Miracle-dz/UniFAR-FTUs huggingface dataset:
Diversity and Dynamics of the Canadian Coastal Vibrio Community: an Emerging Trend Detected in the Temperate Regions

Proliferation and abundance of the harmful biotypes of Vibrio spp. in the estuaries of Canada indicate the possibility of producing contaminated seafood for human consumption. The findings of this surveillance study may lead to awareness which may help efforts to reduce the occurrence of illnesses or outbreaks caused by Vibrio spp. in seafood. ABSTRACT Vibrio species are indigenous to the marine and estuarine environments around the world and are the leading cause of water- and seafood-borne illnesses due to conditions favoring the transmission and growth of the species. Horizontal gene transfer, recombination, and mutation enable Vibrio spp. to adapt rapidly to environmental challenges from biotic and abiotic parameters, including temperature, salinity, and nutrient status of the coastal waters. This surveillance study provides evidence of Vibrio cholerae emerging in the temperate estuaries of Canada, thereby redefining the diversity and dynamics of its coastal Vibrio population. The presence of the pathogenic context in Vibrio parahaemolyticus was also detected with an increasing trend during the study period. IMPORTANCE Proliferation and abundance of the harmful biotypes of Vibrio spp. in the estuaries of Canada indicate the possibility of producing contaminated seafood for human consumption. The findings of this surveillance study may lead to awareness which may help efforts to reduce the occurrence of illnesses or outbreaks caused by Vibrio spp. in seafood.
Effect of pH on Structure and Conductivity of PEDOT/PSS

Poly(3,4-ethylenedioxythiophene) doped with poly(4-styrenesulfonate) (PEDOT/PSS) was synthesized by oxidative polymerization and pH dependence of structure and electrical conductivity of the cast films were investigated by means of UV-vis-NIR, XRD, AFM analyses, and four-point technique. It was found that the neutralization of PEDOT/PSS with NaOH decreased the absorption of bipolarons representing the PEDOT in the highly doped state and disrupted the π-π stacking of the PEDOT crystalline structure, which lowered the electrical conductivity by six orders of magnitude with increasing the pH from 1.7 to 13.
Excellent real‐world outcomes of adults with Burkitt lymphoma treated with CODOX‐M/IVAC plus or minus rituximab

Treatment of Burkitt lymphoma (BL) with intensive, multi‐agent chemotherapy with aggressive central nervous system (CNS) prophylaxis results in high cure rates, although no regimen is standard of care. We examined population‐based survival outcomes of adults with BL treated with a modified combination of cyclophosphamide, vincristine, doxorubicin, prednisone and systemic high‐dose methotrexate (MTX) (CODOX‐M) with IVAC (ifosfamide, mesna, etoposide, cytarabine and intrathecal MTX) (CODOX‐M/IVAC) ± rituximab over a 15‐year period in British Columbia. For the 81 patients identified (including 8 with CNS involvement and 18 with human immunodeficiency virus‐associated BL), 5‐year progression‐free survival (PFS) and overall survival (OS) were 75% [95% confidence interval (CI): 63–83%] and 77% (95% CI: 66–85%), respectively, with no treatment‐related deaths. Those who completed the regimen per protocol (n = 38) had significantly improved 5‐year PFS 86% (P = 0·04) and OS 92% (P = 0·008), as did those under 60 years with 5‐year PFS 82% (P = 0·005) and OS 86% (P = 0·002), which remained significant in multivariate analysis [PFS: hazard ratio (HR) 3·36, P = 0·018; OS HR 4·03, P = 0·012]. Incorporation of high‐dose systemic methotrexate also significantly affected multivariate survival outcomes (OS HR 0·28, P = 0·025). Stem cell transplant in first remission had no effect on OS or PFS. This large, real‐world analysis of BL patients treated with CODOX‐M/IVAC ± rituximab demonstrates excellent survival outcomes comparable to clinical trials. These results help to serve as a benchmark when comparing curative therapies for BL patients as novel regimens are incorporated into clinical practice.
Process vs. Product: Arabic and English Writing Classrooms in Oman

Learning how to write has long been perceived as an extremely complex and demanding task. Perhaps as an acknowledgement of this complexity, writing instruction in the Arab world in both English and Arabic has traditionally occurred in teacher-centred classrooms where product-oriented approaches dominate. However, recent reforms in many countries in the region, including in Oman, have favoured a more process-oriented approach to writing instruction in both languages. Despite this, much of the current research raises questions about whether more process-oriented approaches to writing are actually being implemented. This chapter, therefore, examines whether more processor product-oriented approaches are being employed in English and Arabic writing classrooms in Omani schools. Results indicate that, despite the Basic Education curriculum in Oman stipulating a process approach to writing in English and Arabic, instruction in both languages tends to be more product-oriented, especially in English classrooms.
Molecular and clinical characterization of de novo and familial cases with microduplication 3q29: guidelines for copy number variation case reporting

Microdeletions of 3q29 have previously been reported, but the postulated reciprocal microduplication has only recently been observed. Here, cases from four families, two ascertained in Toronto (Canada) and one each from Edinburgh (UK) and Leiden (Netherlands), carrying microduplications of 3q29 are presented. These families have been characterized by cytogenetic and molecular techniques, and all individuals have been further characterized with genome-wide, high density single nucleotide polymorphism (SNP) arrays run at a single centre (The Centre for Applied Genomics, Toronto). In addition to polymorphic copy-number variants (CNV), all carry duplications of 3q29 ranging in size from 1.9 to 2.4 Mb, encompassing multiple genes and defining a minimum region of overlap of about 1.6 Mb bounded by clusters of segmental duplications that is remarkably similar in location to previously reported 3q29 microdeletions. Consistent with other reports, the phenotype is variable, although developmental delay and significant ophthalmological findings were recurrent, suggesting that dosage sensitivity of genes located within 3q29 is important for eye and CNS development. We also consider CNVs found elsewhere in the genome for their contribution to the phenotype. We conclude by providing preliminary guidelines for management and anticipatory care of families with this microduplication, thereby establishing a standard for CNV reporting.
Predicting the biomechanical strength of proximal femur specimens with bone mineral density features and support vector regression

To improve the clinical assessment of osteoporotic hip fracture risk, recent computer-aided diagnosis systems explore new approaches to estimate the local trabecular bone quality beyond bone density alone to predict femoral bone strength. In this context, statistical bone mineral density (BMD) features extracted from multi-detector computed tomography (MDCT) images of proximal femur specimens and different function approximations methods were compared in their ability to predict the biomechanical strength. MDCT scans were acquired in 146 proximal femur specimens harvested from human cadavers. The femurs' failure load (FL) was determined through biomechanical testing. An automated volume of interest (VOI)-fitting algorithm was used to define a consistent volume in the femoral head of each specimen. In these VOIs, the trabecular bone was represented by statistical moments of the BMD distribution and by pairwise spatial occurrence of BMD values using the gray-level co-occurrence (GLCM) approach. A linear multi-regression analysis (MultiReg) and a support vector regression algorithm with a linear kernel (SVRlin) were used to predict the FL from the image feature sets. The prediction performance was measured by the root mean square error (RMSE) for each image feature on independent test sets; in addition the coefficient of determination R2 was calculated. The best prediction result was obtained with a GLCM feature set using SVRlin, which had the lowest prediction error (RSME = 1.040±0.143, R2 = 0.544) and which was significantly lower that the standard approach of using BMD.mean and MultiReg (RSME = 1.093±0.133, R2 = 0.490, p<0.0001). The combined sets including BMD.mean and GLCM features had a similar or slightly lower performance than using only GLCM features. The results indicate that the performance of high-dimensional BMD features extracted from MDCT images in predicting the biomechanical strength of proximal femur specimens can be significantly improved by using support vector regression.
Adherence With NCEP Recommendations When Prescribing Simvastatin: A Comparison Between Primary Care and Lipid Clinic Providers

• Objective: To assess adherence with the National Cholesterol Education Program (NCEP) guidelines among primary care and lipid clinic providers prescribing simvastatin. • Design: Retrospective review of medical records. • Patients and setting: Outpatients treated at the Veterans Affairs Medical Center, Prescott, AZ, who were prescribed simvastatin. • Methods: Patients prescribed simvastatin between December 1997 and November 1998 were randomly selected from a computer generated list for review. Patients reviewed were those prescribed simvastatin by either a primary care or lipid clinic provider. The lipid clinic is managed primarily by clinical pharmacists. Data collected included cardiac risk factors, pretreatment and post-treatment lipid profiles, dose of simvastatin, and number of patients in adherence with the NCEP guidelines for treatment initiation and post-treatment lipid values. • Results: 122 patients were reviewed (60 primary care, 62 lipid clinic). Post-treatment lipid values, dose of simvastatin, and percentage of patients meeting target lipid goals were not statistically different between groups. Of patients prescribed simvastatin, 43% and 10% of patients were below recommended treatment thresholds in the primary care and lipid clinic groups, respectively (P < 0.001). • Conclusion: Simvastatin is prescribed more often below NCEP treatment thresholds by primary care providers than lipid clinic providers.
Homeobox B 3 , FoxA 1 and FoxA 2 interactions in epithelial lung cell differentiation of the multipotent M 3 E 3 / C 3 cell line

HOM/C homeobox (Hox) and forkhead box (Fox) factors are reported to be expressed in the foregut endoderm and are subsequently detected in a spatio-temporal pattern during lung development. Some of these factors were reported to influence the expression of lung marker proteins or to modulate lung development. To clarify the molecular mechanisms for generating functional lung cells from progenitor cell populations, we introduced the forkhead box factors, FoxA1 and FoxA2, and the homeobox factor, HoxB3, into the differentiation process in a multipotent hamster lung epithelial M3E3/C3 cell line. Ectopic expression of FoxA2 promoted differentiation to Clara-like cells with up-regulation of the expression of the lung marker proteins, Clara cell-specific 10-kDa protein and surfactant protein-B. In contrast, FoxA1 repressed the differentiation. HoxB3 transfection induced FoxA2 expression transiently at the pre-differentiation stage. The endogenous HoxB3 expression level decreased at later stages of Clara-like cell differentiation, and the attenuation was enhanced by FoxA2 transfection. HoxB3 is a putative upstream regulator that enhances FoxA2 expression at the pre-differentiation stage. In addition, we found that the expression of HoxA4, HoxA5, and HoxC9 increased differentially during Clara-like cell differentiation. These results suggest that HoxB3 may be a putative positive regulator of FoxA2 expression at the pre-differentiation stage, and those interactions of Fox factors and Hox factors could participate in Clara cell differentiation. r 2005 Elsevier GmbH. All rights reserved.
Fabrication and characterisation of miniature parabolic acoustic lenses

As recently demonstrated, all-optical B-mode ultrasound imaging can be performed with a pair of coated optical fibres for transmission and reception that is translated to create a virtual array of elements. However, with translation in the in-plane dimension, the small lateral dimensions of the fibres results in out-of-plane acoustic divergence, which leads to image clutter and loss of sensitivity.
Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses

T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.
The Role of scaRNAs in Adjusting Alternative mRNA Splicing in Heart Development

Congenital heart disease (CHD) is a leading cause of death in children <1 year of age. Despite intense effort in the last 10 years, most CHDs (~70%) still have an unknown etiology. Conotruncal based defects, such as Tetralogy of Fallot (TOF), a common complex of devastating heart defects, typically requires surgical intervention in the first year of life. We reported that the noncoding transcriptome in myocardial tissue from children with TOF is characterized by significant variation in levels of expression of noncoding RNAs, and more specifically, a significant reduction in 12 small cajal body-associated RNAs (scaRNAs) in the right ventricle. scaRNAs are essential for the biochemical modification and maturation of small nuclear RNAs (spliceosomal RNAs), which in turn are critical components of the spliceosome. This is particularly important because we also documented that splicing of mRNAs that are critical for heart development was dysregulated in the heart tissue of infants with TOF. Furthermore, we went on to show, using the zebrafish model, that altering the expression of these same scaRNAs led to faulty mRNA processing and heart defects in the developing embryo. This review will examine how scaRNAs may influence spliceosome fidelity in exon retention during heart development and thus contribute to regulation of heart development.
Estimating Large Correlation Matrices for International Migration April

The United Nations is the major organization producing and regularly updating probabilistic population projections for all countries. International migration is a critical component of such projections, and between-country correlations are important for forecasts of regional aggregates. However, in the data we consider there are 200 countries and only 12 data points, each one corresponding to a five-year time period. Thus a 200×200 correlation matrix must be estimated on the basis of 12 data points. Using Pearson correlations produces many spurious correlations. We propose a maximum a posteriori estimator for the correlation matrix with an interpretable informative prior distribution. The prior serves to regularize the correlation matrix, shrinking a priori untrustworthy elements towards zero. Our estimated correlation structure improves projections of net migration for regional aggregates, producing narrower projections of migration for Africa as a whole and wider projections for Europe. A simulation study confirms that our estimator outperforms both the Pearson correlation matrix and a simple shrinkage estimator when estimating a sparse correlation matrix.
Effects of whole and refined grains in a weight-loss diet on markers of metabolic syndrome in individuals with increased waist circumference: a randomized controlled-feeding trial.

BACKGROUND Higher whole-grain (WG) intake is associated with a lower prevalence of metabolic syndrome (MetS); however, there is inconsistent clinical evidence with regard to the benefit of WGs compared with refined grains (RGs) on MetS. OBJECTIVE We hypothesized that consuming WGs in the place of RGs would improve MetS criteria in individuals with or at risk of MetS. DESIGN A randomized, controlled, open-label parallel study was conducted in 50 overweight and obese individuals with increased waist circumference and one or more other MetS criteria. Participants consumed a controlled weight-loss diet containing either WG or RG (control) products for 12 wk. Body composition, MetS criteria and related markers, and plasma alkylresorcinols (compliance marker of WG intake) were measured at baseline and at 6 and 12 wk. A subgroup (n = 28) underwent magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue (AT). RESULTS Baseline variables were not significantly different between groups; however, the RG group tended to have higher triglycerides and lower high-density lipoprotein (HDL) cholesterol (P = 0.06). Alkylresorcinols increased with consumption of the WG diet and did not change with consumption of the RG diet (time × treatment, P < 0.0001), which showed dietary compliance. There were no differences in anthropometric changes between groups; however, weight, body mass index, and percentage of body AT decreased at both 6 and 12 wk (P < 0.05), and reductions in percentage of abdominal AT occurred by 6 wk and did not change between 6 and 12 wk (P = 0.09). Both glucose (P = 0.02) and HDL cholesterol (P = 0.04) were lower with the consumption of the WG compared with the RG diet. However, when noncompliant individuals (n = 3) were removed, the glucose effect was stronger (P = 0.01) and the HDL-cholesterol effect was no longer significant (P = 0.14). CONCLUSIONS Replacing RGs with WGs within a weight-loss diet does not beneficially affect abdominal AT loss and has modest effects on markers of MetS. WGs appear to be effective at normalizing blood glucose concentrations, especially in those individuals with prediabetes.
Suppressor mutation analysis combined with 3D modeling explains cohesin’s capacity to hold and release DNA

Significance The heterodimeric cohesin SMC complex embraces duplex DNA and is associated with Rad21, which is cleaved in mitotic anaphase by a protease called separase/Cut1. Upon Rad21 cleavage, chromosomal DNAs are released from cohesin and segregated. We identified extragenic suppressors for separase and cohesin temperature-sensitive (ts) mutants using whole-genome sequencing and made the surprising discovery that cleavage of Rad21 is largely dispensable if suppressor causes physical disorders of cohesin interfaces among essential subunits. The predicted disorders provide insights into a DNA “hold-and-release” model in which hinge and head of SMC subunits are proximal to form arched coiled coils that close or open by their orientation. The model is distinct from the “ring” model and may promote further study. Cohesin is a fundamental protein complex that holds sister chromatids together. Separase protease cleaves a cohesin subunit Rad21/SCC1, causing the release of cohesin from DNA to allow chromosome segregation. To understand the functional organization of cohesin, we employed next-generation whole-genome sequencing and identified numerous extragenic suppressors that overcome either inactive separase/Cut1 or defective cohesin in the fission yeast Schizosaccharomyces pombe. Unexpectedly, Cut1 is dispensable if suppressor mutations cause disorders of interfaces among essential cohesin subunits Psm1/SMC1, Psm3/SMC3, Rad21/SCC1, and Mis4/SCC2, the crystal structures of which suggest physical and functional impairment at the interfaces of Psm1/3 hinge, Psm1 head–Rad21, or Psm3 coiled coil–Rad21. Molecular-dynamics analysis indicates that the intermolecular β-sheets in the cohesin hinge of cut1 suppressor mutants remain intact, but a large mobility change occurs at the coiled coil bound to the hinge. In contrast, suppressors of rad21-K1 occur in either the head ATPase domains or the Psm3 coiled coil that interacts with Rad21. Suppressors of mis4-G1326E reside in the head of Psm3/1 or the intragenic domain of Mis4. These may restore the binding of cohesin to DNA. Evidence is provided that the head and hinge of SMC subunits are proximal, and that they coordinate to form arched coils that can hold or release DNA by altering the angles made by the arched coiled coils. By combining molecular modeling with suppressor sequence analysis, we propose a cohesin structure designated the “hold-and-release” model, which may be considered as an alternative to the prevailing “ring” model.
Nanopore Fabrication by Controlled Dielectric Breakdown

Nanofabrication techniques for achieving dimensional control at the nanometer scale are generally equipment-intensive and time-consuming. The use of energetic beams of electrons or ions has placed the fabrication of nanopores in thin solid-state membranes within reach of some academic laboratories, yet these tools are not accessible to many researchers and are poorly suited for mass-production. Here we describe a fast and simple approach for fabricating a single nanopore down to 2-nm in size with sub-nm precision, directly in solution, by controlling dielectric breakdown at the nanoscale. The method relies on applying a voltage across an insulating membrane to generate a high electric field, while monitoring the induced leakage current. We show that nanopores fabricated by this method produce clear electrical signals from translocating DNA molecules. Considering the tremendous reduction in complexity and cost, we envision this fabrication strategy would not only benefit researchers from the physical and life sciences interested in gaining reliable access to solid-state nanopores, but may provide a path towards manufacturing of nanopore-based biotechnologies.
Multivariate longitudinal data analysis with censored and intermittent missing responses

The multivariate linear mixed model (MLMM) has emerged as an important analytical tool for longitudinal data with multiple outcomes. However, the analysis of multivariate longitudinal data could be complicated by the presence of censored measurements because of a detection limit of the assay in combination with unavoidable missing values arising when subjects miss some of their scheduled visits intermittently. This paper presents a generalization of the MLMM approach, called the MLMM‐CM, for a joint analysis of the multivariate longitudinal data with censored and intermittent missing responses. A computationally feasible expectation maximization–based procedure is developed to carry out maximum likelihood estimation within the MLMM‐CM framework. Moreover, the asymptotic standard errors of fixed effects are explicitly obtained via the information‐based method. We illustrate our methodology by using simulated data and a case study from an AIDS clinical trial. Experimental results reveal that the proposed method is able to provide more satisfactory performance as compared with the traditional MLMM approach.