Multimodal detection of molecular residual disease in high-risk locally advanced squamous cell carcinoma of the head and neck.

Up to 30% of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) relapse. Molecular residual disease (MRD) detection using multiple assays after definitive therapy has not been reported. In this study, we included patients with LA-HNSCC (stage III Human Papilloma virus (HPV)-positive, III-IVB HPV-negative) treated with curative intent.

Clinical Validation of Human Papilloma Virus Circulating Tumor DNA for Early Detection of Residual Disease After Chemoradiation in Cervical Cancer.

Purpose: Most cervical cancers are caused by human papilloma virus (HPV), and HPV circulating tumor DNA (ctDNA) may identify patients at highest risk of relapse. Our pilot study using digital polymerase chain reaction (dPCR) showed that detectable HPV ctDNA at the end of chemoradiation (CRT) is associated with inferior progression-free survival (PFS) and that a next-generation sequencing approach (HPV-seq) may outperform dPCR. We aimed to prospectively validate HPV ctDNA as a tool for early detection of residual disease.

Circulating tumour DNA kinetics in recurrent/metastatic head and neck squamous cell cancer patients.

Purpose: Immune checkpoint blockade (ICB) has become a standard of care in the treatment of recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC). However, only a subset of patients benefit from treatment. Quantification of plasma circulating tumour DNA (ctDNA) levels and on-treatment kinetics may permit real-time assessment of disease burden under selective pressures of treatment.

Efficacy of Long-Term Spinal Nerve Posterior Ramus Pulsed Radiofrequency in Treating Subacute Herpetic Neuralgia: A Prospective Randomized Controlled Trial.

Objective: This study aimed to observe the clinical efficacy of long-term spinal nerve posterior ramus pulsed radiofrequency (PRF) in treating subacute herpes zoster neuralgia (HZN).

Methods: A total of 120 patients with subacute HZN in the thoracolumbar region and back were equally randomized to the conventional PRF group (P group, = 60), with a pulse of 180 s, or to the long-term PRF group (LP group, = 60), with a pulse of 600 s. The patients' baseline characteristics, the incidence rate of postherpetic neuralgia (PHN), and the dose of analgesics were compared between the two groups.

HPV Sequencing Facilitates Ultrasensitive Detection of HPV Circulating Tumor DNA.

Purpose: Human papillomavirus (HPV) DNA offers a convenient circulating tumor DNA (ctDNA) marker for HPV-associated malignancies, but current methods, such as digital PCR (dPCR), provide insufficient accuracy for clinical applications in patients with low disease burden. We asked whether a next-generation sequencing approach, HPV sequencing (HPV-seq), could provide quantitative and qualitative assessment of HPV ctDNA in low disease burden settings.

Experimental Design: We conducted preclinical technical validation studies on HPV-seq and applied it retrospectively to a prospective multicenter cohort of patients with locally advanced cervix cancer (NCT02388698) and a cohort of patients with oropharynx cancer.

Tumor-Naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma.

Purpose: Circulating tumor DNA (ctDNA) enables personalized treatment strategies in oncology by providing a noninvasive source of clinical biomarkers. In patients with low ctDNA abundance, tumor-naïve methods are needed to facilitate clinical implementation. Here, using locoregionally confined head and neck squamous cell carcinoma (HNSCC) as an example, we demonstrate tumor-naïve detection of ctDNA by simultaneous profiling of mutations and methylation.

eTumorMetastasis: A Network-based Algorithm Predicts Clinical Outcomes Using Whole-exome Sequencing Data of Cancer Patients.

Continual reduction in sequencing cost is expanding the accessibility of genome sequencing data for routine clinical applications. However, the lack of methods to construct machine learning-based predictive models using these datasets has become a crucial bottleneck for the application of sequencing technology in clinics. Here, we develop a new algorithm, eTumorMetastasis, which transforms tumor functional mutations into network-based profiles and identifies network operational gene (NOG) signatures.

Germline variants associated with leukocyte genes predict tumor recurrence in breast cancer patients.

Germline variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. However, only a small fraction (i.e.

Effect of Shock Wave on Vascular Lesions in Diabetic Rats.

Background: Diabetes is one of the most common diseases in today's society. Diabetes can cause multiple vascular lesions in the body, renal insufficiency, blindness, and so on. However, the evidence concerning the role of extracorporeal shock wave therapy in diabetic vascular disease is insufficient.

Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk.

Importance: Only a small fraction of patients with cancer receiving immune checkpoint therapy (ICT) respond, which is associated with tumor immune microenvironment (TIME) subtypes and tumor-infiltrating lymphocytes (TILs).

Objective: To examine whether germline variants of natural killer (NK) cells, a key component of the immune system, are associated with TIME subtypes, the abundance of TILs, response to ICT, clinical outcomes, and cancer risk.

Design, Setting, And Participants: This genetic association study explored TIME subtypes and examined the association of the germline genomic information of patients with cancer with TIME subtypes, abundance of TILs, response to ICT, prognosis, and cancer risk.

Impact of preleukemic mutations and their persistence on hematologic recovery after induction chemotherapy for AML.

, , , and mutations identified at the time of diagnosis are associated with delayed count recovery. Persistence of preleukemic mutations in remission at high variant allele frequency is associated with delayed count recovery.

High efficiency error suppression for accurate detection of low-frequency variants.

Detection of cancer-associated somatic mutations has broad applications for oncology and precision medicine. However, this becomes challenging when cancer-derived DNA is in low abundance, such as in impure tissue specimens or in circulating cell-free DNA. Next-generation sequencing (NGS) is particularly prone to technical artefacts that can limit the accuracy for calling low-allele-frequency mutations.

Effects of transection of cervical sympathetic trunk on cognitive function of traumatic brain injury rats.

To observe the effects of transection of cervical sympathetic trunk (TCST) on the cognitive function of traumatic brain injury (TBI) rats and the potential mechanisms. A total of 288 adult male SD rats were divided into 3 groups using a random number table: TBI group (n=96), TBI + TCST group (n=96) and Sham group (n=96). The water maze test was performed before TBI (T0) and at day 1 (T), day 2 (T), day 3 (T), 1 week (T), 2 weeks (T), 6 weeks (T) and 12 weeks (T) after TBI.

Cancer Biomarker Discovery for Precision Medicine: New Progress.

Background: Precision medicine puts forward customized healthcare for cancer patients. An important way to accomplish this task is to stratify patients into those who may respond to a treatment and those who may not. For this purpose, diagnostic and prognostic biomarkers have been pursued.

A Protocol for Epigenetic Imprinting Analysis with RNA-Seq Data.

Genomic imprinting is an epigenetic regulatory mechanism that operates through expression of certain genes from maternal or paternal in a parent-of-origin-specific manner. Imprinted genes have been identified in diverse biological systems that are implicated in some human diseases and in embryonic and seed developmental programs in plants. The molecular underpinning programs and mechanisms involved in imprinting are yet to be explored in depth in plants.

Lewis-Base-Mediated Diastereoselective Silylations of Alcohols: Synthesis of Silicon-Stereogenic Dialkoxysilanes Controlled by Chiral Aryl BINMOLs.

In the past years, stereoselective functionalizations of hydroxyl groups of alcohol substrates with chlorosilanes leading to silyl ether formation have evolved from a functional-group protection to an enantioselective synthetic strategy. This work comprises a controlled desymmetrization of dichlorosilanes by using a family of structurally specific chiral diols, chiral 1,1'-binaphthalene-2-α-arylmethanol-2'-ol (Ar-BINMOL). This process led to the facile construction of silicon-stereogenic organosilicon compounds with high yields and good diastereoselectivities.

eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood.

With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has.

BRPF1 is essential for development of fetal hematopoietic stem cells.

Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful for a variety of HSC transplantation-based therapies. Understanding the role of chromatin organization and regulation in HSC homeostasis may provide important insights into HSC development. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications.

Synthesis and characterization of amylose-zinc inclusion complexes.

Amylose-zinc inclusion complexes were synthesized using zinc chloride and amylose, which is obtained by completely debranching potato starch using pullulanase. Based on the zinc content (W-Zn) and zinc conversion (C-Zn), the reaction parameters, such as reaction time, reaction temperature, pH value and amount of zinc chloride added, were evaluated. The W-Zn and C-Zn of the zinc-loaded amylose, which was prepared under optimal conditions, were 128 mg/g and 82.

Identification and Construction of Combinatory Cancer Hallmark-Based Gene Signature Sets to Predict Recurrence and Chemotherapy Benefit in Stage II Colorectal Cancer.

Importance: Decisions regarding adjuvant therapy in patients with stage II colorectal cancer (CRC) have been among the most challenging and controversial in oncology over the past 20 years.

Objective: To develop robust combinatory cancer hallmark-based gene signature sets (CSS sets) that more accurately predict prognosis and identify a subset of patients with stage II CRC who could gain survival benefits from adjuvant chemotherapy.

Design, Setting, And Participants: Thirteen retrospective studies of patients with stage II CRC who had clinical follow-up and adjuvant chemotherapy were analyzed.

The chromatin regulator Brpf1 regulates embryo development and cell proliferation.

With hundreds of chromatin regulators identified in mammals, an emerging issue is how they modulate biological and pathological processes. BRPF1 (bromodomain- and PHD finger-containing protein 1) is a unique chromatin regulator possessing two PHD fingers, one bromodomain and a PWWP domain for recognizing multiple histone modifications. In addition, it binds to the acetyltransferases MOZ, MORF, and HBO1 (also known as KAT6A, KAT6B, and KAT7, respectively) to promote complex formation, restrict substrate specificity, and enhance enzymatic activity.

The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors.

Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability.

Deficiency of the chromatin regulator BRPF1 causes abnormal brain development.

Epigenetic mechanisms are important in different neurological disorders, and one such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1 (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein 1) recognizes different epigenetic marks and activates three histone acetyltransferases, so it is both a reader and a co-writer of the epigenetic language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively.