The UBA1-STUB1 axis mediates cancer immune escape and resistance to checkpoint blockade.

How cancer cells escape immune surveillance and resist immune checkpoint blockade (ICB) remains to be fully elucidated. By screening candidate genes frequently gained in cancer, we identified expression of ubiquitin-like modifier activating enzyme 1 (UBA1) as being the most negatively correlated with signatures related to effector CD8+ T-cells. High UBA1 expression was strongly predictive of treatment resistance and poor survival in ICB cohorts.

PIKfyve, expressed by CD11c-positive cells, controls tumor immunity.

Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic cells (DC) and other myeloid cells with antigen presenting and cancer cell killing capacities is an attractive but not fully exploited approach. Here, we show that PIKFYVE is a shared gene target of clinically relevant protein kinase inhibitors and high expression of this gene in DCs is associated with poor patient response to immune checkpoint blockade (ICB) therapy.

PIKfyve controls dendritic cell function and tumor immunity.

The modern armamentarium for cancer treatment includes immunotherapy and targeted therapy, such as protein kinase inhibitors. However, the mechanisms that allow cancer-targeting drugs to effectively mobilize dendritic cells (DCs) and affect immunotherapy are poorly understood. Here, we report that among shared gene targets of clinically relevant protein kinase inhibitors, high expression was least predictive of complete response in patients who received immune checkpoint blockade (ICB).

Targeting the lipid kinase PIKfyve upregulates surface expression of MHC class I to augment cancer immunotherapy.

Despite the remarkable clinical success of immunotherapies in a subset of cancer patients, many fail to respond to treatment and exhibit resistance. Here, we found that genetic or pharmacologic inhibition of the lipid kinase PIKfyve, a regulator of autophagic flux and lysosomal biogenesis, upregulated surface expression of major histocompatibility complex class I (MHC-I) in cancer cells via impairing autophagic flux, resulting in enhanced cancer cell killing mediated by CD8 T cells. Genetic depletion or pharmacologic inhibition of PIKfyve elevated tumor-specific MHC-I surface expression, increased intratumoral functional CD8 T cells, and slowed tumor progression in multiple syngeneic mouse models.

A Rare Case of Localized Hypertrichosis in Conjunction with Erythema Nodosum.

Acquired hypertrichosis can occur in local inflammation. Erythema nodosum (EN) is a hypersensitivity reaction to various underlying antigenic stimuli including , which causes inflammation in the septa of subcutaneous fat. There were several case reports that describe the association of localized hypertrichosis (LH) with traumatic panniculitis and lupus panniculitis.

Clinical characteristics of chronic rhinitis following stroke.

Background: We previously observed that patients with stroke complained of rhinitis symptoms that developed following the occurrence of stroke.

Objectives: To investigate the relationship between chronic rhinitis (CR) and stroke.

Methods: This retrospective study analyzed the medical records and questionnaires of patients with stroke who visited our outpatient clinic from June to December 2020.

Relation of Flatfoot Severity with Flexibility and Isometric Strength of the Foot and Trunk Extensors in Children.

Background: Flatfoot is a deformity in which the foot is flattened due to a decrease in or loss of the medial longitudinal arch.

Statement Of The Problem: Few studies have investigated the relationship between the severity of flat feet, trunk strength, and joint flexibility.

Purpose: The aim of this study is to investigate the relationship between the severity of flatfoot and joint flexibility and foot and trunk strength in children with flexible flatfoot.

Intersection of immune and oncometabolic pathways drives cancer hyperprogression during immunotherapy.

Immune checkpoint blockade (ICB) can produce durable responses against cancer. We and others have found that a subset of patients experiences paradoxical rapid cancer progression during immunotherapy. It is poorly understood how tumors can accelerate their progression during ICB.

Reliability of electroencephalogram indicator and event related potential in subacute stroke.

Cognitive impairment is observed in 12% to 56% of stroke patients, and screening for cognitive impairment is often complex and time-consuming, with results dependent on patient compliance. Therefore, there is a need for an objective method to assess cognitive impairment regardless of patient compliance. Objective evaluation methods include electroencephalogram (EEG) and event-related potential (ERP).

Distribution Analysis of according to Sex and Age in Clinical Specimen Testing for Sexually Transmitted Diseases.

The prevalence of candidiasis, a contagious disease with high morbidity and mortality, has sharply increased globally over the last two decades. Candida albicans can cause serious infections in patients with weak immunity and in recipients of prolonged antibiotic treatment. Consequently, rapid and accurate identification of species can play an important role in the treatment of candidiasis.

The Low-Fluence Q-Switched Nd:YAG Laser Treatment for Melasma: A Systematic Review.

Melasma is a common pigmentary disorder with a complex pathogenesis, of which the treatment is challenging. Conventional treatment often leads to inconsistent results with unexpected pigmentary side effects and high recurrence rates. Recently, the low-fluence Q-switched Nd:YAG laser (LFQSNY) has been widely used for treating melasma, especially in Asia.

Age and sex trends of infection in patients with sexually transmitted infections in Korea.

Background And Objectives: and are the most common causative agents of bacterial vaginosis, and infections with these pathogens lead to inflammation, endometritis, and pruritus. The aim of this retrospective study was to determine the trends of infections based on real-time PCR data according to age and sex in patients with sexually transmitted diseases.

Materials And Methods: A total of 59,381 specimens isolated at a clinical laboratory from September 2018 to December 2020 were subjected to real-time PCR for the detection of DNA.

Autophagy Inhibition by Targeting PIKfyve Potentiates Response to Immune Checkpoint Blockade in Prostate Cancer.

Multi-tyrosine kinase inhibitors (MTKIs) have thus far had limited success in the treatment of castration-resistant prostate cancer (CRPC). Here, we report a phase I-cleared orally bioavailable MTKI, ESK981, with a novel autophagy inhibitory property that decreased tumor growth in diverse preclinical models of CRPC. The anti-tumor activity of ESK981 was maximized in immunocompetent tumor environments where it upregulated expression through the interferon gamma pathway and promoted functional T cell infiltration, which resulted in enhanced therapeutic response to immune checkpoint blockade.

Viral Status Predicts the Patterns of Genome Methylation and Decitabine Response in Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that is classified as Merkel cell polyomavirus-positive (virus positive [VP]) or Merkel cell polyomavirus-negative (virus negative [VN]). Epigenetic changes, such as DNA methylation, can alter gene expression and influence cancer progression. However, patterns of DNA methylation and the therapeutic efficacy of hypomethylating agents have not been fully explored in MCC.

Hormesis effects of gamma radiation on growth of quinoa ().

Purpose: Quinoa is an annual plant that grows well in high altitude regions with high radiation and ultraviolet intensity. It has known that high-dose radiation damages living organisms, but low-dose radiation also has a beneficial effect. Therefore, the purpose of this study is to investigate the hormesis effect of gamma-ray on quinoa by growth analysis and hyperspectral imaging.

Augmented reality in anesthesia, pain medicine and critical care: a narrative review.

Augmented reality (AR) is the integration of computer-generated information with the user's environment in real time. AR is used in many industries, including healthcare, where it has gained significant popularity. Recent strides in hardware and software engineering have reduced the cost of AR, while significantly improving the experience for users and developers.