Long-Term Clinical Efficacy of Radiotherapy for Patients with Stage I-II Gastric Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue: A Retrospective Multi-Institutional Study.

Purpose: To evaluate long-term treatment outcomes in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma treated with radiation therapy (RT). Materials and Methods: A total of 229 patients who received RT in ten tertiary hospitals between 2010 and 2019 were included in this multi-center analysis. Response after RT was based on esophagogastroduodenoscopy after RT. Locoregional relapse-free survival (LRFS) and disease-free survival (DFS) were evaluated. Results: After a median follow-up time of 93.2 months, 5-year LRFS, DFS, and OS rates were 92.8%, 90.4%, and 96.1%, respectively. LRFS, DFS, and OS rates at 10 years were 90.3%, 87.7%, and 92.8%, respectively. Of 229 patients, 228 (99.6%) patients achieved complete remission after RT. Five-year LRFS was significantly lower in patients with stage IIE than in those with stage IE (77.4% vs. 94.2%, p=0.047). Patients with age ≥ 60 had significantly lower LRFS than patients with age < 60 (89.3% vs. 95.1%, p=0.003). In the multivariate analysis, old age (≥ 60 years) was a prognostic factor for LRFS [hazard ratio (HR) of 3.72 and confidence interval (CI), 1.38-10.03; p=0.009). Grade 2 or higher gastritis was reported in 69 (30.1%) patients. Secondary malignancies including gastric adenocarcinoma, malignant lymphoma, lung cancer, breast cancer, and prostate cancer were observed in 11 (4.8%) patients after RT. Conclusion: Patients treated with RT for localized gastric MALT lymphoma showed favorable 10-year outcomes. Radiation therapy is an effective treatment without an increased risk of secondary cancer. The toxicity for radiotherapy to the stomach is not high.

Tumor Deposits as an Adverse Prognostic Indicator in Stage III Colon Cancer: A Multicenter Database Study.

Objective: We explored the oncological impact of tumor deposits (TDs) on colon cancer and proposed optimal modifications to the current staging system. Background: In the existing American Joint Committee on Cancer colon cancer staging system, TDs are incorporated into the N category as N1c. When lymph node metastases (LNMs) are present, their number is considered to determine nodal stages, such as N1a/b or N2a/b, regardless of TDs. Methods: 4212 patients with primary colon cancer who underwent surgical resection in the Seoul Colorectal Group (2010-2020) and 93,057 patients from the Surveillance, Epidemiology, and End Results*Stat database (2000-2017) were included in this study. Patients were classified according to the number of metastatic lymph nodes (LNs) (0/1-3/≥4) and the presence of TDs. Results: TDs were significantly associated with left colon cancer, a higher T category, and vascular/perineural invasion. Patients with TDs had higher recurrence rates (23.1 vs 7.5%, P < 0.001). The TD-positive patients had notably worse overall survival (OS) and recurrence-free survival rates. The survival outcomes of TD-positive patients without LNM were inferior to those of TD-negative patients with LN1-3 (5-year OS: 78.9 vs 87.8%, P = 0.04). The survival outcomes of TD-positive patients with LN1-3 were similar to those of TD-negative patients with LN ≥4 (5-year OS: 87.0 vs 77.1%, P = 0.11). Survival outcomes obtained using the Surveillance, Epidemiology, and End Results *Stat database yielded consistent results. Conclusions: TDs were associated with poor prognostic factors and had a significant impact on survival outcomes. The incorporation of tumor deposits into nodal classifications beyond the current N1c criteria may improve the staging system and more accurately reflect the recurrence and survival rates among patients with colon cancer. TD-positive in N1a or N1b could be categorized as N2.

Dating drainage reversal using mineral provenance along the Yangsan Fault, South Korea.

Tectonics is broadly accepted as one of the main factors controlling long-term landscape evolution. The impact of tectonics on short timescales is most often observed through earthquake rupturings that produce localized, metric-scale deformations. Although these deformations significantly affect the landscape, it remains challenging to precisely correlate major landscape changes with these localized earthquake deformations. Therefore, linking instantaneous deformation to long-term morphological changes often involves a thought experiment with potentially limited temporal resolution. At a paleoseismological site along the slow-moving strike-slip Yangsan Fault in South Korea, we employed optically stimulated luminescence (OSL) dating and detrital zircon analysis on all exposed unconsolidated layers in trench walls. The results reveal a significant provenance shift in the sediments accumulating in the trench, indicating a major reorganization of the drainage network. Based on our OSL and detrital zircon data, we estimate that this change occurred around 70 ka. We propose that this drastic drainage reorganization was caused by a combination of very slow, yet continuous, earthquake activity and a temporary reduction in river erosion during the onset of the cold, dry spell characteristic of the MIS4 stage across the Korean Peninsula.

Biodistribution of synthesized polyethylene terephthalate fibers in adult zebrafish, their sex hormone disruption effect, and mitigation using natural organic matter.

Although polyethylene terephthalate (PET) fibers are a representative form of plastic pollutants, studies on their toxicity are currently limited compared to other plastic types. Moreover, the effect of natural organic matter (NOM) on their toxicity has not been investigated. In this study, female and male adult zebrafish were exposed to synthesized PET fibers at concentrations of 0.1, 1, 10, and 100 mg/L in the presence and absence of 10 mg/L of NOM for 10 d. Bioaccumulation of PET fibers in zebrafish intestine, liver, and gills was identified and expression levels of reactive oxygen species (ROS) generation, sex hormones, and oxidative stress and sex hormone-related genes were measured. In addition, the developmental stages of gonadal cells were examined through histological analysis. We found that PET fibers bioaccumulated in the intestine and liver of zebrafish. ROS generation significantly increased at 100 mg/L of PET fibers, the expression of oxidative stress-related genes decreased in female and increased in male zebrafish. Exposure to 100 mg/L of PET fibers did not affect 17-beta estradiol, but significantly decreased the testosterone levels in male zebrafish. Sex hormone-related genes significantly decreased in both female and male zebrafish, except for androgen receptor in female zebrafish. However, these changes were exacerbated by the removal of NOM, suggesting a protective effect of NOM against PET fibers toxicity. We demonstrated that the accumulated PET fibers may lead to oxidative stress and sex hormone alteration, and disrupt the development of gonadal cells. Additionally, the NOM coating did not alter bioaccumulation considerably, but mitigated the adverse effects at the hormone level in PET fiber-exposed zebrafish. Thus, this study provides a basis for further research on the toxicity assessment of PET fibers and interactions between NOM and PET fiber-related toxicity.

Identifying infrequent genetic changes in monozygotic twins afflicted with hypospadias via targeted panel sequencing.

PURPOSE: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). MATERIALS AND METHODS: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. RESULTS: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%. In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. CONCLUSIONS: This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role.

Advances in Understanding Hepatocellular Carcinoma Vasculature: Implications for Diagnosis, Prognostication, and Treatment.

Hepatocellular carcinoma (HCC) progresses through multiple stages of hepatocarcinogenesis, with each stage characterized by specific changes in vascular supply, drainage, and microvascular structure. These vascular changes significantly influence the imaging findings of HCC, enabling non-invasive diagnosis. Vascular changes in HCC are closely related to aggressive histological characteristics and treatment responses. Venous drainage from the tumor toward the portal vein in the surrounding liver facilitates vascular invasion, and the unique microvascular pattern of vessels that encapsulate the tumor cluster (known as a VETC pattern) promotes vascular invasion and metastasis. Systemic treatments for HCC, which are increasingly being used, primarily target angiogenesis and immune checkpoint pathways, which are closely intertwined. By understanding the complex relationship between histopathological vascular changes in hepatocarcinogenesis and their implications for imaging findings, radiologists can enhance the accuracy of imaging diagnosis and improve the prediction of prognosis and treatment response. This, in turn, will ultimately lead to better patient care.

Sarcomatoid change in combined hepatocellular carcinoma and cholangiocarcinoma as a poor prognostic factor.

Background: Sarcomatoid change is rarely seen in epithelial malignancy that can be observed in diverse organs. Although a sarcomatoid change in combined hepatocellular-cholangiocarcinoma (cHCC-CC) is assumed to be a poor prognostic factor, this issue has not been studied due to its rare incidence. In this study, we aimed to identify the oncological impact of sarcomatoid change in patients with cHCC-CC and verify that sarcomatoid change is a poor prognostic factor for resected cHCC-CC. Methods: Between January 2006 and December 2020, 102 patients who underwent surgical resection for cHCC-CC were retrospectively reviewed. The hazard ratio (HR) according to sarcomatoid change was calculated using other known prognostic factors for cHCC-CC. In addition, the patients were divided into two groups according to the sarcomatoid change, and their survival was compared. Results: The multivariate analysis demonstrated that sarcomatoid change in cHCC-CC is a poor prognostic factor {disease-free survival (DFS), HR =3.84 [95% confidence interval (CI): 1.63-9.10], P=0.002; overall survival (OS), HR =3.94 (95% CI: 1.67-9.31), P=0.002}. In the survival analysis, the sarcomatoid change group displayed a worse prognosis compared to the non-sarcomatoid change group {DFS: 4.0 [interquartile range (IQR): 1.2-6.8] vs. 23.0 (IQR: 9.3-36.7) months, P=0.001; OS: 19.0 (IQR: 7.2-30.8) vs. 85.0 (IQR: 31.8-138.2) months, P=0.004}. Conclusions: Sarcomatoid change is a poor prognostic factor for resected cHCC-CC.

Merkel cells and corpuscles of Stannius as putative targets for polyethylene terephthalate microfibers in sheepshead minnow larvae.

Polyethylene terephthalate (PET) fibers are contaminated in wastewater from various primary sources, such as washing textile waters. PET fibers in the environment can be degraded into microfibers because of weathering processes such as sunlight, physical wear, and heat. Although recent studies reported adverse effects of PET microfibers on aquatic organisms, the lack of information on their toxicity and mode of action hampers the risk assessment of PET microfibers. Therefore, this study aimed to investigate the biological effects of PET microfibers and their underlying mechanisms in early-staged sheepshead minnows (Cyprinodon variegatus). PET microfibers (about 13 µm diameter × 106 µm length) were prepared by cutting PET threads and treated to sheepshead minnow larvae at 10 and 100 mg/L for 10 days. No acute toxicity was found in the minnow, but PET microfibers significantly produced reactive oxygen species and reduced behavioral responses of traveled distance and maximum velocity. The transcriptomic data suggested that Merkel cells (flow sensors) and corpuscles of Stannius (calcium regulator) are putative targets, which were derived from oxidative stress, sensory neuropathy, cognitive impairment, and movement disorders. These findings underscore that although PET microfibers are not directly lethal to sheepshead minnows, they could impact their survival by damaging swimming-related key genes. This study provides new insights into how PET microfibers are toxic to aquatic organisms and disrupt ecosystems beyond survival and pathological changes.

The Biocompatibility and the Effect of Titanium and PEKK on the Osseointegration of Customized Facial Implants.

The purpose of this study was to investigate the optimization of computer-aided design/computer-aided manufacturing (CAD/CAM) patient-specific implants for mandibular facial bone defects and compare the biocompatibility and osseointegration of machined titanium (Ma), Sandblasted/Large-grit/Acid-etched (SLA) titanium, and polyetherketoneketone (PEKK) facial implants. We hypothesized that the facial implants made of SLA titanium had superior osseointegration when applied to the gonial angle defect and prevented the senile atrophy of the bone. Histologic findings of the soft-tissue reaction, hard-tissue reaction, and bone-implant contact (BIC (%) of 24 Ma, SLA, and PEKK facial implants at 8 and 12 weeks were investigated. There was no statistical difference in the soft tissue reaction. Bone was formed below the periosteum in all facial implants at 12 weeks and the BIC values were significantly different at both 8 and 12 weeks (p < 0.05). Ma, SLA, and PEKK facial implants are biocompatible with osseointegration properties. SLA can enhance osseointegration and provoke minimal soft tissue reactions, making them the most suitable choice. They provide an excellent environment for bone regeneration and, over the long term, may prevent atrophy caused by an aging mandible. The bone formation between the lateral surface of the facial implant and periosteum may assist in osseointegration and stabilization.

Recent advances in two-dimensional materials for the diagnosis and treatment of neurodegenerative diseases.

With the size of the aging population increasing worldwide, the effective diagnosis and treatment of neurodegenerative diseases (NDDs) has become more important. Two-dimensional (2D) materials offer specific advantages for the diagnosis and treatment of NDDs due to their high sensitivity, selectivity, stability, and biocompatibility, as well as their excellent physical and chemical characteristics. As such, 2D materials offer a promising avenue for the development of highly sensitive, selective, and biocompatible theragnostics. This review provides an interdisciplinary overview of advanced 2D materials and their use in biosensors, drug delivery, and tissue engineering/regenerative medicine for the diagnosis and/or treatment of NDDs. The development of 2D material-based biosensors has enabled the early detection and monitoring of NDDs via the precise detection of biomarkers or biological changes, while 2D material-based drug delivery systems offer the targeted and controlled release of therapeutics to the brain, crossing the blood-brain barrier and enhancing treatment effectiveness. In addition, when used in tissue engineering and regenerative medicine, 2D materials facilitate cell growth, differentiation, and tissue regeneration to restore neuronal functions and repair damaged neural networks. Overall, 2D materials show great promise for use in the advanced treatment of NDDs, thus improving the quality of life for patients in an aging population.