Quantitative image-based collagen structural features predict the reversibility of hepatitis C virus-induced liver fibrosis post antiviral therapies.

The novel targeted therapeutics for hepatitis C virus (HCV) in last decade solved most of the clinical needs for this disease. However, despite antiviral therapies resulting in sustained virologic response (SVR), a challenge remains where the stage of liver fibrosis in some patients remains unchanged or even worsens, with a higher risk of cirrhosis, known as the irreversible group. In this study, we provided novel tissue level collagen structural insight into early prediction of irreversible cases via image based computational analysis with a paired data cohort (of pre- and post-SVR) following direct-acting-antiviral (DAA)-based treatment.

Automatic DNA replication tract measurement to assess replication and repair dynamics at the single-molecule level.

Motivation: DNA fibre assay has a potential application in genomic medicine, cancer and stem cell research at the single-molecule level. A major challenge for the clinical and research implementation of DNA fibre assays is the slow speed in which manual analysis takes place as it limits the clinical actionability. While automatic detection of DNA fibres speeds up this process considerably, current publicly available software have limited features in terms of their user interface for manual correction of results, which in turn limit their accuracy and ability to account for atypical structures that may be important in diagnosis or investigative studies.

Constructing and optimizing 3D atlases from 2D data with application to the developing mouse brain.

3D imaging data necessitate 3D reference atlases for accurate quantitative interpretation. Existing computational methods to generate 3D atlases from 2D-derived atlases result in extensive artifacts, while manual curation approaches are labor-intensive. We present a computational approach for 3D atlas construction that substantially reduces artifacts by identifying anatomical boundaries in the underlying imaging data and using these to guide 3D transformation.

Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients.

Background: Stromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis.

Obeticholic Acid Modulates Serum Metabolites and Gene Signatures Characteristic of Human NASH and Attenuates Inflammation and Fibrosis Progression in Ldlr-/-.Leiden Mice.

Concerns have been raised about whether preclinical models sufficiently mimic molecular disease processes observed in nonalcoholic steatohepatitis (NASH) patients, bringing into question their translational value in studies of therapeutic interventions in the process of NASH/fibrosis. We investigated the representation of molecular disease patterns characteristic for human NASH in high-fat diet (HFD)-fed Ldlr-/-.Leiden mice and studied the effects of obeticholic acid (OCA) on these disease profiles.

Cortical forces and CDC-42 control clustering of PAR proteins for Caenorhabditis elegans embryonic polarization.

Cell polarization enables zygotes to acquire spatial asymmetry, which in turn patterns cellular and tissue axes during development. Local modification in the actomyosin cytoskeleton mediates spatial segregation of partitioning-defective (PAR) proteins at the cortex, but how mechanical changes in the cytoskeleton are transmitted to PAR proteins remains elusive. Here we uncover a role of actomyosin contractility in the remodelling of PAR proteins through cortical clustering.

Membrane tension controls adhesion positioning at the leading edge of cells.

Cell migration is dependent on adhesion dynamics and actin cytoskeleton remodeling at the leading edge. These events may be physically constrained by the plasma membrane. Here, we show that the mechanical signal produced by an increase in plasma membrane tension triggers the positioning of new rows of adhesions at the leading edge.

OpenSegSPIM: a user-friendly segmentation tool for SPIM data.

Unlabelled: OpenSegSPIM is an open access and user friendly 3D automatic quantitative analysis tool for Single Plane Illumination Microscopy data. The software is designed to extract, in a user-friendly way, quantitative relevant information from SPIM image stacks, such as the number of nuclei or cells. It provides quantitative measurement (volume, sphericity, distance, intensity) on Light Sheet Fluorescent Microscopy images.

The assessment of combined first trimester screening in women of advanced maternal age in an Asian cohort.

Introduction: First trimester screening (FTS) is a validated screening tool that has been shown to achieve detection rates of 84%-90% for trisomies 21, 18 and 13. However, its effectiveness for different maternal ages has not been assessed. The present study aimed to assess the performance of FTS in an Asian population, and to compare its effectiveness in older (≥ 35 years) and younger (< 35 years) women.

Modified cIg-FISH protocol for multiple myeloma in routine cytogenetic laboratory practice.

The International Myeloma Working Group recommends that fluorescence in situ hybridization (FISH) be performed on specifically identified plasma cells (PC). This is because chromosomal abnormalities are not frequently detected by traditional karyotyping due to the low proliferative rate of PC in multiple myeloma (MM). Conventional FISH enhances the sensitivity but lacks the specificity, as it does not distinguish PC from other hematopoetic cells.

Same-day prenatal diagnosis of common chromosomal aneuploidies using microfluidics-fluorescence in situ hybridization.

Rapid molecular prenatal diagnostic methods, such as fluorescence in situ hybridization (FISH), quantitative fluorescence-PCR, and multiplex ligation-dependent probe amplification, can detect common fetal aneuploidies within 24 to 48 h. However, specific diagnosis or aneuploidy exclusion should be ideally available within the same day as fetal sampling to alleviate parental anxiety. Microfluidic technologies integrate different steps into a microchip, saving time and costs.

A tapered channel microfluidic device for comprehensive cell adhesion analysis, using measurements of detachment kinetics and shear stress-dependent motion.

We have developed a method for studying cellular adhesion by using a custom-designed microfluidic device with parallel non-connected tapered channels. The design enables investigation of cellular responses to a large range of shear stress (ratio of 25) with a single input flow-rate. For each shear stress, a large number of cells are analyzed (500-1500 cells), providing statistically relevant data within a single experiment.

A quorum-sensing factor in vegetative Dictyostelium discoideum cells revealed by quantitative migration analysis.

Background: Many cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS). In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase.

Development of quantitative-fluorescence polymerase chain reaction for the rapid prenatal diagnosis of common chromosomal aneuploidies in 1,000 samples in Singapore.

Introduction: We aimed to develop a rapid quantitative-fluorescence polymerase chain reaction (QF-PCR) to detect common foetal aneuploidies in the Singapore population within 48 hours of sample collection in order to alleviate parental anxiety.

Methods: DNA from 1,000 foetal samples (978 amniotic fluids, 14 chorion villi and eight foetal blood samples) was analysed using a QF-PCR of 19 microsatellite markers located on chromosomes 13, 18, 21, X and Y. A total of 523 samples were archived before the QF-PCR analysis (archived), while QF-PCR was performed and the results obtained within 48 hours of sample collection in the remaining 477 samples (live).

Follicular lymphomas with plasmacytic differentiation include two subtypes.

Follicular lymphomas with plasmacytic differentiation were described more than two decades ago. However, the possibility that some of these reported cases are marginal zone lymphomas or composite lymphomas must be considered. In addition, it is also uncertain whether follicular lymphomas with plasmacytic differentiation have any unique cytogenetic or other features.

Refining quantitative fluorescent polymerase chain reaction for prenatal detection of X chromosomal anomalies in the major Southeast Asian populations.

Introduction: This study aimed to refine the current quantitative fluorescent polymerase chain reaction (QF-PCR) screen to detect X chromosome anomalies for prenatal diagnosis in the major Southeast-Asian populations.

Methods: 100 amniotic fluid samples from Chinese, Malay and Indian origins were subjected to QF-PCR using the X chromosome markers, HPRT, X22 and AMXY, along with the autosomal marker D21S1411.

Results: Out of the 100 samples tested by markers X22 and HPRT, eight samples were homozygous for both markers, of which seven were resolved by comparison with the autosomal marker D21S1411.

Prenatal detection of isochromosome 21 by QF-PCR. A comparison between FISH and traditional karyotyping.

Objective: To compare rapid aneuploidy diagnostic tests with traditional karyotyping in the prenatal detection of Down syndrome due to isochromosome 21.

Methods: Quantitative fluorescence PCR (QF-PCR) and fluorescent in situ hybridization (FISH) for chromosomes 13, 18, 21, X and Y were performed on uncultured amniotic fluid, followed by routine karyotyping. chromosomal and microsatellite analysis of peripheral blood from parents was also carried out.

Gonadal mosaicism 45,X/46,X,psu dic(Y)(q11.2) resulting in a Turner phenotype with mixed gonadal dysgenesis.

A two-year-and-eight-month-old girl presented with clitoromegaly and short stature. Two cell lines, 45,X and 46,X,idic(Y)(q11.2), were observed.

Characterization of a small supernumerary marker chromosome as r(8) at prenatal diagnosis by MFISH.

Objective: To identify the mosaic marker chromosome detected in amniotic fluid cells of a 26-year-old woman, with raised triple test values and an ultrasound scan, which showed a fetus with echogenic bowels.

Methods: Routine karyotyping with G- and C-banding was carried out for both, amniotic fluid at 18 weeks of gestation as well as fetal blood at 22(+6) weeks. Peripheral blood of both parents was karytoyped.

Characterization of breakpoints in the GABRG3 and TSPY genes in a family with a t(Y;15)(p11.2;q12).

We report the clinical, cytogenetic, and molecular findings in a family in which a t(Y;15)(p11.2;q12) is segregating. The Y chromosome breakpoint disrupts the DYZ5 sequence containing the TSPY genes that are exclusively expressed in the testes while the chromosome 15 breakpoint is within the GABRG3 gene.