bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Molecular Detection of Gastrointestinal Pathogens and Its Role in Antimicrobial Stewardship
Authors: Keske Şiran , Zabun Burak , Aksoy Kahraman , Can Füsun , Palaoğlu Erhan , Ergönül Önder
Published: March 2018

We aimed to detect the etiological agents of acute diarrhea by a molecular gastrointestinal pathogen test (MGPT) and to assess the impact of MGPT on antimicrobial stewardship programs (ASP). This is a prospective observational study and was conducted between 1 January 2015 and 30 June 2017. We included consequent patients who had acute diarrhea. At the end of 2015, we implemented ASP in acute diarrhea cases and compared the outcomes in the pre-ASP and post-ASP periods. An FDA-cleared multiplexed gastrointestinal PCR panel system, the BioFire FilmArray (Idaho Technology, Salt Lake City, UT), which detects 20 pathogens in stool, was used. In 499 out of 699 patients (71%), at least one pathogen was detected. Among 314 adults with positive MGPT, 101 (32%) enteropathogenic
Escherichia coli
(EPEC), 71 (23%) enteroaggregative
E. coli
(EAEC), 68 (22%) enterotoxigenic
E. coli
(ETEC), 55 (18%) Shiga toxin-producing
E. coli
(STEC) (17%)
Norovirus
, 48 (15%)
Campylobacter
, 21 (7%)
Salmonella
, and 20 (6%)
Clostridium difficile
strains were detected. Among 185 children, 55 (30%) EPEC, 37 (20%)
C. difficile
, 32 (17%)
Norovirus
, 29 (16%) EAEC, 22 (12%) STEC, 21 (11%) ETEC, 21 (11%)
Campylobacter
, 20 (11%)
Salmonella
, and 16 (5%)
Rotavirus
strains were detected. Inappropriate antibiotic use decreased in the post-ASP period compared with the pre-ASP period among inpatients (42.9% and 25.8%, respectively;
P
= 0.023). Using MGPT in clinical practice significantly decreased the unnecessary use of antibiotics. Detection of high rates of
C. difficile
in children and
Salmonella
spp., as well as relatively high rates of
Campylobacter
spp., which were hard to isolate by routine stool culture, were remarkable.
Potential Point-of-Care Testing for Dengue Virus in the Field
Authors: Wang Wei-Kung , Gubler Duane J.
Published: March 2018

The four serotypes of dengue virus (DENV) cause one of the most important and rapidly emerging mosquito-borne viral diseases in humans. Of the currently available diagnostic tests for dengue, the reverse transcription-PCR (RT-PCR) assay is the most sensitive and specific, and so it is commonly used as the gold standard. However, the requirement of a sophisticated and expensive thermal cycler makes it very difficult to use as a point-of-care diagnostic test in resource-limited regions where dengue is endemic. Tsai et al. (J Clin Microbiol 56:e01865-17, 2018,
https://doi.org/10.1128/JCM.01865-17
) report the analytical and clinical performances of a reverse transcription-insulated isothermal PCR (RT-iiPCR) assay with a portable nucleic acid analyzer for rapid detection of the four DENV serotypes; its reproducibility and complete agreement on clinical samples with the multiplex RT-PCR assay developed by the Centers for Disease Control and Prevention suggest that the dengue RT-iiPCR is a potential point-of-care test. Compared with other DENV RNA detection methods, the unique isothermal PCR design of RT-iiPCR, together with further improvements, would represent a promising new type of field-deployable diagnostic test for dengue.
Multi- and Extensively Drug Resistant Mycobacterium tuberculosis in South Africa: a Molecular Analysis of Historical Isolates
Authors: Maningi Nontuthuko E. , Daum Luke T. , Rodriguez John D. , Said Halima M. , Peters Remco P. H. , Sekyere John Osei , Fischer Gerald W. , Chambers James P. , Fourie P. Bernard
Published: March 2018

Modern advances in genomics provide an opportunity to reinterpret historical bacterial culture collections. In this study, genotypic antibiotic resistance profiles of
Mycobacterium tuberculosis
isolates from a historical 20-year-old multidrug-resistant tuberculosis (MDR-TB) culture collection in South Africa are described. DNA samples extracted from the phenotypically MDR-TB isolates (
n
= 240) were assayed by Hain line probe assay (LPA) for the confirmation of MDR-TB and by Illumina Miseq whole-genome sequencing (WGS) for the characterization of mutations in eight genes (
rpoB
,
katG
,
inhA
,
rpsL
,
pncA
,
embB
,
gyrA
, and
rrs
) that are known to code for resistance to commonly used anti-TB agents. LPA identified 71.3% of the TB isolates as MDR-TB, 18.3% as rifampin (RIF) monoresistant, 2% as isoniazid (INH) monoresistant, and 8.3% as susceptible to both RIF and INH (RIF+INH). In a subset of 42 randomly selected isolates designated as RIF+INH resistant by Löwenstein-Jensen (LJ) culture in 1993, LPA and WGS results confirmed MDR-TB. In all five INH-monoresistant isolates by LPA and in all but one (the wild type) of the 34 successfully sequenced RIF-monoresistant isolates, WGS revealed matching mutations. Only 26% of isolates designated as susceptible by LPA, however, were found to be wild type by WGS. Novel mutations were found in the
rpoB
(Thr480Ala, Gln253Arg, Val249Met, Val251Tyr, Val251Phe),
katG
(Trp477STOP, Gln88STOP, Trp198STOP, Trp412STOP),
embB
(Thr11Xaa, Gln59Pro), and
pncA
(Thr100Ile, Thr159Ala, Ala134Arg, Val163Ala, Thr153Ile, DelGpos7, Phe106Ser) genes. Three MDR-TB isolates showed mutations in both the
gyrA
and
rrs
genes, suggesting that extensively drug-resistant tuberculosis existed in South Africa well before its formal recognition in 2006.
Experimental Analysis of Mimivirus Translation Initiation Factor 4a Reveals Its Importance in Viral Protein Translation during Infection of Acanthamoeba polyphaga
Authors: Bekliz Meriem , Azza Said , Seligmann Hervé , Decloquement Philippe , Raoult Didier , La Scola Bernard
Published: March 2018

The
Acanthamoeba polyphaga
mimivirus is the first giant virus ever described, with a 1.2-Mb genome which encodes 979 proteins, including central components of the translation apparatus. One of these proteins, R458, was predicted to initiate translation, although its specific role remains unknown. We silenced the R458 gene using small interfering RNA (siRNA) and compared levels of viral fitness and protein expression in silenced versus wild-type mimivirus. Silencing decreased the growth rate, but viral particle production at the end of the viral cycle was unaffected. A comparative proteomic approach using two-dimensional difference-in-gel electrophoresis (2D-DIGE) revealed deregulation of the expression of 32 proteins in silenced mimivirus, which were defined as up- or downregulated. Besides revealing proteins with unknown functions, silencing R458 also revealed deregulation in proteins associated with viral particle structures, transcriptional machinery, oxidative pathways, modification of proteins/lipids, and DNA topology/repair. Most of these proteins belong to genes transcribed at the end of the viral cycle. Overall, our data suggest that the R458 protein regulates the expression of mimivirus proteins and, thus, that mimivirus translational proteins may not be strictly redundant in relation to those from the amoeba host. As is the case for eukaryotic initiation factor 4a (eIF4a), the R458 protein is the prototypical member of the ATP-dependent DEAD box RNA helicase mechanism. We suggest that the R458 protein is required to unwind the secondary structures at the 5′ ends of mRNAs and to bind the mRNA to the ribosome, making it possible to scan for the start codon. These data are the first experimental evidence of mimivirus translation-related genes, predicted to initiate protein biosynthesis.

IMPORTANCE
The presence in the genome of a mimivirus of genes coding for many translational processes, with the exception of ribosome constituents, has been the subject of debate since its discovery in 2003. In this work, we focused on the R458 mimivirus gene, predicted to initiate protein biosynthesis. After silencing was performed, we observed that it has no major effect on mimivirus multiplication but that it affects protein expression and fitness. This suggests that it is effectively used by mimivirus during its developmental cycle. Until large-scale genetic manipulation of giant viruses becomes possible, the silencing strategy used here on mimivirus translation-related factors will open the way to understanding the functions of these translational genes.
Human T Lymphocytes Are Permissive for Dengue Virus Replication
Authors: Silveira Guilherme F. , Wowk Pryscilla F. , Cataneo Allan H. D. , dos Santos Paula F. , Delgobo Murilo , Stimamiglio Marco A. , Lo Sarzi Maria , Thomazelli Ana Paula F. S. , Conchon-Costa Ivete , Pavanelli Wander R. , Antonelli Lis R. V. , Báfica André , Mansur Daniel S. , dos Santos Claudia N. Duarte , Bordignon Juliano
Published: March 2018

Dengue virus (DV) infection can cause either a self-limiting flu-like disease or a threatening hemorrhage that may evolve to shock and death. A variety of cell types, such as dendritic cells, monocytes, and B cells, can be infected by DV. However, despite the role of T lymphocytes in the control of DV replication, there remains a paucity of information on possible DV-T cell interactions during the disease course. In the present study, we have demonstrated that primary human naive CD4+and CD8+T cells are permissive for DV infection. Importantly, both T cell subtypes support viral replication and secrete viable virus particles. DV infection triggers the activation of both CD4+and CD8+T lymphocytes, but preactivation of T cells reduces the susceptibility of T cells to DV infection. Interestingly, the cytotoxicity-inducing protein granzyme A is highly secreted by human CD4+but not CD8+T cells after exposure to DVin vitro. Additionally, using annexin V and polycaspase assays, we have demonstrated that T lymphocytes, in contrast to monocytes, are resistant to DV-induced apoptosis. Strikingly, both CD4+and CD8+T cells were found to be infected with DV in acutely infected dengue patients. Together, these results show that T cells are permissive for DV infectionin vitroandin vivo, suggesting that this cell population may be a viral reservoir during the acute phase of the disease.

IMPORTANCEInfection by dengue virus (DV) causes a flu-like disease that can evolve to severe hemorrhaging and death. T lymphocytes are important cells that regulate antibody secretion by B cells and trigger the death of infected cells. However, little is known about the direct interaction between DV and T lymphocytes. Here, we show that T lymphocytes from healthy donors are susceptible to infection by DV, leading to cell activation. Additionally, T cells seem to be resistant to DV-induced apoptosis, suggesting a potential role as a viral reservoir in humans. Finally, we show that both CD4+and CD8+T lymphocytes from acutely infected DV patients are infected by DV. Our results raise new questions about DV pathogenesis and vaccine development.
Dal81 Regulates Expression of Arginine Metabolism Genes in Candida parapsilosis
Authors: Turner Siobhan A. , Ma Qinxi , Ola Mihaela , Martinez de San Vicente Kontxi , Butler Geraldine
Published: March 2018

Utilization of nitrogen by fungi is controlled by
n
itrogen
c
atabolite
r
epression (NCR). Expression of many genes is switched off during growth on nonpreferred nitrogen sources. Gene expression is regulated through a combination of activation and repression. Nitrogen regulation has been studied best in the model yeast
Saccharomyces cerevisiae
. We found that although many nitrogen regulators have a conserved function in
Saccharomyces
species, some do not. The Dal81 transcriptional regulator has distinctly different functions in
S. cerevisiae
and
C. parapsilosis
. In the former, it regulates utilization of nitrogen from GABA and allantoin, whereas in the latter, it regulates expression of arginine synthesis genes. Our findings make an important contribution to our understanding of nitrogen regulation in a human-pathogenic fungus.
A Critical Analysis of the Scientific and Commercial Rationales for theDe NovoSynthesis of Horsepox Virus
Authors: Koblentz Gregory D.
Published: March 2018

This article evaluates the scientific and commercial rationales for the synthesis of horsepox virus. I find that the claimed benefits of using horsepox virus as a smallpox vaccine rest on a weak scientific foundation and an even weaker business case that this project will lead to a licensed medical countermeasure.
Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of
Bifidobacterium
over the Past Century
Authors: Henrick Bethany M. , Hutton Andra A. , Palumbo Michelle C. , Casaburi Giorgio , Mitchell Ryan D. , Underwood Mark A. , Smilowitz Jennifer T. , Frese Steven A.
Published: March 2018

Historically,
Bifidobacterium
species were reported as abundant in the breastfed infant gut. However, recent studies in resource-rich countries show an increased abundance of taxa regarded as signatures of dysbiosis.
Prevalence of multimorbidity in general practice: a cross-sectional study within the Swiss Sentinel Surveillance System (Sentinella)
Authors: Excoffier Sophie , Herzig Lilli , N’Goran Alexandra A , Déruaz-Luyet Anouk , Haller Dagmar M
Published: March 2018

Objectives

To estimate the prevalence of multimorbidity using a list of 75 chronic conditions derived from the International Classification for Primary Care, Second edition and developed specifically to assess multimorbidity in primary care. Our aim was also to provide prevalence data for multimorbidity in primary care in a country in which general practitioners (GPs) do not play a gatekeeping role in the health system.

Setting

A representative sample of GPs within the Swiss Sentinel Surveillance Network.

Participants

118 GPs completed a paper-based questionnaire about 25 consecutive patients of all ages between September and November 2015. There were no patient exclusion criteria. Recorded data included date of birth, gender and the patients’ chronic conditions.

Primary and secondary outcome measures

We estimated the prevalence of multimorbidity, defined as ≥2, and ≥3 chronic conditions stratified by gender and age group, and adjusted for clustering by GPs. We also computed the prevalence of each chronic condition individually and grouped by system.

Results

Data from 2904 patients were included (mean age (SD)=56.5 (20.5) years; male=43.7%). Prevalence was 52.1% (95% CI 48.6% to 55.5%) for ≥2 and 35.0% (95% CI 31.6% to 38.5%) for ≥3 chronic conditions, with no significant gender differences. Prevalence of two or more chronic conditions was low (6.2%, 95% CI 2.8% to 13.0%) in those below 20 but affected more than 85% (85.8%, 95% CI 79.6% to 90.3%) of those above the age of 80. The most prevalent conditions were cardiovascular (42.7%, 95% CI 39.7% to 45.7%), psychological (28.5%, 95% CI 26.1% to 31.1%) and metabolic or endocrine disorders (24.1%, 95% CI 21.6% to 26.7%). Elevated blood pressure was the most prevalent cardiovascular condition and depression the most common psychological disorder.

Conclusion

In a country in which GPs do not play a gatekeeping role within the health system, the prevalence of multimorbidity, as assessed using a list of chronic conditions specifically relevant to primary care, is high and increases with age.
Risk of bias and methodological issues in randomised controlled trials of acupuncture for knee osteoarthritis: a cross-sectional study
Authors: Jia Pengli , Tang Li , Yu Jiajie , Lee Andy H , Zhou Xu , Kang Deying , Luo Yanan , Liu Jiali , Sun Xin
Published: March 2018

Objective

To assess risk of bias and to investigate methodological issues concerning the design, conduct and analysis of randomised controlled trials (RCTs) testing acupuncture for knee osteoarthritis (KOA).

Methods

PubMed, EMBASE, Cochrane Central Register of Controlled Trials and four major Chinese databases were searched for RCTs that investigated the effect of acupuncture for KOA. The Cochrane tool was used to examine the risk of bias of eligible RCTs. Their methodological details were examined using a standardised and pilot-tested questionnaire of 48 items, together with the association between four predefined factors and important methodological quality indicators.

Results

A total of 248 RCTs were eligible, of which 39 (15.7%) used computer-generated randomisation sequence. Of the 31 (12.5%) trials that stated the allocation concealment, only one used central randomisation. Twenty-five (10.1%) trials mentioned that their acupuncture procedures were standardised, but only 18 (7.3%) specified how the standardisation was achieved. The great majority of trials (n=233, 94%) stated that blinding was in place, but 204 (87.6%) did not clarify who was blinded. Only 27 (10.9%) trials specified the primary outcome, for which 7 used intention-to-treat analysis. Only 17 (6.9%) trials included details on sample size calculation; none preplanned an interim analysis and associated stopping rule. In total, 46 (18.5%) trials explicitly stated that loss to follow-up occurred, but only 6 (2.4%) provided some information to deal with the issue. No trials prespecified, conducted or reported any subgroup or adjusted analysis for the primary outcome.

Conclusion

The overall risk of bias was high among published RCTs testing acupuncture for KOA. Methodological limitations were present in many important aspects of design, conduct and analyses. These findings inform the development of evidence-based methodological guidance for future trials assessing the effect of acupuncture for KOA.
“I think maybe 10 years seems a bit long.” Beliefs and attitudes of women who had never used intrauterine contraception
Authors: Walker Susan , Newton Victoria Louise , Hoggart Lesley , Parker Michael
Published: March 2018

Aim

To explore, in a general practice setting, the concerns, beliefs and attitudes about intrauterine contraception (IUC) reported by women, who had never used the methods.

Methods

We used a sequential mixed-method (QUAL/quant) approach. A pragmatic, self-selecting sample of 30 women, aged 18–46 years, who had never used IUC), was recruited through seven general practices in South East England. Themes arising from qualitative interviews were used to construct a quantitative survey, completed by a pragmatic sample of 1195 women, aged 18–49 years, attending 32 general practices in the same region, between February and August 2015.

Results

Qualitative themes were concerns about the long-acting nature of IUC, concerns about body boundaries, and informal knowledge of IUC, especially ‘friend of a friend’ stories. Women were not sure if the devices can be removed before their full 5- or 10-year duration of use, and felt that these timeframes did not fit with their reproductive intentions. Quantitative survey data showed that the most commonly endorsed concerns among never-users were painful fitting (55.8%), unpleasant removal of the device (60.1%), and concern about having a device ’inside me' (60.2%).

Conclusions

To facilitate fully informed contraceptive choice, information provided to women considering IUC should be tailored to more fully address the concerns expressed by never-users, particularly around the details of insertion and removal, and concerns about the adverse, long-term effects of the device. Women need to be reassured that IUC can be removed and fertility restored at any time following insertion.

Trial registration

Trial registration NIHR CRN portfolio; 15912.
Establishing objective benchmarks in robotic virtual reality simulation at the level of a competent surgeon using the RobotiX Mentor simulator
Authors: Watkinson William , Raison Nicholas , Abe Takashige , Harrison Patrick , Khan Shamim , Van der Poel Henk , Dasgupta Prokar , Ahmed Kamran
Published: March 2018

Background

To establish objective benchmarks at the level of a competent robotic surgeon across different exercises and metrics for the RobotiX Mentor virtual reality (VR) simulator suitable for use within a robotic surgical training curriculum.

Methods

This retrospective observational study analysed results from multiple data sources, all of which used the RobotiX Mentor VR simulator. 123 participants with varying experience from novice to expert completed the exercises. Competency was established as the 25th centile of the mean advanced intermediate score. Three basic skill exercises and two advanced skill exercises were used.

Setting

King’s College London.

Participants

84 Novice, 26 beginner intermediates, 9 advanced intermediates and 4 experts were used in this retrospective observational study.

Results

Objective benchmarks derived from the 25th centile of the mean scores of the advanced intermediates provided suitably challenging yet also achievable targets for training surgeons. The disparity in scores was greatest for the advanced exercises. Novice surgeons are able to achieve the benchmarks across all exercises in the majority of metrics.

Conclusion

We have successfully created this proof-of-concept study, which requires validation in a larger cohort. Objective benchmarks obtained from the 25th centile of the mean scores of advanced intermediates provide clinically relevant benchmarks at the standard of a competent robotic surgeon that are challenging yet also attainable. That can be used within a VR training curriculum allowing participants to track and monitor their progress in a structured and progressional manner through five exercises. Providing clearly defined targets, ensuring that a universal training standard has been achieved across training surgeons.
Defining the regulatory role of programmed cell death 4 in laryngeal squamous cell carcinoma
Authors: Xu Yuan-Teng , Chen Rui-Qing , Lin Gong-Biao , Fang Xiu-Ling , Yu Shu-Juan , Liang Xiao-Hua , Zhang Rong
Published: March 2018

Programmed cell death 4 (PDCD4) is decreased in many different kinds of malignant tumors. EMT endows tumor cells invasive and metastatic properties. However, few studies have determined the role of PDCD4 in the regulation of EMT in the context of laryngeal carcinoma. We examined the relationship between PDCD4 and EMT-associated proteins E-cadherin and N-cadherin using laryngeal carcinoma tissues. Gene manipulation was used to define the regulatory capacity of PDCD4. We report that PDCD4 and E-cadherin/N-cadherin expression were significantly changed in the carcinoma tissues, and their expression was associated with pathological grade, metastatic state, and clinical stage. The suppression of PDCD4 (and consequently, E-cadherin) was concomitant with increased proliferation and G2-phase arrest, decreased apoptosis, and increased cell invasion. PDCD4 upregulation reversed the above-mentioned results. In nude mice, PDCD4 knockdown increased tumor growth and pathological features, confirming the tumorigenic role of PDCD4. Finally, PDCD4 silencing was associated with dysregulation of the carcinogenic Wnt–β-catenin and the STAT3–miR-21 signaling pathways. This study revealed a dynamic regulatory relationship between PDCD4 and critical factors for EMT, establishing a broad, functional role for PDCD4 in laryngeal carcinoma, which may be propagated by the STAT3–miR-21 pathway. These findings provide new information on an EMT-associated target that may lead to a novel therapy.
Influence of vertical cylindrical tetrahydrofuran hydrate veins on fine-grained soil behaviour
Authors: Smith William E. , Priest Jeffrey A. , Hayley Jocelyn L.H.
Published: March 2018

Over the last 10 years, marine gas hydrate drilling expeditions utilizing advances in pressure coring techniques and imaging have routinely encountered gas hydrates residing in fine-grained sediments. The hydrate typically occurs as fracture-filling, near vertical, veins that displace the sediment, potentially leading to increased sediment strength that may prevent normal consolidation of the sediment thus leading to underconsolidation. Destabilization of this hydrate, through climate change or human activity on the seafloor, may cause dramatic loss of strength of the sediment and pose a significant geohazard. To assess the impact of hydrate veins on sediment behaviour, this paper reports on a series of consolidated (CU) and unconsolidated undrained (UU) triaxial tests carried out on fine-grained soil specimens hosting simplified, vertical, cylindrical tetrahydrofuran (THF) hydrate veins of varying diameters. The results show that increasing hydrate vein diameter significantly increases strength and stiffness, including the development of post-peak strain-softening. The mode of failure of the hydrate veins influenced the specimen strength, but did not affect the specimen stiffness. Hydrate dissolution during CU tests prevented quantitative comparison with UU tests. However, CU test results on the soil specimens containing the largest hydrate vein suggest that increasing lateral confining stresses increase the sediment strength.
Microbial diversity associated with the anaerobic sediments of a soda lake (Mono Lake, California, USA)
Authors: Rojas Patricia , Rodríguez Nuria , de la Fuente Vicenta , Sánchez-Mata Daniel , Amils Ricardo , Sanz José L.
Published: March 2018

Soda lakes are inhabited by important haloalkaliphilic microbial communities that are well adapted to these extreme characteristics. The surface waters of the haloalkaline Mono Lake (California, USA) are alkaline but, in contrast to its bottom waters, do not present high salinity. We have studied the microbiota present in the shoreline sediments of Mono Lake using next-generation sequencing techniques. The statistical indexes showed that Bacteria had a higher richness, diversity, and evenness than Archaea. Seventeen phyla and 8 “candidate divisions” were identified among the Bacteria, with a predominance of the phyla Firmicutes, Proteobacteria, and Bacteroidetes. Among the Proteobacteria, there was a notable presence of Rhodoplanes and a high diversity of sulfate-reducing Deltaproteobacteria, in accordance with the high sulfate-reducing activity detected in soda lakes. Numerous families of bacterial fermenters were identified among the Firmicutes. The Bacteroides were represented by several environmental groups that have not yet been isolated. Since final organic matter in anaerobic environments with high sulfate contents is mineralized mainly by sulfate-reducing bacteria, very little methanogenic archaeal biodiversity was detected. Only 2 genera, Methanocalculus and Methanosarcina, were retrieved. The species similarities described indicate that a significant number of the operational taxonomic units identified may represent new species.
Star-coupled Hindmarsh–Rose neural network with chemical synapses
Authors: Usha K. , Subha P. A.
Published: March 2018

We analyze the patterns like synchrony, desynchrony, and Drum head mode in a network of Hindmarsh–Rose (HR) neurons interacting via chemical synapse in unidirectional and bidirectional star topology. A two-coupled system has been studied for synchronization by varying the coupling strength and the parameter describing the activation and inactivation of the fast ion channel. The transverse Lyapunov exponent spectrum is plotted to observe the point of transition from desynchrony to synchrony. The synchronized, desynchronized, and drum head mode regions are observed when the neurons are connected in unidirectional and bidirectional coupling configurations. A detailed analysis about the time evolution of membrane potential corresponding to each region is presented. The annihilation of synchronized region and the expansion of drum head mode region in bidirectional coupling is discussed using parameter space. Our work provides finer insight into the existence and stability of Drum head mode and is useful for designing communication networks.
MANUFACTURING PRODUCTIVITY IN THE INDIAN STATES
Authors: KHANNA RUPIKA , SHARMA CHANDAN
Published: March 2018

In this paper, we study the total factor productivity (TFP) of manufacturing industries in 22 Indian states for the periods 2008–2009 and 2011–2012 using industry data from ASI database. We estimate TFP by ordinary least squares using cross-sectional data. For correcting potential endogeneity, we apply two-stage least-squares approach using intermediate inputs as instruments. Our results show that despite a faster growth in the industries in the sample period, there appear wide regional disparities in the TFP in most industries assessed. We note that low-productivity states display a higher variation in TFP across industries than high-productivity states. Our results also confirm the dominance of capital-intensive techniques in Indian manufacturing. In addition, more importantly, there appears to be no sign of change in elasticity of inputs over the sample period.
Simultaneous localization of photons and phonons in defect-free dodecagonal phoxonic quasicrystals
Authors: Xu Bihang , Wang Zhong , Tan Yixiang , Yu Tianbao
Published: March 2018

In dodecagonal phoxonic quasicrytals (PhXQCs) with a very high rotational symmetry, we demonstrate numerically large phoxonic band gaps (PhXBGs, the coexistence of photonic and phononic band gaps). By computing the existence and dependence of PhXBGs on the choice of radius of holes, we find that PhXQCs can possess simultaneous photonic and phononic band gaps over a rather wide range of geometric parameters. Furthermore, localized modes of THz photons and tens of MHz phonons may exist inside and outside band gaps in defect-free PhXQCs. The electromagnetic and elastic field can be confined simultaneously around the quasicrytals center and decay in a length scale of several basic cells. As a kind of quasiperiodic structures, 12-fold PhXQCs provide a good candidate for simultaneously tailoring electromagnetic and elastic waves. Moreover, these structures exhibit some interesting characteristics due to the very high symmetry.
Inhomogeneous shearlet coorbit spaces
Authors: Feise Fabian , Sawatzki Lukas
Published: March 2018

In this paper, we establish inhomogeneous coorbit spaces related to the continuous shearlet transform and the weighted Lebesgue spaces [Formula: see text] for certain weights [Formula: see text]. We present an inhomogeneous shearlet frame for [Formula: see text] which gives rise to a reproducing kernel [Formula: see text] that is not contained in the space [Formula: see text]. We show that the inhomogeneous shearlet coorbit spaces are Banach spaces by introducing a generalization of the approach of Fornasier, Rauhut and Ullrich.
Wavelets in Sobolev space over local fields of positive characteristics
Authors: Pathak Ashish , Singh Guru P.
Published: March 2018

The Sobolev space over local fields [Formula: see text] is defined. A multiresolution analysis for the Sobolev space is developed. Orthonormal wavelets with respect to these space are constructed and an example is also presented.
Online Learning: Bridging the Cultural Gaps
Authors: Arafeh Alia
Published: March 2018

The pervasiveness of online education created opportunities for learners across the world to pursue their higher education at accredited universities of their choice. However, this form of education generated several challenges for both educators and learners due to several cultural differences. As the world is a global village, it has become crucial to satisfy the academic and professional needs of these learners who aspire to get the best scholastic aptitude. Yet, there are many benefits of cultural diversity for both educators and learners. The rich examples of the impact of culture on online learning stated throughout "Culture and Online Learning: Global perspectives and research" help understand the effect of cultural differences on creating a successful and effective learning environment, which embraces online students and provides them with the tools to assist their success. The integration of philosophy and practice is vital for the success of online education to reach a larger number of students across the world, students who aspire to receive better education opportunities that might not be available in their home countries.
Targeting KRAS Directly
Authors: McCormick Frank
Published: March 2018

RAS proteins play a major, causal role in many human cancers. No therapies have been developed for these cancers because the RAS protein has been considered undruggable given that it has no accessible pocket to which a drug could bind with high affinity, and the mutant proteins that cause cancer are virtually identical to their essential, wild-type counterparts. New technologies in drug development, such as nuclear magnetic resonance–based fragment screening and covalent tethering, and new insights into RAS structure and function have changed this perception and facilitated the development of several drug candidates.
Myeloid-specific deletion of Zfp36 protects against insulin resistance and fatty liver in diet-induced obese mice
Authors: Caracciolo Valentina , Young Jeanette , Gonzales Donna , Ni Yingchun , Flowers Stephen J. , Summer Ross , Waldman Scott A. , Kim Jason K. , Jung Dae Young , Noh Hye Lim , Kim Taekyoon , Blackshear Perry J. , O'Connell Danielle , Bauer Robert C. , Kallen Caleb B.
Published: March 2018

Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc finger protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild-type (Control) mice became obese and diabetic on a high-fat diet, and obese mice with myeloid-specific loss of Zfp36 [knockout (KO)] demonstrated increased adipose tissue and liver cytokine mRNA expression compared with Control mice. Unexpectedly, in glucose tolerance testing and hyperinsulinemic-euglycemic clamp studies, myeloid Zfp36 KO mice demonstrated improved insulin sensitivity compared with Control mice. Obese KO and Control mice had similar macrophage infiltration of the adipose depots and similar peripheral cytokine levels, but lean and obese KO mice demonstrated increased Kupffer cell (KC; the hepatic macrophage)-expressed Mac2 compared with lean Control mice. Insulin resistance in obese Control mice was associated with enhanced Zfp36 expression in KCs. Compared with Control mice, KO mice demonstrated increased hepatic mRNA expression of a multitude of classical (M1) inflammatory cytokines/chemokines, and this M1-inflammatory hepatic milieu was associated with enhanced nuclear localization of IKKβ and the p65 subunit of NF-κB. Our data confirm the important role of innate immune cells in regulating hepatic insulin sensitivity and lipid metabolism, challenge-prevailing models in which M1 inflammatory responses predict insulin resistance, and indicate that myeloid-expressed Zfp36 modulates the response to insulin in mice.
Impact of estrogens and estrogen receptor-α in brain lipid metabolism
Authors: Morselli Eugenia , Santos Roberta de Souza , Gao Su , Ávalos Yenniffer , Criollo Alfredo , Palmer Biff F. , Clegg Deborah J.
Published: March 2018

Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system.
Quality Evaluation of the Traditional Medicine Majun Mupakhi ELA via Chromatographic Fingerprinting Coupled with UHPLC‐DAD‐Quadrupole‐Orbitrap‐MS and the Antioxidant Activity In Vitro
Authors: Reheman Ayinuer , Aisa Haji Akber , Ma Qing Ling , Nijat Dilaram , Abdulla Rahima
Published: March 2018

By merging a high‐performance liquid chromatography diode array detector (HPLC‐DAD) method with high‐performance thin‐layer chromatography (HPTLC), an assay was developed for chemical fingerprinting and quantitative analysis of traditional medicine Majun Mupakhi ELA (MME), and constituent compounds were identified using HPLC coupled with UHPLC‐DAD‐Quadrupole‐Orbitrap‐MS method. In addition, the antioxidant capacity of MME was assessed based on the ability of components to scavenge radicals using in vitro method. Using a HPLC‐DAD method with HPTLC easily validated the chemical fingerprinting results and quantified three characteristic components, namely, gallic acid (1), daidzein (2), and icariin (3), in commercial MMEs. The three compounds presented excellent regression values (R2 = 0.9999) in the ranges of the test and the method recovery was in the range from 100.49% to 100.68%. The fingerprints had 27 common characteristic peaks, of which 13 were verified by rapid UHPLC‐DAD‐Q‐Orbitrap‐MS analysis. In vitro antioxidant assays rapidly assessed and contrasted antioxidant activity or the free radical scavenging activity of the main polyphenolic classes in MMEs, and the antioxidant capacity was mostly affected by the presence of gallic acid. Thus, this study establishes a powerful and meaningful approach for MME quality control and for assessing in vitro antioxidant activity.
Sexual Dimorphism for the Association between Vitamin D and Insulin Resistance in Chinese People
Authors: Han Bing , Li Qin , Wang Ningjian , Chen Yi , Zhu Chunfang , Chen Yingchao , Xia Fangzhen , Cang Zhen , Lu Meng , Meng Ying , Chen Chi , Lu Yingli
Published: March 2018

Background. The relationship between vitamin D and insulin resistance is still controversial. Many factors could influence this relationship. In addition, this relationship in different genders was still unclear. Methods. A total of 6597 subjects, including 2813 males and 3784 females, were analyzed. The serum levels of 25(OH)D, fasting blood glucose (FBG), fasting insulin, HbA1c, and other metabolic parameters were tested. The waist circumference (WC), weight, and height were also measured. Questionnaires regarding smoking and drinking were collected from these subjects. Results. Serum 25(OH)D was categorized into quartiles. Increasing 25(OH)D levels were associated with reduced trend of homeostasis model assessment of insulin resistance (HOMA-IR) in both males and females. Pearson’s correlation indicated 25(OH)D level was inversely associated with the HOMA-IR for male subjects (r=−0.055, P=0.028) but not for female subjects (r=−0.005, P=0.798). Age, triglyceride (TG), and low-density lipoprotein (LDL) were associated with the vitamin D levels in males and females. In regression analysis, serum 25(OH)D concentration was significantly associated with HOMA-IR only in overweight males. Conclusion. We found an inverse association between 25(OH)D and HOMA-IR in Chinese overweight males. Vitamin D supplementation might be beneficial in this population. However, further clinical trials are needed to confirm this association.
A Novel Technique Based on Visual Words Fusion Analysis of Sparse Features for Effective Content-Based Image Retrieval
Authors: Yousuf Muhammad , Mehmood Zahid , Habib Hafiz Adnan , Mahmood Toqeer , Saba Tanzila , Rehman Amjad , Rashid Muhammad
Published: March 2018

Content-based image retrieval (CBIR) is a mechanism that is used to retrieve similar images from an image collection. In this paper, an effective novel technique is introduced to improve the performance of CBIR on the basis of visual words fusion of scale-invariant feature transform (SIFT) and local intensity order pattern (LIOP) descriptors. SIFT performs better on scale changes and on invariant rotations. However, SIFT does not perform better in the case of low contrast and illumination changes within an image, while LIOP performs better in such circumstances. SIFT performs better even at large rotation and scale changes, while LIOP does not perform well in such circumstances. Moreover, SIFT features are invariant to slight distortion as compared to LIOP. The proposed technique is based on the visual words fusion of SIFT and LIOP descriptors which overcomes the aforementioned issues and significantly improves the performance of CBIR. The experimental results of the proposed technique are compared with another proposed novel features fusion technique based on SIFT-LIOP descriptors as well as with the state-of-the-art CBIR techniques. The qualitative and quantitative analysis carried out on three image collections, namely, Corel-A, Corel-B, and Caltech-256, demonstrate the robustness of the proposed technique based on visual words fusion as compared to features fusion and the state-of-the-art CBIR techniques.
The Effect of Gentle Handling on Depressive-Like Behavior in Adult Male Mice: Considerations for Human and Rodent Interactions in the Laboratory
Authors: Neely Caroline , Lane Christina , Torres Julio , Flinn Jane
Published: March 2018

Environmental factors play a significant role in well-being of laboratory animals. Regulations and guidelines recommend, if not require, that stressors such as bright lighting, smells, and noises are eliminated or reduced to maximize animal well-being. A factor that is often overlooked is handling and how researchers interact with their animals. Researchers, lab assistants, and husbandry staff in animal facilities may use inconsistent handling methods when interacting with rodents, but humans should be considered a part of the animal’s social environment. This study examined the effects of different handling techniques on depressive-like behavior, measured by the Porsolt forced swim test, in adult C57BL/6J male mice. The same two researchers handled the mice in a gentle, aggressive, or minimal (control) fashion over approximately two weeks prior to testing. The results demonstrated a beneficial effect of gentle handling: gentle handling reduced swimming immobility in the forced swim test compared to mice that were aggressively or minimally handled. We argue that gentle handling, rather than methodical handling, can foster a better relationship between the handlers and rodents. Although handling is not standardized across labs, consistent gentle handling allows for less challenging behavioral testing, better data collection, and overall improved animal welfare.
Unusual Presentation of Prostate Cancer Metastatic to the Cricoid Cartilage and Oral Cavity
Authors: Olvera Marlene , Delgado Miriam , Vázquez Melchor , Zavala José , Macedo Verónica , Puentes Martha
Published: March 2018

In Mexico, prostate cancer is the second leading cause of death in men. Prostate cancer usually presents metastasis to the regional lymph nodes and bone. Hereby, we present an unusual case of metastatic prostate cancer, with affectation to the cricoid cartilage and oral cavity, being the first case to have ever been reported in Mexico. A 68-year-old Mexican man was diagnosed with prostate cancer and cribriform architecture histology with low serum level of prostate-specific antigen, debuting with laryngeal stridor. The biopsy came back positive for metastatic prostate carcinoma. During treatment with radiotherapy, metastasis developed to the oral cavity.
Effect of Yeast Fermentation of Green Coffee Beans on Antioxidant Activity and Consumer Acceptability
Authors: Kwak Han Sub , Jeong Yoonhwa , Kim Misook
Published: March 2018

This study assessed the functionality and consumer acceptance of yeast fermented coffee beans. Green coffee beans were fermented for 24 h with three different yeast strains to increase functionality. The yeast fermentation was effective in fortifying the functionality of coffee by significantly increasing antioxidant activity according to the results of ORAC and SOD-like assay (P<0.05). The TPC and TFC contents in the fermented coffee beans were significantly higher than those in the controls (P<0.05). The consumer acceptance for the fermented coffee beans was slightly lower than that of the controls. Fermentation seemed to influence the aroma and flavor of coffee. However, agglomerative hierarchical clustering analysis revealed that approximately 39% of consumers significantly liked one of the fermented coffees (F3) more than the controls (P<0.05). These consumers indicated that the yeast fermentation of green coffee beans did not generate a negative aroma or flavor and can be attractive with high antioxidant activity.
Autophagy and LAP in the Fight against Fungal Infections: Regulation and Therapeutics
Authors: Oikonomou Vasileios , Renga Giorgia , De Luca Antonella , Borghi Monica , Pariano Marilena , Puccetti Matteo , Paolicelli Giuseppe , Stincardini Claudia , Costantini Claudio , Bartoli Andrea , Zelante Teresa , Romani Luigina
Published: March 2018

Phagocytes fight fungi using canonical and noncanonical, also called LC3-associated phagocytosis (LAP), autophagy pathways. However, the outcomes of autophagy/LAP in shaping host immune responses appear to greatly vary depending on fungal species and cell types. By allowing efficient pathogen clearance and/or degradation of inflammatory mediators, autophagy proteins play a broad role in cellular and immune homeostasis during fungal infections. Indeed, defects in autophagic machinery have been linked with aberrant host defense and inflammatory states. Thus, understanding the molecular mechanisms underlying the relationship between the different forms of autophagy may offer a way to identify drugable molecular signatures discriminating between selective recognition of cargo and host protection. In this regard, IFN-γ and anakinra are teaching examples of successful antifungal agents that target the autophagy machinery. This article provides an overview of the role of autophagy/LAP in response to fungi and in their infections, regulation, and therapeutic exploitation.
The Association of Thyroid Nodules with Metabolic Status: A Cross-Sectional SPECT-China Study
Authors: Chen Yi , Zhu Chunfang , Chen Yingchao , Wang Ningjian , Li Qin , Han Bing , Zhao Li , Chen Chi , Zhai Hualing , Lu Yingli
Published: March 2018

Purpose. The aim of this study was to investigate the association of thyroid nodules (TNs) and their ultrasound (US) characteristics related to malignancy with metabolic status. Methods. The data were obtained from a cross-sectional study (SPECT-China, 2014-2015). The study included 9898 participants older than 18 years. Participants underwent several checkups, which included the measurement of anthropometric parameters, blood pressure, TSH levels, glucose, and lipid profiles. TN and nonalcoholic fatty liver disease (NAFLD) were diagnosed by US. TN US characteristics, including microcalcification and a taller-than-wide shape, were recorded. Results. Participants with TN [TN(+)] had a higher prevalence of metabolic syndrome (Met-S), obesity, central obesity, hyperlipidaemia, diabetes, hypertension, and NAFLD, especially women (all P≤0.001). After full adjustment, logistic regression analysis indicated that metabolic syndrome, obesity, central obesity, and hyperlipidaemia were all independent risk factors for the increased prevalence of TN in both genders (P<0.05). In terms of TN US imaging characteristics associated with malignancy, being female with obesity, central obesity, and NAFLD had 1.91-fold, 2.09-fold, and 1.75-fold increased risks of developing a taller-than-wide nodule (P=0.014, 0.004, and 0.027, resp.). Conclusions. The status of metabolic disorders might be associated with higher risks of TN in both genders. In women, obesity, central obesity, and NAFLD might contribute to the development of a taller-than-wide nodule. The potential role of metabolic status in the pathogenesis of the thyroid nodule and thyroid cancer remains to be elucidated.