Multiple remotely sensed datasets and machine learning models to predict chlorophyll-a concentration in the Nakdong River, South Korea.

The Nakdong River is a crucial water resource in South Korea, supplying water for various purposes such as potable water, irrigation, and recreation. However, the river is vulnerable to algal blooms due to the inflow of pollutants from multiple points and non-point sources. Monitoring chlorophyll-a (Chl-a) concentrations, a proxy for algal biomass is essential for assessing the trophic status of the river and managing its ecological health. This study aimed to improve the accuracy and reliability of Chl-a estimation in the Nakdong River using machine learning models (MLMs) and simultaneous use of multiple remotely sensed datasets. This study compared the performances of four MLMs: multi-layer perceptron (MLP), support vector machine (SVM), random forest (RF), and eXetreme Gradient Boosting (XGB) using three different input datasets: (1) two remotely sensed datasets (Sentinel-2 and Landsat-8), (2) standalone Sentinel-2, and (3) standalone Landsat-8. The results showed that the MLP model with multiple remotely sensed datasets outperformed other MLMs with 0.43 - 0.86 greater in R2 and 0.36 - 5.88 lower in RMSE. The MLP model demonstrated the highest performance across the range of Chl-a concentrations and predicted peaks above 20 mg/m3 relatively well compared to other models. This was likely due to the capacity of MLP to handle imbalanced datasets. The predictive map of the spatial distribution of Chl-a generated by MLP well captured the areas with high and low Chl-a concentrations. This study pointed out the impacts of imbalanced Chl-a concentration observations (dominated by low Chl-a concentrations) on the performance of MLMs. The data imbalance likely led to MLMs poorly trained for high Chl-a values, producing low prediction accuracy. In conclusion, this study demonstrated the value of multiple remotely sensed datasets in enhancing the accuracy and reliability of Chl-a estimation, mainly when using the MLP model. These findings would provide valuable insights into utilizing MLMs effectively for Chl-a monitoring.

A sensorineural hearing loss harboring novel compound heterozygous variant in the TRIOBP gene: A case report.

Background: Autosomal recessive non-syndromic deafness-28 (DFNB28; OMIM #609823) specifically refers to prelingual sensorineural hearing loss (SNHL) resulting from homozygous or compound heterozygous mutations in the TRIO- and F-actin-binding protein, TRIOBP gene. In this report, we present a pediatric patient exhibiting novel compound heterozygous deleterious variants in the TRIOBP gene. Methods: The auditory brainstem response result revealed both left- and right-sided deafness with a threshold of 20 dB normal hearing level in the proband. A comprehensive trio whole exome sequencing (WES) using the Celemics G-Mendeliome Whole Exome Sequencing Panel was employed. Results: The WES analysis revealed compound heterozygous TRIOBP variants in the proband, namely c.1192_1195delCAACinsT/p.Gln398* classified as pathogenic and c.3661C > T/p.Arg1221Trp categorized as a variant of uncertain significance according to American College of Medical Genetics and Genomics guidelines. These variants are considered the most probable cause of the proband's SNHL. Conclusion: TRIOBP isoforms are predominantly expressed in the inner ear, contributing to the formation of stereocilia rootlets. Further investigations are required to fully understand the phenotypic variability and establish the pathogenicity of the identified variant in relation to the TRIOBP gene and SNHL.

Proteogenomic characterization identifies clinical subgroups in EGFR and ALK wild-type never-smoker lung adenocarcinoma.

Patients with lung adenocarcinoma who have never smoked (NSLA) and lack key driver mutations, such as those in the EGFR and ALK genes, face limited options for targeted therapies. They also tend to have poorer outcomes with immune checkpoint inhibitors than lung cancer patients who have a history of smoking. The proteogenomic profile of nonsmoking lung adenocarcinoma patients without these oncogenic driver mutations is poorly understood, which complicates the precise molecular classification of these cancers and highlights a significant area of unmet clinical need. This study analyzed the genome, transcriptome, and LC‒MS/MS-TMT-driven proteome data of tumors obtained from 99 Korean never-smoker lung adenocarcinoma patients. NSLA tumors without EGFR or ALK driver oncogenes were classified into four proteogenomic subgroups: proliferation, angiogenesis, immune, and metabolism subgroups. These 4 molecular subgroups were strongly associated with distinct clinical outcomes. The proliferation and angiogenesis subtypes were associated with a poorer prognosis, while the immune subtype was associated with the most favorable outcome, which was validated in an external lung cancer dataset. Genomic-wide impacts were analyzed, and significant correlations were found between copy number alterations and both the transcriptome and proteome for several genes, with enrichment in the ERBB, neurotrophin, insulin, and MAPK signaling pathways. Proteogenomic analyses suggested several targetable genes and proteins, including CDKs and ATR, as potential therapeutic targets in the proliferation subgroup. Upregulated cytokines, such as CCL5 and CXCL13, in the immune subgroup may serve as potential targets for combination immunotherapy. Our comprehensive proteogenomic analysis revealed the molecular subtypes of EGFR- and ALK-wild-type NSLA with significant unmet clinical needs.

Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.

BACKGROUND: Neurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear. METHODS: To explore their putative causalities, we conducted bidirectional two-sample Mendelian randomization (MR) using genetic variants associated with 317 human blood metabolites (nmax = 215,551), g-Factor (an integrated index of multiple neurocognitive tests with nmax = 332,050), and 10 different psychiatric disorders (n = 9,725 to 807,553) from the large-scale genome-wide association studies of European ancestry. Mediation analysis was used to assess the potential causal pathway among the candidate metabolite, neurocognitive trait and corresponding psychiatric disorder. RESULTS: MR evidence indicated that genetically predicted acetylornithine was positively associated with g-Factor (0.035 standard deviation units increase in g-Factor per one standard deviation increase in acetylornithine level; 95% confidence interval, 0.021 to 0.049; P = 1.15 × 10-6). Genetically predicted butyrylcarnitine was negatively associated with g-Factor (0.028 standard deviation units decrease in g-Factor per one standard deviation increase in genetically proxied butyrylcarnitine; 95% confidence interval, -0.041 to -0.015; P = 1.31 × 10-5). There was no evidence of associations between genetically proxied g-Factor and metabolites. Furthermore, the mediation analysis via two-step MR revealed that the causal pathway from acetylornithine to bipolar disorder was partly mediated by g-Factor, with a mediated proportion of 37.1%. Besides, g-Factor mediated the causal pathway from butyrylcarnitine to schizophrenia, with a mediated proportion of 37.5%. Other neurocognitive traits from different sources provided consistent findings. CONCLUSION: Our results provide genetic evidence that acetylornithine protects against bipolar disorder through neurocognitive abilities, while butyrylcarnitine has an adverse effect on schizophrenia through neurocognition. These findings may provide insight into interventions at the metabolic level for risk of neurocognitive and related disorders.

A Korean Family Presenting with Renal Cysts and Maturity-Onset Diabetes of the Young Caused by a Novel In-Frame Deletion of HNF1B.

Maturity-onset diabetes of the young (MODY; OMIM # 606391) comprises a cluster of inherited disorders within non-autoimmune diabetes mellitus (DM), typically emerging during adolescence or young adulthood. We report a novel in-frame deletion of HNF1B in a family with renal cysts and MODY, furthering our understanding of HNF1B-related phenotypes. We conducted sequential genetic testing to investigate the glucose intolerance, renal cysts, hepatic cysts, and agenesis of the dorsal pancreas observed in the proband. A comprehensive clinical exome sequencing approach using a Celemics G-Mendeliome Clinical Exome Sequencing Panel was employed. Considering the clinical manifestations observed in the proband, gene panel sequencing identified a heterozygous HNF1B variant, c.36_38delCCT/p.(Leu13del) (reference transcript ID: NM_000458.4), as the most likely cause of MODY in the proband. The patient's clinical presentation was consistent with MODY caused by the HNF1B variant, showing signs of glucose intolerance, renal cysts, hepatic cysts, and agenesis of the dorsal pancreas. Sanger sequencing confirmed the same HNF1B variant and established the paternally inherited autosomal dominant status of the heterozygous variant in the patient, as well as in his father and sister. The presence of early-onset diabetes, renal cysts, a family history of the condition, and nephropathy appearing before or after the diagnosis of diabetes mellitus (DM) suggests a diagnosis of HNF1B-MODY5. Early diagnosis is crucial for preventing complications of DM, enabling family screening, providing pre-conceptional genetic counseling, and monitoring kidney function decline.

Promising Approach for Optimizing In Vivo Fluorescence Imaging in a Tumor Mouse Model: Precision in Cancer Research.

BACKGROUND/AIM: Cancer remains a major global health concern due to its high mortality rates. Advanced diagnostic imaging, such as in vivo near-infrared (NIR) fluorescence imaging, enhances early detection by reducing autofluorescence and enabling deeper tissue penetration, addressing some limitations of conventional methods. Understanding the underlying causes of autofluorescence, even in mouse model fluorescence imaging, is crucial for accurate interpretation. This study investigated the origins of autofluorescence observed in experimental animals under NIR wavelengths, achieving successful fluorescence imaging in a clinically relevant tumor mouse model. MATERIALS AND METHODS: Both fasting and non-fasting groups were evaluated to assess the dietary impact on autofluorescence, with various feeds tested. Subcutaneous and lung tumor models were established in C57BL/6 and BALB/c nude mice using LL/2-iRFP cells. Cryo-sectioning and lung tissue imaging were conducted to confirm tumor presence and assess fluorescence signals. RESULTS: It was found that autofluorescence, notably common in the abdomen, is attributed to dietary factors. By selecting feed that lacks autofluorescence, the impact of dietary fluorescence on imaging was evaluated, leading to the establishment of optimized imaging conditions suited to the presence or absence of autofluorescence. Subsequently, utilizing lung cancer cells expressing near-infrared proteins (LL/2-iRFP), intratracheal, and subcutaneous tumor mouse models were developed, and successful in vivo imaging was achieved using the optimized imaging protocols, effectively bypassing autofluorescence. CONCLUSION: This study emphasizes the importance of understanding and addressing autofluorescence in fluorescence imaging, presenting valuable insights for enhancing the reliability and accuracy of diagnostic imaging techniques in cancer research and clinical practice.

Masticatory Function, Sex, and Risk of Dementia Among Older Adults: A Population-Based Cohort Study.

BACKGROUND: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia. METHODS: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer's disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses. RESULTS: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18-7.18) and AD (HR, 3.22; 95% CI, 1.14-9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females. CONCLUSION: Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories.

ctDNA dynamics and mechanisms of acquired resistance in patients treated with osimertinib with or without bevacizumab from the randomised phase II ETOP-BOOSTER trial.

BACKGROUND: ETOP 10-16 BOOSTER study was a randomised phase II trial of osimertinib and bevacizumab versus osimertinib in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously. METHODS: Next generation sequencing (Guardant360®) was conducted in serial plasma samples. The association between ctDNA and efficacy outcomes was explored and molecular alterations at progression were described. RESULTS: 136 patients (88% of 155 randomised) had plasma samples at baseline (68 per arm), 110 (71%) at week 9 and 65 (42%) at progression. In a multivariable model for progression-free survival (PFS), the treatment effect was found different by smoking status (interaction p=0.046), with the effect of smoking also different by baseline EGFR T790M (interaction p=0.033), while both TP53 at baseline and tissue EGFR Exon 21 L858R mutation were significantly associated with worse PFS outcome. Smokers (current/former) without baseline EGFR T790M showed a significant improvement in PFS under combination treatment, albeit with small numbers (p=0.015). Week-9 EGFR T790M clearance was associated with improved PFS in the osimertinib arm (p=0.0097). Acquired EGFR C797S mutations were detected in 22% and 13% of patients in the combination and osimertinib arm, respectively. CONCLUSIONS: The differential effect of treatment by smoking was not explained by TP53 mutation or other molecular alterations examined. Molecular mechanisms of acquired resistance were detected but no novel molecular alterations were identified in the combination arm.

Association of Compensatory Mechanisms in Prefrontal Cortex and Impaired Anatomical Correlates in Semantic Verbal Fluency: A Functional Near-Infrared Spectroscopy Study.

OBJECTIVE: Semantic verbal fluency (SVF) engages cognitive functions such as executive function, mental flexibility, and semantic memory. Left frontal and temporal lobes, particularly the left inferior frontal gyrus (IFG), are crucial for SVF. This study investigates SVF and associated neural processing in older adults with mild SVF impairment and the relationship between structural abnormalities in the left IFG and functional activation during SVF in those individuals. METHODS: Fifty-four elderly individuals with modest level of mild cognitive impairment whose global cognition were preserved to normal but exhibited mild SVF impairment were participated. Prefrontal oxyhemoglobin (HbO2) activation and frontal cortical thickness were collected from the participants using functional near-infrared spectroscopy (fNIRS) and brain MRI, respectively. We calculated the ß coefficient of HbO2 activation induced by tasks, and performed correlation analysis between SVF induced HbO2 activation and cortical thickness in frontal areas. RESULTS: We observed increased prefrontal activation during SVF task compared to the resting and control task. The activation distinct to SVF was identified in the midline superior and left superior prefrontal regions (p<0.05). Correlation analysis revealed an inverse relationship between SVF-specific activation and cortical thickness in the left IFG, particularly in pars triangularis (r(54)=-0.304, p=0.025). CONCLUSION: The study contributes to understanding the relationship between reduced cortical thickness in left IFG and increased functional activity in cognitively normal individuals with mild SVF impairment, providing implications on potential compensatory mechanisms for cognitive preservation.

Wet Mechanochemical Synthesis of BH4-Substituted Lithium Argyrodites.

In all-solid-state batteries, a solid electrolyte with high ionic conductivity is required for fast charging, uniform lithium deposition, and increased cathode capacity. Lithium argyrodite with BH4 - substitution has promising potential due to its higher ionic conductivity compared to argyrodites substituted with halides. In this study, Li5.25PS4.25(BH4)1.75, characterized by a high ionic conductivity of 13.8 mS cm-1 at 25 °C, is synthesized via wet ball-milling employing o-xylene. The investigation focused on optimizing wet ball-milling parameters such as ball size, xylene content, drying temperature, as well as the amount of BH4 - substitution in argyrodite. An all-solid-state battery prepared using Li5.25PS4.25(BH4)1.75 as the electrolyte and LiNbO3 coated NCM811 as the cathode exhibits an initial coulombic efficiency of 90.2% and maintains 93.9% of its initial capacity after 100 cycles at fast charging rate (5C). It is anticipated that the application of this wet mechanochemical synthesis will contribute further to the commercialization of all-solid-state batteries using BH4-substituted argyrodites.

Construction of Metal/Zeolite Hybrid Nanoframe Reactors via in-Situ-Kinetics Transformations.

Metal/zeolite hybrid nanoframes featuring highly accessible compartmental environments, abundant heterogeneous interfaces, and diverse chemical compositions are expected to possess significant potential for heterogeneous catalysis, yet their general synthetic methodology has not yet been established. In this study, we developed a two-step in-situ-kinetics transformation approach to prepare metal/ZSM-5 hybrid nanoframes with exceptionally open nanostructures, tunable metal compositions, and abundant accessible active sites. Initially, the process involved the formation of single-crystalline ZSM-5 nanoframes through an anisotropic etching and recrystallization kinetic transformation process. Subsequently, through an in situ reaction of the Ni2+ ions and the silica species etched from ZSM-5 nanoframes, layered nickel silicate emerged on both the inner and outer surfaces of the zeolite nanoframes. Upon reduction under a hydrogen atmosphere, well-dispersed Ni nanoparticles were produced and immobilized onto the ZSM-5 nanoframes. Strikingly, this strategy can be extended to immobilize a variety of ultrasmall monometallic and bimetallic alloy nanoparticles on zeolite nanoframes. Benefiting from the structural and compositional advantages, the resultant hybrid nanoframes with a high loading of discrete Ni nanoparticles exhibited enhanced performance in the hydrodeoxygenation of stearic acid into liquid fuels. Overall, the methodology shares fresh insights into the rational construction of intricate frame-like metal/zeolite hybrid nanoreactors for many potential catalytic applications.

Optimal cut-offs of transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background/aims: Opinions differ regarding transient elastography and magnetic resonance elastography (TE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of TE and MRE for diagnosing AF. Methods: Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating TE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for TE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. Results: A total of 19,199 patients from 63 studies using TE showed diagnostic AUC of 0.83(95% confidence interval: 0.80-0.86), 0.83(0.80-0.86), 0.87(0.84-0.90), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89(0.86-0.92), 0.92(0.89-0.94), 0.89(0.86-0.92), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages respectively. The diagnostic AUC for AF using TE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa. Conclusions: TE(7.1-7.9 kPa) and MRE(3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

Assessment of the postoperative prognosis in patients with hepatocellular carcinoma using transient elastography: A systemic review and meta-analysis.

Background and Aims: This meta-analysis examined whether preoperative vibration-controlled transient elastography (VCTE) can predict postoperative complications and recurrence in patients undergoing hepatic resection for hepatocellular carcinoma (HCC). Methods: A systematic literature search was conducted using Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases. Out of 431 individual studies, thirteen published between 2008 and 2022 were included. Five studies focused on HCC recurrence, while eight examined postoperative complications. Results: The meta-analysis of five studies on HCC recurrence showed that the high-risk group with a high VCTE score had a significantly increased recurrence rate after hepatic resection (hazard ratio [HR], 2.14). The cutoff value of VCTE in the high-risk group of HCC recurrence was 7.4-13.4kPa, the sensitivity was 0.60 (95% CI 0.47-0.72), and the specificity was 0.60 (95% CI 0.46-0.72). The area under the receiver operating characteristic curve (AUC) of the liver stiffness measured by VCTE to predict the HCC recurrence was 0.63 (95% CI 0.59-0.67). The meta-analysis on the postoperative complications revealed a significantly increased risk of postoperative complications in the high-risk group (12-25.6kPa) with a high VCTE value (risk ratio [RR], 8.32). The AUC of the liver stiffness measured by VCTE to predict the postoperative complications was 0.87(95% CI 0.84-0.90), the sensitivity was 0.76 (95% CI 0.55-0.89) and the specificity was 0.85 (95% CI 0.73-0.92). Conclusions: This meta-analysis suggests that preoperative VCTE in patients undergoing hepatic resection for HCC is useful in identifying individuals at a high risk of postoperative complications and HCC recurrence.

Diagnostic Accuracy of Transient Elastography for Staging Liver Fibrosis in Autoimmune Liver Diseases: A Systematic Review and Meta-Analysis.

Background/Aims: The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests (NITs) for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease. Methods: Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, defined as METAVIR stages F≥2, F≥3, and F=4, respectively, according to liver biopsy. Results: Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87 (95% confidence interval, 0.80-0.94), 0.89 (0.85-0.94), and 0.99 (0.96-1.00) for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88 (0.84-0.92), 0.88 (0.83-0.93), and 0.92 (0.88-0.96), respectively, while in PSC, they were 0.88 (0.82-0.95), 0.95 (0.90-1.00), and 0.92 (0.84-0.99), respectively. The cutoff values for AF were 7.5-17.9 kPa in PBC, 8.18-12.1 kPa in AIH, and 9.6 kPa in PSC. Conclusions: VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases such as PBC, AIH, and PSC. This non-invasive and reliable method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.

Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Construction and Preparation of the Novel ADN/CL-20 Cocrystal via Directional Hydrogen Bonding Design for Turning Hygroscopicity.

Ammonium dinitramide (ADN), as a novel and environmentally friendly oxidizer, has strong hygroscopicity when exposed to high-humidity air, which seriously hinders its application in solid propellants. Modification of oxidizers by cocrystallization is an effective strategy to improve the hygroscopicity of energetic components. In this paper, the theoretical simulation of ADN/CL-20 cocrystals was developed via a directional hydrogen bonding design to establish a cocrystal with improved hygroscopicity. Intermolecular interaction analyses reveal that hydrogen bonds and van der Waals interactions synergistically lead to the formation of cocrystals. The ADN/CL-20 cocrystal was prepared experimentally by the spray drying self-assembly technique, and the corresponding thermal analysis and sensitivity properties were conducted to illustrate the thermal stability and high safety. Furthermore, the critical relative humidity (CRH) measurement was carried out to evaluate the hygroscopicity of the cocrystal, exhibiting a certain degree of antihygroscopic effect with a CRH of 65%. The hydrogen bonds formed between ADN and CL-20 saturate the ammonium ions of ADN, further preventing ADN from absorbing water molecules in the air. The ADN/CL-20 cocrystal has high specific impulse characteristics (Isp: 272.6 s). Accordingly, this work clearly demonstrates that the ADN/CL-20 cocrystal is expected to be used in a solid propellant to make up for the deficiency of the ADN oxidizer.

LONGITUDINAL CHANGE OF RETINAL LAYER THICKNESS IN COGNITIVELY NORMAL ELDERLY SUBJECTS: Population-Based Cohort Study.

PURPOSE: To identify longitudinal retinal layer thickness changes in normal eyes of cognitively healthy elderly people. METHODS: Post hoc analysis was performed on 57 cognitively healthy elderly participants from the population-based Korean Longitudinal Study on Health and Aging and Korean Longitudinal Study on Cognitive Aging and Dementia cohort studies who underwent baseline and final optical coherence tomography scans. The peripapillary retinal nerve fiber layer, subfoveal choroid, and average retinal layer thickness at four quadrant (nasal, temporal, superior, and inferior) points 1 mm, 2 mm, and 3 mm from the center of the fovea were measured. RESULTS: The mean age of subjects was 75.1 years and the mean follow-up period was 55.9 months. Among the analyzed retinal layers, both the ganglion cell-inner plexiform layer and the outer nuclear layer at all 1 mm, 2 mm, and 3 mm points showed a statistically significant decrease in thickness at the final visit compared with baseline. The annual decrease rates were -1.2 µm/year at 1 mm (total -6.6%), -1.3 µm/year at 2 mm (total -8.4%), and -1.1 µm/year at 3 mm (total -9.7%) for ganglion cell-inner plexiform layer and -0.6 µm/year at 1 mm (total -4.2%), -0.5 µm/year at 2 mm (total -3.9%), and -0.4 µm/year at 3 mm (total -4.1%) for outer nuclear layer. CONCLUSION: Aging plays a significant role in the reduction of ganglion cell-inner plexiform layer and outer nuclear layer thicknesses in cognitively healthy elderly individuals.

Subcritical Water Extraction of Undaria pinnatifida: Comparative Study of the Chemical Properties and Biological Activities across Different Parts.

The subcritical water extraction of Undaria pinnatifida (blade, sporophyll, and root) was evaluated to determine its chemical properties and biological activities. The extraction was conducted at 180 °C and 3 MPa. Root extracts exhibited the highest phenolic content (43.32 ± 0.19 mg phloroglucinol/g) and flavonoid content (31.54 ± 1.63 mg quercetin/g). Sporophyll extracts had the highest total sugar, reducing sugar, and protein content, with 97.35 ± 4.23 mg glucose/g, 56.44 ± 3.10 mg glucose/g, and 84.93 ± 2.82 mg bovine serum albumin (BSA)/g, respectively. The sporophyll contained the highest fucose (41.99%) and mannose (10.37%), whereas the blade had the highest galactose (48.57%) and glucose (17.27%) content. Sporophyll had the highest sulfate content (7.76%). Key compounds included sorbitol, glycerol, L-fucose, and palmitic acid. Root extracts contained the highest antioxidant activity, with IC50 values of 1.51 mg/mL (DPPH), 3.31 mg/mL (ABTS+), and 2.23 mg/mL (FRAP). The root extract exhibited significant α-glucosidase inhibitory activity with an IC50 of 5.07 mg/mL, indicating strong antidiabetic potential. The blade extract showed notable antihypertensive activity with an IC50 of 0.62 mg/mL. Hence, subcritical water extraction to obtain bioactive compounds from U. pinnatifida, supporting their use in functional foods, cosmetics, and pharmaceuticals is highlighted. This study uniquely demonstrates the variation in bioactive compound composition and bioactivities across different parts of U. pinnatifida, providing deeper insights. Significant correlations between chemical properties and biological activities emphasize the use of U. pinnatifida extracts for chronic conditions.

Comprehensive analysis of nationwide anticancer drug-related complications in Korea: incidence, types, and cancer-specific considerations in contemporary oncology.

Background: The rising global incidence of cancer has increased the demand for chemotherapy, which is a crucial treatment modality. Recent advancements in cancer treatment, including targeted agents and immunotherapy, have introduced complications owing to their specific mechanisms. However, comprehensive studies of the combined complications of these approaches are lacking. Objectives: This study aimed to comprehensively assess and analyze the overall incidence of anticancer drug-related complications in a nationwide patient cohort, utilizing a customized National Health Insurance Sharing Service database in Korea. Design: Retrospective cohort study. Methods: We included patients who were prescribed anticancer drugs (excluding endocrine agents) and diagnosed with cancer. For the type of cancer classification, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) was used and anticancer drugs were classified based on the Anatomical Therapeutic Chemical code. We classified cancer into 18 types based on the ICD-10 code and delineated cancer-related complications into 12 categories. Complications included hematological, gastrointestinal, infectious, cardiovascular, major bleeding, endocrine, neurotoxic, nephrotoxic, dermatological, pulmonary, musculoskeletal, and hepatotoxic effects. Result: We included 294,544 patients diagnosed with cancer and administered anticancer drugs between 2016 and 2018, with follow-up continuing until 2021. We identified 486,929 anticancer drug-related complications, with an incidence of 1843.6 per 1000 person-years (PY). Anemia was the most common complication, with a rate of 763.7 per 1000 PY, followed by febrile neutropenia (295.7) and nausea/vomiting (246.9). Several complications peaked during the first months following the initiation of anticancer drug therapy; however, herpes, skin infection, heart failure, and peripheral neuropathy peaked at 6-12 months. Among major cancers, breast cancer had the lowest overall incidence of complications. Targeted therapies revealed lower complication rates than cytotoxic chemotherapy; however, they also required careful monitoring of rash. Conclusion: This study highlights the importance of the proactive management of anticancer drug-related complications for patient care improvement.

Effect of Sortilin1 on promoting angiogenesis and systemic metastasis in hepatocellular carcinoma via the Notch signaling pathway and CD133.

Hepatocellular carcinoma (HCC) is known to be lethal disease. However, its prognosis remains poor, primarily because the precise oncogenic mechanisms underlying HCC progression remain elusive, thus hampering effective treatment. Here, we aimed to identify the potential oncogenes in HCC and elucidate the underlying mechanisms of their action. To identify potential candidate genes, an integrative analysis of eight publicly available genomic datasets was performed, and the functional implications of the identified genes were assessed in vitro and in vivo. Sortilin 1 (SORT1) was identified as a potential candidate oncogene in HCC, and its overexpression in HCC cells was confirmed by analyzing spatial transcriptomic and single-cell data. Silencing SORT1 in Huh-7 and Hep3B cells significantly reduced HCC progression in vitro and in vivo. Functional analyses of oncogenic pathways revealed that SORT1 expression regulated the Notch signaling pathway activation and CD133 expression. Furthermore, analysis of epigenetic regulation of the candidate gene and its clinical implications using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) and our HCC cohort (AJOU_HCC cohort) data demonstrated an inverse correlation between the methylation status of the SORT1 promoter region, specifically at the cg16988986 site, and SORT1 mRNA expression, indicating the epigenetic regulation of SORT1 in HCC. In addition, the distinct methylation status of cg16988986 was significantly associated with patient survival. In conclusion, SORT1 plays a pivotal role in HCC by activating the Notch signaling pathway and increasing CD133 expression. These findings suggest SORT1 as a promising therapeutic target for HCC.