bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic evaluations of onchocerciasis interventions: a systematic review and research needs
Authors: Turner Hugo C. , Walker Martin , Pion Sébastien D. S. , McFarland Deborah A. , Bundy Donald A. P. , Basáñez María‐Gloria
Published: April 2019

Objective

To provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps.

Method

A systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) andISIWeb of Science electronic databases. No date or language stipulations were applied to the searches.

Results

We identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost‐effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis‐associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost‐effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability‐adjusted life year (DALY) averted of annualMDAvaries betweenUS$3 andUS$30 (cost year variable).

Conclusions

The cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond.
Analytical Modeling of White Layer Formation in Orthogonal Cutting of AerMet100 Steel Based on Phase Transformation Mechanism
Authors: Zeng Haohao , Yan Rong , Hu Tiantian , Du Pengle , Wang Wei , Peng Fangyu
Published: April 2019

The white layer formed in machining has significant impacts on the friction property, fatigue resistance, and service life of products. This paper presents an analytical model for white layer prediction in orthogonal cutting based on phase transformation mechanism. The effects of stress, elastic, and plastic strain on phase transformation temperature are taken into consideration. A function related to cutting temperature and phase transformation temperature is defined to determine the white layer thickness. The theoretical model is validated by machining AerMet100 steel under different cutting conditions. Optical microscope and X-ray diffraction (XRD) are employed to analyze the microstructures of the white layer. A phase transformation is detected in the white layer region, and the predicted white layer thicknesses are in good agreement with the measured values. In addition, the plastic strain is found to be the major factor that causes a reduction in phase transformation temperature. This work can be further applied to optimize cutting conditions to improve machined surface integrity.
Cross-modal association between vowels and colours: A cross-linguistic perspective
Authors: Mok Peggy P. K. , Li Guo , Li Joanne Jingwen , Ng Hezul T. Y. , Cheung Him
Published: April 2019

Previous studies showed similar mappings between sounds and colours for synaesthetes and non-synaesthetes alike, and proposed that common mechanisms underlie such cross-modal association. The findings between vowels and colours, and between pitch and lightness, were investigated separately, and it was also unknown how language background would influence such association. The present study investigated the cross-modal association between sounds (vowels and pitch) and colours in a tone language using three groups of non-synaesthetes: Cantonese (native), Mandarin (foreign, tonal), and English (foreign, non-tonal). Strong associations were found between /a/ and red, /i/ with light colours, and /u/ with dark colours, and a robust pitch effect with a high tone eliciting lighter colours than a low tone in general. The pitch effect is stronger than the vowel associations. Significant differences among the three language groups in colour choices of other vowels and the strength of association were found, which demonstrate the language-specificity of these associations. The findings support the notion that synaesthesia is a general phenomenon, which can be influenced by linguistic factors.
Experimental characterization of the sound field in a reverberation room
Authors: Nolan Mélanie , Verburg Samuel A. , Brunskog Jonas , Fernandez-Grande Efren
Published: April 2019

Measured values of acoustic absorption obtained from standardized reverberation-chamber measurements often differ across laboratories. These discrepancies arise due to non-isotropic sound incidence on the absorbing specimen, diffraction at the sample edges, and differences in the chambers' shapes and dimensions. The present study examines an experimental method for characterizing the distribution of sound incidence on the specimen in the steady state. The methodology relies on a plane wave decomposition (i.e., estimation of the wavenumber spectrum) to determine the magnitude of the sound waves arriving from definite directions onto the absorbing sample. Based on this decomposition, the sound pressure, particle velocity, and sound intensity can be reconstructed in the vicinity of the absorbing specimen. One can distinguish between the incident and reflected components of the sound field, making it possible to characterize the incident energy flows. Measurements with a programmable robotic arm are conducted in a reverberation chamber in two damping conditions (empty and with absorption on the floor). The quantitative accuracy of the method is examined via an estimation of the sample's angle-dependent absorption coefficient, showing good agreement with theoretical predictions. It is anticipated that the proposed method will be of value in explaining the deviations encountered across standardized laboratories.
Task Constraints and Coordination Flexibility in Young Swimmers
Authors: Silva Ana F. , Figueiredo Pedro , Morais Sara , Vilas-Boas João P. , Fernandes Ricardo J. , Seifert Ludovic
Published: April 2019

This study aimed to examine young swimmers’ behavioral flexibility when facing different task constraints, such as swimming speed and stroke frequency. Eighteen (five boys and 13 girls) 13- to 15-year-old swimmers performed a 15 × 50-m front crawl with five trials, at 100%, 90%, and 70% each of their 50 m maximal swimming speed and randomly at 90%, 95%, 100%, 105%, and 110% of their preferred stroke frequency. Seven aerial and six underwater cameras were used to assess kinematics (one cycle), with upper-limb coordination computed through a continuous relative phase and index of coordination. A cluster analysis identified six patterns of coordination used by swimmers when facing various speed and stroke frequency constraints. The patterns’ nature and the way the swimmers shifted between them are more important than getting the highest number of patterns (range of repertoire), that is, a change in the motor pattern in order to adapt correctly is more important than being able to execute a great number of patterns.
Establishment Limitation Constrains the Abundance of Lactic Acid Bacteria in the Napa Cabbage Phyllosphere
Authors: Miller Esther R. , Kearns Patrick J. , Niccum Brittany A. , O’Mara Schwartz Jonah , Ornstein Alexa , Wolfe Benjamin E.
Published: April 2019

The quality and safety of vegetable fermentations are dependent on the activities of LAB naturally present in the phyllosphere. Despite their critical role in determining the success of fermentation, the processes that determine the abundance and diversity of LAB in vegetables used for fermentation are poorly characterized. Our work demonstrates that the limited ability of LAB to grow in the cabbage phyllosphere environment may constrain their abundance on cabbage leaves. These results suggest that commercial fermentation of Napa cabbage proceeds despite low and variable abundances of LAB across different growing regions. Propagule limitation may also explain ecological distributions of other rare members of phyllosphere microbes.
Genomic Diversity and Recombination among Xylella fastidiosa Subspecies
Authors: Vanhove Mathieu , Retchless Adam C. , Sicard Anne , Rieux Adrien , Coletta-Filho Helvecio D. , De La Fuente Leonardo , Stenger Drake C. , Almeida Rodrigo P. P.
Published: April 2019

Xylella fastidiosa
is an important vector-borne plant pathogen. We used a set of 72 genomes that constitutes the largest assembled data set for this bacterial species so far to investigate genetic relationships and the impact of recombination on phylogenetic clades and to compare genome content at the subspecies level, and we used a molecular dating approach to infer the evolutionary rate of
X. fastidiosa
. The results demonstrate that recombination is important in shaping the genomes of
X. fastidiosa
and that each of the main subspecies is under different selective pressures. We hope insights from this study will improve our understanding of
X. fastidiosa
evolution and biology.
Production of a Functional Factor, p40, by Lactobacillus rhamnosus GG Is Promoted by Intestinal Epithelial Cell-Secreted Extracellular Vesicles
Authors: Yang Luyao , Higginbotham James N. , Liu Liping , Zhao Gang , Acra Sari A. , Peek Richard M. , Polk D. Brent , Li Hui , Yan Fang
Published: April 2019

The symbiotic relationship between the gut microbiome and the host provides a nutrient-rich environment for gut microbes and has beneficial effects on host health. Although the composition of the gut microbiome is known to be influenced by both host genetics and environmental factors, host effects on the activities and functions of the gut microbial communities remain poorly understood.
Subclinical Cytomegalovirus DNA Is Associated with CD4 T Cell Activation and Impaired CD8 T Cell CD107a Expression in People Living with HIV despite Early Antiretroviral Therapy
Authors: Christensen-Quick Aaron , Massanella Marta , Frick Andrew , Rawlings Stephen A. , Spina Celsa , Vargas-Meneses Milenka , Schrier Rachel , Nakazawa Masato , Anderson Christy , Gianella Sara
Published: April 2019

Chronic viral infections such as with HIV and CMV last a lifetime and can continually antagonize the immune system. Both viruses are associated with higher expression of inflammation markers, and recent evidence suggests that CMV may complicate efforts to deplete HIV reservoirs. Our group and others have shown that CMV shedding is associated with a larger HIV reservoir. Subclinical CMV replication could favor HIV persistence via bystander effects on our immune system. In this study, we collected longitudinal PBMC samples from people starting ART and measured immune changes associated with detectable CMV. We found that when CMV was detectable, CD4+T cell activation was higher and CD8+T cell degranulation was lower. Both results may contribute to the slower decay of the size of the reservoir during CMV replication, since activated CD4+T cells are more vulnerable to HIV infection, while the loss of CD8+T cell degranulation may impede the proper killing of infected cells.
BspR/BtrA, an Anti-σ Factor, Regulates the Ability of
Bordetella bronchiseptica
To Cause Cough in Rats
Authors: Nakamura Keiji , Shinoda Noriko , Hiramatsu Yukihiro , Ohnishi Shinya , Kamitani Shigeki , Ogura Yoshitoshi , Hayashi Tetsuya , Horiguchi Yasuhiko
Published: April 2019

Whooping cough is a contagious respiratory disease caused by
Bordetella pertussis
. This disease is characterized by severe paroxysmal coughing, which becomes a heavy burden for patients and occasionally results in death; however, its pathogenesis remains largely unknown. The major obstacle to analyzing
Bordetella
-induced coughing is the lack of conventional animal models that replicate coughing. As
Bordetella pertussis
is highly adapted to humans, infection models in experimental animals are not considered to be well established. In the present study, we examined coughing in rats infected with
B. bronchiseptica
, which shares many virulence factors with
B. pertussis
. Using this rat model, we demonstrated that some of the major virulence factors of
Bordetella
are not involved in cough production, but an anti-σ factor, BspR/BtrA, of
B. bronchiseptica
regulates the production of unknown cough-causing bacterial factor(s). Our results provide important clues to understand the mechanism by which
Bordetella
induces cough.
Comprehensive molecular imaging of malignant transformation of giant cell tumour of bone reveals diverse disease biology
Authors: Kairemo Kalevi , Wang Wei-Lien , Subbiah Vivek
Published: April 2019

Malignant transformation of giant cell tumour of the bone is extremely rare. In addition, bone transformation in giant cell tumour may occur in different phases. With conventional X-rays, CT scans or MRIs, it may be challenging to distinguish among different phases of bone transformation, normal bone, soft tissue disease and bone disease (benign vs malignant lesions) and changes in multiple organs such as lung, liver and lymph nodes unless every lesion is biopsied, which is not practical. Molecular imaging with different isotopes (Tc-99m phosphonate, 2-deoxy-2-(18F)fluoro-d-glucose and sodium fluoride-18) may help to better characterise the disease. We hypothesised that molecular imaging could offer qualitative and quantitative characterisation of all stages of bone formation, destruction, reactivity or neoplasia in a patient with giant cell tumour of the bone, and we present the first case of molecular imaging where bone formation was seen in multiple soft tissues, such as lungs, muscles, lymph nodes and liver.
Splenic rupture after elective cardioversion
Authors: Kehdy Farid John , Bond Emily Rapstine
Published: April 2019

Splenic laceration and rupture are common phenomena among patients in a traumatic setting, especially in blunt trauma. Much more unusual, however, is splenic injury without a known insult. Several case reports and studies have been written about spontaneous splenic injury in patients with viral, haematological or malignant processes. Recently, we encountered a patient with a spontaneous splenic rupture and no preceding trauma apart from semielective cardioversion. Operative decision-making was complicated by the fact that he required systemic anticoagulation for atrial fibrillation. He eventually underwent splenectomy and made an uneventful recovery.
Reversible hypoxic brain injury: the penumbra conundrum of Grinker
Authors: Balan Shiva , Gupta Kartik , Balasundaram Parthiban , Jadon Ranveer
Published: April 2019

A female patient, aged 61 years, presented to us with a 3-day history of fever and altered sensorium. She was discharged from another hospital 1 week back where she was admitted for community-acquired pneumonia. She was put on mechanical ventilation for threatened airway and her magnetic resonance brain imaging showed evidence of delayed posthypoxic leucoencephalopathy, also known as Grinker’s myelinopathy. She was discharged 1 month later, on room air with a tracheostomy tube in situ. On follow-up after 5 months, she was ambulating with support and carried out activities of daily living independently.
Randomised prospective study of using intraoperative, intraincisional and intraperitoneal ropivacaine for the early discharge of post-laparoscopic cholecystectomy patients as a day case in a cost-effective way in government setup of low-income and middle-income countries: Opening new horizons
Authors: Kaushal-Deep Singh Mathuria , Lodhi Mehershree , Anees Afzal , Khan Shehtaj , Khan Mohammad Amanullah
Published: April 2019

Background

Pain is the main reason for staying overnight at hospital after an uncomplicated laparoscopic cholecystectomy.

Objectives

A randomised prospective study was planned to compare the efficacy of intraincisional and intraperitoneal use of 0.2% ropivacaine so that patients undergoing an uncomplicated laparoscopic cholecystectomy can be discharged as a day case in a cost-effective way.

Methods

191 patients were operated by elective four-port laparoscopic cholecystectomy. They were randomised into three groups after triple blinding according to location of 0.2% ropivacaine use. All patients were given ~23 mL of solution (drug or normal saline depending on the group), 20 mL of which was given at intraperitoneal location and ~1 mL/cm of incision intraincisionally. Pain scores (Visual Analogue Scale (VAS), Numeric Rating Scale (NRS) and Faces Pain Scale-Revised (FPS-R)) were evaluated at 4 and 8 hours postoperatively. Only those patients with a VAS ≤3, NRS ≤3 and FPS-R ≤2, no requirement of rescue analgesia, no shoulder pain, ambulated at least once, passed urine and taking oral sips were offered discharge as a day case.

Results

31% of patients in intraperitoneal group (n=62) could be discharged as a day case as compared with 48% in intraincisional group (n=68) (p>0.05) and 89% in combined group (n=61) (p<0.05, with respect to both other groups).

Conclusion

The combined use of intraincisional and intraperitoneal ropivacaine is a cost-effective way of discharging approximately 9 in 10 patients as a day case. This study is unique as this is the first study in which only a local anaesthetic has been used to predict discharges as a day case.
Hierarchical exact controllability of semilinear parabolic equations with distributed and boundary controls
Authors: Araruna F. D. , Fernández-Cara E. , da Silva L. C.
Published: April 2019

We present some exact controllability results for parabolic equations in the context of hierarchic control using Stackelberg–Nash strategies. We analyze two cases: in the first one, the main control (the leader) acts in the interior of the domain and the secondary controls (the followers) act on small parts of the boundary; in the second one, we consider a leader acting on the boundary while the followers are of the distributed kind. In both cases, for each leader, an associated Nash equilibrium pair is found; then, we obtain a leader that leads the system exactly to a prescribed (but arbitrary) trajectory. We consider linear and semilinear problems.
Fujita–Kato solution for compressible Navier–Stokes equations with axisymmetric initial data and zero Mach number limit
Authors: Haspot Boris
Published: April 2019

In this paper, we investigate the question of the existence of global strong solution for the compressible Navier–Stokes equations for small initial data such that the rotational part of the velocity [Formula: see text] belongs to [Formula: see text] (in dimension [Formula: see text]). We show then an equivalent of the so-called Fujita–Kato theorem to the case of the compressible Navier–Stokes equations when we consider axisymmetric initial data. The main difficulty is linked to the fact that in this case the velocity is not Lipschitz, as a consequence we have to study carefully the coupling between the rotational and irrotational part of the velocity. In a second part, we address the question of convergence to the incompressible model (for ill-prepared initial data) when the Mach number goes to zero.
On minimal decay at infinity of Hardy-weights
Authors: Kovařík Hynek , Pinchover Yehuda
Published: April 2019

We study the behavior of Hardy-weights for a class of variational quasilinear elliptic operators of [Formula: see text]-Laplacian type. In particular, we obtain necessary sharp decay conditions at infinity on the Hardy-weights in terms of their integrability with respect to certain integral weights. Some of the results are extended also to nonsymmetric linear elliptic operators. Applications to various examples are discussed as well.
Synthetic aspects of carbazole containing porphyrins and porphyrinoids
Authors: Das Sudipta , Gupta Iti
Published: April 2019

Porphyrins are tetrapyrrolic aromatic macrocycles and ubiquitous in nature. They are excellent dyes with strong absorption in the visible region (400–700 nm) and they exhibit decent fluorescence in the red region (620–900 nm). Carbazole is a nitrogen-containing electron rich aromatic heterocycle which can be linked to porphyrins and other chromophores. This review provides an overview of the different synthetic strategies that have been employed to prepare carbazole-substituted porphyrins and carbazole-fused porphyrinoids and similar systems. It also shows that how the substitution of carbazole occurs on the porphyrin core can alter its optical and electronic features. Introduction of carbazole moieties in the porphyrin ring resulted in fused porphyrinoids with changed aromaticity and significantly altered electronic features of the molecules.
The Origins of the ASEAN Community’s Humanitarian Component
Authors: Huang Kwei-Bo
Published: April 2019

The birth of the ASEAN Community in 2007 has strengthened a long ignored part of ASEAN, i.e., humanitarian assistance and development. The three major pillars of the ASEAN Community have either direct or indirect influence on the institutional expansion and capacity building of ASEAN’s humanitarianism-related tasks. The direct influence is usually derived from the ASEAN Political and Security Community and the ASEAN Social and Cultural Community, while the indirect influence can rest on the advance of the ASEAN Economic Community. Meanwhile, leaders of ASEAN also work with extra-regional state and non-state actors to ensure the positive humanitarian development within the region of Southeast Asia. Yet, due to the principle of non-interference and the lack of resources, ASEAN’s early effort — mainly in capacity building — has apparently been less effective after the brief study of three cases.
AI profiles
Authors: Neumann Marion
Published: April 2019

Welcome to the eighth interview in our series profiling senior AI researchers. This month we are especially happy to interview our SIGAI advisory board member, Thomas Dietterich, Director of Intelligent Systems at the Institute for Collaborative Robotics and Intelligence Systems (CoRIS) at Oregon State University.
Events
Authors: Rovatsos Michael
Published: April 2019

This section features information about upcoming events relevant to the readers of AI Matters, including those supported by SIGAI. We would love to hear from you if you are are organizing an event and would be interested in cooperating with SIGAI, or if you have announcements relevant to SIGAI. For more information about conference support visit sigai.acm.org/activities/requesting_sponsor-ship.html.
Analysis of SC5C7p,q and NPHXp,q Nanotubes via Topological Indices
Authors: Ge Ye-Jun , Liu Jia-Bao , Younas Muhammad , Yousaf Muhammad , Nazeer Waqas
Published: April 2019

Scientists are creating materials, for example, a carbon nanotube-based composite created by NASA that bends when a voltage is connected. Applications incorporate the use of an electrical voltage to change the shape (transform) of air ship wings and different structures. Topological indices are numbers related with molecular graphs to allow quantitative structure activity/property/poisonous relationships. Topological indices catch symmetry of molecular structures and give it a scientific dialect to foresee properties, for example, boiling points, viscosity, and the radius of gyrations. We compute M-polynomials of two nanotubes, SC5C7p,q and NPHXp,q. The closed form of M-polynomials for these nanotubes produces formulas of numerous degree-based topological indices which are functions relying on parameters of the structure and, in combination, decide properties of the concerned nanotubes. Moreover, we sketch our results by using Maple 2015 to see the dependence of our results on the involved parameters.
Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study
Authors: Chen Fei , Childs Erica J. , Mocci Evelina , Bracci Paige , Gallinger Steven , Li Donghui , Neale Rachel E. , Olson Sara H. , Scelo Ghislaine , Bamlet William R. , Blackford Amanda L. , Borges Michael , Brennan Paul , Chaffee Kari G. , Duggal Priya , Hassan Manal J. , Holly Elizabeth A. , Hung Rayjean J. , Goggins Michael G. , Kurtz Robert C. , Oberg Ann L. , Orlow Irene , Yu Herbert , Petersen Gloria M. , Risch Harvey A. , Klein Alison P.
Published: April 2019

Background:

Pancreatic cancer is the fourth-leading cause of cancer death in both men and women in the United States. The currently identified common susceptibility loci account for a small fraction of estimated heritability. We sought to estimate overall heritability of pancreatic cancer and partition the heritability by variant frequencies and functional annotations.

Methods:

Analysis using the genome-based restricted maximum likelihood method (GREML) was conducted on Pancreatic Cancer Case-Control Consortium (PanC4) genome-wide association study (GWAS) data from 3,568 pancreatic cancer cases and 3,363 controls of European Ancestry.

Results:

Applying linkage disequilibrium- and minor allele frequency-stratified GREML (GREML-LDMS) method to imputed GWAS data, we estimated the overall heritability of pancreatic cancer to be 21.2% (SE = 4.8%). Across the functional groups (intronic, intergenic, coding, and regulatory variants), intronic variants account for most of the estimated heritability (12.4%). Previously identified GWAS loci explained 4.1% of the total phenotypic variation of pancreatic cancer. Mutations in hereditary pancreatic cancer susceptibility genes are present in 4% to 10% of patients with pancreatic cancer, yet our GREML-LDMS results suggested these regions explain only 0.4% of total phenotypic variance for pancreatic cancer.

Conclusions:

Although higher than previous studies, our estimated 21.2% overall heritability may still be downwardly biased due to the inherent limitation that the contribution of rare variants in genes with a substantive overall impact on disease are not captured when applying these commonly used methods to imputed GWAS data.

Impact:

Our work demonstrated the importance of rare and common variants in pancreatic cancer risk.
Plasma Fibrinogen and sP-Selectin are Associated with the Risk of Lung Cancer in a Prospective Study
Authors: Grafetstätter Mirja , Hüsing Anika , González Maldonado Sandra , Sookthai Disorn , Johnson Theron , Pletsch-Borba Laura , Katzke Verena A. , Hoffmeister Michael , Bugert Peter , Kaaks Rudolf , Kühn Tilman
Published: April 2019

Background:

While enhanced platelet activation and a procoagulant state may drive lung cancer progression and metastases, less is known about their role in earlier phases of cancer development. Thus, we evaluated whether prediagnostic biomarkers of platelet activation and coagulation are related to the risk of lung cancer in the prospective EPIC-Heidelberg Study using a case–cohort design.

Methods:

Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n = 2,480) and incident cases of lung cancer (n = 190). Multivariable-adjusted Cox proportional hazards regression analyses were used to obtain HRs of lung cancer across quartiles of biomarker levels.

Results:

Fibrinogen [HR highest vs. lowest quartile: 1.91 (95% confidence interval: 1.09–3.34)] and sP-Selectin [HR: 2.51 (1.39–4.52)] were significantly associated with lung cancer risk in multivariable adjusted Cox regression models. Adding both biomarkers to the established PLCOm2012 algorithm, which alone showed a C-statistic of 0.788, led to a slight increment in lung cancer risk prediction, with a C-statistic of 0.814.

Conclusion:

Our findings indicate that enhanced platelet activation and a procoagulative state contribute to lung carcinogenesis.

Impact:

The current prospective study supports the hypothesis of increased coagulation being a possible driver of lung carcinogenesis, as strong positive associations were found between two procoagulative markers, sP-Selectin and fibrinogen, with lung cancer risk. Both biomarkers could improve lung cancer risk prediction, but external validation of the results is needed.
Repurposing EGFR Inhibitor Utility in Colorectal Cancer in Mutant APC and TP53 Subpopulations
Authors: Yang Mingli , Schell Michael J. , Loboda Andrey , Nebozhyn Michael , Li Jiannong , Teer Jamie K. , Pledger W. Jack , Yeatman Timothy J.
Published: April 2019

Background:

EGFR is a major therapeutic target for colorectal cancer. Currently, extended RAS/RAF testing identifies only nonresponders to EGFR inhibitors (EGFRi). We aimed to develop a mutation signature that further refines drug-sensitive subpopulations to improve EGFRi outcomes.

Methods:

A prespecified, 203-gene expression signature score measuring cetuximab sensitivity (CTX-S) was validated with two independent clinical trial datasets of cetuximab-treated patients with colorectal cancer (n = 44 and n = 80) as well as an in vitro dataset of 147 cell lines. The CTX-S score was then used to decipher mutated genes that predict EGFRi sensitivity. The predictive value of the identified mutation signature was further validated by additional independent datasets.

Results:

Here, we report the discovery of a 2-gene (APC+TP53) mutation signature that was useful in identifying EGFRi-sensitive colorectal cancer subpopulations. Mutant APC+TP53 tumors were more predominant in left- versus right-sided colorectal cancers (52% vs. 21%, P = 0.0004), in microsatellite stable (MSS) versus microsatellite instable (MSI) cases (47% vs. 2%, P < 0.0001), and in the consensus molecular subtype 2 versus others (75% vs. 37%, P < 0.0001). Moreover, mutant APC+TP53 tumors had favorable outcomes in two cetuximab-treated patient-derived tumor xenograft (PDX) datasets (P = 0.0277, n = 52; P = 0.0008, n = 98).

Conclusions:

Our findings suggest that the APC and TP53 combination mutation may account for the laterality of EGFRi sensitivity and provide a rationale for refining treated populations. The results also suggest addition of APC+TP53 sequencing to extended RAS/RAF testing that may directly increase the response rates of EGFRi therapy in selected patients.

Impact:

These findings, if further validated through clinical trials, could also expand the utility of EGFRi therapies that are currently underutilized.
High-throughput Screening of Human Tumor Antigen–specific CD4 T Cells, Including Neoantigen-reactive T Cells
Authors: Costa-Nunes Carla , Cachot Amélie , Bobisse Sara , Arnaud Marion , Genolet Raphael , Baumgaertner Petra , Speiser Daniel E. , Sousa Alves Pedro M. , Sandoval Federico , Adotévi Olivier , Reith Walter , Protti Maria Pia , Coukos George , Harari Alexandre , Romero Pedro , Jandus Camilla
Published: April 2019

Purpose:

Characterization of tumor antigen–specific CD4 T-cell responses in healthy donors and malignant melanoma patients using an in vitro amplified T-cell library screening procedure.

Patients and Methods:

A high-throughput, human leukocyte antigen (HLA)-independent approach was used to estimate at unprecedented high sensitivity level precursor frequencies of tumor antigen- and neoantigen-specific CD4 T cells in healthy donors and patients with cancer. Frequency estimation was combined with isolation and functional characterization of identified tumor-reactive CD4 T-cell clones.

Results:

In healthy donors, we report frequencies of naïve tumor-associated antigen (TAA)-specific CD4 T cells comparable with those of CD4 T cells specific for infectious agents (Tetanus toxoid). Interestingly, we also identified low, but consistent numbers of memory CD4 T cells specific for several TAAs. In patients with melanoma, low frequencies of circulating TAA-specific CD4 T cells were detected that increased after peptide-based immunotherapy. Such antitumor TAA-specific CD4 T-cell responses were also detectable within the tumor-infiltrated tissues. TAA-specific CD4 T cells in patients displayed a highly polyfunctional state, with partial skewing to Type-2 polarization. Finally, we report the applicability of this approach to the detection and amplification of neoantigen-specific CD4 T cells.

Conclusions:

This simple, noninvasive, high-throughput screening of tumor- and neoantigen-specific CD4 T cells requires little biologic material, is HLA class II independent and allows the concomitant screening for a large number of tumor antigens of interest, including neoantigens. This approach will facilitate the immunomonitoring of preexisting and therapy-induced CD4 T-cell responses, and accelerate the development of CD4 T-cell–based therapies.
Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery
Authors: Hernandez Vargas Servando , Kossatz Susanne , Voss Julie , Ghosh Sukhen C. , Tran Cao Hop S. , Simien Jo , Reiner Thomas , Dhingra Sadhna , Fisher William E. , Azhdarinia Ali
Published: April 2019

Purpose:

Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS).

Experimental Design:

A multimodality chelator (MMC) was used as a “radioactive linker” to synthesize the fluorescently labeled somatostatin analog, 67/68Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso- and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs.

Results:

Direct labeling with 67Ga/68Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings.

Conclusions:

The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.
Phase II Trial of Chemopreventive Effects of Levonorgestrel on Ovarian and Fallopian Tube Epithelium in Women at High Risk for Ovarian Cancer: An NRG Oncology Group/GOG Study
Authors: Rodriguez Gustavo C. , Kauderer James , Hunn Jessica , Thaete Larry G. , Watkin William G , Russell Samantha , Yozwiak Michael , Basil Jack , Hurteau Jean , Lele Shashikant , Modesitt Susan C. , Zivanovic Oliver , Zhang Hao Helen , Bartels Peter H. , Alberts David S
Published: April 2019

A large body of epidemiologic evidence has shown that use of progestin-containing preparations lowers ovarian cancer risk. The purpose of the current study was to gather further preclinical evidence supporting progestins as cancer chemopreventives by demonstrating progestin-activation of surrogate endpoint biomarkers pertinent to cancer prevention in the genital tract of women at increased risk of ovarian cancer. There were 64 women enrolled in a multi-institutional randomized trial who chose to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) and to receive the progestin levonorgestrel or placebo for 4 to 6 weeks prior to undergoing BSO. The ovarian and fallopian tube epithelia (FTE) were compared immunohistochemically for effects of levonorgestrel on apoptosis (primary endpoint). Secondary endpoints included TGFβ isoform expression, proliferation, and karyometric features of nuclear abnormality. In both the ovary and fallopian tube, levonorgestrel did not confer significant changes in apoptosis or expression of the TGFβ1, 2, or 3 isoforms. In the ovarian epithelium, treatment with levonorgestrel significantly decreased the proliferation index. The mean ovarian Ki-67 value in the placebo arm was 2.027 per 100 cells versus 0.775 per 100 cells in the levonorgestrel arm (two-sided P value via Mann–Whitney U test = 0.0114). The karyometric signature of nuclei in both the ovarian and FTE deviated significantly from normal controls (women at average risk of ovarian cancer), but was significantly less abnormal in women treated with levonorgestrel. These karyometric data further support the idea that progestins may clear genetically abnormal cells and act as chemopreventive agents against ovarian and fallopian tube cancer.
CBIR of Brain MR Images Using Histogram of Fuzzy Oriented Gradients and Fuzzy Local Binary Patterns
Authors: TR Athira , Varghese Abraham
Published: April 2019

Retrieval of similar images from large dataset of brain images across patients would help the experts in the decision diagnosis process of diseases. Generally used feature extraction methods are color, texture and shape. In medical images texture and shape features are most efficient. Histogram of Oriented Gradients (HOG) and Local Binary Pattern (LBP) are good descriptor for brain MR image retrieval. But there are many challenges facing in medical application. An empirical study of the impact of increasing bins number in the HOG descriptor concluded that larger the number is more accurate the descriptor is. In fact this is due to the reduction of orientations range that each bin covers. Despite the efficiency of augmenting the bins number, this technique has limited spatial support as the augmentation of the number of bins used leads to increase the histogram dimension. So here proposed a method called Histogram of Fuzzy Oriented Gradients (HFOG), in which a pixel can belong several bins with different degrees. The Local Binary Patterns feature extraction method is widely used for texture analysis; however, the original LBP is based on hard thresholding the neighborhood of each pixel. Therefore, texture representation with LBP is very sensitive to noise and cannot distinguish between a strong and a weak pattern. In this study, Fuzzy Local Binary Patterns was introduced to improve the original LBP.
Is Parameters Quantification in Genetic Algorithm Important, How to do it?
Authors: Pandey Hari Mohan
Published: April 2019

The term “appropriate parameters” signifies the correct choice of values has considerable effect on the performance that directs the search process towards the global optima. The performance typically is measured considering both quality of the results obtained and time requires in finding them. A genetic algorithm is a search and optimization technique, whose performance largely depends on various factors – if not tuned appropriately, difficult to get global optima. This paper describes the applicability of orthogonal array and Taguchi approach in tuning the genetic algorithm parameters. The domain of inquiry is grammatical inference has a wide range of applications. The optimal conditions were obtained corresponding to performance and the quality of results with reduced cost and variability. The primary objective of conducting this study is to identify the appropriate parameter setting by which overall performance and quality of results can be enhanced. In addition, a systematic discussion presented will be helpful for researchers in conducting parameters quantification for other algorithms.
An Approch based on Genetic Algorithm for Multi-tenant Resource Allocation in SaaS Applications
Authors: Kheiri Elaheh , Arani Mostafa Ghobaei , Taghizadeh Alireza
Published: April 2019

In recent years, the use of cloud services has been significantly expanded. The providers of software as a service employ multi-tenant architectures to deliver services to their users. In these multi-tenant applications the resource allocation would suffer from over-utilization or under-utilization issues. Considering the significant effects of resource allocation on the service performance and cost, in this paper we have proposed an approach based on genetic algorithm for resource allocation which guarantees service quality through providing adequate resources. The proposed approach also improves system performance, meets the requirements of users and provides maximum resource efficiency. Simulation results show that the proposed approach has better response rate and availability comparing to other approaches, while provides an efficient resource usage.
Neural KDE Based Behaviour Model for Detecting Intrusions in Network Environment
Authors: Devi V. Brindha , Shunmuganathan K.L.
Published: April 2019

Network intrusion is one of the growing concern throughout the globe about the information stealing and data exfiltration. In recent years this was coupled with the data exfiltration and infiltration through the internal threats. Various security encounters have been taken in order to reduce the intrusion and to prevent intrusion, since the stats reveals that every 4 seconds, at least one intrusion is detected in the detection engines. An external software mechanism is required in order to detect the network intrusions. Based on the above stated problem, here we proposed a new hybrid behaviour model based on Neural KDE and correlation method to detect intrusions.
 The proposed work is splitted into two phases. Initial phase is setup with the Neural KDE as the learning phase and the basic network parameters are profiled for each hosts, here the neural KDE is generated based on the input and learned parameters of the network. Next phase is the detection phase, here the Neural KDE is computed for the identified parameters and the learned KDE feature value is correlated with the present KDE values and correlated values are calculated using cross correlation method. Experimental results show that the proposed model is robust in detecting the intrusions over the network.
Computational Morphological Analysis of Yorùbá Language Words
Authors: Eludiora Safiriyu Ijiyemi , Ayemonisan O R
Published: April 2019

Nigeria official languages are English, Yorùbá, Igbo and Hausa. The focus of the study reported in this paper is to develop learning tool that can assist learners to learn the Yorùbá language using its alphabets. The study is critical to Yorùbá language, because of its endangerment. There is need to introduce different learning tools that can mitigate its extinction. A Yorùbá word perfect system was developed to assist people in learning the Yorùbá language. English and Yorùbá words formation are experimented using computational morphological approach (word formation). The theoretical framework considered Finite state automata (FSA) to realise different ways of combining the consonants and vowels to form word. Two to five letter words were considered. The system was designed and implemented using UML tools and python programming language.The system will teach the users on how the words are formed, and the number of syllables in each word. The user  need not to know how to tone mark word before he/she can use the system. Any word typed will be analysed according to its number of syllables. This approach produces representatives of all parts of speech (POS) of the two languages. It produces corpora for the two languages
Challenging Issues in Automated Oil Palm Fruit Grading
Authors: Patkar Gaurang S , G.S.G.N Anjaneyulu , P.V.S.S.R Chandra Mouli
Published: April 2019

Late advancement in Agriculture segment utilizing Image preparing and fuzzy logic methods has empowered ranchers to expand the yield of harvest and served the nourishment needs of the whole people. Look into in horticulture is pointed towards increment in the profitability, quality and lessening the likelihood of blunder presented by people. The biggest oil palm creation is in Malaysia and Indonesia and they send out palm oil to different nations on the planet. The most outrageous enthusiasm for palm oil is in India. This came to fruition India into Palm Oil advancement and era in various states . With a specific end goal to expand the efficiency of palm oil organic products, palm oil industry and in addition analysts utilizes different machine-vision systems to review the natural products. Tragically, the information caught and prepared is confronted with restricted learning and accuracy. There are a few difficulties required with the outline and usage of palm oil organic product reviewing. This paper introduces an outline of different Image handling and fuzzy logic methods, distinguishes and addresses testing issues in computerized palm natural product evaluating.
A Novel Optimization Algorithm Based on Stinging Behavior of Bee
Authors: Jayalakshmi S. , Aswini R.
Published: April 2019

Optimization algorithms are search methods to find an optimal solution to a problem with a set of constraints. Bio-Inspired Algorithms (BIAs) are based on biological behavior to solve a real world problem. BIA with optimization technique is to improve the overall performance of BIA. The aim of this paper is to introduce a novel optimization algorithm which is inspired by natural stinging behavior of honey bee to find the optimal solution. This algorithm performs both monitor and sting if any occurrence of predators. By applying a novel optimization algorithm based on stinging behavior of bee, used to solve the intrusion detection problems. In this paper, a new host intrusion detection system based on novel optimization algorithm has been proposed and implemented. The performance of the proposed Anomaly-based Host Intrusion Detection System (A-HIDS) using a novel optimization algorithm based on stinging behavior of bee has been tested. In this paper, after an explanation of the natural stinging behavior of honey bee, a novel optimization algorithm and A-HIDS are described and implemented. The results show that the novel optimization algorithm offers some advantage according to the nature of the problem.
Modeling, Analysis and Control of Different DC-DC Converter Topologies for Photo Voltaic Emulator
Authors: Iqbal Mohammad Tauquir , Tariq Mohd
Published: April 2019

This paper presents the modeling, analysis and control of different DC-DC converter topologies to emulate the photovoltaic (PV) system. A PV emulator is basically a DC-DC converter having same electrical characteristics that of solar PV panel. The emulator helps to achieve real characteristics of PV system in a better way in an environment where using actual PV systems can produce inconsistent results due to variation in weather conditions. The paper describes different types of DC-DC converters like buck, Resonant and Quasi Resonant Converter. The complete system is modelled in MATLAB® Simulink SimPowerSystem software package. The Simulation results obtained from the MATLAB® Simulink SimPowerSystem software package for different topologies under steady and dynamic conditions are analyzed and presented. An evaluation table is also presented at the end of the paper, presenting the effectiveness of each topology.