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Variants in cis-regulatory elements link the noncoding genome to human pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS), enhances noncoding variant analysis by integrating both whole-genome sequencing (WGS) and user-provided functional data. With simplified parameter settings and an efficient multiple testing correction method, CWAS-Plus conducts the CWAS workflow 50 times faster than CWAS, making it more accessible and user-friendly for researchers. Here, we used a single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type-specific enhancers and promoters. Examining autism spectrum disorder WGS data (n = 7280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimer's disease WGS data (n = 1087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Plus's utility in genomic disorders and scalability for processing large-scale WGS data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively.
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Secuenciación Completa del Genoma , Humanos , Secuenciación Completa del Genoma/métodos , Enfermedad de Alzheimer/genética , Estudio de Asociación del Genoma Completo/métodos , Trastorno del Espectro Autista/genética , Variación Genética , Programas Informáticos , Cromatina/genética , Cromatina/metabolismo , Genoma HumanoRESUMEN
The implementation of polymer-based Li-metal batteries is hindered by their low coulombic efficiency and poor cycling stability attributed to continuous electrolyte decomposition. Enhancement of the solid electrolyte interface (SEI) stability is key to mitigating electrolyte decomposition. This study proposes surface-functionalized silica mesoball fillers to fabricate a composite polymer electrolyte (MSBM-CPE). As a result of surface modification, the polyethylene oxide matrix benefits from the uniform distribution of the filler, which provides a large surface area and Lewis acid sites. Molecular dynamics simulations reveal that the dissociation energy of lithium bis(trifluoromethanesulfonyl)imide in the filler is fourfold higher (-1.95 eV) than that of the filler-free electrolyte. Consequently, the MSMB-CPE diffusivity is 30 times higher than its filler-free counterpart. The MSMB-CPE of ionic conductivity of 1.16 × 10-2 S cm-1 @60 °C and a venerable Li-ion transference number of 0.81. The excellent compatibility of MSMB-CPE with the Li anode is demonstrated by its stable symmetric cell performance under high current density (200 µA cm-2 @60 °C) for over 5000 h. Approximately 85.60% retention capacity of the [Li/MSMB-CPE/LiFePO4] full cell after 700 cycles. Furthermore, compositional analysis reveals that the SEI layer in MSMB-CPE is smooth with fewer by-products at the electrolyte/Li interface.
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Osteogenesis imperfecta (OI) is the most common inherited form of bone fragility and includes a heterogeneous group of genetic disorders that most commonly result from defects associated with type I collagen. Although genetic analyses have been developed, nationwide research on the incidence and associated fractures in OI is lacking. This study aimed to investigate the patterns of OI prevalence, incidence, fracture rate, etc. in South Korea using National Health Insurance Service (NHIS) claims data. We found 1596 patients newly diagnosed with OI between March 2002 and February 2020. We evaluated the incidence, prevalence, and history of fractures, fracture site, prescription of anti-osteoporosis drugs, etc. To compare medical costs, fracture rates, and scoliosis rates, we created a control group comprising patients without OI using 1:1 propensity score matching. The prevalence of OI increased slightly each year, with an annual incidence of 20.20 per 100,000 live births. Mean fracture frequency in OI patients was 17 (2-32) times per patient and the most frequent fracture site was the lower leg. A total of 21.4% patients were prescribed anti-osteoporosis drugs, and the most popular drug was pamidronate. After 1:1 propensity score matching, in terms of scoliosis, OI patients had a 3.91 times higher prevalence of scoliosis than in healthy patients which was statistically significant. The sum of medical care expenses for patients with OI was 3.5 times higher than that for patients without OI. We identified nationwide trends in OI occurrence, fractures, and medication use. This study also highlighted the real-world data of scoliosis and medical costs compared to the control group.
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OBJECTIVE: To investigate whether a deep learning (DL) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE) technique can improve image quality, lesion conspicuity, and lesion detection compared to a standard CAIPIRINHA-VIBE technique in gadoxetic acid-enhanced liver MRI. METHODS: This retrospective single-center study included 168 patients who underwent gadoxetic acid-enhanced liver MRI at 3 T using both standard CAIPIRINHA-VIBE and DL CAIPIRINHA-VIBE techniques on pre-contrast and hepatobiliary phase (HBP) images. Additionally, high-resolution (HR) DL CAIPIRINHA-VIBE was obtained with 1-mm slice thickness on the HBP. Three abdominal radiologists independently assessed the image quality and lesion conspicuity of pre-contrast and HBP images. Statistical analyses involved the Wilcoxon signed-rank test for image quality assessment and the generalized estimation equation for lesion conspicuity and detection evaluation. RESULTS: DL and HR-DL CAIPIRINHA-VIBE demonstrated significantly improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE (p < 0.001), with a shorter acquisition time (DL vs standard, 11 s vs 17 s). However, the former presented a more synthetic appearance (both p < 0.05). HR-DL CAIPIRINHA-VIBE showed superior lesion conspicuity to standard and DL CAIPIRINHA-VIBE on HBP images (p < 0.001). Moreover, HR-DL CAIPIRINHA-VIBE exhibited a significantly higher detection rate of small (< 2 cm) solid focal liver lesions (FLLs) on HBP images compared to standard CAIPIRINHA-VIBE (92.5% vs 87.4%; odds ratio = 1.83; p = 0.036). CONCLUSION: DL and HR-DL CAIPIRINHA-VIBE achieved superior image quality compared to standard CAIPIRINHA-VIBE. Additionally, HR-DL CAIPIRINHA-VIBE improved the lesion conspicuity and detection of small solid FLLs. DL and HR-DL CAIPIRINHA-VIBE hold the potential clinical utility for gadoxetic acid-enhanced liver MRI. CLINICAL RELEVANCE STATEMENT: DL and HR-DL CAIPIRINHA-VIBE hold promise as potential alternatives to standard CAIPIRINHA-VIBE in routine clinical liver MRI, improving the image quality and lesion conspicuity, enhancing the detection of small (< 2 cm) solid focal liver lesions, and reducing the acquisition time. KEY POINTS: ⢠DL and HR-DL CAIPIRINHA-VIBE demonstrated improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE, in addition to a shorter acquisition time. ⢠DL and HR-DL CAIPIRINHA-VIBE yielded a more synthetic appearance than standard CAIPIRINHA-VIBE. ⢠HR-DL CAIPIRINHA-VIBE showed improved lesion conspicuity than standard CAIPIRINHA-VIBE on HBP images, with a higher detection of small (< 2 cm) solid focal liver lesions.
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Radiofrequency ablation (RFA) offers a minimally invasive treatment for small hepatocellular carcinoma (HCC), but it faces challenges such as high local recurrence rates. This prospective study, conducted from January 2020 to July 2022, evaluated a novel approach using a three-channel, dual radiofrequency (RF) generator with separable clustered electrodes to improve RFA's efficacy and safety. The study employed a high-power, gradual, stepwise RFA method on HCCs (≤ 4 cm), utilizing real-time ultrasound-computed tomography (CT)/magnetic resonance imaging (MRI) fusion imaging. Involving 110 participants with 116 HCCs, the study reported no major complications. Local tumor progression (LTP) and intrahepatic remote recurrence (IRR) rates were low, with promising cumulative incidences at 1, 2, and 3 years for LTP (0.9%, 3.6%, 7.0%) and IRR (13.9%, 20.5%, 31.4%). Recurrence-free survival (RFS) rates were similarly encouraging: LTP (99.1%, 96.4%, 93.0%) and IRR (86.1%, 79.5%, 68.6%). This innovative gradual, incremental high-power RFA technique, featuring a dual switching monopolar mode and three electrodes, represents an effective and safer management option for small HCCs. TRIAL REGISTRATION: clinicaltrial.gov identifier: NCT05397860, first registered on 26/05/2022.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Ablación por Radiofrecuencia , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico por imagen , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Ablación por Radiofrecuencia/métodos , Electrodos , Imagen por Resonancia Magnética , Adulto , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Progresión de la Enfermedad , Anciano de 80 o más Años , Ablación por Catéter/métodosRESUMEN
BACKGROUND: Post-treatment evaluation of patients with rectal cancer (RC) using magnetic resonance imaging (MRI) burdens medical resources, necessitating an exploration of abbreviated protocols. PURPOSE: To evaluate the diagnostic performance of abbreviated MRI (A-MRI) for the post-treatment evaluation of RC patients. MATERIAL AND METHODS: This retrospective study included RC patients who underwent non-contrast rectal MRI and standard liver MRI, as well as abdominal contrast-enhanced computed tomography (CECT) for post-treatment evaluation. A-MRI comprised diffusion-weighted imaging (DWI) and T2-weighted imaging of the upper abdomen and the pelvic cavity. Three radiologists independently reviewed A-MRI, CECT, and standard liver MRI in the detection of viable disease. The diagnostic performances were compared using a reference standard considering all available information, including pathology, FDG-PET, endoscopic results, and clinical follow-up. RESULTS: We included 78 patients (50 men, 28 women; mean age=60.9 ± 10.2 years) and observed viable disease in 34 (43.6%). On a per-patient-basis analysis, A-MRI showed significantly higher sensitivity (95% vs. 81%, P = 0.04) and higher accuracy (93% vs. 82%, P < 0.01), compared to those of CECT, while A-MRI showed comparable sensitivity (91% vs. 91%, P = 0.42) and accuracy (97% vs. 98%, P = 0.06) to that of standard liver MRI. On a per-lesion-based analysis, A-MRI exhibited significantly superior lesion detectability than that of CECT (figure of merit 0.91 vs. 0.77, P < 0.01) and comparable to that of standard liver MRI (figure of merit 0.91 vs. 0.92, P = 0.75). CONCLUSION: A-MRI exhibited higher sensitivity and diagnostic accuracy than those of CECT in the post-treatment evaluation of RC, while it showed comparable performances with standard liver MRI. A-MRI provides diagnostic added value in the follow-up of RC patients.
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Imagen por Resonancia Magnética , Neoplasias del Recto , Sensibilidad y Especificidad , Humanos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Medios de Contraste , Anciano , Reproducibilidad de los Resultados , Recto/diagnóstico por imagenRESUMEN
BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.
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Enfermedad Hepática en Estado Terminal , Accidente Cerebrovascular Hemorrágico , Aneurisma Intracraneal , Trasplante de Hígado , Accidente Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/cirugía , Accidente Cerebrovascular Hemorrágico/complicaciones , Trasplante de Hígado/efectos adversos , Amoníaco , Enfermedad Hepática en Estado Terminal/complicaciones , Índice de Severidad de la Enfermedad , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/etiología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.
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Trastorno del Espectro Autista , Repeticiones de Microsatélite , Humanos , Trastorno del Espectro Autista/genética , Repeticiones de Microsatélite/genética , Masculino , Femenino , Corteza Cerebral/patología , Fenotipo , Niño , Secuenciación Completa del Genoma , Aprendizaje Profundo , Índice de Severidad de la Enfermedad , Adulto , Expansión de las Repeticiones de ADN/genéticaRESUMEN
Additive manufacturing, or 3D printing, is quickly becoming a widespread manufacturing method offering timely and cost-effective build times for unique part geometries with an increasing range of material offerings. One unique use for additive manufacturing is constructing the housing for reference solar cells, which are crucial instruments for evaluating the electrical performance of photovoltaic solar cells and modules. These instruments, which require good thermal conduction, are costly to manufacture because they are usually machined from aluminum using precision milling machines. In this work, we set out to evaluate several presently available additive manufacturing materials for their thermal properties when used to house reference solar cells. We fabricated several types of reference cell instruments with a tabletop, filament-based 3D printer using polylactic acid (PLA) and composite PLA/metal materials with different infill percentages. Furthermore, we fabricated several all-metal 3D printed reference cells using a binder jet printed stainless steel-bronze material blend and compared the thermal properties of all 3D printed instruments against a standard aluminum housing reference cell. Measurements included temperature monitoring of an embedded thermocouple sensor on an isothermal plate under the ambient environment and when exposed to high irradiation under a solar simulator. Current vs voltage measurements were also taken under the solar simulator and the open circuit voltage results were used to verify the actual silicon cell temperature. Our findings indicate that the stainless steel-bronze option can function well as an alternative to traditional aluminum-based housings, while the lower-cost metal-PLA composite can only be used under indoor light spectra or when used in a flash-type solar simulator when the instrument is not exposed to excessive radiation and heat.
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Background and Objectives: The older members of a population might experience unmet medical needs, despite desiring medical care due to activity limitations driven by their perception of aging. This study conducted a cross-sectional analysis of the association between perceived activity restriction (PAR) due to people's own perception of aging and unmet medical needs (UMN) in late middle-aged and older Koreans based on the Korean National Health and Nutrition Examination Survey (KNHANES). Materials and Methods: The 2016-2020 KNHANES was used to analyze a total of 2008 participants among groups aged 45 years or older by applying individual weights imposed from the raw data. The independent variable of PAR was assessed using self-reported questionnaires based on the global activity limitation indicator. Also, the dependent variable of UMN, referring to the state in which a patient's medical care or service was insufficient, inadequate, or lacking, was assessed using a single question. After excluding missing values, the data on 2008 individuals were analyzed using a chi-square test, weighted logistic regression, and a stratified analysis of gender, age, and the presence of chronic illnesses. Results: The group that experienced PAR had an OR 2.13 higher (odds ratio [OR]: 2.13; 95% confidence interval [CI]: 1.27-3.56) to present UMN than the group that did not experience PAR. Furthermore, the results of the stratified analysis indicated that, in the group of female participants with chronic illness and in the group of elderly people, experiencing PAR was associated with a higher experience of UMN. Conclusions: There was a close association between PAR and UMN. In particular, when PAR occurred in the group of female participants with chronic illness and in the group of elderly people, the incidence rate of UMN was also found to be high. This finding highlights the need for policies and institutional measures to reduce UMN within vulnerable groups with an increased risk of medical inaccessibility due to activity restriction.
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Envejecimiento , Percepción , Anciano , Persona de Mediana Edad , Humanos , Femenino , Estudios Transversales , Encuestas Nutricionales , Enfermedad CrónicaRESUMEN
BACKGROUND: Social isolation (SI) was recently identified as a significant public health issue in the United States. Consequently, several studies on the association between SI and mental health were conducted. However, few studies have considered the duration and intensity of SI. In the present study, a longitudinal analysis was conducted to determine the effect of the intensity of persistent SI on the mental health status of late middle-aged and older Koreans. METHODS: After excluding missing values, data on 6200 participants were analyzed using the group-based trajectory model (GBTM) from the first to fifth Korean Longitudinal Study of Ageing (KLoSA) to categorise the SI trajectory (SIT). The Chi-square test, t-test, analysis of variance, and time-lagged generalised estimation equations were utilised from the fifth to eighth KLoSA to determine the association between SIT and the incidence of cognitive decline (the group with a Korean version Mini-Mental State Examination score of 23 or lower), cognitive function score, and depression score. RESULTS: Four SIT groups were identified in the GBTM analysis. These were the non-SIT (21.7%), mild (46.8%), moderate (21.1%), and severe SIT (10.4%) groups. Compared to the non-SIT group, the severe SIT group experienced a greater incidence of cognitive decline (odds ratio = 1.57, P < 0.0001) as well as poorer cognitive function scores (B = -0.63, P < 0.0001) and depression scores (B = 0.90, P < 0.0001). Furthermore, stratified analysis by sex and age showed that mental health status was inversely proportionate to the intensity of SIT, particularly in males and patients, aged 65 years and above. CONCLUSION: A close association was observed between SIT and mental health. This finding highlighted the need for policies and institutional measures to reduce the incidence of mental health deterioration among vulnerable groups due to the intensity of SI.
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Salud Mental , Aislamiento Social , Masculino , Humanos , Persona de Mediana Edad , Anciano , Estudios Longitudinales , Envejecimiento , República de Corea/epidemiologíaRESUMEN
Australian Mandarin-English bilingual preschoolers must acquire linguistic structures that occur only in the community language (e.g., English inflectional grammar). This study investigated how they acquire such structures and any relationship between linguistic knowledge and language experience on their performance. Twenty 4-6-year-olds showed known monolingual acquisition patterns with good performance for producing the progressive, developing ability for plurals, but only emerging ability for past and present tense. Better performance was related to a larger English vocabulary, more mixed language input and use, but less Mandarin input and use. On average, these children received less than 50% input in English and were performing behind monolinguals.
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OBJECTIVES: Through the use of FDA adverse event reporting system (FAERS) dataset, this study analyzes the pattern of time-to-event (TTE) for drugs and adverse events, and suggest ways to identify candidate late-onset events for monitoring. METHODS: The duration between administration date of the drug and the onset of adverse events was explored with using FAERS data from 2012-2021. The fold change of proportional reporting ratios or reporting odds ratios were calculated to identify enriched events in the later period and to suggest the late-onset events for further monitoring. To compare the findings, we used the claims database of the Korean National Health Insurance Service (NHIS). RESULTS: A total of 1,426,781 reports were included. The median TTE was 10 days (interquartile range [IQR]: 0-98 days), with 11.5% (n = 164,093) reporting events that occurred at least one year after administration. TTE and fold change analysis captured historical cases of late-onset events, while generating an additional less-explored list of events. The results for tumor necrosis factor (TNF) inhibitors were compared using the NHIS dataset. CONCLUSION: Our study provides a comprehensive analysis of the FAERS dataset, focusing on TTE data. Periodic summarization of reports would be helpful in monitoring the late-onset events.
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Remedial actions for groundwater contamination such as containment, in-situ remediation, and pump-and-treat have been developed. This study investigates the hydraulic containment of Trichloroethylene (TCE) contaminated groundwater by using pulsed pump-and-treat technology. The hypothetical research site assumed the operation of pulsed pump-and-treat to manage groundwater contaminated with 0.1 mg/L of TCE. at the pump-and-treat facility. Numerical models, employing MODFLOW and MT3DMS for groundwater flow and contamination simulations, were used for case studies to evaluate the performance and risks of pump-and-treat operation strategies. Evaluation criteria included capture width, removal efficiency, and contaminant leakage. Health risks from TCE leakage were assessed using a vapor intrusion risk assessment tool in adjacent areas. In the facility-scale case study, the capture width of the pump-and-treat was controlled by pumping/injection well operations, including schedules and rates. Pumping/injection well configurations impacted facility efficiencies. Pulsed operation led to TCE leakage downstream. Site-scale case studies simulated contaminant transport through pump-and-treat considering various operation stages (continuous; pulsed), as well as various reactions of TCE in subsurface environment (non-reactive; sorption; sorption and biodegradation). Assuming non-reactive tracer, TCE in groundwater was effectively blocked during continuous operation stage but released downstream in the following pulsed operation stage. Considering chemical reactions, the influences of the pump-and-treat operation followed similar trends of the non-reactive tracer but occurred at delayed times. Groundwater contamination levels were reduced through biodegradation. Cancer and non-cancer risks could occur at points of exposure (POEs) where the contamination levels approached or fell below TCE groundwater standards.
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Agua Subterránea , Tricloroetileno , Contaminantes Químicos del Agua , Tricloroetileno/metabolismo , Contaminantes Químicos del Agua/análisis , Gases , Biodegradación AmbientalRESUMEN
Motor skill repertoire can be stably retained over long periods, but the neural mechanism underlying stable memory storage remains poorly understood. Moreover, it is unknown how existing motor memories are maintained as new motor skills are continuously acquired. Here we tracked neural representation of learned actions throughout a significant portion of a mouse's lifespan, and we show that learned actions are stably retained in motor memory in combination with context, which protects existing memories from erasure during new motor learning. We used automated home-cage training to establish a continual learning paradigm in which mice learned to perform directional licking in different task contexts. We combined this paradigm with chronic two-photon imaging of motor cortex activity for up to 6 months. Within the same task context, activity driving directional licking was stable over time with little representational drift. When learning new task contexts, new preparatory activity emerged to drive the same licking actions. Learning created parallel new motor memories while retaining the previous memories. Re-learning to make the same actions in the previous task context re-activated the previous preparatory activity, even months later. At the same time, continual learning of new task contexts kept creating new preparatory activity patterns. Context-specific memories, as we observed in the motor system, may provide a solution for stable memory storage throughout continual learning. Learning in new contexts produces parallel new representations instead of modifying existing representations, thus protecting existing motor repertoire from erasure.
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OBJECTIVES: The aim of this study was to analyze the relationship between objective social isolation (SI) and unmet medical needs (UMN) in adults aged 19 and older. METHODS: A cross-sectional analysis was conducted of 208 619 adults aged 19 and older, excluding missing data, using the 2019 Korea Community Health Survey. To analyze the association between objective SI and UMN, the chi-square test and logistic regression analysis were performed. RESULTS: The prevalence of UMN was 1.14 times higher (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06 to 1.23) among those with SI than among those without SI, and the OR for groups with 5 SI types was 2.77 (95% CI, 1.86 to 4.12) compared to those with no SI types. In addition, a stratified analysis by age group showed that the association between SI and UMN existed even in groups under 64 years old. However, among those aged 65 and older, SI was associated with an OR of 1.53 (95% CI, 1.37 to 1.71) for UMN compared to non-SI. As the number of SI types increased, the prevalence of UMN also increased, indicating a strong association between SI and UMN in older adults. CONCLUSIONS: This study found that individuals with SI experienced UMN due to fear and anxiety about interpersonal relationships. Therefore, based on the results of this cross-sectional study, it is necessary to investigate the causal relationship between SI and UMN through future longitudinal data.
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Aislamiento Social , Humanos , Estudios Transversales , Persona de Mediana Edad , República de Corea/epidemiología , Aislamiento Social/psicología , Femenino , Adulto , Masculino , Anciano , Adulto Joven , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Prevalencia , Modelos Logísticos , Anciano de 80 o más Años , Encuestas EpidemiológicasRESUMEN
Zeolite is a versatile and effective reactive material used in permeable reactive barriers (PRBs) for remediating groundwater contaminated with heavy metals. In this study, we evaluated the influence of subsurface environmental conditions, namely contamination level (C0) and groundwater velocity (v), on predicting the longevity of zeolite for cadmium (Cd) removal. Batch experiments were performed to investigate the effect of C0 on Cd removal, and column experiments were performed to examine how Cd transportation through zeolite varies at different C0 and v. Breakthrough curves (BTCs) were analyzed with an advection-dispersion equation (ADE) coupled with nonequilibrium sorption rate models. The reaction parameters indicating the performance metrics of zeolite were determined using an iterative fitting approach-retardation factor (R), partitioning coefficient (ß), and mass transfer coefficient (ω). R exhibited dependence on C0, but was unrelated to v; its rapid increase at lower C0 was explained by Langmuir sorption isotherms. ß and ω, integral to sorption dynamics and mass transfer, respectively, showcased functional relationships with v. ß decreased gradually as v increased, described by the nonequilibrium sorption model, whereas ω increased steadily with v, guided by the Monod function. Using the relationship of these parameters, the fate and transport of Cd within zeolite was simulated under various subsurface environmental conditions to construct the longevity prediction function. Thus, this study introduces a method for predicting the longevity of reactive materials, which can be valuable for designing PRBs with high longevity in the future.
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Agua Subterránea , Contaminantes Químicos del Agua , Zeolitas , Cadmio , Contaminantes Químicos del Agua/análisis , AdsorciónRESUMEN
This study explores the relationship between landscape features and avian diversity in South Korea, examining both taxonomic and functional diversity. The Korean Peninsula serves as a pivotal habitat for resident bird species and a migratory pathway in the East Asia-Pacific flyway. Using a national dataset with block sizes ranging from 3.5 to 4.5 kilometers per side, we found that less urbanized open plains exhibit higher taxonomic diversity, while coastal regions with diverse water bird populations show higher functional diversity. These findings underscore the significance of conserving the existing land types and qualities in specific regions to substantially impact bird distribution and regional biodiversity. Remarkably, closed forests display diversity patterns akin to urban/built-up areas, despite their disparate land use characteristics. The stability of bird diversity indices across different land use types enables us to predict bird diversity indices based on the particular land use and land cover configurations. This study emphasizes the complementary nature of functional biodiversity indices in comprehending bird distribution patterns alongside taxonomic diversity indices.
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Biodiversidad , Aves , Animales , República de Corea , Conservación de los Recursos Naturales , Ecosistema , BosquesRESUMEN
Background: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of East Asian herbal medicine (HM) for iron deficiency anemia (IDA) in children and adolescents. Methods: Twelve electronic databases were searched in 28 May 2023 for randomized controlled trials (RCTs) evaluating the efficacy of HM in children with IDA. The primary outcome measures for treatment included blood hemoglobin and serum ferritin levels, whereas the secondary outcomes included the total effective rate (TER), incidence of adverse events (AEs), average healing time, and hematologic indicators related to IDA. Meta-analysis was performed using Review Manager 5.4 and R studio 4.3 software, and subgroup analyses were performed according to the different groups (type of intervention and duration of treatment). The effect size measures used were the risk ratio, mean difference, and standardized mean difference with 95% confidence intervals. The risk of bias was assessed using a revised Cochrane risk of bias tool for randomized trials, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tools. Results: The meta-analysis included 28 studies. Five studies compared the efficacy of HM alone with that of oral iron alone, whereas 23 compared the efficacy of a combination of HM and oral iron with that of oral iron alone. The meta-analysis revealed that the HM treatment group showed significant improvements in all outcome measures compared to those observed in the oral iron group. Moreover, HM significantly reduced the incidence of gastrointestinal AE, compared to that associated with oral iron. Among the 28 studies, the most commonly used HM prescription was Xingpi Yanger Granules, and the most commonly used botanical drug was Astragali Radix, followed by Atractylodis Rhizoma Alba and Angelicae Sinensis Radix. Conclusion: This meta-analysis identified evidence of the efficacy and safety of HM in children with IDA. Compared to conventional oral iron therapy, HM improved IDA-related blood markers and TER, with fewer AEs and shorter mean healing times. However, further well-designed, large-scale clinical trials are necessary to strengthen the evidence of the efficacy and safety of botanical drugs. Systematic Review Registration: PROSPERO 2022 CRD42022334670. (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022334670).
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Objective: This study aimed to assess the potential of PARP inhibitors to prevent cardiotoxicity. Methods: First, a re-analysis and update of a previously published study was conducted. Additional searches were conducted of the PubMed and Cochrane Central Register of Controlled Trials databases on 2 June 2023. After the selection process, the pooled odds ratio (OR) for cardiac adverse events (AEs) was calculated. Second, the FAERS database was examined for 10 frequently co-administered anticancer agents. The reporting odds ratio (ROR) was calculated based on the occurrence of cardiac AEs depending on the co-administration of PARP inhibitors. Results: Seven studies were selected for the meta-analysis. Although not statistically significant, co-administration of PARP inhibitors with chemotherapy/bevacizumab decreased the risk of cardiac AEs (Peto OR = 0.61; p = 0.36), while co-administration with antiandrogens increased the risk of cardiac AEs (Peto OR = 1.83; p = 0.18). A total of 19 cases of cardiac AEs were reported with co-administration of PARP inhibitors in the FAERS database. Co-administration of PARP inhibitors with chemotherapy/bevacizumab significantly decreased the risk of cardiac AEs (ROR = 0.352; 95% confidence interval (CI), 0.194-0.637). On the other hand, for antiandrogens co-administered with PARP inhibitors, the ROR was 3.496 (95% CI, 1.539-7.942). The ROR for immune checkpoint inhibitors co-administered with PARP inhibitors was 0.606 (95% CI, 0.151-2.432), indicating a non-significant effect on cardiac AEs. Conclusion: This study reports that PARP inhibitors show cardioprotective effects when used with conventional anticancer agents.