Reliable detection of subchromosomal deletions and duplications using cell-based noninvasive prenatal testing

Objective To gather additional data on the ability to detect subchromosomal abnormalities of various sizes in single fetal cells isolated from maternal blood, using low-coverage shotgun next-generation sequencing for cell-based noninvasive prenatal testing (NIPT). Method Fetal trophoblasts were recovered from approximately 30 mL of maternal blood using maternal white blood cell depletion, density-based cell separation, immunofluorescence staining, and high-resolution scanning. These trophoblastic cells were picked as single cells and underwent whole genome amplification for subsequent genome-wide copy number analysis and genotyping to confirm the fetal origin of the cells. Results Applying our fetal cell isolation method to a series of 125 maternal blood samples, we detected on average 4.17 putative fetal cells/sample. The series included 15 cases with clinically diagnosed fetal aneuploidies and five cases with subchromosomal abnormalities. This method was capable of detecting findings that were 1 to 2 Mb in size, and all were concordant with the microarray or karyotype data obtained on a fetal sample. A minority of fetal cells showed evidence of genome degradation likely related to apoptosis. Conclusion We demonstrate that this cell-based NIPT method has the capacity to reliably diagnose fetal chromosomal abnormalities down to 1 to 2 Mb in size

The experience of admission to psychiatric hospital among Chinese adult patients in Hong Kong

<p>Abstract</p> <p>Background</p> <p>The paper reports on a study to evaluate the psychometric properties and cultural appropriateness of the Chinese translation of the Admission Experience Survey (AES).</p> <p>Methods</p> <p>The AES was translated into Chinese and back-translated. Content validity was established by focus groups and expert panel review. The Chinese version of the Admission Experience Survey (C-AES) was administered to 135 consecutively recruited adult psychiatric patients in the Castle Peak Hospital (Hong Kong SAR, China) within 48 hours of admission. Construct validity was assessed by comparing the scores from patients admitted voluntarily versus patients committed involuntarily, and those received physical or chemical restraint versus those who did not. The relationship between admission experience and psychopathology was examined by correlating C-AES scores with the Brief Psychiatric Rating Scale (BPRS) scores.</p> <p>Results</p> <p>Spearman's item-to-total correlations of the C-AES ranged from 0.50 to 0.74. Three factors from the C-AES were extracted using factor analysis. Item 12 was omitted because of poor internal consistency and factor loading. The factor structure of the Process Exclusion Scale (C-PES) corresponded to the English version, while some discrepancies were noted in the Perceived Coercion Scale (C-PCS) and the Negative Pressure Scale (C-NPS). All subscales had good internal consistencies. Scores were significantly higher for patients either committed involuntarily or subjected to chemical or physical restrain, independent on severity of psychotic symptoms.</p> <p>Conclusion</p> <p>The Chinese AES is a psychometrically sound instrument assessing the three different aspects of the experience of admission, namely "negative pressure, "process exclusion" and "perceived coercion". The potential of C-AES in exploring subjective experience of psychiatric admission and effects on treatment adherence should be further explored.</p

A Common and Unstable Copy Number Variant Is Associated with Differences in Glo1 Expression and Anxiety-Like Behavior

Glyoxalase 1 (Glo1) has been implicated in anxiety-like behavior in mice and in multiple psychiatric diseases in humans. We used mouse Affymetrix exon arrays to detect copy number variants (CNV) among inbred mouse strains and thereby identified a ∼475 kb tandem duplication on chromosome 17 that includes Glo1 (30,174,390–30,651,226 Mb; mouse genome build 36). We developed a PCR-based strategy and used it to detect this duplication in 23 of 71 inbred strains tested, and in various outbred and wild-caught mice. Presence of the duplication is associated with a cis-acting expression QTL for Glo1 (LOD>30) in BXD recombinant inbred strains. However, evidence for an eQTL for Glo1 was not obtained when we analyzed single SNPs or 3-SNP haplotypes in a panel of 27 inbred strains. We conclude that association analysis in the inbred strain panel failed to detect an eQTL because the duplication was present on multiple highly divergent haplotypes. Furthermore, we suggest that non-allelic homologous recombination has led to multiple reversions to the non-duplicated state among inbred strains. We show associations between multiple duplication-containing haplotypes, Glo1 expression and anxiety-like behavior in both inbred strain panels and outbred CD-1 mice. Our findings provide a molecular basis for differential expression of Glo1 and further implicate Glo1 in anxiety-like behavior. More broadly, these results identify problems with commonly employed tests for association in inbred strains when CNVs are present. Finally, these data provide an example of biologically significant phenotypic variability in model organisms that can be attributed to CNVs

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Near Infrared-Sensitive Nanoparticles for Targeted Drug Delivery

The invasive nature and undesirable side-effects related to conventional cancer therapy, such as surgery and chemotherapy, have led to the development of novel drug delivery systems (DDS). A minimally invasive DDS using near-infrared (NIR) light as a trigger for drug release is investigated to reduce the adverse side-effects triggered by systemic delivery of chemotherapeutic drugs. The low tissue absorbance in the NIR region, λ = 650–2500 nm, allows the irradiation to penetrate through tissues to release cisplatin from a NIR-sensitive nanocomposite of Au-Au&#x2082;S. Our laboratory has recently shown that cisplatin can be effectively released from Au-Au&#x2082;S upon NIR irradiation. Cisplatin was loaded onto Au-Au&#x2082;S through its adsorption on COOH-functionalized alkanethiols coated on Au-Au&#x2082;S. The current work focuses on the development of methods to control the release of cisplatin. Drug release is controlled by either the irradiation parameters or the type of coatings. The effect of different coatings on NIR sensitivity and drug release is investigated. Molecular layers of HS-(CH&#x2082;)n-COOH and HS-CH&#x2082;-COO-CH&#x2082;(CH&#x2082;CH&#x2082;O)xCH&#x2082;-COOH have been successfully coated onto Au-Au&#x2082;S. The effect of different surface layers on drug adsorption is being examined. In addition, a mathematical model has been developed to describe the thermal effects of different irradiation parameters on soft tissues.Singapore-MIT Alliance (SMA

NIR-sensitive nanoparticle

US20060099146A1Published Applicatio

Structure and microstructure of near infrared-absorbing Au-Au2S nanoparticles

10.1557/jmr.2007.0314Journal of Materials Research2292531-2538JMRE

NIR-sensitive nanoparticle

US7601331Granted Paten