Cancer-Associated Fibroblasts Together with a Decline in CD8+ T Cells Predict a Worse Prognosis for Breast Cancer Patients.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in tumor microenvironment regulation and cancer progression. This study assessed the significance and predictive potential of CAFs in breast cancer prognosis. METHODS: The study included 1503 breast cancer patients. Cancer-associated fibroblasts were identified using morphologic features from hematoxylin and eosin slides. The study analyzed clinicopathologic parameters, survival rates, immune cells, gene sets, and prognostic models using gene-set enrichment analysis, in silico cytometry, pathway analysis, in vitro drug-screening, and gradient-boosting machine (GBM)-learning. RESULTS: The presence of CAFs correlated significantly with young age, lymphatic invasion, and perineural invasion. In silico cytometry showed altered leukocyte subsets in the presence of CAFs, with decreased CD8+ T cells. Gene-set enrichment analysis showed associations with critical processes such as the epithelial-mesenchymal transition and immune modulation. Drug sensitivity analysis in breast cancer cell lines with varying fibroblast activation protein-α expression suggested that CAF-targeted therapies might enhance the efficacy of certain anticancer drugs including ARRY-520, ispinesib-mesylate, paclitaxel, and docetaxel. Integrating CAF presence with machine-learning improved survival prediction. For breast cancer patients, CAFs were independent prognostic markers for worse disease-specific survival and disease-free survival. CONCLUSION: This study highlighted the significance of CAFs in breast cancer biology and provided compelling evidence of their impact on patient outcomes and treatment response. The findings offer valuable insights into the potential of CAFs as prognostic and predictive biomarkers and support the development of CAF-targeted therapies to improve breast cancer management.

Fluorescent Phenotyping of Blood Cells Using a Differential Sensing Strategy: Differentiating Physiological Aging Stages and Neuro-Degenerative Disease Drugs.

Blood continually contributes to the maintenance of homeostasis of the body and contains information regarding the health state of an individual. However, current hematological analyses predominantly rely on a limited number of CD markers and morphological analysis. In this work, differentially sensitive fluorescent compounds based on TCF scaffolds are introduced that are designed for fluorescent phenotyping of blood. Depending on their structures, TCF compounds displayed varied responses to reactive oxygen species, biothiols, redox-related biomolecules, and hemoglobin, which are the primary influential factors within blood. Contrary to conventional CD marker-based analysis, this unbiased fluorescent phenotyping method produces diverse fingerprints of the health state. Precise discrimination of blood samples from 37 mice was demonstrated based on their developmental stages, ranging from 10 to 19 weeks of age. Additionally, this fluorescent phenotyping method enabled the differentiation between drugs with distinct targets, serving as a simple yet potent tool for pharmacological analysis to understand the mode of action of various drugs.

TGFß4 alleviates the phenotype of Charcot-Marie-Tooth disease type 1A.

The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFß4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells, which might be one of the downstream effectors in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced the demyelinating phenotype in vivo. Second, we further isolated TGFß4 as an antagonist that could abolish Nodal-induced demyelination. Finally, we developed a recombinant TGFß4-fragment crystallizable (Fc) fusion protein, CX201, and demonstrated that its application had promyelinating efficacy in Schwann cells. CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFß4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A.

Prevalence and Burden of Human Adenovirus-Associated Acute Respiratory Illness in the Republic of Korea Military, 2013 to 2022.

BACKGROUND: Human adenovirus (HAdV) is a common cause of acute respiratory disease (ARD) and has raised significant concerns within the Korean military. Here, we conducted a comprehensive epidemiological analysis of HAdV-associated ARD by evaluating its prevalence, clinical outcomes, and prognosis. METHODS: We reviewed data from multiple sources, including the New Defense Medical Information System, Defense Medical Statistical Information System, Ministry of National Defense, Army Headquarters, Navy Headquarters, Air Force Headquarters, and Armed Forces Medical Command. We analyzed data of patients who underwent polymerase chain reaction (PCR) testing for respiratory viruses between January 2013 and July 2022 in all 14 Korean military hospitals. The analysis included the PCR test results, demographic characteristics, health care utilization, and prognosis including types of treatments received, incidence of pneumonia, and mortality. RESULTS: Among the 23,830 individuals who underwent PCR testing at Korean military hospitals, 44.78% (10,670 cases) tested positive for respiratory viruses. Across all military types and ranks, HAdV was the most prevalent virus, with a total of 8,580 patients diagnosed, among HAdV, influenza virus, human metapneumovirus, human parainfluenza virus, and human respiratory syncytial virus. HAdV-infected patients exhibited higher rates of healthcare use compared to non-HAdV-infected patients, including a greater number of emergency visits (1.04 vs. 1.02) and outpatient visits (1.31 vs. 1.27), longer hospitalizations (8.14 days vs. 6.84 days), and extended stays in the intensive care unit (5.21 days vs. 3.38 days). Furthermore, HAdV-infected patients had a higher proportion of pneumonia cases (65.79% vs. 48.33%) and greater likelihood of receiving advanced treatments such as high flow nasal cannula or continuous renal replacement therapy. CONCLUSION: Our findings indicate that HAdV posed a significant public health concern within the Korean military prior to the coronavirus disease 2019 (COVID-19) pandemic. Given the potential for a resurgence of outbreaks in the post-COVID-19 era, proactive measures, such as education, environmental improvements, and the development of HAdV vaccines, are crucial for effectively preventing future outbreaks.

JAK2 Loss Arising From Tumor-Spread-Through-Air-Spaces (STAS) Promotes Tumor Progression by Suppressing CD8+ T Cells in Lung Adenocarcinoma: A Machine Learning Approach.

BACKGROUND: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. METHODS: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. RESULTS: The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. CONCLUSION: In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

Cytarabine induces cachexia with lipid malabsorption via zippering the junctions of lacteal in murine small intestine.

Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel.

Parametric cerebral blood flow and arterial transit time mapping using a 3D convolutional neural network.

PURPOSE: To reduce the total scan time of multiple postlabeling delay (multi-PLD) pseudo-continuous arterial spin labeling (pCASL) by developing a hierarchically structured 3D convolutional neural network (H-CNN) that estimates the arterial transit time (ATT) and cerebral blow flow (CBF) maps from the reduced number of PLDs as well as averages. METHODS: A total of 48 subjects (38 females and 10 males), aged 56-80 years, compromising a training group (n = 45) and a validation group (n = 3) underwent MRI including multi-PLD pCASL. We proposed an H-CNN to estimate the ATT and CBF maps using a reduced number of PLDs and a separately reduced number of averages. The proposed method was compared with a conventional nonlinear model fitting method using the mean absolute error (MAE). RESULTS: The H-CNN provided the MAEs of 32.69 ms for ATT and 3.32 mL/100 g/min for CBF estimations using a full data set that contains six PLDs and six averages in the 3 test subjects. The H-CNN also showed that the smaller number of PLDs can be used to estimate both ATT and CBF without significant discrepancy from the reference (MAEs of 231.45 ms for ATT and 9.80 mL/100 g/min for CBF using three of six PLDs). CONCLUSION: The proposed machine learning-based ATT and CBF mapping offers substantially reduced scan time of multi-PLD pCASL.

Association between health-related quality of life and heart rate variability in elderly individuals with cognitive impairment in Korea: cross-sectional study.

BACKGROUND: Cognitive impairment, a characteristic and prior stage of dementia, is a serious public health concern in Korea a country with rapidly aging population. In a neurovisceral integration model, cognitive ability is connected to emotional and autonomic regulation via an interconnection in the brain, which may be associated with health-related quality of life (HRQoL). METHODS: This study investigated the association between the HRQoL and the autonomic nervous system (ANS) via EuroQoL-5 Dimension (EQ-5D) and heart rate variability (HRV) among 417 patients who visited the Neurology Department in Veterans Health Service Medical Center, Seoul, South Korea. RESULTS: The mean age of 275 patients in the cognitive impairment group (CIG) was higher than that of 142 patients in the normal cognition group (NCG) (74.85 years vs. 72.96 years, p < 0.001). In a generalized linear model with a beta coefficient (ß), an increase in HRQoL was associated with higher HRV levels was observed only in CIG (CIG: the standard deviation of all NN intervals (SDNN) (ln, ms): ß = 0.02, p = 0.007; Total power spectral density (TP) (ln, ms2): ß = 0.01, p = 0.007; High frequency (HF) (ln, ms2): ß = 0.01, p = 0.015; Low frequency (LF) (ln, ms2): ß = 0.01, p = 0.003) (NCG: SDNN (ln, ms): ß = 0.01, p = 0.214; TP (ln, ms2): ß = 0.01, p = 0.144; HF (ln, ms2): ß = 0.00, p = 0.249; LF (ln, ms2): ß = 0.01, p = 0.294). CONCLUSIONS: We found a significant association between HRQoL and HRV in Korean elders with cognitive impairment. However, this study is cross-sectional, so we cannot define direct causation. Further studies are needed to support our findings and to elucidate the biological mechanisms underlying these associations, especially in people cognitively impaired.

Sex differences in the association between sarcopenia and mild cognitive impairment in the older Korean population.

BACKGROUND: A link between sarcopenia and cognitive function has been proposed and is supported by several investigations. Nevertheless, the sex-linked relationship between these two diseases has been scarcely investigated. This cross-sectional study investigated sex differences in the association between sarcopenia and mild cognitive impairment. METHODS: We included all 286 participants aged 60 years or older with MCI who visited the Department of Neurology at Veterans Health Service Medical Center in South Korea from January to December 2021. The diagnosis of MCI was confirmed by two neurologists based on the participants' neuropsychological test scores. Diagnosis of sarcopenia was based on the algorithm of Asian Working Group for Sarcopenia (AWGS) 2019 including bioelectrical impedance analysis and handgrip strength, and cognitive function was assessed using Seoul Neuropsychological Screening Battery Core (SNSB-C) test. RESULTS: Among the 286 participants, 171 and 112 were men and women. After adjustment for potential covariates including APOE genotype, in women participants, there were significant associations between diagnosis of sarcopenia and MCI (OR = 4.72, 95%CI [1.39-15.97]), while there was no significant relationship in men participants. In eight subdomains of SNSB-C, we also found that women participants with sarcopenia demonstrated a significant memory decline (OR = 3.21, 95%CI [1.01-10.19]) as compared with the reference women group without sarcopenia after adjusting all covariates mentioned above. No significant association between any SNSB-C subdomain and MCI was demonstrated in men participants. CONCLUSIONS: We demonstrated that there was a different relationship between sarcopenia and MCI by sex and that sarcopenia may affect the cognitive subdomain differently by sex. These results imply that, with regard to cognitive function, maintaining muscle function and muscle mass might be more crucial for women than for men.

Hyperkalemia Detection in Emergency Departments Using Initial ECGs: A Smartphone AI ECG Analyzer vs. Board-Certified Physicians.

BACKGROUND: Hyperkalemia is a potentially fatal condition that mandates rapid identification in emergency departments (EDs). Although a 12-lead electrocardiogram (ECG) can indicate hyperkalemia, subtle changes in the ECG often pose detection challenges. An artificial intelligence application that accurately assesses hyperkalemia risk from ECGs could revolutionize patient screening and treatment. We aimed to evaluate the efficacy and reliability of a smartphone application, which utilizes camera-captured ECG images, in quantifying hyperkalemia risk compared to human experts. METHODS: We performed a retrospective analysis of ED hyperkalemic patients (serum potassium ≥ 6 mmol/L) and their age- and sex-matched non-hyperkalemic controls. The application was tested by five users and its performance was compared to five board-certified emergency physicians (EPs). RESULTS: Our study included 125 patients. The area under the curve (AUC)-receiver operating characteristic of the application's output was nearly identical among the users, ranging from 0.898 to 0.904 (median: 0.902), indicating almost perfect interrater agreement (Fleiss' kappa 0.948). The application demonstrated high sensitivity (0.797), specificity (0.934), negative predictive value (NPV) (0.815), and positive predictive value (PPV) (0.927). In contrast, the EPs showed moderate interrater agreement (Fleiss' kappa 0.551), and their consensus score had a significantly lower AUC of 0.662. The physicians' consensus demonstrated a sensitivity of 0.203, specificity of 0.934, NPV of 0.527, and PPV of 0.765. Notably, this performance difference remained significant regardless of patients' sex and age (P < 0.001 for both). CONCLUSION: Our findings suggest that a smartphone application can accurately and reliably quantify hyperkalemia risk using initial ECGs in the ED.

Effects of Chest Mobilization and Breathing Exercises on Respiratory Function, Trunk Stability, and Endurance in Chronic Stroke Patients after Coronavirus Disease.

Background and objectives: This study investigates the effects of chest mobilization and breathing exercises on respiratory function, trunk stability, and endurance in chronic stroke patients who have contracted coronavirus disease (COVID-19). Materials and Methods: Thirty inpatients of a tertiary hospital in South Korea, who had a history of COVID-19 and were diagnosed with stroke within the last 6 months, were randomly assigned to either chest mobilization exercise with breathing exercise (CMEBE) or conservative physical therapy with breathing exercise (CPTBE) groups. The respiratory function, trunk stability, and endurance were measured at baseline and 6 weeks after the interventions. Results: Both CMEBE and CPTBE groups showed improvements in respiratory function, trunk stability, and endurance after the intervention (p < 0.05). However, the CMEBE group showed significantly greater improvements in forced expiratory volume in 1 s (p < 0.05), trunk stability (p < 0.05), and endurance (p < 0.05) than the CPTBE group. No significant intergroup difference was observed in forced vital capacity and peak expiratory flow. Conclusions: The combination of chest mobilization and breathing exercises improved respiratory muscle mobility and endurance, stabilized the trunk, and enhanced balance and the transfer of weight. The findings suggest that this intervention could be beneficial in improving respiratory function and endurance in stroke patients.

Monitoring energy balance through clinical and serum biomarkers in patients with hematologic malignancies undergoing chemotherapy.

Despite widespread concern about energy imbalance due to tumor and chemotherapy-related side effects, little is known about detailed variations in energy input, metabolic rate, and physical activity. This study explored changes in energy balance components and serum biomarkers of patients with hematologic malignancies undergoing chemotherapy. Our prospective study included 40 patients with hematologic malignancies hospitalized for chemotherapy. We measured energy balance components, physical function, and serum biomarkers at baseline and weekly after chemotherapy for 3 weeks. Significant weight loss, representing negative energy balance, occurred at 2 (p = 0.002) and 3 weeks (p < 0.001) post-chemotherapy. Statistically reduced oral intake was observed at 3 weeks post-chemotherapy (p = 0.040), and resting energy expenditure statistically decreased according to Harris-Benedict equation, but not to Penn State University equation. Physical function according to DEMMI score decreased significantly at 3 weeks post-chemotherapy (p = 0.002). Serum biomarker analysis demonstrated significant changes in albumin, total protein, CXCL13, and GDF15, with exception of leptin. Although conventional serum biomarkers (total protein and albumin) did not reach pathological states despite their statistical differences, subgroup analysis showed CXCL13 in weight loss group and GDF15 in reduced oral intake group were significantly changed. Over half of patients (65.0%, n = 26) suffered from energy imbalance associated with weight loss and reduced oral intake during chemotherapy. Serial laboratory results suggested that novel biomarkers (CXCL13, GDF15) could be correlated with cachexic state and reduced food intake. Monitoring clinical and serum biomarkers associated with energy balance together can help identify needs for nutritional support in patients with hematologic malignancies undergoing chemotherapy.

Antiobesity therapeutics with complementary dual-agonist activities at glucagon and glucagon-like peptide 1 receptors.

AIM: To develop more effective and long-lasting antiobesity and antidiabetic therapeutics by employing novel chemical modifications of glucagon-like peptide-1 receptor (GLP-1R) agonists. METHODS: We constructed novel unimolecular dual agonists of GLP-1R and glucagon receptor prepared by linking sEx-4 and native glucagon (GCG) via lysine or triazole [sEx4-GCG(K) and sEx4-GCG(T), respectively] and evaluated their antiobesity and antidiabetic efficacy in the diabetic and obese mouse model. RESULTS: Both sEx4-GCG(K) and sEx4-GCG(T) showed the beneficial metabolic effects of GLP-1 and glucagon: they promoted weight loss and ameliorated insulin resistance and hepatic steatosis. They also increased thermogenesis in brown adipose tissue, and lipolysis and ß-oxidation in white adipose tissue, with concomitant suppression of lipogenesis. Furthermore, both dual agonists activated the 5'-AMP-activated protein kinase signalling pathway and prevented palmitate-induced oxidative stress in skeletal muscle cells. CONCLUSION: Through their complementary dual agonism, sEx4-GCG(T) and sEx4-GCG(K) induce more marked weight loss and metabolic improvements than conventional agonists, and could be developed as novel therapeutic agents for the treatment of obesity and associated metabolic disorders in humans.

Association between serum klotho levels and cardiovascular disease risk factors in older adults.

BACKGROUND: Klotho deficiency is a significant predictor of cardiovascular disease (CVD)-related mortality and morbidity. However, research assessing the association between klotho and individual risk factors of CVD is limited. This study aimed to explore the association between circulating serum klotho levels and risk factors for CVD in adults. METHODS: We used the 2007-2016 National Health and Nutrition Examination Survey and included 13,154 participants for whom serum klotho levels were available. Body mass index (BMI), exercise, smoking status, alcohol consumption, hypertension, dyslipidemia, serum lipid parameters, and blood pressure were considered as CVD risk factors. RESULTS: Circulating klotho levels were negatively associated with being overweight (beta coefficient: - 22.609, p = 0.0025), obesity (beta coefficient: - 23.716, p = 0.0011), current smoking (beta coefficient: - 46.412, p < 0.0001), and alcohol consumption (beta coefficient: - 51.194, p < 0.0001). There was a positive association between serum klotho levels and no history of dyslipidemia (beta coefficient: 15.474, p = 0.0053). Serum klotho levels were significantly decreased by a unit increase in triglycerides (beta coefficient: - 0.117, p = 0.0006) and total cholesterol (beta coefficient: - 0.249, p = 0.0002). There was a significant non-linear relationship between serum klotho levels, triglycerides, and total cholesterol. CONCLUSIONS: Lower serum klotho levels are associated with certain CVD risk factors, including high BMI, smoking, alcohol consumption, and lipid parameters (triglycerides and total cholesterol). This study suggests that the soluble klotho level may be a potential marker for CVD risk.

Analyses of Confirmed COVID-19 Cases Among Korean Military Personnel After Mass Vaccination.

BACKGROUND: The military was one of the first groups in Korea to complete mass vaccination against the coronavirus disease 2019 (COVID-19) due to their high vulnerability to COVID-19. To confirm the effect of mass vaccination, this study analyzed the patterns of confirmed cases within Korean military units. METHODS: From August 1 to September 15, 2021, all epidemiological data regarding confirmed COVID-19 cases in military units were reviewed. The number of confirmed cases in the units that were believed to have achieved herd immunity (i.e., ≥ 70% vaccination) was compared with the number of cases in the units that were not believed to have reached herd immunity (< 70% vaccination). Additionally, trends in the incidence rates of COVID-19 in the military and the entire Korean population were compared. RESULTS: By August 2021, 85.60% of military personnel were fully vaccinated. During the study period, a total of 174 COVID-19 cases were confirmed in the 39 units. More local transmission (herd immunity group vs. non-herd immunity group [%], 1 [0.91] vs. 39 [60.94]) and hospitalizations (12 [11.01] vs. 13 [27.08]) occurred in the units that were not believed to have achieved herd immunity. The percentage of fully vaccinated individuals among the confirmed COVID-19 cases increased over time, possibly due to the prevalence of the delta variant. Nevertheless, the incidence rate remained lower in military units than in the general Korean population. CONCLUSION: After completing mass vaccination, the incidence rates of COVID-19 infection in the military were lower than those in the national population. New cluster infections did not occur in vaccinated units, thereby suggesting that herd immunity has been achieved in these military units. Further research is needed to determine the extent to which levels of non-pharmacological intervention can be reduced in the future.

Trends in Confirmed COVID-19 Cases in the Korean Military Before and After the Emergence of the Omicron Variant.

BACKGROUND: Due to the higher transmissibility and increased immune escape of the omicron variant of severe acute respiratory syndrome coronavirus 2, the number of patients with coronavirus disease 2019 (COVID-19) has skyrocketed in the Republic of Korea. Here, we analyzed the change in trend of the number of confirmed COVID-19 cases in the Korean military after the emergence of the omicron variant on December 5, 2021. METHODS: An interrupted time-series analysis was performed of the daily number of newly confirmed COVID-19 cases in the Korean military from September 1, 2021 to April 10, 2022, before and after the emergence of the omicron variant. Moreover, the daily number of newly confirmed COVID-19 cases in the Korean military and in the population of Korean civilians adjusted to the same with military were compared. RESULTS: The trends of COVID-19 occurrence in the military after emergence of the omicron variant was significantly increased (regression coefficient, 23.071; 95% confidence interval, 16.122-30.020; P < 0.001). The COVID-19 incidence rate in the Korean military was lower than that in the civilians, but after the emergence of the omicron variant, the increased incidence rate in the military followed that of the civilian population. CONCLUSION: The outbreak of the omicron variant occurred in the Korean military despite maintaining high vaccination coverage and intensive non-pharmacological interventions.

Automated Detection of Rice Bakanae Disease via Drone Imagery.

This paper proposes a system for the forecasting and automated inspection of rice Bakanae disease (RBD) infection rates via drone imagery. The proposed system synthesizes camera calibrations and area calculations in the optimal data domain to detect infected bunches and classify infected rice culm numbers. Optimal heights and angles for identification were examined via linear discriminant analysis and gradient magnitude by targeting the morphological features of RBD in drone imagery. Camera calibration and area calculation enabled distortion correction and simultaneous calculation of image area using a perspective transform matrix. For infection detection, a two-step configuration was used to recognize the infected culms through deep learning classifiers. The YOLOv3 and RestNETV2 101 models were used for detection of infected bunches and classification of the infected culm numbers, respectively. Accordingly, 3 m drone height and 0° angle to the ground were found to be optimal, yielding an infected bunches detection rate with a mean average precision of 90.49. The classification of number of infected culms in the infected bunch matched with an 80.36% accuracy. The RBD detection system that we propose can be used to minimize confusion and inefficiency during rice field inspection.

Graphene Quantum Dots Alleviate Impaired Functions in Niemann-Pick Disease Type C in Vivo.

While the neuropathological characteristics of Niemann-Pick disease type C (NPC) result in a fatal diagnosis, the development of clinically available therapeutic agent remains a challenge. Here we propose graphene quantum dots (GQDs) as a potential candidate for the impaired functions in NPC in vivo. In addition to the previous findings that GQDs exhibit negligible long-term toxicity and are capable of penetrating the blood-brain barrier, GQD treatment reduces the aggregation of cholesterol in the lysosome through expressed physical interactions. GQDs also promote autophagy and restore defective autophagic flux, which, in turn, decreases the atypical accumulation of autophagic vacuoles. More importantly, the injection of GQDs inhibits the loss of Purkinje cells in the cerebellum while also demonstrating reduced activation of microglia. The ability of GQDs to alleviate impaired functions in NPC proves the promise and potential of the use of GQDs toward resolving NPC and other related disorders.

Complement and Coagulation Cascades are Potentially Involved in Dopaminergic Neurodegeneration in α-Synuclein-Based Mouse Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder that results in motor dysfunction and, eventually, cognitive impairment. α-Synuclein protein is known as a central protein to the pathophysiology of PD, but the underlying pathological mechanism still remains to be elucidated. In an effort to understand how α-synuclein underlies the pathology of PD, various PD mouse models with α-synuclein overexpression have been developed. However, systemic analysis of the brain proteome of those mouse models is lacking. In this study, we established two mouse models of PD by injecting α-synuclein preformed fibrils (PFF) or by inducing overexpression of human A53T α-synuclein to investigate common pathways in the two different types of the PD mouse models. For more accurate quantification of mouse brain proteome, the proteins were quantified using the method of stable isotope labeling with amino acids in mammals . We identified a total of 8355 proteins from the two mouse models; ∼6800 and ∼7200 proteins from α-synuclein PFF-injected mice and human A53T α-synuclein transgenic mice, respectively. Through pathway analysis of the differentially expressed proteins common to both PD mouse models, it was discovered that the complement and coagulation cascade pathways were enriched in the PD mice compared to control animals. Notably, a validation study demonstrated that complement component 3 (C3)-positive astrocytes were increased in the ventral midbrain of the intrastriatal α-synuclein PFF-injected mice and C3 secreted from astrocytes could induce the degeneration of dopaminergic neurons. This is the first study that highlights the significance of the complement and coagulation pathways in the pathogenesis of PD through proteome analyses with two sophisticated mouse models of PD.

Universal Thermal Entanglement of Multichannel Kondo Effects.

Quantum entanglement between an impurity and its environment is expected to be central in quantum impurity problems. We develop a method to compute the entanglement in spin-1/2 impurity problems, based on the entanglement negativity and the boundary conformal field theory (BCFT). Using the method, we study the thermal decay of the entanglement in the multichannel Kondo effects. At zero temperature, the entanglement has the maximal value independent of the number of the screening channels. At low temperature, the entanglement exhibits a power-law thermal decay. The power-law exponent equals two times of the scaling dimension of the BCFT boundary operator describing the impurity spin, and it is attributed to the energy-dependent scaling behavior of the entanglement in energy eigenstates. These agree with numerical renormalization group results, unveiling quantum coherence inside the Kondo screening length.