THOR: a TMB heterogeneity-adaptive optimization model predicts immunotherapy response using clonal genomic features in group-structured data.

With the increasing number of indications for immune checkpoint inhibitors in early and advanced cancers, the prospect of a tumor-agnostic biomarker to prioritize patients is compelling. Tumor mutation burden (TMB) is a widely endorsed biomarker that quantifies nonsynonymous mutations within tumor DNA, essential for neoantigen production, which, in turn, correlates with the immune response and guides decision-making. However, the general clinical application of TMB-relying on simple mutational counts targeted at a single endpoint-does not adequately capture the complex clonal structure of tumors nor the multifaceted nature of prognostic indicators.

Electromagnetic-Driven Spider-Inspired Soft Robot Using Electroelastic Materials and Conductive Actuators.

Soft robots have developed gradually in the fields of portability, high precision, and low noise level due to their unique advantages of low noise and low energy consumption. This paper proposes an electromagnetically driven elastomer, using gelatin and glycerol (GG) as matrix materials and a mixture of multiwalled carbon nanotubes (MWCNTs) and Ag NWs (MA) as the conductive medium. Inchworm-inspired and spider-inspired soft robots have been developed, demonstrating fast movement speed, flexibility, and loading performance.

SAFE-MIL: a statistically interpretable framework for screening potential targeted therapy patients based on risk estimation.

Patients with the target gene mutation frequently derive significant clinical benefits from target therapy. However, differences in the abundance level of mutations among patients resulted in varying survival benefits, even among patients with the same target gene mutations. Currently, there is a lack of rational and interpretable models to assess the risk of treatment failure In this study, we investigated the underlying coupled factors contributing to variations in medication sensitivity and established a statistically interpretable framework, named SAFE-MIL, for risk estimation.

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas.

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) should follow the guidelines of small-cell lung cancer (SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.

Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts.

ARID1A deficiency promotes progression and potentiates therapeutic antitumour immunity in hepatitis B virus-related hepatocellular carcinoma.

Background: Exploring predictive biomarkers and therapeutic strategies of ICBs has become an urgent need in clinical practice. Increasing evidence has shown that ARID1A deficiency might play a critical role in sculpting tumor environments in various tumors and might be used as pan-cancer biomarkers for immunotherapy outcomes. The current study aims to explored the immune-modulating role of ARID1A deficiency in Hepatitis B virus (HBV) related hepatocellular carcinoma (HBV-HCC) and its potential immunotherapeutic implications.

Molecular insights into complexation between protein and silica: Spectroscopic and simulation investigations.

The synergistic effect of protein-silica complexation leads to exacerbated membrane fouling in the membrane desalination process, exceeding the individual impacts of silica scaling or protein fouling. However, the molecular-level dynamics of silica binding to proteins and the resulting structural changes in both proteins and silica remain poorly understood. This study investigates the complexation process between silica and proteins-negatively charged bovine serum albumin (BSA) and positively charged lysozyme (LYZ) at neutral pH-using infrared spectroscopy (IR), in situ attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and multiple computational simulations.

DELFMUT: duplex sequencing-oriented depth estimation model for stable detection of low-frequency mutations.

Duplex sequencing technology has been widely used in the detection of low-frequency mutations in circulating tumor deoxyribonucleic acid (DNA), but how to determine the sequencing depth and other experimental parameters to ensure the stable detection of low-frequency mutations is still an urgent problem to be solved. The mutation detection rules of duplex sequencing constrain not only the number of mutated templates but also the number of mutation-supportive reads corresponding to each forward and reverse strand of the mutated templates. To tackle this problem, we proposed a Depth Estimation model for stable detection of Low-Frequency MUTations in duplex sequencing (DELFMUT), which models the identity correspondence and quantitative relationships between templates and reads using the zero-truncated negative binomial distribution without considering the sequences composed of bases.

SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy.

Background: SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer.

Methods: This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020.

Fabrication and Separation of EGaIn Microparticles from Human Blood Based on Dielectrophoresis Force and a W-Type Electrode.

Harmful particles such as heavy metal particles in the human body can cause many problems such as kidney stones, gallstones, and cerebrovascular diseases. Therefore, it is critical to separate them from the blood and perform a systematic analysis as early as possible. Here, we apply eutectic gallium indium (EGaIn) microparticles as a model to study the separation of particles from blood, thanks to their properties of low toxicity, excellent degradability, and negligible vapor pressure.

Analysis of genomic and immune intratumor heterogeneity in linitis plastica via multiregional exome and T-cell receptor sequencing.

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole-exome sequencing (WES) and T-cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported.

A Noninvasive Sweat Glucose Biosensor Based on Glucose Oxidase/Multiwalled Carbon Nanotubes/Ferrocene-Polyaniline Film/Cu Electrodes.

Diabetes remains a great threat to human beings' health and its world prevalence is projected to reach 9.9% by 2045. At present, the detection methods used are often invasive, cumbersome and time-consuming, thus increasing the burden on patients.

Maximum Somatic Allele Frequency-Adjusted Blood-Based Tumor Mutational Burden Predicts the Efficacy of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer.

Introduction: Recent studies exhibited the unstable prediction ability of blood-based tumor mutational burden (bTMB) when predicting the response of immune checkpoint inhibitors (ICIs) therapy in patients with non-small cell lung cancer (NSCLC). Circulating tumor DNA (ctDNA) abundance, usually represented by maximum somatic allele frequency (MSAF), was one possible confounding factor influencing bTMB ability in ICIs response prediction.

Methods: MSAF-adjusted bTMB (Ma-bTMB) was established and validated in patients with advanced NSCLC among Geneplus Cancer Genome Database (GCGD, = 1679), Zhuo ( = 35), Wang ( = 45), POPLAR (NCT01903993, = 211) and OAK (NCT02008227, = 642) cohorts.

Utility of cell-free DNA from bronchial washing fluid in diagnosis and genomic determination for radiology-suspected pulmonary nodules.

Background: Bronchial washing fluid (BWF) is a less-invasive specimen. Due to the limited sensitivity of BWF cellular component diagnosis, the aim of this study was to explore the potential role of BWF supernatant as a source of liquid biopsy of lung cancer.

Methods: This prospective study enrolled 76 suspected and 5 progressed lung cancer patients.

Circulating Tumor DNA: Less Invasive, More Representative Method to Unveil the Genomic Landscape of Newly Diagnosed Multiple Myeloma Than Bone Marrow Aspirates.

Multiple myeloma (MM) is highly heterogenous and dynamic in its genomic abnormalities. Capturing a representative image of these alterations is essential in understanding the molecular pathogenesis and progression of the disease but was limited by single-site invasive bone marrow (BM) biopsy-based genomics studies. We compared the mutational landscapes of circulating tumor DNA (ctDNA) and BM in 82 patients with newly diagnosed MM.

Microparticle Manipulation Based on the Bulk Acoustic Wave Combined with the Liquid Crystal Backflow Effect Driving in 2D/3D Platforms.

Microparticle manipulation has been widely used in clinical diagnosis, cell separation, and biochemical analysis via optics, electronics, magnetics, or acoustic wave driving. Among them, the bulk acoustic wave (BAW) driving method has been increasingly adopted because of non-contact, easy control, and precise manipulation. However, its low manipulation efficiency limits the usage of the BAW driving in high viscosity solutions.

Contrasting behaviors of pre-ozonation on ceramic membrane biofouling: Early stage vs late stage.

Pre-ozonation coupled with ceramic membrane filtration has been widely used to alleviate membrane fouling. However, information on the efficiency and underlying mechanism of pre-ozonation in the evolution of ceramic membrane biofouling is limited. Herein, filtration experiments with a synthesis wastewater containing activated sludge were conducted in a cross-flow system to evaluate the effects of pre-ozonation on ceramic membrane biofouling.

A plantar wearable pressure sensor based on hybrid lead zirconate-titanate/microfibrillated cellulose piezoelectric composite films for human health monitoring.

Flexible and wearable electronic sensors hold great promise for improving the quality of life, especially in the field of healthcare monitoring, owing to their low cost, flexibility, high electromechanical coupling performance, high sensitivity, and biocompatibility. To achieve high piezoelectric performance similar to that of rigid materials while satisfying the flexible requirements for wearable sensors, we propose novel hybrid films based on lead zirconate titanate powder and microfibrillated cellulose (PZT/MFC) for plantar pressure measurements. The flexible films made using the polarization process are tested.

Longitudinal Undetectable Molecular Residual Disease Defines Potentially Cured Population in Localized Non-Small Cell Lung Cancer.

Unlabelled: The efficacy and potential limitations of molecular residual disease (MRD) detection urgently need to be fully elucidated in a larger population of non-small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent definitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the population, only six patients (3.

Genomic and TCR profiling data reveal the distinct molecular traits in epithelial ovarian cancer histotypes.

Epithelial ovarian cancer (EOC) is classified into five major histotypes: high-grade serous (HGSOC), low-grade serous (LGSOC), clear cell (CCOC), endometrioid (ENOC), and mucinous (MOC). However, the landscape of molecular and immunological alterations in these histotypes, especially LGSOC, CCOC, ENOC, and MOC, is largely uncharacterized. We collected 101 treatment-naive EOC patients.

Molecular landscape of TP53 mutations in breast cancer and their utility for predicting the response to HER-targeted therapy in HER2 amplification-positive and HER2 mutation-positive amplification-negative patients.

Purpose: We used targeted capture sequencing to analyze TP53-mutated circulating tumor DNA (ctDNA) in metastatic breast cancer patients and to determine whether TP53 mutation has predictive value for anti-human epidermal growth factor receptor 2 (HER2) treatment for in HER2 amplification-positive patients (HER2+) and HER2 mutation-positive, amplification-negative (HER2-/mut) patients.

Patients And Methods: TP53 mutation features were analyzed in the Geneplus cohort (n = 1184). The MSK-BREAST cohort was used to explore the value of TP53 mutation in predicting anti-HER-2 antibody efficacy.

Next-generation Sequencing Reveals Age-dependent Genetic Underpinnings in Lung adenocarcinoma.

: More than 40% of lung cancer patients are diagnosed at ages over 70. However, the genomic and clinical characteristics among them remain elusive. Here, we performed targeted capture sequence to characterize the mutational spectrum of Chinese lung adenocarcinoma (LUAD) patients across ages.

Safety and efficacy of mutant neoantigen-specific T-cell treatment combined anti-PD-1 therapy in stage IV solid tumors.

This trial explored the safety and efficacy of neoantigen-specific T cells (Nas-Ts) combined with anti-PD-1 (Nas-T + anti-PD-1). This non-randomized trial recruited participants with solid tumors treated with at least two prior systemic treatment lines. For comparison, 1:1-matched controls who received anti-PD-1 alone were recruited.