 AACR.
Downregulation of Human Endogenous Retrovirus Type K (HERV-K) Viral env RNA in Pancreatic Cancer Cells Decreases Cell Proliferation and Tumor Growth
Authors: Li Ming , Radvanyi Laszlo , Yin Bingnan , Rycaj Kiera , Li Jia , Chivukula Raghavender , Lin Kevin , Lu Yue , Shen JianJun , Chang David Z. , Li Donghui , Johanning Gary L. , Wang-Johanning Feng
Published: July 2017

Purpose: We investigated the role of the human endogenous retrovirus type K (HERV-K) envelope (env) gene in pancreatic cancer.

Experimental Design: shRNA was employed to knockdown (KD) the expression of HERV-K in pancreatic cancer cells.

Results: HERV-K env expression was detected in seven pancreatic cancer cell lines and in 80% of pancreatic cancer patient biopsies, but not in two normal pancreatic cell lines or uninvolved normal tissues. A new HERV-K splice variant was discovered in several pancreatic cancer cell lines. Reverse transcriptase activity and virus-like particles were observed in culture media supernatant obtained from Panc-1 and Panc-2 cells. HERV-K viral RNA levels and anti-HERV-K antibody titers were significantly higher in pancreatic cancer patient sera (N = 106) than in normal donor sera (N = 40). Importantly, the in vitro and in vivo growth rates of three pancreatic cancer cell lines were significantly reduced after HERV-K KD by shRNA targeting HERV-K env, and there was reduced metastasis to lung after treatment. RNA-Seq results revealed changes in gene expression after HERV-K env KD, including RAS and TP53. Furthermore, downregulation of HERV-K Env protein expression by shRNA also resulted in decreased expression of RAS, p-ERK, p-RSK, and p-AKT in several pancreatic cancer cells or tumors.

Conclusions: These results demonstrate that HERV-K influences signal transduction via the RAS–ERK–RSK pathway in pancreatic cancer. Our data highlight the potentially important role of HERV-K in tumorigenesis and progression of pancreatic cancer, and indicate that HERV-K viral proteins may be attractive biomarkers and/or tumor-associated antigens, as well as potentially useful targets for detection, diagnosis, and immunotherapy of pancreatic cancer. Clin Cancer Res; 23(19); 5892–911. ©2017 AACR.
Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer
Authors: Ma Cynthia X. , Bose Ron , Gao Feng , Freedman Rachel A. , Telli Melinda L. , Kimmick Gretchen , Winer Eric , Naughton Michael , Goetz Matthew P. , Russell Christy , Tripathy Debu , Cobleigh Melody , Forero Andres , Pluard Timothy J. , Anders Carey , Niravath Polly Ann , Thomas Shana , Anderson Jill , Bumb Caroline , Banks Kimberly C. , Lanman Richard B. , Bryce Richard , Lalani Alshad S. , Pfeifer John , Hayes Daniel F. , Pegram Mark , Blackwell Kimberly , Bedard Philippe L. , Al-Kateb Hussam , Ellis Matthew J.C.
Published: July 2017

Purpose: Based on promising preclinical data, we conducted a single-arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2mut nonamplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxicity, and circulating tumor DNA (ctDNA) HER2mut detection.

Experimental Design: Tumor tissue positive for HER2mut was required for eligibility. Neratinib was administered 240 mg daily with prophylactic loperamide. ctDNA sequencing was performed retrospectively for 54 patients (14 positive and 40 negative for tumor HER2mut).

Results: Nine of 381 tumors (2.4%) sequenced centrally harbored HER2mut (lobular 7.8% vs. ductal 1.6%; P = 0.026). Thirteen additional HER2mut cases were identified locally. Twenty-one of these 22 HER2mut cases were estrogen receptor positive. Sixteen patients [median age 58 (31–74) years and three (2–10) prior metastatic regimens] received neratinib. The CBR was 31% [90% confidence interval (CI), 13%–55%], including one CR, one PR, and three SD ≥24 weeks. Median PFS was 16 (90% CI, 8–31) weeks. Diarrhea (grade 2, 44%; grade 3, 25%) was the most common adverse event. Baseline ctDNA sequencing identified the same HER2mut in 11 of 14 tumor-positive cases (sensitivity, 79%; 90% CI, 53%–94%) and correctly assigned 32 of 32 informative negative cases (specificity, 100%; 90% CI, 91%–100%). In addition, ctDNA HER2mut variant allele frequency decreased in nine of 11 paired samples at week 4, followed by an increase upon progression.

Conclusions: Neratinib is active in HER2mut, nonamplified MBC. ctDNA sequencing offers a noninvasive strategy to identify patients with HER2mut cancers for clinical trial participation. Clin Cancer Res; 23(19); 5687–95. ©2017 AACR.
Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome
Authors: Nishino Mizuki , Dahlberg Suzanne E. , Adeni Anika E. , Lydon Christine A. , Hatabu Hiroto , Jänne Pasi A. , Hodi F. Stephen , Awad Mark M.
Published: July 2017

Purpose: We evaluated tumor burden dynamics in patients with advanced non–small cell lung cancer (NSCLC) treated with commercial PD-1 inhibitors to identify imaging markers associated with improved overall survival (OS).

Experimental Design: The study included 160 patients with advanced NSCLC treated with commercial nivolumab or pembrolizumab monotherapy as a part of clinical care. Tumor burden dynamics were studied for the association with OS.

Results: Tumor burden change at best overall response (BOR) ranged from −100% to +278% (median, +3.5%). Response rate (RR) was 18% (29/160). Current and former smokers had a higher RR than never smokers (P = 0.04). Durable disease control for at least 6 months was noted in 26 patients (16%), which included 10 patients with stable disease as BOR. Using a landmark analysis, patients with <20% tumor burden increase from baseline within 8 weeks of therapy had longer OS than patients with ≥20% increase (median OS, 12.4 vs. 4.6 months, P < 0.001). Patients with <20% tumor burden increase throughout therapy had significantly reduced hazards of death (HR, 0.24; Cox P < 0.0001) after adjusting for smoking (HR, 0.86; P = 0.61) and baseline tumor burden (HR, 1.55; P = 0.062), even though some patients met criteria for RECIST progression while on therapy. One patient (0.6%) had atypical response pattern consistent with pseudoprogression.

Conclusions: Objective response or durable disease control was noted in 24% of patients with advanced NSCLC treated with commercial PD-1 inhibitors. A tumor burden increase of <20% from baseline during therapy was associated with longer OS, proposing a practical marker of treatment benefit. Pseudoprogression is rare in NSCLCs treated with PD-1 inhibitors. Clin Cancer Res; 23(19); 5737–44. ©2017 AACR.
Design of Finasteride-Loaded Nanoparticles for Potential Treatment of Alopecia
Authors: Roque Luís V. , Dias Inês S. , Cruz Nuno , Rebelo Ana , Roberto Amílcar , Rijo Patrícia , Reis Catarina P.
Published: July 2017

Background/Aims: Androgenetic alopecia is an extremely common dermatological disorder affecting both men and women. Oral finasteride (FNS), a synthetic 4-aza-3-oxosteroid compound with poor aqueous solubility, blocks the peripheral conversion of testosterone to dihydrotestosterone (DHT) in a significant reduction in DHT concentration, achieving satisfactory results in alopecia treatment. However, its oral intake generally causes severe side effects. Considering that there is currently no scientifically proven treatment, new drug delivery systems able to improve alopecia therapy are urgently required. Methods: In this study, polymeric nanoparticles have been proposed as a new carrier for topical delivery of FNS in hair follicles. Results and Conclusions: Polymeric nanoparticles, prepared by using a modified method of the emulsification/solvent diffusion, showed a mean particle size around 300 nm, which may be sufficient for reaching the dermis and hair follicles and negative zeta potential values. Scanning electron microscope measurements showed that all the polymeric nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. A high encapsulation efficiency was achieved for FNS (79.49 ± 0.47%). In vitro release assays in physiological conditions demonstrated that nanoparticles yielded a prolonged release of FNS for 3 h. Skin assays through an in vitro permeation study demonstrated that nanoparticles had low levels of penetration of FNS, improving its time residence onto the skin. All excipients used in nanoparticle composition and in 3 different vehicles were safe. These results suggest that the proposed novel formulation presents several good characteristics indicating its suitability for dermal delivery of FNS for alopecia treatment.
101 Long-Term Survivors Who Had Metastatic Gastroesophageal Cancer and Received Local Consolidative Therapy
Authors: Mizrak Kaya Dilsa , Wang Xuemei , Harada Kazuto , Blum Murphy Mariela A. , Das Prajnan , Minsky Bruce D. , Estrella Jeannelyn S. , Lin Quan , Amlashi Fatemeh G. , Lee Jeffrey H. , Weston Brian , Bhutani Manoop S. , Matamoros Jr. Aurelio , Sagebiel Tara , Wu Carol C. , Rogers Jane E. , Thomas Irene , Maru Dipen M. , Skinner Heath D. , Badgwell Brian D. , Hofstetter Wayne L. , Ajani Jaffer A.
Published: July 2017

Background: Through a multidisciplinary decision-making process, we developed a strategy of systemic therapy followed by local consolidative therapy (chemoradiation with/without surgery) in selected patients with metastatic gastroesophageal carcinoma (mGEAC). Only after a consensus during multidisciplinary discussions, local therapy was initiated. Methods: We identified 101 patients with mGEAC who had local consolidation. We evaluated the association between various clinical variables (location of the primary, location of metastases, duration of initial chemotherapy, histologic grade, and radiation dose) and overall survival (OS). Results: Of 101 patients, 71 had a proximal primary (esophageal, Siewert type I or II), and 30 patients had a distal primary (Siewert type III or distal). The median OS was 25.7 months (95% confidence interval [CI] 22.3-32.8). The OS rates at 2 and 5 years were 53.8% (95% CI 44.7-64.8) and 20.7% (95% CI 13.4-31.9), respectively. OS was highly associated with the location of the primary (median of 22.8 months for Siewert I/II vs. 41.5 months for Siewert III or distal, p = 0.03). The duration of initial chemotherapy was highly associated with OS (median of 21.8 months for <3 months vs. 32.5 months for ≥3 months, p = 0.004). Conclusion: Some mGEAC patients with a favorable clinical course can achieve a ∼20% 5-year survival rate with an approach that uses initial chemotherapy followed by multidisciplinary discussion to proceed with consolidation with local therapy. Patients with distal GEAC and those who receive initial chemotherapy for ≥3 months are the maximum beneficiaries.
Pelvic Catastrophe after Elastic Band Ligation in an Irradiated Rectum
Authors: Pita Inês , Bastos Pedro , Dinis-Ribeiro Mário
Published: July 2017

Chronic radiation proctopathy is a frequent complication after both pelvic external radiation therapy and brachytherapy and most commonly presents as rectal bleeding. Deep rectal ulcers and fistulae are much rarer and more clinically challenging consequences. We present the case of a 72-year-old male with a history of prostate adenocarcinoma treated with brachytherapy, who was referred to our institution due to a deep painful rectal ulcer refractory to medical treatment. The ulcer presented shortly after a haemorrhoid elastic band ligation and progressed to rectourethral fistulisation despite both faecal and urinary diversion. Our case demonstrates the importance of favouring a conservative approach when dealing with an irradiated rectum.
MiR-9 Regulates the Expression of BACE1 in Dementia Induced by Chronic Brain Hypoperfusion in Rats
Authors: Xie Hailong , Zhao Ying , Zhou You , Liu Lin , Liu Yueting , Wang Dongxue , Zhang Shuang , Yang Mingyan
Published: July 2017

Background/Aims: MicroRNA-9 (miR-9) plays important roles in nervous system diseases such as glioblastoma and neurodegenerative disorders. However, how miR-9 contributes to dementia requires further study. In this study, we evaluated the role of miR-9 in dementia and the molecular mechanisms underlying its effects. Methods: A rat model of dementia was created by occlusion of the bilateral common carotid artery (2VO) for 8 weeks. Learning and memory were assessed using the Morris Water Maze (MWM). MicroRNA expression profiling was performed according to a protocol provided by LC Sciences, and quantitative real-time PCR (qRT-PCR) was used to detect the level of miR-9. Transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining were used to assess pathological changes in brain tissue. Western blot and immunofluorescence were employed to detect the expression of β-site APP cleaving enzyme 1 (BACE1) and c-AMP response element-binding protein (CREB). Results: Learning and memory were significantly impaired in 2VO rats, and these changes were accompanied by neuronal loss and glial activation in brain tissues. miR-9 was greatly upregulated in both the hippocampus and cortex of rats following 2VO. Knockdown of endogenous miR-9 via lentiviral vector-mediated delivery of its antisense molecule (lenti-pre-AMO-miR-9) reduced the vulnerability to dementia, reversed the increase in BACE1 expression, and ameliorated the reduction in CREB expression triggered by 2VO. BACE1 protein levels were significantly increased, but CREB protein levels were significantly decreased in the presence of miR-9 in cultured neonatal rat neurons (NRNs). AMO-miR-9 rescued the upregulation of BACE1 and downregulation of CREB elicited by miR-9 in rats. Dual luciferase assay experiments showed that overexpression of miR-9 inhibited the expression of CREB by targeting its 3’UTR domain. CREB protein was downregulated by miR-9 overexpression which was reversed by miR-9 inhibition in cultured NRNs. TEM imaging showed that miR-9 caused damage to NRNs, which was reversed by addition of AMO-miR-9. Conclusion: We conclude that miR-9 plays an important role in regulating the process of dementia induced by 2VO in rats by increasing BACE1 expression via downregulation of CREB.
Optimization Circuit Based Buck-Boost Converter for Charging the Solar Power Plant
Authors: Rohana Rohana , Suwarno Suwarno
Published: July 2017

This paper discusses the optimization circuit based buck-boost converter for charging a battery from solar panel modules. The combination of the circuit buck-bust converter and a step-up current can increase the percentage of battery chargers. The method used in the optimization of solar power plants by increasing the output current from the solar panel to be optimized for battery charging, so it does not requires time and the batteries are safe. This is because sunlight can be used when bright about 4-5 hours per day. By increasing the output current of the current produced solar modules can accelerate the battery charging time. The combination of using the voltage stabilizer can produce a steady output voltage and current riser, although the voltage to an output of the solar panels is quite small (± 6 volts), can optimize the charger works well. By combining between the voltage stabilizer and a step-up current is obtained that the incoming voltage to the battery at 12,4V the current rise of 21.5% for a 12V battery, 7Ah, whereas the incoming voltage to the battery at 12,1V the current rise 10.99% for battery 12V, 120Ah. This study shows that the current rise is already above 10%.
Suitability of Demand Response Program Equipped with Solar Energy in UTHM
Authors: Jefry N A , Zambri N A
Published: July 2017

Demand Response Program (DRP) is a program developed in western country to cater high load demand. This system enhance the quality of the current smart grid system. This program encourage two-ways interaction between the consumer and the utility provider. The consumers are required to reduce their load consumption upon request by the utility provider, thus avoiding them from paying for the high load demand. However, the current design of DRP is seem to put the user at disadvantages. Thus, deployment of the new practice equipped with renewable energy sources will make the system more user- friendly. As DRP prove to be beneficial in many terms, this project is conducted to find DRP relevancy to be implemented in Universiti Tun Hussein Onn Malaysia (UTHM). According to the electrical consumption data disclosed by Facility Management Division, the power consumed by UTHM is remarkably high especially during 11.00 am to 12.00 pm. Thus, DRP is being proposed to be put into practise during this period. Nonetheless, it is not economically wise to implement the program to the whole campus. Therefore, three buildings with the most power consumption had been chosen for this study. They are the library, Faculty of Civil and Environmental Engineering (FKAAS) building and Faculty of Technology and Vocational Education (FPTV) building. The building power consumption and economic evaluation had been analysed using HOMER simulation. From the analysis, the combination of FPTV and FKAAS had been chosen for DRP implementation. The reason are, these buildings have superiority over the library in term of reliability and effectiveness. In terms of economy, it is almost equivalent to each other.
An Improved Photovoltaic Array Configuration for Photovoltaic System in the Presence of Maximum Power Point Tracking during Partial Shading Condition
Authors: Burhanudin K. , Kamarzaman N.A. , Samat A.A.A. , Tajudin A.I. , Ramli S.S. , Hidayat N.
Published: July 2017

Power-Voltage (P-V) curve and Current-Voltage (I-V) curve determine the performance of the PV system. In this work, the arrangements of the PV module were reconstructed by adding the number of PV module in 3 strings configuration from 5 to 45. This method enhance the performance of the PV system as it able to show the characteristic of the P-V and I-V curve during partial shading and maximum irradiance despite higher number of PV panel. This study focuses on improving the PV array configuration and simulation speed of the PV panel. The simulation of small size PV array is possible, but the problem lies when the number of string and PV module used increases. New PV array configuration is flexible and easy to add string and increase the number of PV module. PV array configuration was modeled using MATLAB/SIMULINK software.