The Effect of the Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 Combination (BN-202M) on Body Fat Percentage Loss in Overweight Individuals: A Randomized, Double-Blind, Placebo-Controlled Study.

BN-202M is derived from humans and consists of two strains, Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53. Body fat reduction effect and safety of BN-202M were assessed in overweight participants. A total of 150 participants were randomly assigned to the BN-202M and placebo groups at a 1:1 ratio. Dual-energy X-ray absorptiometry was used to objectively measure body fat. After 12 weeks of oral administration, the body fat percentage (-0.10 ± 1.32% vs. 0.48 ± 1.10%; p = 0.009) and body fat mass (-0.24 ± 1.19 kg vs. 0.23 ± 1.05 kg; p = 0.023) of the BN-202M group decreased significantly compared to those of the placebo group. The body weight (-0.58 kg, p = 0.004) and body mass index (BMI; -0.23, p = 0.003) was found to decrease significantly at 12 weeks in the BN-202M group, but not in the placebo group. Metabolome analysis revealed that ß-alanine, 3-aminoisobutyric acid, glutamic acid, and octopamine decreased in the weight-decreased BN-202M post-intake group. In the gut microbiota analysis, Akkermansia showed a statistically significant increase in the BN-202M group post-intake compared to the placebo group. No serious adverse events were observed in either group. These results suggest that BN-202M is safe and effective for reducing body fat and weight.

Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort.

Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Comparing the safety and effectiveness of overlapping stents with flow diverters for unruptured vertebral artery dissecting aneurysms.

BACKGROUND: Endovascular treatment for vertebral artery dissecting aneurysms (VADAs) includes overlapping stents and flow diverters. This study compared the safety and effectiveness of overlapping stents and flow diverters for unruptured VADAs. METHODS: We retrospectively enrolled patients with unruptured VADAs who underwent overlapping stents or flow diverters at two tertiary hospitals in South Korea. The primary clinical outcome was the occurrence of stroke. The primary angiographic outcomes (>12 months) were categorized as regression, no decrease in size, recanalization, or stent occlusion, of which only regression was defined as a favorable angiographic outcomes. RESULTS: Of the 146 patients with VADAs, 25 (17.1%) had flow diverters and 121 (82.9%) had overlapping stents. For the primary angiographic outcomes over 12 months, the rate of favorable angiographic outcomes for flow diverters was 81.8% and for overlapping stents (triple stents) was 98.8% (P=0.006). In the multivariale analysis, after adjusting for partially thrombosed aneurysms, aneurysm shape, non-dominant vessel, posterior inferior cerebellar artery involvement, and procedure type, overlapping stents (triple stents) was not associated with favorable angiographic outcomes compared with flow diverters (OR 7.040, 95% CI 0.549 to 90.294; P=0.134), but partially thrombosed aneurysms was inversely associated with favorable angiographic outcomes (OR 0.056, 95% CI 0.005 to 0.589; P=0.016). The primary clinical outcome followed up to the last angiography did not occur in all patients. CONCLUSION: There was no difference in safety and effectiveness between overlapping stents and flow diverters in unruptured VADAs. Further endovascular treatment studies are needed regarding the association of partially thrombosed aneurysms with unfavorable angiographic outcomes.

Characterization of Yeast Protein Hydrolysate for Potential Application as a Feed Additive.

Yeast protein can be a nutritionally suitable auxiliary protein source in livestock food. The breakdown of proteins and thereby generating high-quality peptide, typically provides nutritional benefits. Enzyme hydrolysis has been effectively uesed to generate peptides; however, studies on the potential applications of different types of enzymes to produce yeast protein hydrolysates remain limited. This study investigated the effects of endo- (alcalase and neutrase) and exotype (flavourzyme and prozyme 2000P) enzyme treatments on yeast protein. Endotype enzymes facilitate a higher hydrolysis efficiency in yeast proteins than exotype enzymes. The highest degree of hydrolysis was observed for the protein treated with neutrase, which was followed by alcalase, prozyme 2000P, and flavourzyme. Furthermore, endotype enzyme treated proteins exhibited higher solubility than their exotype counterparts. Notably, the more uniform particle size distribution was observed in endotype treated yeast protein. Moreover, compared with the original yeast protein, the enzymatic protein hydrolysates possessed a higher content of ß-sheets structures, indicating their higher structural stability. Regardless of enzyme type, enzyme treated protein possessed a higher total free amino acid content including essential amino acids. Therefore, this study provides significant insights into the production of protein hydrolysates as an alternative protein material.

Unique cartilage matrix-associated protein inhibits osteoclast differentiation by alleviating RANKL-induced reactive oxygen species.

Unique cartilage matrix-associated protein (UCMA) is a γ-carboxyglutamic acid-rich secretory protein primarily expressed in adult cartilage. UCMA promotes osteoblast differentiation and reduces high glucose-induced reactive oxygen species (ROS) production in osteoblasts; however, its role in osteoclasts remains unclear. Since Ucma is not expressed in osteoclasts, treatment with recombinant UCMA protein (rUCMA) was employed to investigate the effect of UCMA on osteoclasts. The rUCMA-treated osteoclasts exhibited significantly reduced osteoclast differentiation, resorption activity, and osteoclast-specific gene expression. Moreover, rUCMA treatment reduced RANKL-induced ROS production and increased the expression of antioxidant genes in osteoclasts. This study demonstrates that UCMA effectively inhibits RANKL-stimulated osteoclast differentiation and oxidative stress.

Transcriptomic characteristics according to tumor size and SUVmax in papillary thyroid cancer patients.

The SUVmax is a measure of FDG uptake and is related with tumor aggressiveness in thyroid cancer, however, its association with molecular pathways is unclear. Here, we investigated the relationship between SUVmax and gene expression profiles in 80 papillary thyroid cancer (PTC) patients. We conducted an analysis of DEGs and enriched pathways in relation to SUVmax and tumor size. SUVmax showed a positive correlation with tumor size and correlated with glucose metabolic process. The genes that indicate thyroid differentiation, such as SLC5A5 and TPO, were negatively correlated with SUVmax. Unsupervised analysis revealed that SUVmax positively correlated with DNA replication(r = 0.29, p = 0.009), pyrimidine metabolism(r = 0.50, p < 0.0001) and purine metabolism (r = 0.42, p = 0.0001). Based on subgroups analysis, we identified that PSG5, TFF3, SOX2, SL5A5, SLC5A7, HOXD10, FER1L6, and IFNA1 genes were found to be significantly associated with tumor aggressiveness. Both high SUVmax PTMC and macro-PTC are enriched in pathways of DNA replication and cell cycle, however, gene sets for purine metabolic pathways are enriched only in high SUVmax macro-PTC but not in high SUVmax PTMC. Our findings demonstrate the molecular characteristics of high SUVmax tumor and metabolism involved in tumor growth in differentiated thyroid cancer.

Neutrophil diversity is associated with T-cell immunity and clinical relevance in patients with thyroid cancer.

Neutrophil heterogeneity is involved in autoimmune diseases, sepsis, and several cancers. However, the link between neutrophil heterogeneity and T-cell immunity in thyroid cancer is incompletely understood. We investigated the circulating neutrophil heterogeneity in 3 undifferentiated thyroid cancer (UTC), 14 differentiated thyroid cancer (DTC) (4 Stage IV, 10 Stage I-II), and healthy controls (n = 10) by transcriptomic data and cytometry. Participants with UTC had a significantly higher proportion of immature high-density neutrophils (HDN) and lower proportion of mature HDN in peripheral blood compared to DTC. The proportion of circulating PD-L1+ immature neutrophils were significantly increased in advanced cancer patients. Unsupervised analysis of transcriptomics data from circulating HDN revealed downregulation of innate immune response and T-cell receptor signaling pathway in cancer patients. Moreover, UTC patients revealed the upregulation of glycolytic process and glutamate receptor signaling pathway. Comparative analysis across tumor types and stages revealed the downregulation of various T-cell-related pathways, such as T-cell receptor signaling pathway and T-cell proliferation in advanced cancer patients. Moreover, the proportions of CD8+ and CD4+ T effector memory CD45RA+ (TEMRA) cells from peripheral blood were significantly decreased in UTC patients compared to DTC patients. Finally, we demonstrated that proportions of tumor-infiltrated neutrophils were increased and related with poor prognosis in advanced thyroid cancer using data from our RNA-seq and TCGA (The Cancer Genome Atlas) data. In conclusion, observed prevalence of circulating immature high-density neutrophils and their immunosuppressive features in undifferentiated thyroid cancers underscore the importance of understanding neutrophil dynamics in the context of tumor progression in thyroid cancer.

Ambient PM2.5 exposure and rapid population aging: A double threat to public health in the Republic of Korea.

Particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) can infiltrate deep into the respiratory system, posing significant health risks. Notably, the health burden of PM2.5 is more pronounced among the older adult population. With an aging population, the public health burden attributable to PM2.5 could escalate even if the current PM2.5 level remains stable. This study evaluated the number of deaths attributable to long-term PM2.5 exposure in the Republic of Korea between 2020 and 2050 and identified the PM2.5 concentration required at least to maintain the current PM2.5 health burden. To calculate mortality for 2020-2050, we performed a health impact assessment using 3-year (2019-2021) average population-weighted PM2.5 concentrations, age-specific population and mortality rates. In 2020, 33,578 [95% confidence interval (CI) = 31,708-35,448] deaths were attributable to PM2.5 exposure. Projecting forward, if the 2019-2021 average PM2.5 level remains constant, mortality is projected to be 112,953 (95% CI = 109,963-115,943) in 2050, more than three times higher than in 2020. To maintain the same level of health burden in 2050 as in 2020, the PM2.5 concentration needs to be immediately reduced to 5.8 µg/m3. In an age-specific analysis, the proportion of older adults (ages 65+) to total mortality would increase from 83% (2020) to 96% (2050), indicating that the rising mortality is predominantly driven by the aging population. By region, the reduction of PM2.5 concentrations, which is required immediately in 2020 to have the health burden in 2050 equal to that in 2020, varied from 3.6 µg/m3 in Goheung-gun (25% reduction) to 20.8 µg/m3 in Heungdeok-gu (82% reduction). Our study emphasizes the critical need for air quality management to consider aging populations when establishing PM2.5 air quality standards, as well as their associated policies and regulations.

Antibiotic resistance in livestock, environment and humans: One Health perspective.

Antibiotic resistance (AR) is a complex, multifaceted global health issue that poses a serious threat to livestock, humans, and the surrounding environment. It entails several elements and numerous potential transmission routes and vehicles that contribute to its development and spread, making it a challenging issue to address. AR is regarded as an One Health issue, as it has been found that livestock, human, and environmental components, all three domains are interconnected, opening up channels for transmission of antibiotic resistant bacteria (ARB). AR has turned out to be a critical problem mainly because of the overuse and misuse of antibiotics, with the anticipation of 10 million annual AR-associated deaths by 2050. The fact that infectious diseases induced by ARB are no longer treatable with antibiotics foreshadows an uncertain future in the context of health care. Hence, the One Health approach should be emphasized to reduce the impact of AR on livestock, humans, and the environment, ensuring the longevity of the efficacy of both current and prospective antibiotics.

Characterization of TGFß1-induced tendon-like structure in the scaffold-free three-dimensional tendon cell culture system.

The biological mechanisms regulating tenocyte differentiation and morphological maturation have not been well-established, partly due to the lack of reliable in vitro systems that produce highly aligned collagenous tissues. In this study, we developed a scaffold-free, three-dimensional (3D) tendon culture system using mouse tendon cells in a differentially adherent growth channel. Transforming Growth Factor-ß (TGFß) signaling is involved in various biological processes in the tendon, regulating tendon cell fate, recruitment and maintenance of tenocytes, and matrix organization. This known function of TGFß signaling in tendon prompted us to utilize TGFß1 to induce tendon-like structures in 3D tendon constructs. TGFß1 treatment promoted a tendon-like structure in the peripheral layer of the constructs characterized by increased thickness with a gradual decrease in cell density and highly aligned collagen matrix. TGFß1 also enhanced cell proliferation, matrix production, and morphological maturation of cells in the peripheral layer compared to vehicle treatment. TGFß1 treatment also induced early tenogenic differentiation and resulted in sufficient mechanical integrity, allowing biomechanical testing. The current study suggests that this scaffold-free 3D tendon cell culture system could be an in vitro platform to investigate underlying biological mechanisms that regulate tenogenic cell differentiation and matrix organization.

Microstructure of the corneal endothelial transition zone in different laboratory animals.

Purpose: To compare the microstructure of the corneal endothelial transition zone in different laboratory animals. Methods: Flat-mount corneas of rabbits, rats, and mice were stained with Alizarin Red S (ARS) and observed using scanning electron microscopy (SEM). The progenitor cell markers p75 neurotrophin receptor (p75NTR), SRY-box transcription factor 9 (SOX9), leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5), telomerase reverse transcriptase (TERT), and proliferation marker Ki-67 were examined in the flat-mounted corneas of three laboratory animals using immunofluorescence microscopy. Results: On flat mounts, proximity to the trabecular meshwork correlated with weaker ARS staining and greater polymorphism of endothelial cells in the transition zone in all animals. On SEM, distinct and smooth structures of the transition zone were negligibly detected in all animals. The endothelial cells in the transition zone had irregular shapes, with less dense, less wavy intercellular junctions, especially in murine corneas, exhibiting unique intercellular cystic spaces. In the transition zone of the rabbit cornea, progenitor cell markers p75NTR, SOX9, Lgr5, TERT, and proliferation marker Ki-67 were expressed, in contrast to those in other murine corneas. Conclusions: Although the transition zone was not identified clearly, irregular cell morphology and loss of cell-cell contact were observed in all animal corneal endothelial cells. The proliferative capacity and the presence of progenitor cells were confirmed in the transition zone, especially in the rabbit cornea.

Ecological predictors of cultural competence among nurses in the neonatal intensive care unit: A cross-sectional descriptive study.

Active migration and globalization have led to increased opportunities for critical care nurses to care for patients from diverse racial and cultural backgrounds. This study thus aimed to identify the individual, interpersonal, and organizational factors affecting cultural competence levels among neonatal intensive care unit (NICU) nurses based on an ecological model. This was a cross-sectional descriptive study that included 135 NICU nurses in South Korea. A hierarchical multiple linear regression analysis was conducted using the proposed ecological model, and a regression model for each of the four subdomains of cultural competence was constructed and compared. NICU nurses' cultural competencies were influenced not only by the "necessity of multicultural education" and "ethnocultural empathy" at the individual level but by the "hospital's readiness and support for cultural competencies" at the organizational level. To promote the cultural competence of nurses in critical care settings, environmental and organizational support should be improved, along with developing strategies that focus on nurses' individual characteristics. It is also necessary to investigate the "intersectionality" of the effects of individual and environmental factors on cultural competence.

Kinetics-based inference of environment-dependent microbial interactions and their dynamic variation.

Microbial communities in nature are dynamically evolving as member species change their interactions subject to environmental variations. Accounting for such context-dependent dynamic variations in interspecies interactions is critical for predictive ecological modeling. In the absence of generalizable theoretical foundations, we lack a fundamental understanding of how microbial interactions are driven by environmental factors, significantly limiting our capability to predict and engineer community dynamics and function. To address this issue, we propose a novel theoretical framework that allows us to represent interspecies interactions as an explicit function of environmental variables (such as substrate concentrations) by combining growth kinetics and a generalized Lotka-Volterra model. A synergistic integration of these two complementary models leads to the prediction of alterations in interspecies interactions as the outcome of dynamic balances between positive and negative influences of microbial species in mixed relationships. The effectiveness of our method was experimentally demonstrated using a synthetic consortium of two Escherichia coli mutants that are metabolically dependent (due to an inability to synthesize essential amino acids) but competitively grow on a shared substrate. The analysis of the E. coli binary consortium using our model not only showed how interactions between the two amino acid auxotrophic mutants are controlled by the dynamic shifts in limiting substrates but also enabled quantifying previously uncharacterizable complex aspects of microbial interactions, such as asymmetry in interactions. Our approach can be extended to other ecological systems to model their environment-dependent interspecies interactions from growth kinetics.IMPORTANCEModeling environment-controlled interspecies interactions through separate identification of positive and negative influences of microbes in mixed relationships is a new capability that can significantly improve our ability to understand, predict, and engineer the complex dynamics of microbial communities. Moreover, the prediction of microbial interactions as a function of environmental variables can serve as valuable benchmark data to validate modeling and network inference tools in microbial ecology, the development of which has often been impeded due to the lack of ground truth information on interactions. While demonstrated against microbial data, the theory developed in this work is readily applicable to general community ecology to predict interactions among macroorganisms, such as plants and animals, as well as microorganisms.

Qualitative and Quantitative Metabolite Comparison of Korean Traditional Alcoholic Beverages: Takju, Yakju, and Traditional-Soju.

With increasing interest in Korean foods and beverages, Korean traditional alcoholic beverages need to be studied. To characterize Korean traditional alcoholic beverages, we analyzed the metabolites of Takju, Yakju, and Traditional-Soju using 48 commercial products. We performed non-targeted metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and identified 33 significantly discriminant metabolites, including nine organic acids, three amino acids, and seven fatty acids, in the three types of alcoholic beverage. Subsequently, we quantified the profiled metabolites in each product and compared their contents to identify alcoholic beverage type-specific metabolites. Thus, we figured out seven metabolites using receiver operating characteristic (ROC) curves. The results revealed that octadecanoic acid (limit of detection (LOD) to 168.72 mg/L), nonanoic acid (LOD to 112.54 mg/L), and octanoic acid (8.00 to 145.08 mg/L) in Takju; succinic acid (LOD to 1.90 mg/mL), heptanoic acid (LOD to 343.23 mg/L), and hexadecanoic acid (20.28 to 126.45 mg/L) in Yakju; and malonic acid (LOD to 19.13 mg/mL) in Traditional-Soju, with an area under the curve (AUC) > 0.7, are important metabolites that can distinguish the type of alcoholic beverage. Our results provide qualitative and quantitative metabolite information about Korean traditional alcoholic beverages that can be used by consumers and manufacturers.

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

Metabolomics Reveals the Effects of Nitrogen/Phosphorus/Potassium (NPK) Fertilizer Levels on Cucumber Fruit Raised in Different Nutrient Soils.

Fertilizers are widely used to improve the quality of fruits and vegetables. However, the overuse of fertilizers has become an issue because it causes environmental problems and negatively affects productivity and fruit quality. In this study, we examined the effects of nitrogen, phosphorus, and potassium (NPK) fertilizer levels on the metabolism of cucumber fruit in low- and high-nutrient soils using mass-spectrometry-based metabolomics approaches. Cucumber metabolite content was notably different depending on the initial soil nutrient status. Most amino acids and phenylpropanoids were abundant in the cucumbers raised in low-nutrient soil, whereas organic acids, some amino acids (aspartate, glutamate, and ornithine), and carbohydrates were comparatively higher in fruits from high-nutrient soil. The fertilizer supply resulted in an alteration in the metabolite profile, while no change in fruit yield was observed in either low- or high-nutrient soils. Fertilizer treatment perturbed the metabolite contents in cucumbers from low-nutrient soil. In contrast, treatment with higher concentrations of fertilizer in high-nutrient soil increased phenylpropanoid content in the cucumbers, while most metabolites decreased. In conclusion, fertilization levels should be carefully determined, considering culture conditions such as the original soil status, to increase product yield and fruit quality and avoid environmental problems.

Non-papillary thyroid carcinoma diagnoses in The Bethesda System for Reporting Thyroid Cytopathology categories V and VI: An institutional experience.

BACKGROUND: The non-papillary thyroid carcinoma (PTC) subgroups of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) categories V (Suspicious for malignancy) and VI (Malignant) are rare, and specific tumor typing is difficult. We aimed to analyze histologic outcomes and to investigate the points of caution. METHODS: We reviewed the electronic database and identified 12,215 cases of thyroid fine-needle aspiration cytology between 2013 and 2022. In total, 2783 patients were diagnosed with TBSRTC V or VI. Of these, 51 patients with non-PTC diagnosis were identified. Histological outcomes were analyzed with the cytologic findings. RESULTS: The subgroups of non-PTC diagnoses in TBSRTC category V or VI consisted of medullary thyroid carcinoma (MTC) (13/51, 25.5 %), anaplastic thyroid carcinoma (3/51, 5.9 %), lymphoma (2/51, 3.9 %), metastatic tumor (4/51, 7.8 %), and malignant, not otherwise specified (NOS) (29/51, 56.9 %). The concordance rate of the histological outcomes was 30 % (12/40), predominantly comprising MTC cases. The obscuring factors for specific tumor typing in the suspicious for malignancy/malignant NOS cytology diagnosis group was mixed pattern of well differentiated thyroid carcinoma and less differentiated carcinoma cells (9/24, 37.5 %), low cellularity (7/24, 29.2 %) and a history of non-thyroid organ malignancy (6/24, 25 %). The less differentiated carcinoma component in mixed pattern consisted of 2 poorly differentiated thyroid carcinomas, 2 anaplastic thyroid carcinomas, 4 high-grade PTCs and 1 high-grade MTC. CONCLUSION: The high-grade feature of PTC or MTC cytology is a noteworthy obscuring factor in specific tumor typing of non-PTC cytology diagnosis.

Higher HbA1c Is Associated With Greater 2-Year Progression of White Matter Hyperintensities.

White matter hyperintensity (WMH) lesions on brain MRI images are surrogate markers of cerebral small vessel disease. Longitudinal studies examining the association between diabetes and WMH progression have yielded mixed results. Thus, in this study, we investigated the association between HbA1c, a biomarker for the presence and severity of hyperglycemia, and longitudinal WMH change after adjusting for known risk factors for WMH progression. We recruited 64 participants from South Korean memory clinics to undergo brain MRI at the baseline and a 2-year follow-up. We found the following. First, higher HbA1c was associated with greater global WMH volume (WMHV) changes after adjusting for known risk factors (ß = 7.7 × 10-4; P = 0.025). Second, the association between baseline WMHV and WMHV progression was only significant at diabetic levels of HbA1c (P < 0.05, when HbA1c >6.51%), and non-apolipoprotein E (APOE) ε4 carriers had a stronger association between HbA1c and WMHV progression (ß = -2.59 × 10-3; P = 0.004). Third, associations of WMHV progression with HbA1c were particularly apparent for deep WMHV change (ß = 7.17 × 10-4; P < 0.01) compared with periventricular WMHV change and, for frontal (ß = 5.00 × 10-4; P < 0.001) and parietal (ß = 1.53 × 10-4; P < 0.05) lobes, WMHV change compared with occipital and temporal WMHV change. In conclusion, higher HbA1c levels were associated with greater 2-year WMHV progression, especially in non-APOE ε4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease.

Group I pharmaceuticals of IARC and associated cancer risks: systematic review and meta-analysis.

We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.

Characterization of the complete plastome sequence of Korean endemic, Cardamine glechomifolia H.Lév. (Brassicaceae, Brassicales).

In this study, we report the complete plastome sequence of Cardamine glechomifolia H.Lév. 1913 (NCBI acc. no. OP894664). This plastome shows typical quadripartite structure. The plastome size is 154,307 bp, which consists of 84,015 bp large single-copy (LSC), 17,690 bp small single-copy (SSC), and 26,301 bp inverted repeat (IR) regions. The plastome contains 112 genes, including 78 protein-coding, 30 tRNA, and four rRNA genes. The infA gene is pseudogenized. Sixteen genes contain one intron and two genes (clpP and ycf3) have two introns. The phylogenomic analysis conducted in our study reveals that the genus Cardamine, which encompasses C. glechomifolia, exhibits three distinct clades. In order to elucidate the interrelationship among the three clades, it is imperative to conduct additional investigations by augmenting the number of Cardamine samples.