A study of genetic variants associated with skin traits in the Vietnamese population.

BACKGROUND: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. OBJECTIVES: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. METHODS: Vietnamese cohorts of whole-genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrient requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. RESULTS: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst = 0.036, CHB: Fst = 0.031, CHS: Fst = 0.027, CDX: Fst = 0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p = 1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)). CONCLUSION: This is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.

Covalent Organic Framework Membranes and Water Treatment.

Covalent organic frameworks (COFs) are an emerging class of highly porous crystalline organic polymers comprised entirely of organic linkers connected by strong covalent bonds. Due to their excellent physicochemical properties (e.g., ordered structure, porosity, and stability), COFs are considered ideal materials for developing state-of-the-art separation membranes. In fact, significant advances have been made in the last six years regarding the fabrication and functionalization of COF membranes. In particular, COFs have been utilized to obtain thin-film, composite, and mixed matrix membranes that could achieve effective rejection (mostly above 80%) of organic dyes and model organic foulants (e.g., humic acid). COF-based membranes, especially those prepared by embedding into polyamide thin-films, obtained adequate rejection of salts in desalination applications. However, the claims of ordered structure and separation mechanisms remain unclear and debatable. In this perspective, we analyze critically the design and exploitation of COFs for membrane fabrication and their performance in water treatment applications. In addition, technological challenges associated with COF properties, fabrication methods, and treatment efficacy are highlighted to redirect future research efforts in realizing highly selective separation membranes for scale-up and industrial applications.

Controlling Reactivity and Selectivity in the Mizoroki-Heck Reaction: High Throughput Evaluation of 1,5-Diaza-3,7-diphosphacyclooctane Ligands.

We report a high throughput evaluation of the Mizoroki-Heck reaction of diverse olefin coupling partners. Comparison of different ligands revealed the 1,5-diaza-3,7-diphosphacyclooctane (P2N2) scaffold to be more broadly applicable than common "gold standard" ligands, demonstrating that this family of readily accessible diphosphines has unrecognized potential in organic synthesis. In particular, two structurally related P2N2 ligands were identified to enable the regiodivergent arylation of styrenes. By simply altering the phosphorus substituent from a phenyl to tert-butyl group, both the linear and branched Mizoroki-Heck products can be obtained in high regioisomeric ratios. Experimental and computational mechanistic studies were performed to further probe the origin of selectivity, which suggests that both ligands coordinate to the metal in a similar manner but that rigid positioning of the phosphorus substituent forces contact with the incoming olefin in a π-π interaction (for P-Ph ligands) or with steric clash (for P-tBu ligands), dictating the regiocontrol.

epiTCR: a highly sensitive predictor for TCR-peptide binding.

MOTIVATION: Predicting the binding between T-cell receptor (TCR) and peptide presented by human leucocyte antigen molecule is a highly challenging task and a key bottleneck in the development of immunotherapy. Existing prediction tools, despite exhibiting good performance on the datasets they were built with, suffer from low true positive rates when used to predict epitopes capable of eliciting T-cell responses in patients. Therefore, an improved tool for TCR-peptide prediction built upon a large dataset combining existing publicly available data is still needed. RESULTS: We collected data from five public databases (IEDB, TBAdb, VDJdb, McPAS-TCR, and 10X) to form a dataset of >3 million TCR-peptide pairs, 3.27% of which were binding interactions. We proposed epiTCR, a Random Forest-based method dedicated to predicting the TCR-peptide interactions. epiTCR used simple input of TCR CDR3ß sequences and antigen sequences, which are encoded by flattened BLOSUM62. epiTCR performed with area under the curve (0.98) and higher sensitivity (0.94) than other existing tools (NetTCR, Imrex, ATM-TCR, and pMTnet), while maintaining comparable prediction specificity (0.9). We identified seven epitopes that contributed to 98.67% of false positives predicted by epiTCR and exerted similar effects on other tools. We also demonstrated a considerable influence of peptide sequences on prediction, highlighting the need for more diverse peptides in a more balanced dataset. In conclusion, epiTCR is among the most well-performing tools, thanks to the use of combined data from public sources and its use will contribute to the quest in identifying neoantigens for precision cancer immunotherapy. AVAILABILITY AND IMPLEMENTATION: epiTCR is available on GitHub (https://github.com/ddiem-ri-4D/epiTCR).

Amine Chemistry of Porous CO2 Adsorbents.

ConspectusAs renewable energy and CO2 utilization technologies progress to make a more significant contribution to global emissions reduction, carbon capture remains a critical component of the mission. Current CO2 capture technologies involve operations at point sources such as fossil fuel-based power plants or source-agnostic like in direct air capture. Each strategy has its own advantages and limitations, but in common, they all employ sorption-based methods with the use of sorbents strongly adhering to CO2. Amine solutions are the most widely used absorbents for industrial operations due to the robust chemical bonds formed between amines and CO2 under both dry and humid conditions, rendering excellent selectivity. Such strong binding, however, causes problematic regeneration. In contrast, purely physisorptive porous materials with high surface areas allow for the confinement of CO2 inside narrow pores/channels and have a lower regeneration energy demand but with decreased selectivity and capacity. The most promising solution would then be the unification of both types of sorbents in one system, which could bring about a practical adsorption-desorption process. In other words, the development of porous solid materials with tunable amine content is necessary to leverage the high contact surface of porous sorbents with the added ability to manipulate amine incorporation toward lower CO2 binding strength.To answer the call to uncover the most feasible amine chemistry in carbon capture, our group has devoted intense effort to the study of amine-based CO2 adsorbents for the past decade. Oriented along practicality, we put forth a principle for the design of our materials to be produced in no more than three synthetic steps with economically viable starting materials. Porous organic polymers with amine functionalities of various substitutions, meaning primary, secondary, and tertiary amines, were synthesized and studied for CO2 adsorption. Direct synthesis proved to be feasibly applicable for secondary and tertiary amine-incorporated porous polymers whereas primary-amine-based sorbents would be conveniently obtained via postsynthetic modifications. Sorbents based on tertiary amines exhibit purely physical adsorption behavior if the nitrogen atoms are placed adjacent to aromatic cores due to the conjugation effect that reduces the electron density of the amine. However, when such conjugation is inhibited, chemisorptive activity is observed. Secondary amine adsorbents, in turn, express a higher binding strength than tertiary amine counterparts, but both types can merit a strengthened binding by the physical impregnation of small-molecule amines. Sorbents with primary-amine tethers can be obtained via postsynthetic transformation of precursor functionalities, and for them, chemical adsorption is mainly at work. We conclude that mixed-amine systems could exhibit unprecedented binding mechanisms, resulting in exceptionally specific interactions that would be useful for the development of highly selective sorbents for CO2.

Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma.

PURPOSE: NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory. METHODS: The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL). RESULTS: Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores. CONCLUSIONS: Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011).

Enhancing control in spatial atomic layer deposition: insights into precursor diffusion, geometric parameters, and CVD mitigation strategies.

In recent years, spatial atomic layer deposition (SALD) has gained significant attention for its remarkable capability to accelerate ALD growth by several orders of magnitude compared to conventional ALD, all while operating at atmospheric pressure. Nevertheless, the persistent challenge of inadvertent contributions from chemical vapor deposition (CVD) in SALD processes continues to impede control over film homogeneity, and properties. This research underscores the often-overlooked influence of diffusion coefficients and important geometric parameters on the close-proximity SALD growth patterns. We introduce comprehensive physical models complemented by finite element method simulations for fluid dynamics to elucidate SALD growth kinetics across diverse scenarios. Our experimental findings, in alignment with theoretical models, reveal distinctive growth rate trends in ZnO and SnO2films as a function of the deposition gap. These trends are ascribed to precursor diffusion effects within the SALD system. Notably, a reduced deposition gap proves advantageous for both diffusive and low-volatility bulky precursors, minimizing CVD contributions while enhancing precursor chemisorption kinetics. However, in cases involving highly diffusive precursors, a deposition gap of less than 100µm becomes imperative, posing technical challenges for large-scale applications. This can be ameliorated by strategically adjusting the separation distance between reactive gas outlets to mitigate CVD contributions, which in turn leads to a longer deposition time. Furthermore, we discuss the consequential impact on material properties and propose a strategy to optimize the injection head to control the ALD/CVD growth mode.

Validation of Anti-Adeno Associated Virus Serotype rh10 (AAVrh.10) Total and Neutralizing Antibody Immunogenicity Assays.

Immunogenicity assessment of Adeno-Associated Virus (AAV) vectors is a critical part of gene therapy drug development. Whether the assays are used for inclusion/exclusion criteria or to monitor the safety and efficacy of the gene therapy, they are critical bioanalytical assessments. While total anti-AAV assays are perceived as easier to develop and implement than neutralizing anti-AAV assays, the gene therapy field is still nascent, and it is not yet clear which of the assays should be implemented at what stage of drug development. Recently AAVrh.10 has gained interest for use in gene therapies targeting cardiac, neurological, and other diseases due to its enhanced transduction efficiency. There is limited information on anti-AAVrh.10 antibodies and their clinical impact; thus, the information presented herein documents the validation of both a total antibody assay (TAb) and a neutralizing antibody (NAb) assay for anti-AAVrh.10 antibodies. In this manuscript, the validation was performed in accordance with the 2019 FDA immunogenicity guidance with additional evaluations to comply with CLIA where applicable. The AAVrh.10 TAb and NAb assays were compared in terms of sensitivity, drug tolerance, and precision, along with a concordance analysis using the same individual serum samples. This comparison gave insight into the utility of each format as a screening assay for inclusion into clinical studies.

Evaluating f-Orbital Participation in the UV═E Multiple Bonds of [U(E)(NR2)3] (E = O, NSiMe3, NAd; R = SiMe3).

The reaction of 1 equiv of 1-azidoadamantane with [UIII(NR2)3] (R = SiMe3) in Et2O results in the formation of [UV(NR2)3(NAd)] (1, Ad = 1-adamantyl) in good yields. The electronic structure of 1, as well as those of the related U(V) complexes, [UV(NR2)3(NSiMe3)] (2) and [UV(NR2)3(O)] (3), were analyzed with EPR spectroscopy, SQUID magnetometry, NIR-visible spectroscopy, and crystal field modeling. This analysis revealed that, within this series of complexes, the steric bulk of the E2- (E═O, NR) ligand is the most important factor in determining the electronic structure. In particular, the increasing steric bulk of this ligand, on moving from O2- to [NAd]2-, results in increasing U═E distances and E-U-Namide angles. These changes have two principal effects on the resulting electronic structure: (1) the increasing U═E distances decreases the energy of the fσ orbital, which is primarily σ* with respect to the U═E bond, and (2) the increasing E-U-Namide angles increases the energy of fδ, due to increasing antibonding interactions with the amide ligands. As a result of the latter change, the electronic ground state for complexes 1 and 2 is primarily fφ in character, whereas the ground state for complex 3 is primarily fδ.

Organocatalytic synthesis of axially chiral tetrasubstituted allenes.

Asymmetric organocatalysis is a growing method for the synthesis of axially chiral tetrasubstituted allenes, the most challenging one among allene syntheses. In this method, chiral organocatalysts such as phase-transfer catalysts, peptides, disulfonimides, and binaphthyl/bispiro phosphoric acids have displayed remote control of regio- and stereoselectivity. Highly functionalized enantiopure allenes including those with an adjacent tertiary or quaternary stereocenter have been efficiently prepared with high levels of regio-, diastereo-, and enantioselectivity using this method. Several mechanistic pathways, including electrophilic addition to cumulenolate or zwitterionic enolate intermediates, alkynylogous Mukaiyama aldol reaction, nucleophilic addition to quinone methides, and dearomative addition to imino esters, were proposed. The method is necessary for providing access to axially chiral tetrasubstituted allenes, which can be utilized for the preparation of novel ligands, natural products, and organic materials, particularly those having complex structures. This review covers the enantioselective organocatalytic synthesis of these tetrasubstituted allenes and the mechanistic insights into the formation of the chiral axis up to July 2022.

Oligomeric Proanthocyanidin Complex from Avocado Seed as A Promising α-glucosidase Inhibitor: Characteristics and Mechanisms.

Although considered an abundant source of agricultural by-products, avocado (Persea americana Mill.) seed, with several biological activities and bioactive components, might become a promising resource for phytopharmaceutical development. In this study, through bioassay-guided isolation of the main α-glucosidase inhibitors in avocado seed, we discovered the major α-glucosidase inhibitor to be avocado seed oligomeric proanthocyanidin complex (ASOPC). Thiolysis and UPLC-DAD-HRESIMS showed the presence of A- and B-type procyanidins, and B-type propelargonidin with (epi)afzelechin as extension unit. Mean degree of polymerization (mDP) of ASOPC was calculated as 7.3 ± 1. Furthermore, ASOPC appeared to be a strong, reversible, competitive inhibitor of α-glucosidase, with IC50 value of 0.1 µg/mL, which was significantly lower than Acarbose (IC50 = 75.6 µg/mL), indicated that ASOPC is a potential natural α-glucosidase inhibitor. These findings would contribute to the direction of utilizing avocado seed bioactive components with the possibility to be used as natural anti-diabetic agents.

Modification of a Conventional Deep Learning Model to Classify Simulated Breathing Patterns: A Step toward Real-Time Monitoring of Patients with Respiratory Infectious Diseases.

The emergence of the global coronavirus pandemic in 2019 (COVID-19 disease) created a need for remote methods to detect and continuously monitor patients with infectious respiratory diseases. Many different devices, including thermometers, pulse oximeters, smartwatches, and rings, were proposed to monitor the symptoms of infected individuals at home. However, these consumer-grade devices are typically not capable of automated monitoring during both day and night. This study aims to develop a method to classify and monitor breathing patterns in real-time using tissue hemodynamic responses and a deep convolutional neural network (CNN)-based classification algorithm. Tissue hemodynamic responses at the sternal manubrium were collected in 21 healthy volunteers using a wearable near-infrared spectroscopy (NIRS) device during three different breathing conditions. We developed a deep CNN-based classification algorithm to classify and monitor breathing patterns in real time. The classification method was designed by improving and modifying the pre-activation residual network (Pre-ResNet) previously developed to classify two-dimensional (2D) images. Three different one-dimensional CNN (1D-CNN) classification models based on Pre-ResNet were developed. By using these models, we were able to obtain an average classification accuracy of 88.79% (without Stage 1 (data size reducing convolutional layer)), 90.58% (with 1 × 3 Stage 1), and 91.77% (with 1 × 5 Stage 1).

HP1γ Prevents Activation of the cGAS/STING Pathway by Preserving Nuclear Envelope and Genomic Integrity in Colon Adenocarcinoma Cells.

Chronic inflammatory processes in the intestine result in serious conditions such as inflammatory bowel disease (IBD) and cancer. An increased detection of cytoplasmic DNA sensors has been reported in the IBD colon mucosa, suggesting their contribution in mucosal inflammation. Yet, the mechanisms altering DNA homeostasis and triggering the activation of DNA sensors remain poorly understood. In this study, we show that the epigenetic regulator HP1γ plays a role in preserving nuclear envelope and genomic integrity in enterocytic cells, thereby protecting against the presence of cytoplasmic DNA. Accordingly, HP1 loss of function led to the increased detection of cGAS/STING, a cytoplasmic DNA sensor that triggers inflammation. Thus, in addition to its role as a transcriptional silencer, HP1γ may also exert anti-inflammatory properties by preventing the activation of the endogenous cytoplasmic DNA response in the gut epithelium.

RP-HPLC-Based Flavonoid Profiling Accompanied with Multivariate Analysis: An Efficient Approach for Quality Assessment of Houttuynia cordata Thunb Leaves and Their Commercial Products.

Chemical profiling for quality monitoring and evaluation of medicinal plants is gaining attention. This study aims to develop an HPLC method followed by multivariate analysis to obtain HPLC profiles of five specific flavonoids, including rutin (1), hyperin (2), isoquercitrin (3), quercitrin (4), and quercetin (5) from Houttuynia cordata leaves and powder products and assess the quality of H. cordata samples. Eventually, we successfully established HPLC-based flavonoid profiles and quantified the contents of 32 H. cordata fresh leave samples and four powder products. The study also quantified the contents of those five essential flavonoids using an optimized RP-HPLC method. Peak areas of samples were then investigated with principal component analysis (PCA) and hierarchical cluster analysis (HCA) to evaluate the similarity and variance. Principal components in PCA strongly influenced by hyperin and quercetin showed that the samples were clustered into subgroups, demonstrating H. cordata samples' quality. The results of HCA showed the similarity and divided the samples into seven subgroups. In conclusion, we have successfully developed a practical methodology that combined the HPLC-based flavonoid profiling and multivariate analysis for the quantification and quality control of H. cordata samples from fresh leaves and powder products. For further studies, we will consider various environmental factors, including climate and soil factors, to investigate their effects on the flavonoid contents of H. cordata.

Covalent Scrambling in Porous Polyarylthioethers through a Stepwise SN Ar for Tunable Bandgap and Porosity.

Porous poly(aryl thioether)s offer stability and electronic tunability by robust sulfur-aryl conjugated architecture, but synthetic access is hindered due to limited control over the nucleophilic nature of sulfides and the air sensitivity of aromatic thiols. Here, we report a simple, one-pot, inexpensive, regioselective synthesis of highly porous poly(aryl thioether)s through polycondensation of perfluoroaromatic compounds with sodium sulfide. The unprecedented temperature-dependent para-directing formation of thioether linkages leads to a stepwise transition of the polymer extension into a network, thereby allowing fine control of the porosity and optical band gaps. The obtained porous organic polymers with ultra-microporosity (<1 nm) and sulfur as the surface functional groups show size-dependent separation of organic micropollutants and selective removal of mercury ions from water. Our findings offer easy access to poly(aryl thioether)s with accessible sulfur functionalities and higher complexity, which will help in realizing advanced synthetic designs in applications such as adsorption, (photo)catalysis, and (opto)electronics.

Impact of Drug Conjugation on Thermal and Metabolic Stabilities of Aglycosylated and N-Glycosylated Antibodies.

N-linked glycosylation is one of the most common and complex posttranslational modifications that govern the biological functions and physicochemical properties of therapeutic antibodies. We evaluated thermal and metabolic stabilities of antibody-drug conjugates (ADCs) with payloads attached to the C'E loop in the immunoglobulin G (IgG) Fc CH2 domain, comparing the glycosylated and aglycosylated Fc ADC variants. Our study revealed that introduction of small-molecule drugs into an aglycosylated antibody can compensate for thermal destabilization originating from structural distortions caused by elimination of N-linked glycans. Depending on the conjugation site, glycans had both positive and negative effects on plasma stability of ADCs. The findings highlight the importance of consideration for selection of conjugation site to achieve desirable physicochemical properties and plasma stability.

Systematic Modulation of Thiol Functionalities in Inexpensive Porous Polymers for Effective Mercury Removal.

Through accumulation, mercury contamination in aquatic systems still poses serious health risks despite the strict regulations on drinking water and industrial discharge. One effective strategy against this is adsorptive removal, in which a suitably functionalized porous material is added to water treatment protocols. Thiol (SH) group-grafted structures perform commendably; however, insufficient attention is paid to the cost, scalability, and reusability or how the arrangement of sulfur atoms could affect the HgII binding strength. We used an inexpensive and scalable porous covalent organic polymer (COP-130) to systematically introduce thiol functional groups with precise chain lengths and sulfur content. Thiol-functionalized COP-130 demonstrates enhanced wettability and excellent HgII uptake of up to 936 mg g-1 , with fast kinetics and exceptionally high selectivity. These Hg adsorbents are easily regenerated with HCl and can be used at least six times without loss of capacity even after treatment with strong acid, a rare performance in the domain of Hg-removal research.

iCYP-MFE: Identifying Human Cytochrome P450 Inhibitors Using Multitask Learning and Molecular Fingerprint-Embedded Encoding.

The human cytochrome P450 (CYP) superfamily holds responsibilities for the metabolism of both endogenous and exogenous compounds such as drugs, cellular metabolites, and toxins. The inhibition exerted on the CYP enzymes is closely associated with adverse drug reactions encompassing metabolic failures and induced side effects. In modern drug discovery, identification of potential CYP inhibitors is, therefore, highly essential. Alongside experimental approaches, numerous computational models have been proposed to address this biochemical issue. In this study, we introduce iCYP-MFE, a computational framework for virtual screening on CYP inhibitors toward 1A2, 2C9, 2C19, 2D6, and 3A4 isoforms. iCYP-MFE contains a set of five robust, stable, and effective prediction models developed using multitask learning incorporated with molecular fingerprint-embedded features. The results show that multitask learning can remarkably leverage useful information from related tasks to promote global performance. Comparative analysis indicates that iCYP-MFE achieves three predominant tasks, one equivalent task, and one less effective task compared to state-of-the-art methods. The area under the receiver operating characteristic curve (AUC-ROC) and the area under the precision-recall curve (AUC-PR) were two decisive metrics used for model evaluation. The prediction task for CYP2D6-inhibition achieves the highest AUC-ROC value of 0.93 while the prediction task for CYP1A2-inhibition obtains the highest AUC-PR value of 0.92. The substructural analysis preliminarily explains the nature of the CYP-inhibitory activity of compounds. An online web server for iCYP-MFE with a user-friendly interface was also deployed to support scientific communities in identifying CYP inhibitors.

Multimodal analysis of ctDNA methylation and fragmentomic profiles enhances detection of nonmetastatic colorectal cancer.

Aims: Early detection of colorectal cancer (CRC) provides substantially better survival rates. This study aimed to develop a blood-based screening assay named SPOT-MAS ('screen for the presence of tumor by DNA methylation and size') for early CRC detection with high accuracy. Methods: Plasma cell-free DNA samples from 159 patients with nonmetastatic CRC and 158 healthy controls were simultaneously analyzed for fragment length and methylation profiles. We then employed a deep neural network with fragment length and methylation signatures to build a classification model. Results: The model achieved an area under the curve of 0.989 and a sensitivity of 96.8% at 97% specificity in detecting CRC. External validation of our model showed comparable performance, with an area under the curve of 0.96. Conclusion: SPOT-MAS based on integration of cancer-specific methylation and fragmentomic signatures could provide high accuracy for early-stage CRC detection.

A novel blood test for early detection of colorectal cancer. Colorectal cancer is a cancer of the colon or rectum, located at the lower end of the digestive tract. The early detection of colorectal cancer can help people with the disease have a higher chance of survival and a better quality of life. Current screening methods can be invasive, cause discomfort or have low accuracy; therefore newer screening methods are needed. In this study we developed a new screening method, called SPOT-MAS, which works by measuring the signals of cancer DNA in the blood. By combining different characteristics of cancer DNA, SPOT-MAS could distinguish blood samples of people with colorectal cancer from those of healthy individuals with high accuracy.

Clinical Report: Midday Removal and Reinsertion of Soft Contact Lens Cannot Prevent Post-lens Tear-film Hyperosmolarity.

SIGNIFICANCE: Our analysis shows that post-lens tear-film (PoLTF) hyperosmolarity is not preventable with midday removal and reinsertion of soft contact lenses. However, low lens-salt diffusivity can prevent the PoLTF from becoming hyperosmotic. Lens-salt diffusivity should be lowered to minimize PoLTF osmolarity while also avoiding lens adhesion. PURPOSE: Soft contact lenses with high lens-salt diffusivity result in hyperosmotic PoLTFs. If the time it takes for PoLTF osmolarity to reach periodic steady state is multiple hours, simple midday lens removal and reinsertion can prevent the PoLTF from becoming hyperosmotic. We investigate whether midday removal and reinsertion of a soft contact lens can prevent the PoLTF from becoming hyperosmotic. METHODS: Time to periodic steady state for PoLTF osmolarity upon soft-contact-lens wear is determined with a previously developed transient tear-dynamics continuum model. Interblink period, lens-salt diffusivity, and lens thickness was varied to assess their effects on time to periodic steady state for PoLTF osmolarity. Time to periodic steady states were assessed for both normal and dry eyes. RESULTS: Within the physically realistic ranges of lens-salt diffusivity, lens thickness, and interblink period, PoLTF osmolarity reaches the periodic steady state well within the first hour of lens wear for both normal and dry eyes. Time to periodic steady state for PoLTF osmolarity is predominately dictated by the salt transport across the contact lens between the PoLTF and the pre-lens tear film and water transport from the ocular surface to the PoLTF. CONCLUSIONS: Since the time to periodic steady state is less than 1 hour for physically realistic ranges of lens-salt diffusivity, interblink period, and lens thickness, midday lens removal and reinsertion cannot prevent PoLTF hyperosmolarity. Instead, focus should be on using soft contact lenses with low salt diffusivity to prevent PoLTF hyperosmolarity.