Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma.

Immune checkpoint blockade (ICB) has improved outcomes for patients with head and neck squamous cell carcinoma (HNSCC), but predictive biomarkers remain limited. Here, we use a time-resolved, multi-omic approach in a murine HNSCC model to characterize peripheral immune responses to ICB. Single-cell transcriptomics and T/B cell receptor analyses  reveal early on-treatment expansion of effector memory T and B cell repertoires in responders, preceding tumor regression.

Pan-cancer prediction of tumor immune activation and response to immune checkpoint blockade from tumor transcriptomics and histopathology.

Accurately predicting which patients will respond to immune checkpoint blockade (ICB) remains a major challenge. Here, we present TIME_ACT, an unsupervised 66-gene transcriptomic signature of tumor immune activation derived from TCGA melanoma data. First, TIME_ACT scores accurately identify tumors with activated immune microenvironments across cancer types.

A multi-phase approach using supervised algorithms and clinical models to generate high-accuracy signatures for pancreatic cancer.

Background: The in silico analyses provide evidence supporting the potential of methylation-driven differentially expressed genes as therapeutic targets across cancer types. This leads us to identify novel targets and their associated drug compounds for further progress towards pancreatic cancer treatment.

Objective: To identify targeted drugs based on methylation driven genes identified using bulk multi-omics data and single-cell level data to pinpoint important disease markers.

Pan-cancer analysis of cancer-specific transcript isoforms reveals the regulatory impact of isoform switching on the alteration of the interplay between RBPs and miRNAs in cancers.

The switch in the predominantly expressed transcript isoform of the same gene has been identified as a significant factor in the progression of various types of cancer. These switches can impact the gain or loss of different 3'UTRs, which are hotspots for the binding of microRNAs (miRNAs) and RNA-binding proteins (RBPs). In this study, we found that in cancer-specific dominant expressing transcripts, the binding of miRNA and RBP is disrupted, suggesting that transcript switching could play a part in modulating post-transcriptional gene expression during the progression and development of cancer.

Identification of KCNJ5 gene an adverse prognosis associated novel onco-ionchannel in Indian pancreatic cancer cohort.

Background: Pancreatic cancer (PanCa) is one of the most lethal cancers (survival ~ 12%). As the conventional therapeutic interventions are mostly futile, a deep understanding of the disease pathophysiology is an urgent need. Ion channels, located on cell membrane, contribute significantly to cancer hallmarks, through dysregulation of various ion translocation; however, the fundamental mechanisms remain uncertain.

Pitfalls in performing genome-wide association studies on ratio traits.

Genome-wide association studies (GWASs) are often performed on ratios composed of a numerator trait divided by a denominator trait. Examples include body mass index (BMI) and the waist-to-hip ratio, among many others. Explicitly or implicitly, the goal of forming the ratio is typically to adjust for an association between the numerator and denominator.

EmbedGEM: a framework to evaluate the utility of embeddings for genetic discovery.

Summary: Machine learning-derived embeddings are a compressed representation of high content data modalities. Embeddings can capture detailed information about disease states and have been qualitatively shown to be useful in genetic discovery. Despite their promise, embeddings have a major limitation: it is unclear if genetic variants associated with embeddings are relevant to the disease or trait of interest.

Progression of the Immune Escape Mechanism in Tumors.

There exists a long-standing research interest to understand the molecular and signaling interactions between tumor cells and the innate and adaptive immune cells such as dendritic cells, macrophages, NK cells, and B and T cells that occur in the tumor microenvironment (TME) [...

Corrigendum: Dietary polyphenols, resveratrol and pterostilbene exhibit antitumor activity on an HPV E6-positive cervical cancer model: an and analysis.

[This corrects the article DOI: 10.3389/fonc.2019.

Vibrational, optical, and photocatalytic properties of ZnO/layered carbon nanocomposite synthesized by ball milling.

ZnO/layered carbon nanocomposites with varied sizes of ZnO nanoparticles (NPs) were synthesized by mechanical milling of mixture of ZnO NPs and carbon NPs. The NP size of ZnO was controlled with average particle sizes about 19.33, 21.

Factors affecting heterogeneity in breast cancer microenvironment: A narrative mini review.

Breast cancer (BC) heterogeneity is a key trait of BC tumors with crucial implications on tumorigenesis, diagnosis, and therapeutic modalities. It is influenced by tumor intrinsic features and by the tumor microenvironment (TME) composition of different intra-tumoral regions, which in turn affect cancer progression within patients. In this mini review, we will highlight the mechanisms that generate cancer heterogeneity in BC and how they affect the responses to cancer therapies.

Designing RNA switches for synthetic biology using inverse-RNA-folding.

RNA switches respond to specific ligands to control gene expression. They are widely used in synthetic biology applications and hold potential for future RNA-based therapeutic breakthroughs. However, the crux is their precise design.

The mature N-termini of effector proteins confer specificity of export.

Malaria parasites export hundreds of proteins to the cytoplasm of the host red blood cells for their survival. A five amino acid sequence, called the PEXEL motif, is conserved among many exported proteins and is thought to be a signal for export. However, the motif is cleaved inside the endoplasmic reticulum of the parasite, and mature proteins starting from the fourth PEXEL residue travel to the parasite periphery for export.

Using Data Science and a Health Equity Lens to Identify Long-COVID Sequelae Among Medically Underserved Populations.

Understanding how post-acute COVID-19 syndrome (PACS or long COVID) manifests among underserved populations, who experienced a disproportionate burden of acute COVID-19, can help providers and policymakers better address this ongoing crisis. To identify clinical sequelae of long COVID among underserved populations treated in the primary care safety net, we conducted a causal impact analysis with electronic health records (EHR) to compare symptoms among community health center patients who tested positive (n=4,091) and negative (n=7,118) for acute COVID-19. We found 18 sequelae with statistical significance and causal dependence among patients who had a visit after 60 days or more following acute COVID-19.

Activation of the Egress Effector Subtilisin-Like Protease 1 Is Mediated by Plasmepsin X Destruction of the Prodomain.

Following each round of replication, daughter merozoites of the malaria parasite Plasmodium falciparum escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by a parasite serine protease, subtilisin-like protease 1 (SUB1), regulates the membrane breakdown. SUB1 activation involves primary autoprocessing of the 82-kDa zymogen to a 54-kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) postcleavage.

A computational approach for the identification of distant homologs of bacterial riboswitches based on inverse RNA folding.

Riboswitches are conserved structural ribonucleic acid (RNA) sensors that are mainly found to regulate a large number of genes/operons in bacteria. Presently, >50 bacterial riboswitch classes have been discovered, but only the thiamine pyrophosphate riboswitch class is detected in a few eukaryotes like fungi, plants and algae. One of the most important challenges in riboswitch research is to discover existing riboswitch classes in eukaryotes and to understand the evolution of bacterial riboswitches.

Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors.

Immune checkpoint blockade (ICB) has emerged as a novel therapeutic tool for cancer therapy in the last decade. Unfortunately, a small number of patients benefit from approved immune checkpoint inhibitors (ICIs). Therefore, multiple studies are being conducted to find new ICIs and combination strategies to improve the current ICIs.

Activation of the egress effector subtilisin-like protease 1 is achieved by plasmepsin X destruction of the propiece.

Unlabelled: Following each round of replication, daughter merozoites of the malaria parasite escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by the parasite’s serine protease, subtilisin-like protease 1 (SUB1) regulates the membrane breakdown. SUB1 activation involves primary auto-processing of the 82 kDa zymogen to a 54 kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) post cleavage.