Clinical validation of a ctDNA-Based Assay for Multi-Cancer Detection: An Interim Report from a Vietnamese Longitudinal Prospective Cohort Study of 2795 Participants.

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

Genetic landscape of recessive diseases in the Vietnamese population from large-scale clinical exome sequencing.

Accurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies. Here, we reported the first comprehensive study of recessive diseases in the Vietnamese population. Clinical exome sequencing data of 4503 disease-associated genes obtained from a cohort of 985 Vietnamese individuals was analyzed to identify pathogenic variants, associated diseases and their carrier frequencies in the population. A total of 118 recessive diseases associated with 164 pathogenic or likely pathogenic variants were identified, among which 28 diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were prevalent in the Vietnamese population with carrier frequencies of 2-12 times higher than in the world populations, including beta-thalassemia (1 in 23), citrin deficiency (1 in 31), and phenylketonuria (1 in 40). Seven novel pathogenic and two likely pathogenic variants associated with nine recessive diseases were discovered. The comprehensive profile of recessive diseases identified in this study enables the design of cost-effective carrier screening programs specific to the Vietnamese population.

Coupling Metaloid-Directed Self-Assembly and Dynamic Covalent Systems as a Route to Large Organic Cages and Cyclophanes.

The synthesis of large cyclic and caged disulfide structures was achieved by pnictogen-assisted iodine oxidation starting from self-assembled pnictogen thiolate complexes. The directing behavior of pnictogen enables rapid and selective syntheses of many discrete disulfide assemblies over competing oligomers/polymers, ranging from structures that are small and strained to those that are large and multifaceted, including 3D cages. Traditional cyclization reactions carried out under kinetic control are generally low-yielding, which often results in the formation of insoluble oligomers and polymers as unwanted side products. The prospect of self-assembling organic structures efficiently under thermodynamic control adds an attractive tool for the synthesis of cyclophanes and other large cage compounds. This method of metaloid-directed self-assembly within a dynamic covalent system allows for the rapid and discriminant self-assembly of disulfide cyclophanes without the consequences sometimes seen in traditional cyclophane syntheses such as poor yields, long reaction times, low ring-closing selectivity, and extensive purifications. The present paper provides an overview of this approach, explores the role of the pnictogen additive and solvent in this reaction, begins to test the limits of this strategy in complex 3D molecule formation, and extends our strategy to include one-pot syntheses that do not require the use of a pnictogen additive. This Viewpoint also includes an extended introduction to serve as a minireview highlighting the utility of a self-assembly approach to create organic cage structures. From a practical standpoint, the cyclophanes isolated from this method can serve as precursors in the production of insulating plastics (e.g., through the widely used parylene polymerization process, which uses derivatives of paracyclophane as monomers) or as potential hosts for molecular separations or capture.

A consultation and work-up diagnosis protocol for a multicancer early detection test: a case series study.

The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.

New tests can now screen for multiple types of cancer early, offering hope for better health outcomes. If one of these tests shows a positive result, doctors need to confirm it with imaging tests. We have developed a guide to help doctors understand and confirm these results. This guide could help healthcare professionals interpret results for five common types of cancer, making it easier to use these tests in regular medical practice.

Low Genetic Diversity of Hepatitis B Virus Surface Gene amongst Australian Blood Donors.

Variants in the small surface gene of hepatitis B virus (HBV), which codes for viral surface antigen (HBsAg), can affect the efficacy of HBsAg screening assays and can be associated with occult HBV infection (OBI). This study aimed to characterise the molecular diversity of the HBV small surface gene from HBV-reactive Australian blood donors. HBV isolates from 16 HBsAg-positive Australian blood donors' plasma were sequenced and genotyped by phylogenies of viral coding genes and/or whole genomes. An analysis of the genetic diversity of eight HBV small surface genes from our 16 samples was conducted and compared with HBV sequences from NCBI of 164 international (non-Australian) blood donors. Genotypes A-D were identified in our samples. The region of HBV small surface gene that contained the sequence encoding the 'a' determinant had a greater genetic diversity than the remaining part of the gene. No escape mutants or OBI-related variants were observed in our samples. Variant call analysis revealed two samples with a nucleotide deletion leading to truncation of polymerase and/or large/middle surface amino acid sequences. Overall, we found that HBV small surface gene sequences from Australian donors demonstrated a lower level of genetic diversity than those from non-Australian donor population included in the study.

Dynamic Covalent Chemistry as a Facile Route to Unusual Main-Group Thiolate Assemblies and Disulfide Hoops and Cages.

Dynamic Covalent Chemistry (DCC) - combining the robustness of covalent bonds with the self-correcting nature of supramolecular chemistry - facilitates the modular synthesis of complex molecular assemblies in high yields. Although numerous reactions form covalent bonds, only a small set of chemical transformations affect covalent bond formation reversibly under suitable conditions for DCC. Further progress in this area still requires the identification of dynamic motifs and greater insights into their reversibility. We have fruitfully employed DCC of both thiolate coordination to main-group elements and disulfide formation for the facile self-assembly of: (1) metal/metalloid-thiolate assemblies, and (2) purely organic cyclic and caged disulfides, thioethers, and even hydrocarbons, many of which have remained elusive by traditional stepwise synthesis yet form readily through our methods. In this Minireview, we highlight the approaches to prepare these unusual compounds and the factors inducing structural transformations or favoring the formation of certain products over others, given a set of external stimuli or reaction conditions.

In silico Analysis of Genetic Diversity of Human Hepatitis B Virus in Southeast Asia, Australia and New Zealand.

The extent of whole genome diversity amongst hepatitis B virus (HBV) genotypes is not well described. This study aimed to update the current distribution of HBV types and to investigate mutation rates and nucleotide diversity between genotypes in Southeast Asia, Australia and New Zealand. We retrieved 930 human HBV complete genomes from these regions from the NCBI nucleotide database for genotyping, detection of potential recombination, serotype prediction, mutation identification and comparative genome analyses. Overall, HBV genotypes B (44.1%) and C (46.2%) together with predicted serotypes adr (36%), adw2 (29%) and ayw1 (19.9%) were the most commonly circulating HBV types in the studied region. The three HBV variants identified most frequently were p.V5L, c.1896G>A and double mutation c.1762A>T/c.1764G>A, while genotypes B and C had the widest range of mutation types. The study also highlighted the distinct nucleotide diversity of HBV genotypes for whole genome and along the genome length. Therefore, this study provided a robust update to HBV currently circulating in Southeast Asia, Australia and New Zealand as well as an insight into the association of HBV genetic hypervariability and prevalence of well reported mutations.

Self-sorting in dynamic disulfide assembly: new biphenyl-bridged "nanohoops" and unsymmetrical cyclophanes.

We expand on our approach combining dynamic covalent self-assembly and sulfur extrusion to synthesize new biphenyl-linked disulfide and thioether macrocycles, which are variants of the venerable phenyl-bridged paracyclophanes. We then advance this strategy further to use two different thiols in tandem to provide new, elusive unsymmetrical disulfides which can also be trapped as unsymmetrical thioether "nanohoops". This approach enables substantial amplification of two unsymmetrical trimers out of a library of at least 21 possible macrocycles of various sizes.

Copper(ii) serves as an efficient additive for metal-directed self-assembly of over 20 thiacyclophanes.

Cu2+ salts are presented as an alternative to previously reported pnictogen additives in the self-assembly of 23 different thiacyclophanes. This process allows for further tuning of library equilibrium mixtures: for instance, by altering additive types and concentrations, trimeric macrocycles are amplified. These trimeric disulfides can then be covalently trapped to form 2 novel thioethers, highlighting the facile route to access these new naphthalene-bridged cyclophanes.

Direct measurement of the absolute absorption spectrum of individual semiconducting single-wall carbon nanotubes.

The optical properties of single-wall carbon nanotubes are very promising for developing novel opto-electronic components and sensors with applications in many fields. Despite numerous studies performed using photoluminescence or Raman and Rayleigh scattering, knowledge of their optical response is still partial. Here we determine using spatial modulation spectroscopy, over a broad optical spectral range, the spectrum and amplitude of the absorption cross-section of individual semiconducting single-wall carbon nanotubes. These quantitative measurements permit determination of the oscillator strength of the different excitonic resonances and their dependencies on the excitonic transition and type of semiconducting nanotube. A non-resonant background is also identified and its cross-section comparable to the ideal graphene optical absorbance. Furthermore, investigation of the same single-wall nanotube either free standing or lying on a substrate shows large broadening of the excitonic resonances with increase of oscillator strength, as well as stark weakening of polarization-dependent antenna effects, due to nanotube-substrate interaction.