Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation.

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of Piezo1 in lymphatics or systemic administration of Yoda1 in mice with hydrocephalus or Down syndrome resulted in a notable decrease in pathological CSF accumulation, ventricular enlargement and other associated disease symptoms. Together, our study highlights the importance of Piezo1-mediated lymphatic mechanotransduction in maintaining brain fluid drainage and identifies Piezo1 as a promising therapeutic target for treating excessive CSF accumulation and ventricular enlargement.

Effect analysis on waste recycling by introducing a new policy, "Environmental Assessment of Recycling," for establishment of the ESG management system in the Republic of Korea.

To move away from linear system mining-manufacture-production-disposal, most countries have been trying to establish a circular economy, by reusing waste as resources. Responding to this paradigm change, the Ministry of Environment of Korea amended the Wastes Control Act in the 2010s. To increase the recycling rate in Korea, the environmental assessment of recycling (EAR) has been introduced to improve the Wastes Control Act. The whole process of new recycling technologies can be assessed in terms of environmental or technical aspects by assessment institutes of the EAR. Finally, the governmental research institute can approve of an application case, which proves environmental friendliness, even if the technology is not defined in the current act. Recently, 17 companies have been coassessed and approved to recycle steel codes in waste tires as resources for iron smelting via assessments of the whole process, such as environmental analysis and quality assessment. The EAR has been enforcing recycling materials for six years, and the total profit of the companies that were approved was estimated to be approximately 55 million USD. However, many amendments to the EAR continue to be requested by stakeholders. In this study, the effect of the EAR was evaluated, and additional tasks were found to enhance the EAR. Integr Environ Assess Manag 2024;00:1-13. © 2024 SETAC.

Relationship between disproportionately enlarged subarachnoid-space hydrocephalus and white matter tract integrity in normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.

Evolution of the Stethoscope: Advances with the Adoption of Machine Learning and Development of Wearable Devices.

The stethoscope has long been used for the examination of patients, but the importance of auscultation has declined due to its several limitations and the development of other diagnostic tools. However, auscultation is still recognized as a primary diagnostic device because it is non-invasive and provides valuable information in real-time. To supplement the limitations of existing stethoscopes, digital stethoscopes with machine learning (ML) algorithms have been developed. Thus, now we can record and share respiratory sounds and artificial intelligence (AI)-assisted auscultation using ML algorithms distinguishes the type of sounds. Recently, the demands for remote care and non-face-to-face treatment diseases requiring isolation such as coronavirus disease 2019 (COVID-19) infection increased. To address these problems, wireless and wearable stethoscopes are being developed with the advances in battery technology and integrated sensors. This review provides the history of the stethoscope and classification of respiratory sounds, describes ML algorithms, and introduces new auscultation methods based on AI-assisted analysis and wireless or wearable stethoscopes.

The impact of subthreshold levels of amyloid deposition on conversion to dementia in patients with amyloid-negative amnestic mild cognitive impairment.

BACKGROUND: About 40-50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer's pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans. METHODS: This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset together. RESULTS: During the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006). CONCLUSION: Our findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI.

Patterns of Focal Amyloid Deposition Using 18F-Florbetaben PET in Patients with Cognitive Impairment.

Accumulation of aggregated amyloid-ß (Aß) in the brain is considered the first pathological event within the pathogenesis of Alzheimer's disease (AD). It is difficult to accurately identify the initial brain regions of Aß accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aß deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aß accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aß accumulation in the brain of people with AD continuum.

Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion.

BACKGROUND: Mutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion. METHODS: Various mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration. RESULTS: Piezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development. CONCLUSIONS: Piezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.

Prolymphangiogenic Effects of 9-cis Retinoic Acid Are Enhanced at Sites of Lymphatic Injury and Dependent on Treatment Duration in Experimental Postsurgical Lymphedema.

Background: Patients undergoing surgical treatment for solid tumors are at risk for development of secondary lymphedema due to intraoperative lymphatic vessel injury. The damaged lymphatic vessels fail to adequately regenerate and lymphatic obstruction leads to fluid and protein accumulation in the interstitial space and chronic lymphedema develops as a result. There are currently no effective pharmacological agents that reduce the risk of developing lymphedema or treat pre-existing lymphedema, and management is largely palliative. The present study investigated the efficacy of various 9-cis retinoic acid (9-cis RA) dosing strategies in reducing postsurgical lymphedema by utilizing a well-established mouse tail lymphedema model. Methods and Results: Short-duration treatment with 9-cis RA did not demonstrate a significant reduction in postoperative tail volume, nor an improvement in lymphatic clearance. However, long-term treatment with 9-cis RA resulted in decreased overall tail volume, dermal thickness, and epidermal thickness, with an associated increase in functional lymphatic clearance and lymphatic vessel density, assessed by LYVE-1 immunostaining, compared with control. These effects were seen at the site of lymphatic injury, with no significant changes observed in uninjured sites such as ear skin and the diaphragm. Conclusions: Given the reported results indicating that 9-cis RA is a potent promoter of lymphangiogenesis and improved lymphatic clearance at sites of lymphatic injury, investigation of postoperative 9-cis RA administration to patients at high risk of developing lymphedema may demonstrate positive efficacy and reduced rates of postsurgical lymphedema.

The coming era of a new auscultation system for analyzing respiratory sounds.

Auscultation with stethoscope has been an essential tool for diagnosing the patients with respiratory disease. Although auscultation is non-invasive, rapid, and inexpensive, it has intrinsic limitations such as inter-listener variability and subjectivity, and the examination must be performed face-to-face. Conventional stethoscope could not record the respiratory sounds, so it was impossible to share the sounds. Recent innovative digital stethoscopes have overcome the limitations and enabled clinicians to store and share the sounds for education and discussion. In particular, the recordable stethoscope made it possible to analyze breathing sounds using artificial intelligence, especially based on neural network. Deep learning-based analysis with an automatic feature extractor and convoluted neural network classifier has been applied for the accurate analysis of respiratory sounds. In addition, the current advances in battery technology, embedded processors with low power consumption, and integrated sensors make possible the development of wearable and wireless stethoscopes, which can help to examine patients living in areas of a shortage of doctors or those who need isolation. There are still challenges to overcome, such as the analysis of complex and mixed respiratory sounds and noise filtering, but continuous research and technological development will facilitate the transition to a new era of a wearable and smart stethoscope.

Machine learning-based survival rate prediction of Korean hepatocellular carcinoma patients using multi-center data.

AIM: To predict survival time of Korean hepatocellular carcinoma (HCC) patients using multi-center data as a foundation for the development of a predictive artificial intelligence model according to treatment methods based on machine learning. METHODS: Data of patients who underwent treatment for HCC from 2008 to 2015 was provided by Korean Liver Cancer Study Group and Korea Central Cancer Registry. A total of 10,742 patients with HCC were divided into two groups, with Group I (2920 patients) confirmed on biopsy and Group II (5562 patients) diagnosed as HCC according to HCC diagnostic criteria as outlined in Korean Liver Cancer Association guidelines. The data were modeled according to features of patient clinical characteristics. Features effective in predicting survival rate were analyzed retrospectively. Various machine learning methods were used. RESULTS: Target was overall survival time, which divided into approximately 60 months (= /< 60 m, > 60 m). Target distribution in Group I (total 514 samples) was 28.8%: (148 samples) less than 60 months, 71.2% (366 samples) greater than 60 months, and in Group II (total 757 samples) was 66.6% (504 samples) less than 60 months, 33.4% (253 samples) greater than 60 months. Using NG Boost method, its accuracy was 83%, precision 84%, sensitivity 95%, and F1 score 89% for more than 60 months survival time in Group I with surgical resection. Moreover, its accuracy was 79%, precision 82%, sensitivity 87%, and F1 score 84% for less than 60 months survival time in Group II with TACE. The feature importance with gain criterion indicated that pathology, portal vein invasion, surgery, metastasis, and needle biopsy features could be explained as important factors for prediction in case of biopsy (Group I). CONCLUSION: By developing a predictive model using machine learning algorithms to predict prognosis of HCC patients, it is possible to project optimized treatment by case according to liver function and tumor status.

Crossed Hemispheric Accumulation of ß-Amyloid and Tau Protein in a Patient With Typical Alzheimer Disease.

Amyloid (Aß) and tau proteins are pathologic hallmarks of Alzheimer disease (AD). It is well known that there is spatial disparity between Aß and tau protein deposition but, crossed hemispheric accumulation of these 2 proteins has not been reported. Here we report the case of a 76-year-old woman with typical AD who underwent amyloid positron emission tomography (PET) ([ 18 F]-florbetaben) and tau PET scans ([ 18 F]PI-2620), revealing crossed accumulation of Aß and tau in the cerebral hemisphere. A neuropsychological assessment showed impairment in memory with spared activities of daily living. In the PET analysis, amyloid deposition was observed only in the left side of the cerebral hemisphere and tau only in the right side. Neuroimaging follow-up indicated that the spatial pattern of these protein accumulations had not changed. This case suggests the possibility of independent Aß and tau pathogenic pathways in AD.

Application of material flow analysis for plastic waste management in the Republic of Korea.

The indiscriminate use of plastics and careless management of plastic waste have caused serious environmental challenges globally. The Republic of Korea (ROK) aims to address the issue by reducing plastic waste generation by up to 50%, and increasing recycling rate by up to 70%, by 2030. To determine the status and future directions for plastic waste management in the ROK, the present study undertook two tasks: (i) a material flow analysis of plastic waste material from industrial sectors to assess the current status of plastic waste recycling and treatment, (ii) an analysis of the material flow of plastic waste based on the "Waste Classification Code." According to the findings, 6.202 million metric tons of plastic waste were generated in 2018, out of which 69%, 25%, and 0.5% was recycled, incinerated, and landfilled, respectively. The recycling rate of synthetic resin waste, which accounts for 96% of synthetic waste polymers discharged in the industrial sector, was 69%, which is a very high rate. However, the closed-loop recycling rate was only 33%. Therefore, the system of management of synthetic resin waste discharge without classification of raw materials should be improved to increase the closed-loop recycling rate of synthetic waste polymers. Furthermore, to increase the closed-loop recycling rate, we suggest the subdivision of synthetic resin waste (51-03-01) in plastic waste classification to improve the discharge separation system, which has been mismanaged. Furthermore, we suggest the formulation of a new management strategy for plastic waste, in accordance with those of other hazardous substances, as regulated by the Waste Control Act.

Respiratory sound classification for crackles, wheezes, and rhonchi in the clinical field using deep learning.

Auscultation has been essential part of the physical examination; this is non-invasive, real-time, and very informative. Detection of abnormal respiratory sounds with a stethoscope is important in diagnosing respiratory diseases and providing first aid. However, accurate interpretation of respiratory sounds requires clinician's considerable expertise, so trainees such as interns and residents sometimes misidentify respiratory sounds. To overcome such limitations, we tried to develop an automated classification of breath sounds. We utilized deep learning convolutional neural network (CNN) to categorize 1918 respiratory sounds (normal, crackles, wheezes, rhonchi) recorded in the clinical setting. We developed the predictive model for respiratory sound classification combining pretrained image feature extractor of series, respiratory sound, and CNN classifier. It detected abnormal sounds with an accuracy of 86.5% and the area under the ROC curve (AUC) of 0.93. It further classified abnormal lung sounds into crackles, wheezes, or rhonchi with an overall accuracy of 85.7% and a mean AUC of 0.92. On the other hand, as a result of respiratory sound classification by different groups showed varying degree in terms of accuracy; the overall accuracies were 60.3% for medical students, 53.4% for interns, 68.8% for residents, and 80.1% for fellows. Our deep learning-based classification would be able to complement the inaccuracies of clinicians' auscultation, and it may aid in the rapid diagnosis and appropriate treatment of respiratory diseases.

False Memory and Alzheimer's Disease Pathology in Patients with Amnestic Mild Cognitive Impairment: A Study with Amyloid PET.

INTRODUCTION: False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer's disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer's disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination. METHODS: Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into "with" and "without ADP" groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve. RESULTS: Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated "low" to "moderate" in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5. CONCLUSION: Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome.

INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Early Impairment in the Ventral Visual Pathway Can Predict Conversion to Dementia in Patients With Amyloid-negative Amnestic Mild Cognitive Impairment.

BACKGROUND: Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition. OBJECT: We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI. METHODS: This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans. RESULTS: During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole. CONCLUSION: Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population.

The relationship of soluble TREM2 to other biomarkers of sporadic Alzheimer's disease.

Microglial activation is a central player in the pathophysiology of Alzheimer's disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.

Identification of Novel FNIN2 and FNIN3 Fibronectin-Derived Peptides That Promote Cell Adhesion, Proliferation and Differentiation in Primary Cells and Stem Cells.

In recent years, a major rise in the demand for biotherapeutic drugs has centered on enhancing the quality and efficacy of cell culture and developing new cell culture techniques. Here, we report fibronectin (FN) derived, novel peptides fibronectin-based intergrin binding peptide (FNIN)2 (18-mer) and FNIN3 (20-mer) which promote cell adhesion proliferation, and the differentiation of primary cells and stem cells. FNIN2 and 3 were designed based on the in silico interaction studies between FN and its receptors (integrin α5ß1, αvß3, and αIIbß3). Analysis of the proliferation of seventeen-cell types showed that the effects of FNINs depend on their concentration and the existence of expressed integrins. Significant rhodamine-labeled FNIN2 fluorescence on the membranes of HeLa, HepG2, A498, and Du145 cells confirmed physical binding. Double coating with FNIN2 or 3 after polymerized dopamine (pDa) or polymerized tannic acid (pTA) precoating increased HBEpIC cell proliferation by 30-40 percent, suggesting FNINs potently affect primary cells. Furthermore, the proliferation of C2C12 myoblasts and human mesenchymal stem cells (MSCs) treated with FNINs was significantly increased in 2D/3D culture. FNINs also promoted MSC differentiation into osteoblasts. The results of this study offer a new approach to the production of core materials (e.g., cell culture medium components, scaffolds) for cell culture.

Inelastic Responses and Finite Element Predictions of Fiber Cementitious Composite and Concrete Columns.

In this research, reinforced concrete (RC) and strain-hardening cementitious composite (SHCC) columns subjected to lateral loads combined with a constant load were investigated, both by experiments and predictions, with two distributed inelastic finite element models established by the stiffness and flexibility formulations. SHCC applied in the column plastic hinge region could not only enhance the lateral load and displacement capacities of columns but also offer effective advantages in the control of bending and shear cracks induced by multiple microcracks, the prevention of the spalling of cover concrete, and the resistance to buckling of steel bars. With the layered cross-sectional approach using constitutive laws of SHCC considering a proposed model of the post-cracked high-ductile tensile characteristics, as well as concrete and reinforcing steel bars, an inelastic beam-column finite element model was presented with a distributed flexibility formulation. In comparison with experiments concerning the RC and reinforced strain-hardening cementitious composite (R-SHCC) columns, the current flexibility method showed relatively accurate estimations in the lateral load and displacement responses of column systems as well as in localized nonlinear responses of cross-section as estimated in axial strains of longitudinal reinforcing steel bars. In comparison with the stiffness method, the current flexibility method gave more accurate solutions at both element and structural levels, as manifested in the experiments and analysis solutions.

The cerebellum could serve as a potential imaging biomarker of dementia conversion in patients with amyloid-negative amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: As part of network-specific neurodegeneration, changes in cerebellar gray matter (GM) volume and impaired cerebello-cerebral functional networks have been reported in Alzheimer disease (AD). Compared with healthy controls, a volume loss in the cerebellum has been observed in patients with continuum of AD. However, little is known about the anatomical or functional changes in patients with clinical AD but no brain amyloidosis. We aimed to identify the relationship between cerebellar volume and dementia conversion of amyloid-negative mild cognitive impairment (MCI). METHODS: This study was a retrospective cohort study of patients over the age 50 years with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36-month follow-up period. All subjects underwent detailed neuropsychological tests, 3 T brain magnetic resonance imaging scans including three-dimensional T1 imaging, and fluorine-18[F18 ]-florbetaben amyloid positron emission tomography scans. A spatially unbiased atlas template of the cerebellum and brainstem was used for analyzing cerebellar GM volume. RESULTS: During the 36 months of follow-up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairments in all visual memory tasks. In terms of volumetric analysis, reduced crus I/II volume adjusted with total intracranial volume, and age was observed in the converter group. CONCLUSIONS: Significant cerebellar GM atrophy involving the bilateral crus I/II may be a novel imaging biomarker for predicting dementia progression in amyloid-negative amnestic MCI patients.