Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application.

The elucidation of the pathophysiology underlying various diseases necessitates the development of research platforms that faithfully mimic in vivo conditions. Traditional model systems such as two-dimensional cell cultures and animal models have proven inadequate in capturing the complexities of human disease modeling. However, recent strides in organoid culture systems have opened up new avenues for comprehending gastric stem cell homeostasis and associated diseases, notably gastric cancer. Given the significance of gastric cancer, a thorough understanding of its pathophysiology and molecular underpinnings is imperative. To this end, the utilization of patient-derived organoid libraries emerges as a remarkable platform, as it faithfully mirrors patient-specific characteristics, including mutation profiles and drug sensitivities. Furthermore, genetic manipulation of gastric organoids facilitates the exploration of molecular mechanisms underlying gastric cancer development. This review provides a comprehensive overview of recent advancements in various adult stem cell-derived gastric organoid models and their diverse applications.

Alteration of PD-L1 (SP142) status after neoadjuvant chemotherapy and its clinical significance in triple-negative breast cancer.

PURPOSE: The tumor immune microenvironment can change after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC). We aimed to investigate the effects of NAC on PD-L1 (SP142) status and its clinical significance in TNBC. METHODS: Paired samples of biopsy and resection specimens were collected from 182 patients with TNBC before and after NAC. PD-L1 (SP142) expression in immune cells in pre- and post-NAC breast cancer samples and the changes between them were analyzed, along with their relationships with the clinicopathological features and clinical outcomes of the patients. RESULTS: Of the 182 patients, 61 (33.5%) achieved pathologic complete response (pCR) after NAC. PD-L1 (SP142) positivity, defined as immune cell staining in ≥ 1% of tumor area, was a predictor for pCR. PD-L1-positive immune cells significantly increased after NAC (2.8% to 5.2% on average) in 109 patients with measurable residual disease. Alteration of PD-L1 status was observed in 24 (22.0%) of the 109 patients with measurable residual tumors after NAC, and all PD-L1 status-converted patients, except one, revealed negative-to-positive conversion. Regarding chemotherapeutic agents, the use of platinum agents was associated with a significant increase in PD-L1-positive immune cells after NAC. In survival analyses, a positive PD-L1 status after NAC and increase of PD-L1-positive immune cells after NAC were associated with better recurrence-free survival of the patients. CONCLUSION: PD-L1 (SP142) status changes after NAC, mostly as a positive conversion. As PD-L1 (SP142) status can convey prognostic and predictive information, it needs to be tested before and after NAC.

Concordance of HER2 status between core needle biopsy and surgical resection specimens of breast cancer: an analysis focusing on the HER2-low status.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody-drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status. METHODS: This retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed. RESULTS: The overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion. CONCLUSIONS: Incorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity.

Usnic Acid Targets 14-3-3 Proteins and Suppresses Cancer Progression by Blocking Substrate Interaction.

The anticancer therapeutic effects of usnic acid (UA), a lichen secondary metabolite, have been demonstrated in vitro and in vivo. However, the mechanism underlying the anticancer effect of UA remains to be clarified. In this study, the target protein of UA was identified using a UA-linker-Affi-Gel molecule, which showed that UA binds to the 14-3-3 protein. UA binds to 14-3-3, causing the degradation of proteasomal and autophagosomal proteins. The interaction of UA with 14-3-3 isoforms modulated cell invasion, cell cycle progression, aerobic glycolysis, mitochondrial biogenesis, and the Akt/mTOR, JNK, STAT3, NF-κB, and AP-1 signaling pathways in colorectal cancer. A peptide inhibitor of 14-3-3 blocked or regressed the activity of UA and inhibited its effects. The results suggest that UA binds to 14-3-3 isoforms and suppresses cancer progression by affecting 14-3-3 targets and phosphorylated proteins.

A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation.

This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.

Risk Factor Analysis of Complications and Mortality Following Coil Procedures in Patients with Intracranial Unruptured Aneurysms Using a Nationwide Health Insurance Database.

(1) Background: Unruptured intracranial aneurysm (UIA) occurs in 1-2% of the population and is being increasingly detected. Patients with UIA are treated with close observation, endovascular coiling or surgical clipping. The proportion of endovascular coiling has been rising. However, complications such as cerebral infarction (CI), intracranial hemorrhage (ICRH), and death remain crucial issues after coil treatment. (2) Methods: We analyzed the incidence and risk factors of complications after the use of coil in patients with UIA based on the patients' characteristics. We utilized the Health Insurance Review and Assessment (HIRA) database. Patients treated with coils for UIA between 1 January 2015 and 1 December 2021 were retrospectively analyzed. (3) Results: Of the total 35,140 patients, 1062 developed ICRH, of whom 87 died, with a mortality rate of 8.2%. Meanwhile, 749 patients developed CI, of whom 29 died, with a mortality rate of 3.9%. The overall mortality rate was 1.8%. In a univariate analysis of the risk factors, older age, males, a higher Charlson Comorbidity Index (CCI) score, and diabetes increase the risk of CI. Meanwhile, males with higher CCI scores and hemiplegia or paraplegia show increased ICRH risk. Older age, males and metastatic solid tumors relate to increased mortality risk. (4) Conclusions: This study is significant in that the complications based on the patient's underlying medical condition were analyzed.

Anithiactin D, a Phenylthiazole Natural Product from Mudflat-Derived Streptomyces sp., Suppresses Motility of Cancer Cells.

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.

Predictive factors of substance misuse and abuse in South Korean adolescents: a secondary data analysis of the 2021 Youth Risk Behavior Web-based Survey.

PURPOSE: This study aimed to identify the general characteristics and health behaviors of students with non-therapeutic substance use. METHODS: This secondary data analysis used data from the 17th Korea Youth Risk Behavior Web-based Survey (2021). Analyses of the 54,848 adolescents used descriptive statistics, the Rao-Scott χ2 test, and logistic regression. RESULTS: The risk factors for substance use among students were anxiety, loneliness, living separately from family, suicidal ideation, e-cigarette use, and high stress. CONCLUSION: The findings help identify the risk factors for non-therapeutic drug use among adolescents. Since South Korea does not have a drug prevention program for its adolescent population, an educational plan based on these findings could help prevent adolescent substance abuse.

Automated Versus Handheld Breast Ultrasound for Evaluating Axillary Lymph Nodes in Patients With Breast Cancer.

OBJECTIVE: Automated breast ultrasound (ABUS) is a relevant imaging technique for early breast cancer diagnosis and is increasingly being used as a supplementary tool for mammography. This study compared the performance of ABUS and handheld ultrasound (HHUS) in detecting and characterizing the axillary lymph nodes (LNs) in patients with breast cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of women with recently diagnosed early breast cancer (≤ T2) who underwent both ABUS and HHUS examinations for axilla (September 2017-May 2018). ABUS and HHUS findings were compared using pathological outcomes as reference standards. Diagnostic performance in predicting any axillary LN metastasis and heavy nodal-burden metastases (i.e., ≥ 3 LNs) was evaluated. The ABUS-HHUS agreement for visibility and US findings was calculated. RESULTS: The study included 377 women (53.1 ± 11.1 years). Among 385 breast cancers in 377 patients, 101 had axillary LN metastases and 30 had heavy nodal burden metastases. ABUS identified benign-looking or suspicious axillary LNs (average, 1.4 ± 0.8) in 246 axillae (63.9%, 246/385). According to the per-breast analysis, the sensitivity, specificity, positive and negative predictive values, and accuracy of ABUS in predicting axillary LN metastases were 43.6% (44/101), 95.1% (270/284), 75.9% (44/58), 82.6% (270/327), and 81.6% (314/385), respectively. The corresponding results for HHUS were 41.6% (42/101), 95.1% (270/284), 75.0% (42/56), 82.1% (270/329), and 81.0% (312/385), respectively, which were not significantly different from those of ABUS (P ≥ 0.53). The performance results for heavy nodal-burden metastases were 70.0% (21/30), 89.6% (318/355), 36.2% (21/58), 97.3% (318/327), and 88.1% (339/385), respectively, for ABUS and 66.7% (20/30), 89.9% (319/355), 35.7% (20/56), 97.0% (319/329), and 88.1% (339/385), respectively, for HHUS, also not showing significant difference (P ≥ 0.57). The ABUS-HHUS agreement was 95.9% (236/246; Cohen's kappa = 0.883). CONCLUSION: Although ABUS showed limited sensitivity in diagnosing axillary LN metastasis in early breast cancer, it was still useful as the performance was comparable to that of HHUS.

Pre-mixing of omega-3 fatty acid-containing liposomes enhances the drug release rate and therapeutic efficacy of anticancer drugs loaded in liposomes.

The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.

PD-L1 (SP142) Expression in Primary and Recurrent/Metastatic Triple-Negative Breast Cancers and Its Clinicopathological Significance.

PURPOSE: The programmed death-ligand 1 (PD-L1) SP142 assay identifies patients with triple-negative breast cancer (TNBC) who are most likely to respond to the anti-PD-L1 agent atezolizumab. We aimed to compare PD-L1 (SP142) expression between primary and recurrent/metastatic TNBCs and elucidate the clinicopathological features associated with its expression. MATERIALS AND METHODS: Primary and recurrent/metastatic TNBCs tested with PD-L1 (SP142) were collected, and clinicopathological information of these cases was obtained through a review of slides and medical records. RESULTS: PD-L1 (SP142) positivity was observed in 50.9% (144/283) of primary tumors and 37.8% (31/82) of recurrent/metastatic TNBCs with a significant difference. Recurrent or metastatic sites were associated with PD-L1 positivity, with high PD-L1 positivity in the lung, breast, and soft tissues, and low positivity in the bone, skin, liver, and brain. When comparing PD-L1 expression between primary and matched recurrent/metastatic TNBCs using 55 paired samples, 20 cases (36.4%) showed discordance; 10 cases revealed positive conversion, and another 10 cases revealed negative conversion during metastatic progression. In primary TNBCs, PD-L1 expression was associated with a higher histologic grade, lower T category, pushing border, and higher tumor-infiltrating lymphocyte infiltration. In survival analyses, PD-L1 positivity, especially high positivity, was found to be associated with favorable prognosis of patients. CONCLUSION: PD-L1 (SP142) expression was lower in recurrent/metastatic TNBCs, and substantial cases showed discordance in its expression between primary and recurrent/metastatic sites, suggesting that multiple sites may need to be tested for PD-L1 (SP142) when considering atezolizumab therapy. PD-L1 (SP142)-positive TNBCs seems to be associated with favorable clinical outcomes.

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP.

In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia.

BACKGROUND: Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. METHODS: We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3+ CML patients. RESULTS: We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3+ BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3+ BP-CML patients had significantly less favorable prognosis than FLT3- patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3+ BCR::ABL1 cells and mouse xenograft models. CONCLUSION: Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies.

Clinical activity of nivolumab in combination with eribulin in HER2-negative metastatic breast cancer: A phase IB/II study (KCSG BR18-16).

AIM: We evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer (BC) in Asian populations. METHODS: In this parallel phase II study, adult patients with histologically confirmed recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab (360 mg) on day 1 plus eribulin (1.4 mg/m2) on days 1 and 8 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate in each subtype. Secondary endpoints included investigator-assessed objective response rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 1.1, disease control rate, overall survival, and treatment toxicity. The association between PD-L1 expression and efficacy was investigated. RESULTS: Forty-five patients with HR+HER2- BC and 45 with TNBC were enroled. Their median age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2- and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2- and TNBC groups, respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression ≥1%) and PD-L1- tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; the most common immune-related adverse events (AEs) were grades 1/2 hypothyroidism and pruritus. Five patients discontinued therapy because of immune-related AEs. CONCLUSION: Nivolumab plus eribulin showed promising efficacy and tolerable safety in previously treated HER2- metastatic BC. TRIAL REGISTRATION: NCT04061863.

Quantitative radiomics approach to assess acute radiation dermatitis in breast cancer patients.

PURPOSE: We applied a radiomics approach to skin surface images to objectively assess acute radiation dermatitis in patients undergoing radiotherapy for breast cancer. METHODS: A prospective cohort study of 20 patients was conducted. Skin surface images in normal, polarized, and ultraviolet (UV) modes were acquired using a skin analysis device before starting radiotherapy ('Before RT'), approximately 7 days after the first treatment ('RT D7'), on 'RT D14', and approximately 10 days after the radiotherapy ended ('After RT D10'). Eighteen types of radiomic feature ratios were calculated based on the values acquired 'Before RT'. We measured skin doses in ipsilateral breasts using optically stimulated luminescent dosimeters on the first day of radiotherapy. Clinical evaluation of acute radiation dermatitis was performed using the Radiation Therapy Oncology Group scoring criteria on 'RT D14' and 'After RT D10'. Several statistical analysis methods were used in this study to test the performance of radiomic features as indicators of radiodermatitis evaluation. RESULTS: As the skin was damaged by radiation, the energy for normal mode and sum variance for polarized and UV modes decreased significantly for ipsilateral breasts, whereas contralateral breasts exhibited a smaller decrease with statistical significance. The radiomic feature ratios at 'RT D7' had strong correlations to skin doses and those at 'RT D14' and 'after RT D10' with statistical significance. CONCLUSIONS: The energy for normal mode and sum variance for polarized and UV modes demonstrated the potential to evaluate and predict acute radiation, which assists in its appropriate management.

A fatty acid-rich fraction of an endolichenic fungus Phoma sp. suppresses immune checkpoint markers via AhR/ARNT and ESR1.

Lung cancer has the highest mortality rates worldwide. The disease is caused by environmental pollutants, smoking, and many other factors. Recent treatments include immunotherapeutics, which have shown some success; however, the search for new therapeutics is ongoing. Endolichenic fungi produce a whale of a lot of secondary metabolites, the therapeutic effects of which are being evaluated. Here, we used a crude extract and subfractions of the endolichenic fungus, Phoma sp. (EL006848), isolated from the Pseudevernia furfuracea. It was identified the fatty acid components, palmitic acid, stearic acid, and oleic acid, exist in subfractions E1 and E2. In addition, EL006848 and its fatty acids fractions suppressed benzo[a]pyrene (an AhR ligand)- induced expression of PD-L1 to inhibit the activity of multiple immune checkpoints. E2 subfraction, which had a higher fatty acid content than E1, downregulated expression of AhR/ARNT and several human transcription factors related to ESR1. Moreover, E2 showed a strong inhibitory effect on STAT3 expression and mild effect on NF-kB activity. These results suggest that fatty acids extracted from an endolichenic fungus can exert strong immunotherapeutic effects.

Nationwide-incidence and trends of fibromyalgia in South Korea: a population-based study.

Reports of the incidence of fibromyalgia (FM) in Asia are uncommon. Therefore, this study used nationwide representative data to investigate the age- and sex-specific incidence and annual trends of FM in South Korea. This nationwide population-based study used data from the Korean National Health Claims Database. From 2012 to 2021, patients with FM diagnosed according to the ACR 2010 criteria from the entire Korean population aged 20-70 years were included in the enrolment database. Age- and sex-specific cumulative and annual incidences were analyzed and incident cases from 2014 to 2021 were included, considering the 2-year washout period. Among the total cohort of 42 million in the entire Korean population, 270,160 had FM during the study period. The incidence in the general population aged 20-70 years was 751.25 (95% confidence interval [CI] 751.10-751.40) per 100,000 persons (men: 95% CI 608.45-608.98; women: 95% CI 898.02-898.69). The incidence of FM increased with advancing age, peaking at 50-54 years both in men and women. The annual incidence was 88.07 (95% CI 88.02-88.13) in 2014; it increased from 2014 to 2019 and peaked in 2019 (109.20; 95% CI 101.65-101.76). The incidence of FM in South Korea was about twice the global average, with a gradual increase over the study period. These detailed estimates can help with proper planning within the healthcare system.

Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new entity in the 2022 WHO classification. We aimed to investigate the incidence and clinicopathological features of differentiated HG thyroid carcinoma (DHGTC) and compare the clinicopathological parameters of DHGTC, DTC without HG features, and poorly differentiated thyroid carcinoma (PDTC). A total of 1069 DTCs including papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) were included in this study. Consecutive 22 PDTCs were also included for comparative purposes. There were a total of 14 (1.3%) cases of DHGTCs, with 13 HGPTCs (1.2% of PTCs) and one HGFTC (6.7% of FTCs). Compared to DTCs without HG features, DHGTCs were associated with larger tumor size, presence of blood vessel invasion, gross extrathyroidal extension, distant metastasis at the time of diagnosis, higher American Joint Committee on Cancer stage, high American Thyroid Association risk, and TERT promoter mutations. DHGTC and PDTC showed a significantly shorter recurrence-free survival (RFS) than DTC without HG features. Multivariate Cox regression analysis revealed that blood vessel invasion, lateral node metastasis, TERT promoter mutations, and HG features were independent prognostic factors (all p < 0.05). When tumor necrosis and increased mitotic count were evaluated separately, tumor necrosis, but not increased mitotic counts, was found to be an independent prognostic factor (p = 0.006). This study confirmed that DHGTC is significantly associated with aggressive clinicopathological features and poor clinical outcomes, similar to PDTC. Although the incidence is low, careful microscopic examination of HG features in DTC is required.