bluuebunny/crossref_metadata_2025 huggingface dataset:
Insertion Sequences
Authors: Mahillon Jacques , Chandler Michael
Published: December 2019

Insertion sequences (ISs) constitute an important component of most bacterial genomes. Over 500 individual ISs have been described in the literature to date, and many more are being discovered in the ongoing prokaryotic and eukaryotic genome-sequencing projects. The last 10 years have also seen some striking advances in our understanding of the transposition process itself. Not least of these has been the development of various in vitro transposition systems for both prokaryotic and eukaryotic elements and, for several of these, a detailed understanding of the transposition process at the chemical level. This review presents a general overview of the organization and function of insertion sequences of eubacterial, archaebacterial, and eukaryotic origins with particular emphasis on bacterial elements and on different aspects of the transposition mechanism. It also attempts to provide a framework for classification of these elements by assigning them to various families or groups. A total of 443 members of the collection have been grouped in 17 families based on combinations of the following criteria: (i) similarities in genetic organization (arrangement of open reading frames); (ii) marked identities or similarities in the enzymes which mediate the transposition reactions, the recombinases/transposases (Tpases); (iii) similar features of their ends (terminal IRs); and (iv) fate of the nucleotide sequence of their target sites (generation of a direct target duplication of determined length). A brief description of the mechanism(s) involved in the mobility of individual ISs in each family and of the structure-function relationships of the individual Tpases is included where available.
Bacillus thuringiensis
and Its Pesticidal Crystal Proteins
Authors: Schnepf E. , Crickmore N. , Van Rie J. , Lereclus D. , Baum J. , Feitelson J. , Zeigler D. R. , Dean D. H.
Published: December 2019

During the past decade the pesticidal bacterium Bacillus thuringiensis has been the subject of intensive research. These efforts have yielded considerable data about the complex relationships between the structure, mechanism of action, and genetics of the organism’s pesticidal crystal proteins, and a coherent picture of these relationships is beginning to emerge. Other studies have focused on the ecological role of the B. thuringiensis crystal proteins, their performance in agricultural and other natural settings, and the evolution of resistance mechanisms in target pests. Armed with this knowledge base and with the tools of modern biotechnology, researchers are now reporting promising results in engineering more-useful toxins and formulations, in creating transgenic plants that express pesticidal activity, and in constructing integrated management strategies to insure that these products are utilized with maximum efficiency and benefit.
MAP Kinase Pathways in the Yeast
Saccharomyces cerevisiae
Authors: Gustin Michael C. , Albertyn Jacobus , Alexander Matthew , Davenport Kenneth
Published: December 2019

A cascade of three protein kinases known as a mitogen-activated protein kinase (MAPK) cascade is commonly found as part of the signaling pathways in eukaryotic cells. Almost two decades of genetic and biochemical experimentation plus the recently completed DNA sequence of the Saccharomyces cerevisiae genome have revealed just five functionally distinct MAPK cascades in this yeast. Sexual conjugation, cell growth, and adaptation to stress, for example, all require MAPK-mediated cellular responses. A primary function of these cascades appears to be the regulation of gene expression in response to extracellular signals or as part of specific developmental processes. In addition, the MAPK cascades often appear to regulate the cell cycle and vice versa. Despite the success of the gene hunter era in revealing these pathways, there are still many significant gaps in our knowledge of the molecular mechanisms for activation of these cascades and how the cascades regulate cell function. For example, comparison of different yeast signaling pathways reveals a surprising variety of different types of upstream signaling proteins that function to activate a MAPK cascade, yet how the upstream proteins actually activate the cascade remains unclear. We also know that the yeast MAPK pathways regulate each other and interact with other signaling pathways to produce a coordinated pattern of gene expression, but the molecular mechanisms of this cross talk are poorly understood. This review is therefore an attempt to present the current knowledge of MAPK pathways in yeast and some directions for future research in this area.
Prochlorococcus
, a Marine Photosynthetic Prokaryote of Global Significance
Authors: Partensky F. , Hess W. R. , Vaulot D.
Published: December 2019

The minute photosynthetic prokaryote Prochlorococcus, which was discovered about 10 years ago, has proven exceptional from several standpoints. Its tiny size (0.5 to 0.7 μm in diameter) makes it the smallest known photosynthetic organism. Its ubiquity within the 40°S to 40°N latitudinal band of oceans and its occurrence at high density from the surface down to depths of 200 m make it presumably the most abundant photosynthetic organism on Earth. Prochlorococcus typically divides once a day in the subsurface layer of oligotrophic areas, where it dominates the photosynthetic biomass. It also possesses a remarkable pigment complement which includes divinyl derivatives of chlorophyll a (Chl a) and Chl b, the so-called Chl a
2
and Chl b
2
, and, in some strains, small amounts of a new type of phycoerythrin. Phylogenetically, Prochlorococcus has also proven fascinating. Recent studies suggest that it evolved from an ancestral cyanobacterium by reducing its cell and genome sizes and by recruiting a protein originally synthesized under conditions of iron depletion to build a reduced antenna system as a replacement for large phycobilisomes. Environmental constraints clearly played a predominant role in Prochlorococcus evolution. Its tiny size is an advantage for its adaptation to nutrient-deprived environments. Furthermore, genetically distinct ecotypes, with different antenna systems and ecophysiological characteristics, are present at depth and in surface waters. This vertical species variation has allowed Prochlorococcus to adapt to the natural light gradient occurring in the upper layer of oceans. The present review critically assesses the basic knowledge acquired about Prochlorococcus both in the ocean and in the laboratory.
Metabolic Engineering of Poly(3-Hydroxyalkanoates): From DNA to Plastic
Authors: Madison Lara L. , Huisman Gjalt W.
Published: December 2019

Poly(3-hydroxyalkanoates) (PHAs) are a class of microbially produced polyesters that have potential applications as conventional plastics, specifically thermoplastic elastomers. A wealth of biological diversity in PHA formation exists, with at least 100 different PHA constituents and at least five different dedicated PHA biosynthetic pathways. This diversity, in combination with classical microbial physiology and modern molecular biology, has now opened up this area for genetic and metabolic engineering to develop optimal PHA-producing organisms. Commercial processes for PHA production were initially developed by W. R. Grace in the 1960s and later developed by Imperial Chemical Industries, Ltd., in the United Kingdom in the 1970s and 1980s. Since the early 1990s, Metabolix Inc. and Monsanto have been the driving forces behind the commercial exploitation of PHA polymers in the United States. The gram-negative bacterium Ralstonia eutropha, formerly known as Alcaligenes eutrophus, has generally been used as the production organism of choice, and intracellular accumulation of PHA of over 90% of the cell dry weight have been reported. The advent of molecular biological techniques and a developing environmental awareness initiated a renewed scientific interest in PHAs, and the biosynthetic machinery for PHA metabolism has been studied in great detail over the last two decades. Because the structure and monomeric composition of PHAs determine the applications for each type of polymer, a variety of polymers have been synthesized by cofeeding of various substrates or by metabolic engineering of the production organism. Classical microbiology and modern molecular bacterial physiology have been brought together to decipher the intricacies of PHA metabolism both for production purposes and for the unraveling of the natural role of PHAs. This review provides an overview of the different PHA biosynthetic systems and their genetic background, followed by a detailed summation of how this natural diversity is being used to develop commercially attractive, recombinant processes for the large-scale production of PHAs.
Osmosensing by Bacteria: Signals and Membrane-Based Sensors
Authors: Wood Janet M.
Published: December 2019

Bacteria can survive dramatic osmotic shifts. Osmoregulatory responses mitigate the passive adjustments in cell structure and the growth inhibition that may ensue. The levels of certain cytoplasmic solutes rise and fall in response to increases and decreases, respectively, in extracellular osmolality. Certain organic compounds are favored over ions as osmoregulatory solutes, although K+fluxes are intrinsic to the osmoregulatory response for at least some organisms. Osmosensors must undergo transitions between “off” and “on” conformations in response to changes in extracellular water activity (direct osmosensing) or resulting changes in cell structure (indirect osmosensing). Those located in the cytoplasmic membranes and nucleoids of bacteria are positioned for indirect osmosensing. Cytoplasmic membrane-based osmosensors may detect changes in the periplasmic and/or cytoplasmic solvent by experiencing changes in preferential interactions with particular solvent constituents, cosolvent-induced hydration changes, and/or macromolecular crowding. Alternatively, the membrane may act as an antenna and osmosensors may detect changes in membrane structure. Cosolvents may modulate intrinsic biomembrane strain and/or topologically closed membrane systems may experience changes in mechanical strain in response to imposed osmotic shifts. The osmosensory mechanisms controlling membrane-based K+transporters, transcriptional regulators, osmoprotectant transporters, and mechanosensitive channels intrinsic to the cytoplasmic membrane of Escherichia coli are under intensive investigation. The osmoprotectant transporter ProP and channel MscL act as osmosensors after purification and reconstitution in proteoliposomes. Evidence that sensor kinase KdpD receives multiple sensory inputs is consistent with the effects of K+fluxes on nucleoid structure, cellular energetics, cytoplasmic ionic strength, and ion composition as well as on cytoplasmic osmolality. Thus, osmoregulatory responses accommodate and exploit the effects of individual cosolvents on cell structure and function as well as the collective contribution of cosolvents to intracellular osmolality.
Structural Features of the Glutamate Transporter Family
Authors: Slotboom Dirk Jan , Konings Wil N. , Lolkema Juke S.
Published: December 2019

Neuronal and glial glutamate transporters remove the excitatory neurotransmitter glutamate from the synaptic cleft and thus prevent neurotoxicity. The proteins belong to a large and widespread family of secondary transporters, including bacterial glutamate, serine, and C
4
-dicarboxylate transporters; mammalian neutral-amino-acid transporters; and an increasing number of bacterial, archaeal, and eukaryotic proteins that have not yet been functionally characterized. Sixty members of the glutamate transporter family were found in the databases on the basis of sequence homology. The amino acid sequences of the carriers have diverged enormously. Homology between the members of the family is most apparent in a stretch of approximately 150 residues in the C-terminal part of the proteins. This region contains four reasonably well-conserved sequence motifs, all of which have been suggested to be part of the translocation pore or substrate binding site. Phylogenetic analysis of the C-terminal stretch revealed the presence of five subfamilies with characterized members: (i) the eukaryotic glutamate transporters, (ii) the bacterial glutamate transporters, (iii) the eukaryotic neutral-amino-acid transporters, (iv) the bacterial C
4
-dicarboxylate transporters, and (v) the bacterial serine transporters. A number of other subfamilies that do not contain characterized members have been defined. In contrast to their amino acid sequences, the hydropathy profiles of the members of the family are extremely well conserved. Analysis of the hydropathy profiles has suggested that the glutamate transporters have a global structure that is unique among secondary transporters. Experimentally, the unique structure of the transporters was recently confirmed by membrane topology studies. Although there is still controversy about part of the topology, the most likely model predicts the presence of eight membrane-spanning α-helices and a loop-pore structure which is unique among secondary transporters but may resemble loop-pores found in ion channels. A second distinctive structural feature is the presence of a highly amphipathic membrane-spanning helix that provides a hydrophilic path through the membrane. Recent data from analysis of site-directed mutants and studies on the mechanism and pharmacology of the transporters are discussed in relation to the structural model.
Mechanisms of T-Cell Activation by Human T-Cell Lymphotropic Virus Type I
Authors: Höllsberg Per
Published: December 2019

The interactions between human T-cell lymphotropic virus type I (HTLV-I) and the cellular immune system can be divided into viral interference with functions of the infected host T cell and the subsequent interactions between the infected T cell and the cellular immune system. HTLV-I-mediated activation of the infected host T cell is induced primarily by the viral protein Tax, which influences transcriptional activation, signal transduction pathways, cell cycle control, and apoptosis. These properties of Tax may well explain the ability of HTLV-I to immortalize T cells. It is not clear, though, how HTLV-I induces T-cell transformation (interleukin-2 [IL-2] independence). Recent evidence suggests that Tax may promote the G1- to S-phase transition, although this may involve additional proteins. A role for other viral proteins that may constitutively activate the IL-2 receptor pathway has also been suggested. By virtue of their activated state, HTLV-I-infected T cells can nonspecifically activate resting, uninfected T cells via virus-mediated upregulation of adhesion molecules. This may favor viral dissemination. Moreover, the induction of a remarkably high frequency of antiviral CD8+T cells does not appear to eliminate the infection. Indeed, individuals with a high frequency of virus-specific CD8+T cells have a high viral load, indicating a state of chronic immune system stimulation. Thus, while an activated immune system is needed to eradicate the infection, the spread of the HTLV-I is also accelerated under these conditions. A detailed knowledge of the molecular interactions between virus-specific CD8+T cells and immunodominant viral epitopes holds promise for the development of specific antiviral therapy.
Prions in
Saccharomyces
and
Podospora
spp.: Protein-Based Inheritance
Authors: Wickner Reed B. , Taylor Kimberly L. , Edskes Herman K. , Maddelein Marie-Lise , Moriyama Hiromitsu , Roberts B. Tibor
Published: December 2019

Genetic evidence showed two non-Mendelian genetic elements of Saccharomyces cerevisiae, called [URE3] and [PSI], to be prions of Ure2p and Sup35p, respectively. [URE3] makes cells derepressed for nitrogen catabolism, while [PSI] elevates the efficiency of weak suppressor tRNAs. The same approach led to identification of the non-Mendelian element [Het-s] of the filamentous fungus Podospora anserina, as a prion of the het-s protein. The prion form of the het-s protein is required for heterokaryon incompatibility, a normal fungal function, suggesting that other normal cellular functions may be controlled by prions. [URE3] and [PSI] involve a self-propagating aggregation of Ure2p and Sup35p, respectively. In vitro, Ure2p and Sup35p form amyloid, a filamentous protein structure, high in β-sheet with a characteristic green birefringent staining by the dye Congo Red. Amyloid deposits are a cardinal feature of Alzheimer’s disease, non-insulin-dependent diabetes mellitus, the transmissible spongiform encephalopathies, and many other diseases. The prion domain of Ure2p consists of Asn-rich residues 1 to 80, but two nonoverlapping fragments of the molecule can, when overproduced, induce the de nova appearance of [URE3]. The prion domain of Sup35 consists of residues 1 to 114, also rich in Asn and Gln residues. While runs of Asn and Gln are important for [URE3] and [PSI], no such structures are found in PrP or the Het-s protein. Either elevated or depressed levels of the chaperone Hsp104 interfere with propagation of [PSI]. Both [URE3] and [PSI] are cured by growth of cells in millimolar guanidine HCl. [URE3] is also cured by overexpression of fragments of Ure2p or fusion proteins including parts of Ure2p.
Adding the Third Dimension to Virus Life Cycles: Three-Dimensional Reconstruction of Icosahedral Viruses from Cryo-Electron Micrographs
Authors: Baker T. S. , Olson N. H. , Fuller S. D.
Published: December 2019

Viruses are cellular parasites. The linkage between viral and host functions makes the study of a viral life cycle an important key to cellular functions. A deeper understanding of many aspects of viral life cycles has emerged from coordinated molecular and structural studies carried out with a wide range of viral pathogens. Structural studies of viruses by means of cryo-electron microscopy and three-dimensional image reconstruction methods have grown explosively in the last decade. Here we review the use of cryo-electron microscopy for the determination of the structures of a number of icosahedral viruses. These studies span more than 20 virus families. Representative examples illustrate the use of moderate- to low-resolution (7- to 35-Å) structural analyses to illuminate functional aspects of viral life cycles including host recognition, viral attachment, entry, genome release, viral transcription, translation, proassembly, maturation, release, and transmission, as well as mechanisms of host defense. The success of cryo-electron microscopy in combination with three-dimensional image reconstruction for icosahedral viruses provides a firm foundation for future explorations of more-complex viral pathogens, including the vast number that are nonspherical or nonsymmetrical.
Chronic mesenteric ischaemia masked by candida esophagitis in a renal transplant patient
Authors: Scheetz Seth , Pandey Deepali , Pesavento Todd E , Singh Priyamvada
Published: December 2019

Chronic mesenteric ischaemia is a severe disease that is often missed due to its non-specific presentation. Immunosuppressed patients are at risk for infectious gastrointestinal disease, which may further obscure the diagnosis of chronic mesenteric ischaemia. In this case, a patient’s symptoms and diagnostic workup were consistent with candida esophagitis. Worsening leukocytosis despite treatment, however, prompted re-evaluation ultimately revealing a superior mesenteric artery thrombus causing mesenteric ischaemia. The patient required urgent surgical intervention for the management of his disease.
Effectiveness of diabetes self-management education and support via a smartphone application in insulin-treated patients with type 2 diabetes: results of a randomized controlled trial (TRIGGER study)
Authors: Boels Anne Meike , Vos Rimke C , Dijkhorst-Oei Lioe-Ting , Rutten Guy E H M
Published: December 2019

Objective

To investigate the effect of diabetes self-management education and support via a smartphone app in individuals with type 2 diabetes on insulin therapy.

Research design and methods

Open two-arm multicenter parallel randomized controlled superiority trial. The intervention group (n=115) received theory and evidence-based self-management education and support via a smartphone app (optionally two or six times per week, once daily at different times). The control group (n=115) received care as usual. Primary outcome: HbA1c at 6 months. Other outcomes included HbA1c ≤53 mmol/mol (≤7%) without any hypoglycemic event, body mass index, glycemic variability, dietary habits and quality of life. We performed multiple imputation and regression models adjusted for baseline value, age, sex, diabetes duration and insulin dose.

Results

Sixty-six general practices and five hospital outpatient clinics recruited 230 participants. Baseline HbA1c was comparable between groups (8.1% and 8.3%, respectively). At 6 months, the HbA1c was 63.8 mmol/mol (8.0%) in the intervention vs 66.2 mmol/mol (8.2%) in the control group; adjusted difference −0.93 mmol/mol (−0.08%), 95% CI −4.02 to 2.17 mmol/mol (−0.37% to 0.20%), p=0.557. The odds for achieving an HbA1c level ≤7% without any hypoglycemic event was lower in the intervention group: OR 0.87, 95% CI 0.33 to 2.35. There was no effect on secondary outcomes. No adverse events were reported.

Conclusions

This smartphone app providing diabetes self-management education and support had small and clinically not relevant effects. Apps should be more personalized and target individuals who think the app will be useful for them.

Trial registration number

NTR5515.
Right-Site Care Programme with a community-based family medicine clinic in Singapore: secondary data analysis of its impact on mortality and healthcare utilisation
Authors: Ang Ian Yi Han , Ng Sheryl Hui-Xian , Rahman Nabilah , Nurjono Milawaty , Tham Tat Yean , Toh Sue-Anne , Wee Hwee Lin
Published: December 2019

Objective

Stable patients with chronic conditions could be appropriately cared for at family medicine clinics (FMC) and discharged from hospital specialist outpatient clinics (SOCs). The Right-Site Care Programme with Frontier FMC emphasised care organised around patients in community rather than hospital-based providers, with one identifiable primary provider. This study evaluated impact of this programme on mortality and healthcare utilisation.

Design

A retrospective study without randomisation using secondary data analysis of patients enrolled in the intervention matched 1:1 with unenrolled patients as controls.

Setting

Programme was supported by the Ministry of Health in Singapore, a city-state nation in Southeast Asia with 5.6 million population.

Participants

Intervention group comprises patients enrolled from January to December 2014 (n=684) and control patients (n=684) with at least one SOC and no FMC attendance during same period.

Interventions

Family physician in Frontier FMC managed patients in consultation with relevant specialist physicians or fully managed patients independently. Care teams in SOCs and FMC used a common electronic medical records system to facilitate care coordination and conducted regular multidisciplinary case conferences.

Primary outcome measures

Deidentified linked healthcare administrative data for time period of January 2011 to December 2017 were extracted. Three-year postenrolment mortality rates and utilisation frequencies and charges for SOC, public primary care centres (polyclinic), emergency department attendances and emergency, non-day surgery inpatient and all-cause admissions were compared.

Results

Intervention patients had lower mortality rate (HR=0.37, p<0.01). Among those with potential of postenrolment polyclinic attendance, intervention patients had lower frequencies (incidence rate ratio (IRR)=0.60, p<0.01) and charges (mean ratio (MR)=0.51, p<0.01). Among those with potential of postenrolment SOC attendance, intervention patients had higher frequencies (IRR=2.06, p<0.01) and charges (MR=1.86, p<0.01).

Conclusions

Intervention patients had better survival, probably because their chronic conditions were better managed with close monitoring, contributing to higher total outpatient attendance frequencies and charges.
Transitional care quality indicators to assess quality of care following hospitalisation for chronic obstructive pulmonary disease and heart failure: a systematic review protocol
Authors: Michael Faith , Whitelaw Sera , Van Spall Harriette GC
Published: December 2019

Introduction

The period following hospitalisation for chronic obstructive pulmonary disease (COPD) or heart failure (HF)—when patients transition between settings and clinicians—is one of high risk. Transitional care services that bridge the gap from hospital to home can improve outcomes, but there are no widely accepted indicators to assess their quality.

Methods and analysis

In this systematic review, we will summarise transitional care quality indicators, and describe their associations with clinical, patient-reported and cost outcomes. We will search MEDLINE, Embase, CINAHL and HealthSTAR, as well as grey literature and reference lists of included articles. We will screen all studies published between January 1990 and October 2019 that test an intervention that aims to improve the hospital-to-home transition for patients with COPD and/or HF; and measure at least one process (eg, medication errors), clinical (eg, hospital readmissions) or patient-reported (eg, health-related quality of life) outcome which will serve as a transitional care quality indicator . We will include randomised controlled trials, cohort studies, cross-sectional studies, interrupted time series studies and before–after studies. We will extract data in duplicate and classify transitional care quality indicators as structural, process-related or outcome-related. When possible, we will assess associations between transitional care quality indicators and clinical outcomes. In anticipation of conceptual and statistical heterogeneity, we will provide a qualitative synthesis and narrative review of the results.

Ethics and dissemination

This review will provide a list of transitional care quality indicators and their associations with clinical outcomes. These results can be used by hospitals, administrators and clinicians for assessing the quality of transitional care provided to patients with COPD and HF. The findings can also be used by policy-makers to assess and incentivise transitional care quality. We will disseminate results through publications, social media releases and presentations.

PROSPERO registration number

This study is registered on PROSPERO.
Finding/identifying primaries with neck disease (FIND) clinical trial protocol: a study integrating transoral robotic surgery, histopathological localisation and tailored deintensification of radiotherapy for unknown primary and small oropharyngeal head and neck squamous cell carcinoma
Authors: de Almeida John R , Noel Christopher W , Veigas Maria , Martino Rosemary , Chepeha Douglas B , Bratman Scott V , Goldstein David P , Hansen Aaron R , Yu Eugene , Metser Ur , Weinreb Ilan , Perez-Ordonez Bayardo , Xu Wei , Kim John
Published: December 2019

Introduction

Carcinomas of unknown primary site (CUP) of the head and neck have historically been worked up and managed heterogeneously. Failure to identify a primary site may result in large radiotherapy mucosal volumes. Transoral approaches such as Transoral Robotic Surgery (TORS) may improve the yield of identifying hidden primaries. We aim to assess the oncological and functional outcomes of a combined treatment approach with TORS and tailored radiotherapy.

Methods and analysis

Twenty-five patients with metastatic squamous cell carcinoma to the neck without clinical or radiographic evidence of a primary site will be enrolled in a phase II trial. Patients will undergo a diagnostic or therapeutic approach with TORS based on specific algorithms incorporating tailored radiotherapy according to the location and laterality of the primary tumour. The primary outcome is to evaluate the out-of-field failure rate over a 2-year period. Secondary outcomes include identification rates, survival outcomes, patient reported outcomes and functional swallowing outcomes.

Ethics and dissemination

The University Health Network Research Ethics Board approved this study (ID 15–9767). The results will be published in an open access journal.

Trial registration number

NCT03281499.
Enhanced Risk of Traumatic Brain Injury in Patients with Chronic Obstructive Pulmonary Disease
Authors: Huang Tang-Hsiu , Chen Chiung-Zuei , Kuo Hung-I , Er Hong-Ping , Lin Sheng-Hsiang
Published: December 2019

This study tests our hypothesis that patients with chronic obstructive pulmonary disease (COPD) have an increased risk of traumatic brain injury (TBI).

In this nationwide retrospective cohort study, we used a subset of Taiwan's National Health Insurance Research Database, involving 1 million randomly selected beneficiaries. Patients with newly diagnosed COPD between 2000 and 2008 were identified. They were subgrouped as ‘COPDAE+’ (if they had severe acute exacerbation of COPD during the follow-ups) or ‘COPDAE−’ (if they had no acute exacerbation), and were frequency matched with randomly selected subjects without COPD (the ‘non-COPD’ group). Baseline differences were balanced by the inverse probability of treatment weighting based on the propensity score. For each patient, the risk of TBI during the subsequent 5 years was determined. The competing risk of death was controlled.

We identified 3734 patients in ‘COPDAE+’, and frequency matched them with 11,202 patients in ‘COPDAE−’ and 11,202 subjects in ‘non-COPD’. Compared with those in ‘non-COPD’, patients in ‘COPDAE+’ and ‘COPDAE−’ had an increased risk of TBI: the adjusted HR for ‘COPDAE+’ was 1.50, 95% CI 1.31 to 1.73, and that for ‘COPDAE−’ was 1.21, 95% CI 1.09 to 1.34. The highest risk was observed in the ‘COPDAE+’ group that aged <65 (the adjusted HR was 1.92; 95% CI 1.39 to 2.64).

COPD has been linked to complications beyond the respiratory system. In this study we showed that COPD is associated with an increased risk of TBI.
FIRM LOCATION AND INNOVATION: EVIDENCE FROM CHINESE LISTED FIRMS
Authors: XU JIAN , YANG XI , XIN DAQI , ZHOU WENCANG , ZHU XIAOYANG
Published: December 2019

Matching city-level and province-level GDP data with firm headquarters’ locations for a sample of Chinese listed firms from 2003 to 2015, we find that firm locations are positively and significantly associated with firm innovation. In addition, firms with higher government grants have higher R&D inputs. The gap between firms’ innovation performance in ordinary cities and in non-ordinary cities is not significant in the eastern region; however, the gap is significant in the central and western regions of China. Finally, we use firm relocation to tackle the endogeneity issue and find that firms relocated to cities with larger size of economy are associated with higher innovation performance.
Differential intestinal and oral microbiota features associated with gestational diabetes and maternal inflammation
Authors: Xu Yajuan , Zhang Miao , Zhang Jingzhe , Sun Zongzong , Ran Limin , Ban Yanjie , Wang Biao , Hou Xiaofeng , Zhai Shanshan , Ren Lidan , Wang Mengqi , Hu Jianzhong
Published: December 2019

Maternal microbiota is involved in many metabolic diseases. However, its role in the pathophysiology of gestational diabetes mellitus (GDM) remains unclear. In this case-control study, we performed a 16S rRNA sequencing-based microbial survey to compare the intestinal and oral microflora at third trimester during pregnancy between 30 GDM and 31 normal controls. Sequentially, a correlation-based network analysis was further performed to explore the interactions among microbiota, maternal and infant blood sugar, and inflammatory markers. Our results show that, compared with controls, the GDM cases showed significant differences in β-diversity and increased Gammaproteobacteria and Hemophilus in intestinal microbiota. Furthermore, the GDM cases showed lower α-diversity, increased Selenomonas and Bifidobacterium, and decreased Fusobacteria and Leptotrichia in oral microbiota. The ROC curve showed the area under the curve to be equal to 0.70 and 0.66 when using oral Leptotrichia or gut Hemophilus, respectively, to predict GDM status. In addition, the components and topography of microbial cooccurrence and coexclusion network were quite distinct by GDM status. In summary, intestinal and oral microorganisms in pregnant women are closely related to the status of GDM in the third trimester of pregnancy. The changes of intestinal and oral microbial features may be noninvasive biomarkers for monitoring the health management of GDM pregnancy.
Effects of 1-Methylcyclopropene Combined with Modified Atmosphere on Quality of Fig (Ficus carica L.) during Postharvest Storage
Authors: Song Congcong , Li Ang , Chai Yifeng , Li Qingpeng , Lin Qiong , Duan Yuquan
Published: December 2019

Fig (Ficus carica L.) is a highly nutritious fruit, which is rich in sugar, protein, amino acids, vitamins, and mineral elements. However, figs are perishable climacteric fruits, causing difficulty in postharvest storage and preservation. 1-Methylcyclopropene (1-MCP) and modified atmosphere (MA) are preservation methods with many applications, but the effects of their combination on quality of fig during postharvest storage have rarely been studied. The objective of this study was to investigate the effects of MA and MA+1-MCP treatments on postharvest quality of fig fruit stored at −1 ± 0.5°C for 30 days. The results showed that the MA+1-MCP treatment significantly improved the fruit texture, reduced the weight loss rate and malonaldehyde (MDA) accumulation, and inhibited the ethylene production and respiration rate compared with that in the control and MA groups. In summary, the MA+1-MCP treatment will be a good preservation method to maintain fruit quality of figs during postharvest storage.
Hints for Genetic and Clinical Differentiation of Adult-Onset Monogenic Autoinflammatory Diseases
Authors: Gaggiano Carla , Rigante Donato , Vitale Antonio , Lucherini Orso Maria , Fabbiani Alessandra , Capozio Giovanna , Marzo Chiara , Gelardi Viviana , Grosso Salvatore , Frediani Bruno , Renieri Alessandra , Cantarini Luca
Published: December 2019

Monogenic autoinflammatory diseases (mAIDs) are inherited errors of innate immunity characterized by systemic inflammation recurring with variable frequency and involving the skin, serosal membranes, synovial membranes, joints, the gastrointestinal tube, and/or the central nervous system, with reactive amyloidosis as a potential severe long-term consequence. Although individually uncommon, all mAIDs set up an emerging chapter of internal medicine: recent findings have modified our knowledge regarding mAID pathophysiology and clarified that protean inflammatory symptoms can be variably associated with periodic fevers, depicting multiple specific conditions which usually start in childhood, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndrome, and mevalonate kinase deficiency. There are no evidence-based studies to establish which potential genotype analysis is the most appropriate in adult patients with clinical phenotypes suggestive of mAIDs. This review discusses genetic and clinical hints for an ideal diagnostic approach to mAIDs in adult patients, as their early identification is essential to prompt effective treatment and improve quality of life, and also highlights the most recent developments in the diagnostic work-up for the most frequent hereditary periodic febrile syndromes worldwide.
Bu Shen Zhu Yun Decoction Improves Endometrial Receptivity via VEGFR-2-Mediated Angiogenesis
Authors: Li Li , Jiang Huabo , Wei Xuecong , Geng Dandan , He Ming , Du Huilan
Published: December 2019

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.
A New Coupled Fixed Point Result in Extended Metric Spaces with an Application to Study the Stability of Set-Valued Functional Equations
Authors: Soliman Ahmed H. , Zidan A. M.
Published: December 2019

In this paper, we introduce a new coupled fixed point theorem in a generalized metric space and utilize the same to study the stability for a system of set-valued functional equations.
Molecular Modelling and Dynamics Study of nsSNP in STXBP1 Gene in Early Infantile Epileptic Encephalopathy Disease
Authors: Al Mehdi Krami , Fouad Benhnini , Zouhair Elkarhat , Boutaina Belkady , Yassine Naasse , Chaimaa Ait El Cadi , Najat Sifeddine , Hassan Rouba , Rachida Roky , Abdelhamid Barakat , Halima Nahili
Published: December 2019

Early Infantile Epileptic Encephalopathy (known as Ohtahara Syndrome) is one of the most severe and earliest forms of epilepsy, characterized by early seizures onset. It affects newborns and children between two and six years old. Among the genes that have been associated with early infantile epileptic encephalopathy, the STXBP1 gene, which encodes the Syntaxin binding protein1a that is involved in SNARE complex formation, contributes to synaptic vesicles exocytosis. The aim of this study was to identify the most pathogenic polymorphisms of STXBP1 gene and determine their impact on the structure and stability of Stxbp1 protein. The high-risk nonsynonymous single nucleotide polymorphisms (nsSNPs) in the STXBP1 gene were predicted using 13 bioinformatics tools. The conservation analysis was realized by CONSURF web server. The analysis of the impact of the pathogenic SNPs on the structure of Stxbp1 protein was realized using YASARA software, and the molecular dynamics simulation was performed using GROMACS software. Out of 245 nsSNPs, we identified 11 (S42P, H103D R190W, R235G, D238E, L256P, P335S, C354Y, L365V, R406C, and G544D) as deleterious using in silico prediction tools. Conservation analysis results revealed that all these nsSNPs were located in conserved regions. The comparison of the hydrogen and hydrophobic interactions in the wild type Stxbp1 structure and its mutant forms showed that all these nsSNPs affect the protein structure on different levels. The molecular dynamics simulations revealed that the total of nsSNPs affect the protein stability, residual fluctuation, and the compaction at different levels. This study provides helpful information on high risk nsSNPs that may affect the Stxbp1 protein structure and function. Thus, these variants should be taken into consideration during the genetic screening of patients suffering from early infantile epileptic encephalopathy.
Data Analysis and Accuracy Evaluation of a Continuous Glucose-Monitoring Device
Authors: Cai Lijun , Ge Wancheng , Zhu Zhigang , Zhao Xueling , Li Zhanhong
Published: December 2019

This study was aimed at analyzing data and evaluating the accuracy of a new subcutaneous continuous glucose-monitoring device by referring to finger-pricking measurement. The data were obtained from 7 diabetic patients. An improved implanted flex sensor was used to measure the interstitial glucose concentration every 3 min within 6 days, and five finger-pricking samples were collected every day for comparison. A periodic glucose change happened every day. 2.45% of CGM values were in the hypoglycemic range (<70 mg/dl), 55.4% were in the normal range (70-180 mg/dl), and 42.15% were in the hyperglycemic range (>180 mg/dl). The interstitial glucose concentrations (n=204) were well linearly correlated with the capillary glucose concentrations (r=0.94, P<0.01), but a delay occurred between 10 and 40 minutes within two measurements (CGM later), and the individual average delay times were relatively close to 24.6 minutes. Clarke’s error grid analysis showed that 86.7% of the points fell in zone A, 12.7% fell in zone B, and only 0.6% fell in zone D. An overall MARD was 10.22%. This study demonstrated that the CGM was accurate and highly reliable; thus, it constituted a new device for continuous glucose monitoring in diabetic patients.
Time-Frequency Linearization of Reactive Cortical Responses for the Early Detection of Balance Losses
Authors: Mezzina Giovanni , De Venuto Daniela
Published: December 2019

Aiming at finding a fast and accurate preimpact fall detection (PIFD) strategy, this paper proposes a novel methodology that precociously discriminates the occurrence of unexpected loss of balance from the steady walking, by analyzing the subject’s cortical signal modifications (at the scalp level) in the time-frequency domain. In this study, the subjects were asked to walk at their preferred speed on the treadmill platform programmed to provide unexpected bilateral slippages. The proposed PIFD method exploits synchronously recorded electromyographic (EMG: 2 channels from the same lower limb muscle bundle, bilaterally) and electro-encephalographic (EEG: 13 channels from motor, sensory-motor and parietal cortex areas) signals. To validate the method offline, also, the lower limb kinematics has been reconstructed via a motion capture system (23 reflective markers and 8 fixed cameras). During the PIFD system functioning, the EMG signals from the lateral gastrocnemii are first translated in a binary waveform and then used to trigger the EEG analysis. Once enabled via EMG (every gait cycle), the EEG computation branch extracts and linearizes the rate of variation in the EEG power spectrum density (PSD) for five bands of interests: θ (4–7 Hz), α (8–12 Hz), β I, β II, β III rhythms (13–15 Hz, 16–20 Hz, and 21–28 Hz). The slope of the linearized trend identifies, in this context, the cortical responsiveness parameter. Experimental results from six subjects revealed that the proposed system can distinguish the loss of balance with an overall accuracy of ~96% (average value between sensitivity and specificity). The discrimination process requests, on average, 370.6 ms. This value could be considered suitable for the implementation of countermeasures aimed at restoring the balance of the subject.
Detection of Ascorbic Acid Using Green Synthesized Carbon Quantum Dots
Authors: Wei Yuyun , Zhang Di , Fang Yuxin , Wang Hong , Liu Yangyang , Xu Zhifang , Wang Shenjun , Guo Yi
Published: December 2019

In this work, carbon quantum dots (CQDs) were synthesized by microwave irradiation and were electropolymerized on glassy carbon electrode (GCE) to establish an electrochemical sensor for the selective detection of ascorbic acid (AA). Electrochemical behaviors of the prepared sensor were investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). Herein, two wide linear responses were obtained in ranges of 0.01-3 mM and 4-12 mM with a low detection limit of 10 μM to AA. High sensitivities (44.13 μA-1 μM-1 cm-2, 9.66 μA-1 μM-1 cm-2, respectively) corresponding to the linear ranges were also achieved. In addition, the electrochemical sensor exhibited good selectivity and robust anti-interference ability toward AA in the presence of dopamine (DA) and uric acid (UA). These results showed that this sensor can be used as a promising tool to detect AA in real complex systems.
A Retrospective Study of a Chinese Traditional Medicine YIKEER in the Treatment of Verruca Patients in Liaoning District
Authors: Jiang S. B. , Lu Y. S. , Zhang Y. H. , Wu Y. , Wang H. X. , Gao X. H. , Chen H. D.
Published: December 2019

Background. There are many possible ways to treat verruca, but no one is the single perfect treatment. YIKEER is a kind of compound preparation of Chinese traditional medicine, which has been used in the treatment of verruca for several years. Aim. To confirm the effects of YIKEER for verruca. Method. Patients with verruca vulgaris, verruca plantaris, or verruca plana were instructed to apply YIKEER stock solution or diluent to the lesions once or twice daily for 5–7 days. Then, the YIKEER was ceased for 3–4 days, and sea buckthorn oil was used for wound repairing. The total procession was defined as one session. Result. Respective 88.05% verruca vulgaris patients, 86.03% verruca plantaris patients, and 82.42% verruca plana patients achieved complete response. Most patients gained complete or partial responses after 4 treatment sessions. The percentage of patients who achieved at least 50% improvement was 90.34% for verruca vulgaris, 90.60% for verruca plantaris, and 80.91% for verruca plana after 4-session treatment. The efficacy of verruca vulgaris or verruca plantaris was better than that of verruca plana. Conclusion. YIKEER is an effective, safe, and well-tolerated agent for treating verruca including verruca vulgaris, verruca plantaris, and verruca plana.
Relações controversas com o outro na goa de seiscentos
Authors: Silva Regina Célia de Carvalho Pereira da
Published: December 2019

A diferença entre os homens foi sempre uma constante na história da humanidade. Durante os primeiros anos do século XVII, várias fricções relacionais surgiram entre a Santa Sé e o Padroado Português, relativas ao envio de missionários, á ordenação sacerdotal de naturais e á administração das missões. Tal conflitualidade repercutiu-se nas missões presentes nas colónias portuguesas, nomeadamente em Goa. Este trabalho focaliza-se na análise de alguns manuscritos do Fondo Gesuitico Collegia do ARSI e quer evidenciar os elementos históricos e socioculturais dessa conjuntura, no âmbito duma visão transdisciplinar e duma ampla intercompreensão histórico-literária da convivência entre culturas.
ORGANİK ÜRÜNLERDE TÜKETİCİ TUTUMUNU ETKİLEYEN FAKTÖRLER VE SATIN ALMA TÜRLERİ: GÜMÜŞHANE İLİ ÖRNEĞİ
Authors: AVCI İbrahim , YILDIZ Salih
Published: December 2019

Bu araştırmanın amacı organik ürünlerin algılanan kalitesi, algılanan değeri ve dışsal özellikleri ile tüketicilerin geçmiş deneyimleri ve yaşam biçimlerinin organik ürünlere yönelik tutum üzerine etkisi ve organik ürünlere yönelik tutumun gerçek satın alma davranışı ve tekrar satın alma niyeti üzerinde etkisinin olup olmadığını belirlemektir. Araştırma çerçevesinde oluşturulan anket formu 24 Aralık 2018 - 7 Ocak 2019 tarihleri aralığında Gümüşhane ilinde yaşayan 420 tüketiciye yüzyüze uygulanmıştır. Eksik ve hatalı doldurulan 12 anketin elenmesinden sonra 408 anket analize dahil edilmiştir. Elde edilen veriler SPSS 21 ve AMOS 24 ile analiz edilmiştir. Analiz sonucunda tüketicilerin yaşam biçimi ile organik ürünlerin dışsal özelliklerinin organik ürünlere yönelik tutum üzerinde bir anlamlı etkisinin olmadığı, organik ürünlerin algılanan kalitesi, algılanan değeri ve tüketicilerin geçmiş deneyimlerinin organik ürünlere yönelik tutum üzerinde anlamlı ve olumlu etkisinin olduğu belirlenmiştir.