Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating 'lncRNA OTTHUMT00000387022' from monocytes as a novel biomarker for coronary artery disease.

AIMS Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be established whether or not circulating lncRNAs can serve as biomarkers of CAD. METHODS AND RESULTS Using a microarray-based lncRNA expression profiling, we found 86 lncRNAs that were differentially expressed in circulating peripheral blood monocytes and plasma from 15 CAD patients and 15 control subjects. After choosing a consistent criterion (average normalized intensity ≥7 with significance <0.005) and confirmed by quantitative PCR, only three lncRNAs (CoroMarker, BAT5, and IL21R-AS1) remained as candidate CAD biomarkers. Using the analysis of area under the curve (AUC) of the receiver-operating characteristic in another pilot group and another larger cohort, CoroMarker was found to be the best candidate biomarker for CAD with an AUC of 0.920 and 95% confidence interval of 0.892-0.947. CoroMarker was independent from known CAD risk factors and other cardiovascular diseases. In a prospective study, we found that the sensitivity and specificity of CoroMarker were 76 and 92.5%, respectively. Functional enrichment analysis showed CoroMarker to be clustered with genes positively associated with signal transduction, transmembrane transport, synaptic transmission, and innate immunity and negatively associated with inflammation. These findings were validated in THP-1 cells; CoroMarker siRNA treatment decreased the concentrations of proinflammatory cytokines [interleukin (IL)-1β, IL-6, and tumour necrosis factor α] in the culture medium. CONCLUSION The present study suggests that CoroMarker is a novel and specific biomarker of CAD.
Benzodiazepine prescribing variation and clinical uncertainty in treating posttraumatic stress disorder.

OBJECTIVE Despite guideline recommendations against their use, benzodiazepines are among the most commonly prescribed psychotropic medications among veterans with posttraumatic stress disorder (PTSD) in the Veterans Health Administration (VHA). This observation suggests the potential for significant clinical uncertainty concerning the role of benzodiazepines in PTSD, which was examined by characterizing prescribing variation in the VHA across multiple levels of geographic aggregation and over time. METHODS Veterans with PTSD were identified from national VHA administrative data in fiscal years 1999 through 2009. Benzodiazepine prescribing frequencies were aggregated across 137 medical centers, 21 networks, and four U.S. regions, and the extent of variation was characterized at each level. Prescribing variation was also examined by comparing benzodiazepine use between rural and urban veterans and between veterans receiving care at community-based outpatient clinics versus medical centers. RESULTS Benzodiazepine prescribing variation decreased over time, particularly at the network and regional levels. Facility-level variation (medical centers) also declined, but substantial variation persisted through 2009 (range 14.7%–56.8%). At the national level, rural veterans were more likely to receive benzodiazepines in 1999 (odds ratio=1.24; 95% confidence interval=1.22–1.27), and this association persisted through 2009. However, regional subanalyses revealed that rural-versus-urban differences were observed only in the Midwest and South. Benzodiazepine prescribing was similar between community-based outpatient clinics and medical centers. CONCLUSIONS Variability in benzodiazepine prescribing across the VHA reflects uncertainty regarding the adoption of guideline recommendations. Although variation has decreased in recent years, targeted interventions among facilities with high rates of prescribing may be an efficient strategy to promote guideline-concordant care.
Current and Potential Role of Specially Formulated Foods and Food Supplements for Preventing Malnutrition among 6- to 23-Month-Old Children and for Treating Moderate Malnutrition among 6- to 59-Month-Old Children

Reducing child malnutrition requires nutritious food, breastfeeding, improved hygiene, health services, and (prenatal) care. Poverty and food insecurity seriously constrain the accessibility of nutritious diets that have high protein quality, adequate micronutrient content and bioavailability, macrominerals and essential fatty acids, low antinutrient content, and high nutrient density. Diets based largely on plant sources with few animal-source and fortified foods do not meet these requirements and need to be improved by processing (dehulling, germinating, fermenting), fortification, and adding animal-source foods, e.g., milk, or other specific nutrients. Options include using specially formulated foods (fortified blended foods, commercial infant cereals, or ready-to-use foods [RUFs; pastes, compressed bars, or biscuits]) or complementary food supplements (micronutrient powders or powdered complementary food supplements containing micronutrients, protein, amino acids, and/or enzymes or lipid-based nutrient supplements (120 to 250 kcal/day), typically containing milk powder, high-quality vegetable oil, peanut paste, sugar, and micronutrients. Most supplementary feeding programs for moderately malnourished children supply fortified blended foods, such as corn–soy blend, with oil and sugar, which have shortcomings, including too many antinutrients, no milk (important for growth), suboptimal micronutrient content, high bulk, and high viscosity. Thus, for feeding young or malnourished children, fortified blended foods need to be improved or replaced. Based on success with ready-to-use therapeutic foods (RUTFs) for treating severe acute malnutrition, modifying these recipes is also considered. Commodities for reducing child malnutrition should be chosen on the basis of nutritional needs, program circumstances, availability of commodities, and likelihood of impact. Data are urgently required to compare the impact of new or modified commodities with that of current fortified blended foods and of RUTF developed for treating severe acute malnutrition.
Three essays in bank mergers and market structure

I analyze the effects of bank mergers and competitive market structure after the Riegle-Neal Interstate Banking and Branching Efficiency Act. The first chapter studies the incentives to decide mergers and the effects of market competition. Nationwide branching from deregulation and the resulting bank consolidation have brought more a competitive market environment. In particular, branch networks play an important role in bank merger analysis. Using commercial banks’ branch-level location data in Texas from 1994 to 2005, I estimate a two-sided matching model of merging and target banks with transferable utility. To study post-match values, I apply the maximum score estimator developed by Fox (2010). I find the positive assortative matching of bank sizes and I confirm that a bank prefers matching with target banks that have geographically overlapping markets. Moreover, I extend the standard matching model to incorporate externalities of market competition and the merger activities of rivals. Competitive rivals lessen the effects of mergers but mergers that increase market power have positive externalities on unmatched banks. The second chapter develops a structural model of demand and supply for retail banking to predict post-merger price. Ownership consolidation can affect not only price but also product characteristics. Once demand parameters and price elasticities are estimated, the adjustments in banking characteristics following mergers are considered in order to estimate marginal costs. I apply Peters (2006) simulation methods to account for the discrepancy between simulated merger changes and actual changes.
Cold Hardiness of Winter-Acclimated Drosophila suzukii (Diptera: Drosophilidae) Adults

ABSTRACT Drosophila suzukii Matsumura, often called spotted wing drosophila, is an exotic vinegar fly that is native to Southeast Asia and was first detected in the continental United States in 2008. Previous modeling studies have suggested that D. suzukii might not survive in portions of the northern United States or southern Canada due to the effects of cold. As a result, we measured two aspects of insect cold tolerance, the supercooling point and lower lethal temperature, for D. suzukii summer-morph pupae and adults and winter-morph adults. Supercooling points were compared to adults of Drosophila melanogaster Meigen. The lower lethal temperature of D. suzukii winter-morph adults was significantly colder than that for D. suzukii summer-morph adults, while supercooling points of D. suzukii winter-morph adults were actually warmer than that for D. suzukii summer-morph adults and pupae. D. suzukii summer-morph adult supercooling points were not significantly different than those for D. melanogaster adults. These measures indicate that D. suzukii is a chill intolerant insect, and winter-morph adults are the most cold-tolerant life stage. These results can be used to improve predictions of where D. suzukii might be able to establish overwintering populations and cause extensive damage to spring fruit crops.
Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice

Substitution mutations in adjacent amino acids of the N-terminal domain of NPC1, a lysosomal membrane protein, abolish its cholesterol binding activity and impair its ability to export cholesterol from lysosomes of cultured cells lacking npc1 [Kwon HJ, et al. (2009) Cell 137:1213–1224]. Here, we show that the same two mutations (proline-202 and phenylalanine-203, both changed to alanine) reproduce the phenotype of complete NPC1 deficiency when knocked into the mouse npc1 gene by homologous recombination. Homozygous npc1pf/pf mice exhibited neurodegeneration beginning at day 49 and died at a median age of 84 d, as previously reported for mice that lack npc1. Liver and other organs of the npc1pf/pf mice accumulated excess cholesterol in lysosomes. In liver, mRNAs encoding several lysosomal proteins were elevated, including NPC1 and NPC2 and several digestive enzymes (acid lipase, β-glucuronidase, and cathepsins B and D). Weekly treatment with hydroxypropyl-β-cyclodextrin (HPCD) beginning at 7 wk reduced hepatic cholesterol accumulation and diminished the lysosomal mRNAs. We conclude that the cholesterol binding site in the N-terminal domain of NPC1 is essential for cholesterol export from lysosomes in living animals as it is in cultured cells. The HPCD-mediated reduction of excess lysosomal enzymes may contribute to the ability of this drug to delay the progression of NPC disease in mice.
Simulating Locational Equilibria and Evaluating the Empirical Performance of Hedonic Property Value Models

This paper develops an agent-based model of the housing market to investigate the empirical performance of hedonic estimators. The model uses Rosen’s (1974) bid function as the basis for an iterative bidding algorithm which solves for a vector of housing prices and a unique assignment of people to homes which jointly clear the market for housing. We prove that the algorithm will converge to a locational equilibrium, if one exists. The algorithm can also be used to solve for a new equilibrium following a large shock to an urban amenity. We exploit this capability to conduct a Monte Carlo evaluation of a repeat sales model. First we calibrate the model to approximate the distribution of housing prices in San Joaquin, California, where the choice of a home provides access to public schools in a particular school district. Then we introduce a policy which improves school quality in selected districts. After solving for a new equilibrium, we compare the amount that households would be willing to pay for the improvement with the rate at which that improvement is capitalized into housing prices. The results indicate we should be cautious in interpreting capitalization rates as welfare measures.
Disruption of six novel genes from chromosome VII of Saccharomyces cerevisiae reveals one essential gene and one gene which affects the growth rate

Six ORFs of unknown function located on chromosome VII of Saccharomyces cerevisiae were disrupted in two different genetic backgrounds, and the phenotype of the generated mutants was analysed. Disruptions of ORFs YGR256w, YGR272c, YGR273c, YGR275w and YGR276c were carried out using the disruption marker kanMX4 flanked by short homology regions, whereas ORF YGR255c was inactivated with a long flanking homology (LFH) disruption cassette (Wach et al., 1994 ). Tetrad analysis of the heterozygous disruptants revealed that ORF YGR255c, previously identified as COQ6 and encoding a protein involved in the biosynthesis of coenzime Q (Tzagoloff and Dieckmann, 1990 ), is an essential gene. The same analysis also revealed that sporulation of the ygr272cΔ heterozygous diploid produced two small colonies per ascus that were also G418‐resistant, indicating that the inactivation of ORF YGR272c could result in a slower growth rate. This result was confirmed by growth tests of the haploid disruptants and by complementation of the phenotype after transformation with a plasmid carrying the cognate gene. No phenotypes could be associated to the inactivation of ORFs YGR256w, YGR273c, YGR275w and YGR276c. Two of these genes have recently been further characterized: ORF YGR255w, renamed RTT102, encodes a regulator of the Ty1‐element transposition, whereas ORF YGR276c was found to encode the 70 kDa RNase H activity and was renamed RNH70 (Frank et al., 1999 ). Copyright © 2000 John Wiley & Sons, Ltd.
Guided Cell Migration on Microtextured Substrates with Variable Local Density and Anisotropy

This work reports the design of and experimentation with a topographically patterned cell culture substrate of variable local density and anisotropy as a facile and efficient platform to guide the organization and migration of cells in spatially desirable patterns. Using UV‐assisted capillary force lithography, an optically transparent microstructured layer of a UV curable poly(urethane acrylate) resin is fabricated and employed as a cell‐culture substrate after coating with fibronectin. With variable local pattern density and anisotropy present in a single cell‐culture substrate, the differential polarization of cell morphology and movement in a single experiment is quantitatively characterized. It is found that cell shape and velocity are exquisitely sensitive to variation in the local anisotropy of the two‐dimensional rectangular lattice arrays, with cell elongation and speed decreasing on symmetric lattice patterns. It is also found that cells could integrate orthogonal spatial cues when determining the direction of cell orientation and movement. Furthermore, cells preferentially migrate toward the topographically denser areas from sparser ones. Consistent with these results, it is demonstrated that systematic variation of local densities of rectangular lattice arrays enable a planar assembly of cells into a specified location. It is envisioned that lithographically defined substrates of variable local density and anisotropy not only provide a new route to tailoring the cell‐material interface but could serve as a template for advanced tissue engineering.
Cloning and Expression Analysis of the pcbAB-pcbC β-Lactam Genes in the Marine Fungus Kallichroma tethys

ABSTRACT Here we report the identification of the β-lactam biosynthesis genes pcbAB and pcbC from a cosmid genomic DNA library of the marine fungus Kallichroma tethys. A BLAST homology search showed that they share high sequence identity with the δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine (ACV) synthetases and isopenicillin N synthases, respectively, of various fungal and bacterial β-lactam producers, while phylogenetic analysis indicated a close relationship with homologous genes of the cephalosporin-producing pyrenomycete Acremonium chrysogenum. Expression analysis by reverse transciption-PCR suggested that both genes are highly regulated and are expressed in the late growth phase of K. tethys cultures. Complementation of an Aspergillus nidulans strain deficient in ACV synthetase suggested that at least pcbAB is functional, although attempts to isolate active antibiotic from K. tethys were unsuccessful.
Bioengineering strategies to generate artificial protein complexes

For many applications, increasing synergy between distinct proteins through organization is important for the specificity, regulation, and overall reaction efficiency. Although there are many examples of protein complexes in nature, a generalized method to create these complexes remains elusive. Many conventional techniques such as random chemical conjugation, physical adsorption onto surfaces, and encapsulation within matrices are imprecise approaches and can lead to deactivation of protein native functionalities. More “bio‐friendly” approaches such as genetically fused proteins and biological scaffolds often can result in low yields and low complex stability. Alternatively, site‐specific protein conjugation or ligation can generate artificial protein complexes that preserve the native functionalities of protein domains and maintain stability through covalent bonds. In this review, we describe three distinct methods to synthesize artificial protein complexes (genetic incorPoration of unnatural amino acids to introduce bio‐orthogonal azide and alkyne groups to proteins, split‐intein based expressed protein ligation, and sortase mediated ligation) and highlight interesting applications for each technique. Biotechnol. Bioeng. 2015;112: 1495–1505. © 2015 Wiley Periodicals, Inc.
Seroprevalence of Common Viral Diseases: A Hospital Based Study from Amritsar, India.

INTRODUCTION There is a paucity of published data on epidemiology of the viral infections in Punjab, India. The Viral Research and Diagnostic Laboratory (VRDL) located at Government Medical College (GMC), Amritsar conducts the initial diagnosis of common viruses circulating in the region. AIM To report the seroprevalence of various viral diseases in Amritsar and neighboring districts of Punjab along with the demographic and geographical data of the patients. MATERIALS AND METHODS Whole blood sera samples from a total of 5781 patients suspected of various viral diseases (chikungunya, dengue, hepatitis A, hepatitis B, hepatitis C, hepatitis E, herpes simplex-1 or herpes simplex-2) were received at VRDL, GMC, Amritsar from January 2015 to April 2016 and a cross sectional study was conducted. The diagnosis was based on serological assays. RESULTS Out of total 5781 suspected cases, 1790 were diagnosed with antibodies for atleast one of the tested viral diseases. Dengue virus was the highest occurring viral disease (56.77%). Male patients infected with viruses outnumbered female cases, except for hepatitis E and herpes simplex-1. The 21-40 years age group appeared to be the most susceptible age group for nearly all studied viral infections. Among the total nine reported outbreak investigations, largest encompassed 1335 dengue cases from Amritsar district. CONCLUSION VRDL established in GMC, Amritsar has become instrumental in detection of emerging and re-emerging viral diseases including outbreak investigation of communicable diseases. Timely action with the help of adequate information and capacity to diagnose the viruses might help in saving numerous lives.
Critical assessment of proteome‐wide label‐free absolute abundance estimation strategies

There is a great interest in reliable ways to obtain absolute protein abundances at a proteome‐wide scale. To this end, label‐free LC‐MS/MS quantification methods have been proposed where all identified proteins are assigned an estimated abundance. Several variants of this quantification approach have been presented, based on either the number of spectral counts per protein or MS1 peak intensities. Equipped with several datasets representing real biological environments, containing a high number of accurately quantified reference proteins, we evaluate five popular low‐cost and easily implemented quantification methods (Absolute Protein Expression, Exponentially Modified Protein Abundance Index, Intensity‐Based Absolute Quantification Index, Top3, and MeanInt). Our results demonstrate considerably improved abundance estimates upon implementing accurately quantified reference proteins; that is, using spiked in stable isotope labeled standard peptides or a standard protein mix, to generate a properly calibrated quantification model. We show that only the Top3 method is directly proportional to protein abundance over the full quantification range and is the preferred method in the absence of reference protein measurements. Additionally, we demonstrate that spectral count based quantification methods are associated with higher errors than MS1 peak intensity based methods. Furthermore, we investigate the impact of miscleaved, modified, and shared peptides as well as protein size and the number of employed reference proteins on quantification accuracy.
Challenges in the Clinical Development Requirements for the Marketing Authorization of New Medicines in Southeast Asia

A rapid growth of investment into clinical research and new drug development has manifested itself by an exponential increase of new products coming onto the worldwide market. The emerging pharmaceutical and biotech markets in Southeast Asia are believed to be extremely promising from a commercial point of view in the next decade. The unique position of the Asian market and the diversity in clinical research initiatives are linked with diverse regulatory requirements for clinical development and registration of new medicines. Some of these differences have an impact on timelines for marketing authorizations in South Korea, China, Thailand, Japan, Singapore, and other countries. One of the approaches to streamlining regulatory strategy in different countries is the initiation of multicountry international clinical trials trying to address requirements and allowing registration in several regional countries simultaneously. Increasing cooperation between South Asian countries in relation to regulatory requirements and clinical development will facilitate the registration of innovative medicines in this rapidly developing region of the world and enable improved cohesiveness between countries in a drug safety framework.
Interobserver reproducibility of the Berg Balance Scale by novice and experienced physiotherapists

This study aimed to assess the interobserver reliability of the Brazilian–Portuguese version of the Berg Balance Scale (BBS), which consists of 14 items that evaluate body balance during daily activities. The assessment was made by physiotherapists with extensive or little clinical experience in noninstitutionalized elderly individuals. Participants comprised 12 elderly subjects (10 women and 2 men) with mean ages of 75.8±8.4 years (range=63–87) and 18 physiotherapists with varying clinical experience. Interexaminer reliability obtained for each scale item yielded weighted kappa value >0.75 in 11 of the 14 items (varying from 0.37 to 1.0). The intraclass correlation coefficient (ICC) for the total sum of BBS scores between the two groups of physiotherapists was 0.996 (95% confidence interval, 0.987–0.999) with a Cronbach alpha coefficient of 0.996. We found no statistically significant difference between the rater groups when we compared the sum score means obtained with Student's t-test (p=0.86). Although some items had low reliability values, in general our results suggest that the Brazilian–Portuguese version of the BBS showed acceptable levels of interrater reliability and agreement when used by physiotherapists with different clinical practice levels and without previous training on noninstitutionalized elderly patients.