ResearchPad - biotechnology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Comparability of modern contraceptive use estimates between a face-to-face survey and a cellphone survey among women in Burkina Faso]]> https://www.researchpad.co/article/elastic_article_13849 The proliferation of cell phone ownership in Sub-Saharan Africa (SSA) presents the opportunity to collect public health indicators at a lower cost compared to face-to-face (FTF) surveys. This analysis assesses the equivalence of modern contraceptive prevalence estimates between a nationally representative FTF survey and a cell phone survey using random digit dialing (RDD) among women of reproductive age in Burkina Faso.MethodsWe analyzed data from two surveys conducted in Burkina Faso between December 2017 and May 2018. The FTF survey conducted by Performance Monitoring and Accountability (PMA2020) comprised a nationally representative sample of 3,556 women of reproductive age (15–49 years). The RDD survey was conducted using computer-assisted telephone interviewing and included 2,379 women of reproductive age.ResultsCompared to FTF respondents, women in the RDD sample were younger, were more likely to have a secondary degree and to speak French. RDD respondents were more likely to report using modern contraceptive use (40%) compared to FTF respondents (26%) and the difference remained unchanged after applying post-stratification weights to the RDD sample (39%). This difference surpassed the equivalence margin of 4%. The RDD sample also produced higher estimates of contraceptive use than the subsample of women who owned a phone in the FTF sample (32%). After adjusting for women’s sociodemographic factors, the odds of contraceptive use were 1.9 times higher (95% CI: 1.6–2.2) in the RDD survey compared to the FTF survey and 1.6 times higher (95% CI: 1.3–1.8) compared to FTF phone owners.ConclusionsModern contraceptive prevalence in Burkina Faso is over-estimated when using a cell phone RDD survey, even after adjusting for a number of sociodemographic factors. Further research should explore causes of differential estimates of modern contraceptive use by survey modes. ]]> <![CDATA[Fine-scale visualizing the hierarchical structure of mouse biliary tree with fluorescence microscopy method]]> https://www.researchpad.co/article/elastic_article_13843 The liver is a vital organ and the hepatic lobule serves as the most basic structural and functional unit which is mainly assembled with parenchymal cells including hepatocytes and biliary epithelial cells. The continuous tubular arrangement of biliary cells which constitutes the biliary tracts is critical for liver function, however, the biliary tracts are often disrupted in many liver diseases such as cirrhosis and some congenital disorders. Visualization of the biliary tracts in fine-scale and three-dimension will help to understanding the structure basis of these liver diseases. In the present study, we established several biliary tract injury mouse models by diet feeding, surgery or genetic modification. The cytoplasm and nuclei of the parenchymal cells were marked by active uptake of fluorescent dyes Rhodamine B (red) and Hoechst (blue), respectively. After the removal of liver en bloc, the biliary tracts were retrogradely perfused with green fluorescent dye, fluorescein isothiocyanate (FITC). The liver was then observed under confocal microscopy. The fine-scale and three-dimensional (3D) structure of the whole biliary tree, particularly the network of the end-terminal bile canaliculi and neighboring hepatocytes were clearly visualized. The biliary tracts displayed clear distinct characteristics in normal liver and diseased liver models. Taken together, we have developed a simple and repeatable imaging method to visualize the fine-scale and hierarchical architecture of the biliary tracts spreading in the mouse liver.

]]>
<![CDATA[Retrospectively ECG-gated helical vs. non-ECG-synchronized high-pitch CTA of the aortic root for TAVI planning]]> https://www.researchpad.co/article/elastic_article_13825 Multidetector computed tomography (MDCT) plays a key role in patient assessment prior to transcatheter aortic valve implantation (TAVI). However, to date no consensus has been established on what is the optimal pre-procedural imaging protocol. Variability in pre-TAVI acquisition protocols may lead to discrepancies in aortic annulus measurements and may potentially influence prosthesis size selection.PurposeThe current study evaluates the magnitude of differences in aortic annulus measurements using max-systolic, end-diastolic, and non-ECG-synchronized imaging, as well as the impact of method on prosthesis size selection.Material and methodsFifty consecutive TAVI-candidates, who underwent retrospectively-ECG-gated CT angiography (CTA) of the aortic root, directly followed by non-ECG-synchronized high-pitch CT of the entire aorta, were retrospectively included. Aortic root dimensions were assessed at each 10% increment of the R-R interval (0–100%) and on the non-ECG-synchronized scan. Dimensional changes within the cardiac cycle were evaluated using a 1-way repeated ANOVA. Agreement in measurements between max-systole, end-diastole and non-ECG-synchronized scans was assessed with Bland-Altman analysis.ResultsMaximal dimensions of the aortic root structures and minimum annulus-coronary ostia distances were measured during systole. Max-systolic measurements were significantly and substantially larger than end-diastolic (p<0.001) and non-ECG-synchronized measurements (p<0.001). Due to these discrepancies, the three methods resulted in the same prosthesis size selection in only 48–62% of patients.ConclusionsThe systematic differences between max-systolic, end-diastolic and non-ECG-synchronized measurements for relevant aortic annular dimensions are both statistically significant and clinically relevant. Imaging strategy impacts prosthesis size selection in nearly half the TAVI-candidates. End-diastolic and non-ECG-synchronized imaging does not provide optimal information for prosthesis size selection. Systolic image acquisition is necessary for assessment of maximal annular dimensions and minimum annulus-coronary ostia distances. ]]> <![CDATA[Is transjugular insertion of a temporary pacemaker a safe and effective approach?]]> https://www.researchpad.co/article/elastic_article_13814 Temporary pacemakers (TPMs) are usually inserted in an emergency situation. However, there are few reports available regarding which route of access is best or what the most preferred approach is currently in tertiary hospitals. This study aimed to compare procedure times, complication rates, and indications for temporary pacing between the transjugular and transfemoral approaches to TPM placement. We analyzed consecutive patients who underwent TPM placement. Indications; procedure times; and rates of complications including localized infection, any bleeding, and pacing wire repositioning rates were analyzed. A total of 732 patients (361 treated via the transjugular approach and 371 treated via the transfemoral approach) were included. Complete atrioventricular block was the most common cause of TPM placement in both groups, but sick sinus syndrome was especially common in the transjugular approach group. Separately, procedure time was significantly shorter in the transjugular approach group (9.0 ± 8.0 minutes vs. 11.9 ± 9.7 minutes; P < 0.001). Overall complication rates were not significantly different between the two groups, and longer duration of temporary pacing was a risk factor for repositioning. The risk of reposition was significantly increased when the temporary pacing was continued more than 5 days and 3 days in the transjugular approach group and the transfemoral approach group, respectively. The transjugular approach should be considered if the TPM is required for more than 3 days.

]]>
<![CDATA[Chloroplast genomes of Rubiaceae: Comparative genomics and molecular phylogeny in subfamily Ixoroideae]]> https://www.researchpad.co/article/elastic_article_11231 In Rubiaceae phylogenetics, the number of markers often proved a limitation with authors failing to provide well-supported trees at tribal and generic levels. A robust phylogeny is a prerequisite to study the evolutionary patterns of traits at different taxonomic levels. Advances in next-generation sequencing technologies have revolutionized biology by providing, at reduced cost, huge amounts of data for an increased number of species. Due to their highly conserved structure, generally recombination-free, and mostly uniparental inheritance, chloroplast DNA sequences have long been used as choice markers for plant phylogeny reconstruction. The main objectives of this study are: 1) to gain insight in chloroplast genome evolution in the Rubiaceae (Ixoroideae) through efficient methodology for de novo assembly of plastid genomes; and, 2) to test the efficiency of mining SNPs in the nuclear genome of Ixoroideae based on the use of a coffee reference genome to produce well-supported nuclear trees. We assembled whole chloroplast genome sequences for 27 species of the Rubiaceae subfamily Ixoroideae using next-generation sequences. Analysis of the plastid genome structure reveals a relatively good conservation of gene content and order. Generally, low variation was observed between taxa in the boundary regions with the exception of the inverted repeat at both the large and short single copy junctions for some taxa. An average of 79% of the SNP determined in the Coffea genus are transferable to Ixoroideae, with variation ranging from 35% to 96%. In general, the plastid and the nuclear genome phylogenies are congruent with each other. They are well-resolved with well-supported branches. Generally, the tribes form well-identified clades but the tribe Sherbournieae is shown to be polyphyletic. The results are discussed relative to the methodology used and the chloroplast genome features in Rubiaceae and compared to previous Rubiaceae phylogenies.

]]>
<![CDATA[Incidence and determinants of Implanon discontinuation: Findings from a prospective cohort study in three health zones in Kinshasa, DRC]]> https://www.researchpad.co/article/elastic_article_7634 Kinshasa is Africa's third largest city and one of the continent’s most rapidly growing urban areas. PMA2020 data showed that Kinshasa has a modern contraceptive prevalence of 26.5% among married women in 2018. In Kinshasa’s method mix, the contraceptive implant recently became the dominant method among contraceptive users married and in union. This study provides insight into patterns of implant use in a high-fertility setting by evaluating the 24-month continuation rate for Implanon NXT and identifying the characteristics associated with discontinuation.MethodologyThis community-based, prospective cohort study followed 531 Implanon users aged 18–49 years at 6, 12 and 24 months. The following information was collected: socio-demographic characteristics, Method Information Index (MII) and contraceptive history. The main outcome variable for this study was implant discontinuation. The incidence rate of discontinuation is presented as events per 1000 person/months (p-m), from the date of enrolment. The Cox proportional hazards modelling was used to measure predictors of discontinuation.ResultsA total of 9158.13 p-m were available for analysis, with an overall incidence rate of 9.06 (95% CI: 9.04–9.08) removals per 1000 p-m. Of nine possible co-variates tested, the likelihood of discontinuation was higher among women who lived in military camps, had less than three children, never used injectables or implants in the past, had experienced heavy/prolonged bleeding, and whose MII score was less than 3.ConclusionIn addition to four client characteristics that predicted discontinuation, we identified one programmatic factor: quality of counseling as measured by the Method Information Index. Community providers in similar contexts should pay more attention to clients having less than three children, new adopters, and to clients living military camps as underserved population, where clients have less access to health facilities. More targeted counselling and follow-up is needed, especially on bleeding patterns. ]]> <![CDATA[Targeting Acidic Diseased Tissues by pH-Triggered Membrane-Associated Peptide Folding]]> https://www.researchpad.co/article/elastic_article_7494 The advantages of targeted therapy have motivated many efforts to find distinguishing features between the molecular cell surface landscapes of diseased and normal cells. Typically, the features have been proteins, lipids or carbohydrates, but other approaches are emerging. In this discussion, we examine the use of cell surface acidity as a feature that can be exploited by using pH-sensitive peptide folding to target agents to diseased cell surfaces or cytoplasms.

]]>
<![CDATA[State-of-Art Bio-Assay Systems and Electrochemical Approaches for Nanotoxicity Assessment]]> https://www.researchpad.co/article/elastic_article_7452 Innovations in the field of nanotechnology, material science and engineering has rendered fruitful utilities in energy, environment and healthcare. Particularly, emergence of surface engineered nanomaterials offered novel varieties in the daily consumables and healthcare products including therapeutics and diagnostics. However, the nanotoxicity and bioactivity of the nanomaterials upon interaction with biological system has raised critical concerns to individual as well as to the environment. Several biological models including plant and animal sources have been identified to study the toxicity of novel nanomaterials, correlating the physio-chemical properties. Biological interaction of nanomaterials and its mediated physiological functions are studied using conventional cell/molecular biological assays to understand the expression levels of genetic information specific to intra/extra cellular enzymes, cell viability, proliferation and function. However, modern research still demands advanced bioassay methods to screen the acute and chronic effects of nanomaterials at the real-time. In this regard, bioelectrochemical techniques, with the recent advancements in the microelectronics, proved to be capable of providing non-invasive measurement of the nanotoxicity effects (in vivo and in vitro) both at single cellular and multicellular levels. This review attempted to provide a detailed information on the recent advancements made in development of bioassay models and systems for assessing the nanotoxicology. With a short background information on engineered nanomaterials and physiochemical properties specific to consumer application, present review highlights the multiple bioassay models evolved for toxicological studies. Emphasize on multiple mechanisms involved in the cell toxicity and electrochemical probing of the biological interactions, revealing the cytotoxicity were also provided. Limitations in the existing electrochemical techniques and opportunities for the future research focusing the advancement in single molecular and whole cell bioassay has been discussed.

]]>
<![CDATA[Bioprinting Cell- and Spheroid-Laden Protein-Engineered Hydrogels as Tissue-on-Chip Platforms]]> https://www.researchpad.co/article/elastic_article_7430 Human tissues, both in health and disease, are exquisitely organized into complex three-dimensional architectures that inform tissue function. In biomedical research, specifically in drug discovery and personalized medicine, novel human-based three-dimensional (3D) models are needed to provide information with higher predictive value compared to state-of-the-art two-dimensional (2D) preclinical models. However, current in vitro models remain inadequate to recapitulate the complex and heterogenous architectures that underlie biology. Therefore, it would be beneficial to develop novel models that could capture both the 3D heterogeneity of tissue (e.g., through 3D bioprinting) and integrate vascularization that is necessary for tissue viability (e.g., through culture in tissue-on-chips). In this proof-of-concept study, we use elastin-like protein (ELP) engineered hydrogels as bioinks for constructing such tissue models, which can be directly dispensed onto endothelialized on-chip platforms. We show that this bioprinting process is compatible with both single cell suspensions of neural progenitor cells (NPCs) and spheroid aggregates of breast cancer cells. After bioprinting, both cell types remain viable in incubation for up to 14 days. These results demonstrate a first step toward combining ELP engineered hydrogels with 3D bioprinting technologies and on-chip platforms comprising vascular-like channels for establishing functional tissue models.

]]>
<![CDATA[Extension of Genetic Marker List Using Unnatural Amino Acid System: An Efficient Genomic Modification Strategy in <i>Escherichia coli</i>]]> https://www.researchpad.co/article/elastic_article_7429 Genetic manipulations including chromosome engineering are essential techniques used to restructure cell metabolism. Lambda/Red (λ/Red)-mediated recombination is the most commonly applied approach for chromosomal modulation in Escherichia coli. However, the efficiency of this method is significantly hampered by the laborious removal of the selectable markers. To overcome the problem, the integration helper plasmid was constructed, pSBC1a-CtR, which contains Red recombinase, Cre recombinase, and exogenous orthogonal aminoacyl-transfer RNA (tRNA) synthetase/tRNA pairs, allows an unnatural amino acid (UAA) to be genetically encoded at the defined site of the antibiotic resistance gene-encoded protein. When UAAs are not in the culture medium, there was no expression in the antibiotic resistance gene-encoded protein. Accordingly, the next procedure of antibiotic gene excising is not needed. To verify this method, poxB gene was knocked out successfully. Furthermore, sequential deletion of three target genes (galR, ptsG, and pgi) was able to generate neurosporene-producing strain marked by high growth rate. Thus, the site-specific incorporation UAA mutagenesis system were used to control and expand the use of conditional selectable marker, and the technique is used to facilitate a rapid continuous genome editing in Escherichia coli.

]]>
<![CDATA[Simulative Minimization of Mass Transfer Limitations Within Hydrogel-Based 3D-Printed Enzyme Carriers]]> https://www.researchpad.co/article/elastic_article_7421 In biotechnology, immobilization of functional reactants is often done as a surface immobilization on small particles. Examples are chromatography columns and fixed-bed reactors. However, the available surface for immobilization is directly linked to particle diameter and bed porosity for these systems, leading to high backpressure for small particle sizes. When larger molecules, such as enzymes are immobilized, physical entrapment within porous materials like hydrogels is an alternative. An emerging technique for the production of geometrically structured, three-dimensional and scalable hollow bodies is 3D-printing. Different bioprinting methods are available to produce structures of the desired size, resolution and solids content. However, in case of entrapped enzymes mass transfer limitations often determine the achievable reactivities. With increasing complexity of the system, for example a fixed-bed reactor, 3D-simulation is indispensable to understand the local reaction conditions to be able to highlight the optimization potential. Based on experimental data, this manuscript shows the application of the dimensionless numbers effectiveness factor and Thiele modulus for the design of a 3D-printed flow-through reactor. Within the reactor, enzymes are physically entrapped in 3D-printed hydrogel lattices. The local reaction rate of the enzymes is directly dependent on the provided substrate amount at the site of reaction which is limited by the diffusion properties of the hydrogel matrix and the diffusion distance. All three parameters can be summed up by one key figure, the Thiele modulus, which, in short, quantifies mass transfer limitations of a catalytic system. Depending on the rate of the enzymatic reaction in correlation to the diffusional transport, mass transfer limitations will shift the optimum of the system, favoring slow enzyme kinetics and small diffusion distances. Comparison with the enzymatic reaction rate in solution yields the effectiveness factor of the system. As a result, the optimization potential of varying the 3D-printed geometries or the reaction rate within the experimentally available design space can be estimated.

]]>
<![CDATA[Review on Bioenergy Storage Systems for Preserving and Improving Feedstock Value]]> https://www.researchpad.co/article/elastic_article_7417 Long-term storage is a necessary unit operation in the biomass feedstock logistics supply chain, enabling biorefineries to run year-round despite daily, monthly, and seasonal variations in feedstock availability. At a minimum, effective storage approaches must preserve biomass. Uncontrolled loss of biomass due to microbial degradation is common when storage conditions are not optimized. This can lead to physical and mechanical challenges with biomass handling, size reduction, preprocessing, and ultimately conversion. This review summarizes the unit operations of dry and wet storage and how they may contribute to preserving or even improving feedstock value for biorefineries.

]]>
<![CDATA[Enhancing flavonoid production by promiscuous activity of prenyltransferase, BrPT2 from <i>Boesenbergia rotunda</i>]]> https://www.researchpad.co/article/N7adc3fc8-502e-4a64-99a2-eacda43411c6 Flavonoids and prenylated flavonoids are active components in medicinal plant extracts which exhibit beneficial effects on human health. Prenylated flavonoids consist of a flavonoid core with a prenyl group attached to it. This prenylation process is catalyzed by prenyltranferases (PTs). At present, only a few flavonoid-related PT genes have been identified. In this study, we aimed to investigate the roles of PT in flavonoid production. We isolated a putative PT gene (designated as BrPT2) from a medicinal ginger, Boesenbergia rotunda. The deduced protein sequence shared highest gene sequence homology (81%) with the predicted homogentisate phytyltransferase 2 chloroplastic isoform X1 from Musa acuminata subsp. Malaccensis. We then cloned the BrPT2 into pRI vector and expressed in B. rotunda cell suspension cultures via Agrobacterium-mediated transformation. The BrPT2-expressing cells were fed with substrate, pinostrobin chalcone, and their products were analyzed by liquid chromatography mass spectrometry. We found that the amount of flavonoids, namely alpinetin, pinostrobin, naringenin and pinocembrin, in BrPT2-expressing cells was higher than those obtained from the wild type cells. However, we were unable to detect any targeted prenylated flavonoids. Further in-vitro assay revealed that the reaction containing the BrPT2 protein produced the highest accumulation of pinostrobin from the substrate pinostrobin chalcone compared to the reaction without BrPT2 protein, suggesting that BrPT2 was able to accelerate the enzymatic reaction. The finding of this study implied that the isolated BrPT2 may not be involved in the prenylation of pinostrobin chalcone but resulted in high yield and production of other flavonoids, which is likely related to enzyme promiscuous activities.

]]>
<![CDATA[Effect of celecoxib in treatment of burn-induced hypermetabolism]]> https://www.researchpad.co/article/Ndeaf5b05-2afc-45be-92c0-1480786a5c1f Background: Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step of prostanoid biosynthesis. Under pathologic conditions, COX-2 activity can produce reactive oxygen species and toxic prostaglandin metabolites that exacerbate injury and metabolic disturbance. The present study was performed to investigate the effect of Celecoxib (the inhibitor of COX-2) treatment on lipolysis in burn mice.

Methods: One hundred male BALB/c mice were randomly divided into sham group, burn group, celecoxib group, and burn with celecoxib group (25 mice in each group). Thirty percent total body surface area (TBSA) full-thickness injury was made for mice to mimic burn injuries. Volume of oxygen uptake (VO2), volume of carbon dioxide output (VCO2), respiratory exchange ratio (RER), energy expenditure (EE), COX-2 and uncoupled protein-1 (UCP-1) expression in brown adipose tissue (BAT) were measured for different groups.

Results: Adipose tissue (AT) activation was associated with the augmentation of mitochondria biogenesis, and UCP-1 expression in isolated iBAT mitochondria. In addition, VO2, VCO2, EE, COX-2, and UCP-1 expression were significantly higher in burn group than in burn with celecoxib group (P<0.05).

Conclusion: BAT plays important roles in burn injury-induced hypermetabolism through its morphological changes and elevating the expression of UCP-1. Celecoxib could improve lipolysis after burn injury.

]]>
<![CDATA[The Joint Analysis of Multi-Omics Data Revealed the Methylation-Expression Regulations in Atrial Fibrillation]]> https://www.researchpad.co/article/N3550cfca-c0af-459c-8893-c96f0a99e93d

Atrial fibrillation (AF) is one of the most prevalent heart rhythm disorder. The causes of AF include age, male sex, diabetes, hypertension, valve disease, and systolic/diastolic dysfunction. But on molecular level, its mechanisms are largely unknown. In this study, we collected 10 patients with persistent atrial fibrillation, 10 patients with paroxymal atrial fibrillation and 10 healthy individuals and did Methylation EPICBead Chip and RNA sequencing. By analyzing the methylation and gene expression data using machine learning based feature selection method Boruta, we identified the key genes that were strongly associated with AF and found their interconnections. The results suggested that the methylation of KIF15 may regulate the expression of PSMC3, TINAG, and NUDT6. The identified AF associated methylation-expression regulations may help understand the molecular mechanisms of AF from a multi-omics perspective.

]]>
<![CDATA[Microbial Community Redundancy and Resilience Underpins High-Rate Anaerobic Treatment of Dairy-Processing Wastewater at Ambient Temperatures]]> https://www.researchpad.co/article/N0f288abc-5d2c-40b1-b30b-62a7c98e3f92

High-rate anaerobic digestion (AD) is a reliable, efficient process to treat wastewaters and is often operated at temperatures exceeding 30°C, involving energy consumption of biogas in temperate regions, where wastewaters are often discharged at variable temperatures generally below 20°C. High-rate ambient temperature AD, without temperature control, is an economically attractive alternative that has been proven to be feasible at laboratory-scale. In this study, an ambient temperature pilot scale anaerobic reactor (2 m3) was employed to treat real dairy wastewater in situ at a milk processing plant, at organic loading rates of 1.3 ± 0.6 to 10.6 ± 3.7 kg COD/m3/day and hydraulic retention times (HRT) ranging from 36 to 6 h. Consistent high levels of COD removal efficiencies, ranging from 50 to 70% for total COD removal and 70 to 84% for soluble COD removal, were achieved during the trial. Within the reactor biomass, stable active archaeal populations were observed, consisting mainly of Methanothrix (previously Methanosaeta) species, which represented up to 47% of the relative abundant active species in the reactor. The decrease in HRT, combined with increases in the loading rate had a clear effect on shaping the structure and composition of the bacterial fraction of the microbial community, however, without affecting reactor performance. On the other hand, perturbances in influent pH had a strong impact, especially when pH went higher than 8.5, inducing shifts in the microbial community composition and, in some cases, affecting negatively the performance of the reactor in terms of COD removal and biogas methane content. For example, the main pH shock led to a drop in the methane content to 15%, COD removals decreased to 0%, while the archaeal population decreased to ~11% both at DNA and cDNA levels. Functional redundancy in the microbial community underpinned stable reactor performance and rapid reactor recovery after perturbations.

]]>
<![CDATA[A Novel Synthetic Model of the Glucose-Insulin System for Patient-Wise Inference of Physiological Parameters From Small-Size OGTT Data]]> https://www.researchpad.co/article/N8ed61570-afdb-4e56-be39-61b850ced829

Existing mathematical models for the glucose-insulin (G-I) dynamics often involve variables that are not susceptible to direct measurement. Standard clinical tests for measuring G-I levels for diagnosing potential diseases are simple and relatively cheap, but seldom give enough information to allow the identification of model parameters within the range in which they have a biological meaning, thus generating a gap between mathematical modeling and any possible physiological explanation or clinical interpretation. In the present work, we present a synthetic mathematical model to represent the G-I dynamics in an Oral Glucose Tolerance Test (OGTT), which involves for the first time for OGTT-related models, Delay Differential Equations. Our model can represent the radically different behaviors observed in a studied cohort of 407 normoglycemic patients (the largest analyzed so far in parameter fitting experiments), all masked under the current threshold-based normality criteria. We also propose a novel approach to solve the parameter fitting inverse problem, involving the clustering of different G-I profiles, a simulation-based exploration of the feasible set, and the construction of an information function which reshapes it, based on the clinical records, experimental uncertainties, and physiological criteria. This method allowed an individual-wise recognition of the parameters of our model using small size OGTT data (5 measurements) directly, without modifying the routine procedures or requiring particular clinical setups. Therefore, our methodology can be easily applied to gain parametric insights to complement the existing tools for the diagnosis of G-I dysregulations. We tested the parameter stability and sensitivity for individual subjects, and an empirical relationship between such indexes and curve shapes was spotted. Since different G-I profiles, under the light of our model, are related to different physiological mechanisms, the present method offers a tool for personally-oriented diagnosis and treatment and to better define new health criteria.

]]>
<![CDATA[Development, Validation and Comparison of Artificial Neural Network Models and Logistic Regression Models Predicting Survival of Unresectable Pancreatic Cancer]]> https://www.researchpad.co/article/N19720d82-c604-4c5b-bd15-c57b82fc491d

Background: Prediction models for the overall survival of pancreatic cancer remain unsatisfactory. We aimed to explore artificial neural networks (ANNs) modeling to predict the survival of unresectable pancreatic cancer patients.

Methods: Thirty-two clinical parameters were collected from 221 unresectable pancreatic cancer patients, and their prognostic ability was evaluated using univariate and multivariate logistic regression. ANN and logistic regression (LR) models were developed on a training group (168 patients), and the area under the ROC curve (AUC) was used for comparison of the ANN and LR models. The models were further tested on the testing group (53 patients), and k-statistics were used for accuracy comparison.

Results: We built three ANN models, based on 3, 7, and 32 basic features, to predict 8 month survival. All 3 ANN models showed better performance, with AUCs significantly higher than those from the respective LR models (0.811 vs. 0.680, 0.844 vs. 0.722, 0.921 vs. 0.849, all p < 0.05). The ability of the ANN models to discriminate 8 month survival with higher accuracy than the respective LR models was further confirmed in 53 consecutive patients.

Conclusion: We developed ANN models predicting the 8 month survival of unresectable pancreatic cancer patients. These models may help to optimize personalized patient management.

]]>
<![CDATA[Development of a Novel Biosensor-Driven Mutation and Selection System via in situ Growth of Corynebacterium crenatum for the Production of L-Arginine]]> https://www.researchpad.co/article/N05d5801b-8b68-4f22-a617-501d66a939a2

The high yield mutants require a high-throughput screening method to obtain them quickly. Here, we developed an L-arginine biosensor (ARG-Select) to obtain increased L-arginine producers among a large number of mutant strains. This biosensor was constructed by ArgR protein and argC promoter, and could provide the strain with the output of bacterial growth via the reporter gene sacB; strains with high L-arginine production could survive in 10% sucrose screening. To extend the screening limitation of 10% sucrose, the sensitivity of ArgR protein to L-arginine was decreased. Corynebacterium crenatum SYPA5-5 and its systems pathway engineered strain Cc6 were chosen as the original strains. This biosensor was employed, and L-arginine hyperproducing mutants were screened. Finally, the HArg1 and DArg36 mutants of C. crenatum SYPA5-5 and Cc6 could produce 56.7 and 95.5 g L–1 of L-arginine, respectively, which represent increases of 35.0 and 13.5%. These results demonstrate that the transcription factor-based biosensor could be applied in high yield strains selection as an effective high-throughput screening method.

]]>
<![CDATA[Thrombogenic and Inflammatory Reactions to Biomaterials in Medical Devices]]> https://www.researchpad.co/article/Nb9eb8112-3323-4e0c-9df9-4847732622ad

Blood-contacting medical devices of different biomaterials are often used to treat various cardiovascular diseases. Thrombus formation is a common cause of failure of cardiovascular devices. Currently, there are no clinically available biomaterials that can totally inhibit thrombosis under the more challenging environments (e.g., low flow in the venous system). Although some biomaterials reduce protein adsorption or cell adhesion, the issue of biomaterial associated with thrombosis and inflammation still exists. To better understand how to develop more thrombosis-resistant medical devices, it is essential to understand the biology and mechano-transduction of thrombus nucleation and progression. In this review, we will compare the mechanisms of thrombus development and progression in the arterial and venous systems. We will address various aspects of thrombosis, starting with biology of thrombosis, mathematical modeling to integrate the mechanism of thrombosis, and thrombus formation on medical devices. Prevention of these problems requires a multifaceted approach that involves more effective and safer thrombolytic agents but more importantly the development of novel thrombosis-resistant biomaterials mimicking the biological characteristics of the endothelium and extracellular matrix tissues that also ameliorate the development and the progression of chronic inflammation as part of the processes associated with the detrimental generation of late thrombosis and neo-atherosclerosis. Until such developments occur, engineers and clinicians must work together to develop devices that require minimal anticoagulants and thrombolytics to mitigate thrombosis and inflammation without causing serious bleeding side effects.

]]>