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Here we report SUPPORT (statistically unbiased prediction utilizing spatiotemporal information in imaging data), a self-supervised learning method for removing Poisson-Gaussian noise in voltage imaging data. SUPPORT is based on the insight that a pixel value in voltage imaging data is highly dependent on its spatiotemporal neighboring pixels, even when its temporally adjacent frames alone do not provide useful information for statistical prediction. Such dependency is captured and used by a convolutional neural network with a spatiotemporal blind spot to accurately denoise voltage imaging data in which the existence of the action potential in a time frame cannot be inferred by the information in other frames. Through simulations and experiments, we show that SUPPORT enables precise denoising of voltage imaging data and other types of microscopy image while preserving the underlying dynamics within the scene.
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Microscopía , Redes Neurales de la Computación , Relación Señal-Ruido , Distribución Normal , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole-exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age. Language developmental delay varied significantly from nonverbal to simple sentences, which plateaued in all patients. Patients with the best language outcomes typically managed 2-3-word sentences, corresponding to a developmental age of 2-3 years. Epilepsy developed in 77% of patients, with onset consistently following developmental delays at a median age of 31 months. Longitudinal EEG data revealed a shift from occipital to frontal epileptiform discharges with age, suggesting a correlation with synaptic maturation. These findings suggest that the critical developmental plateau occurs between the ages of 2 and 5 years and is potentially influenced by epilepsy. By analyzing longitudinal data, our study contributes to a deeper understanding of SYNGAP1-related DEE, provides potential EEG biomarkers, and underlines the importance of early diagnosis and intervention to address this complex disorder.
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Electroencefalografía , Epilepsia , Genotipo , Mutación , Fenotipo , Proteínas Activadoras de ras GTPasa , Preescolar , Femenino , Humanos , Masculino , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Discapacidades del Desarrollo/fisiopatología , Epilepsia/genética , Epilepsia/patología , Epilepsia/fisiopatología , Secuenciación del Exoma , Estudios de Asociación Genética , Estudios Longitudinales , Mutación/genética , Proteínas Activadoras de ras GTPasa/genética , Estudios RetrospectivosRESUMEN
Optogenetic techniques permit non-invasive, spatiotemporal, and reversible modulation of cellular activities. Here, we report a novel optogenetic regulatory system for insulin secretion in human pluripotent stem cell (hPSC)-derived pancreatic islet-like organoids using monSTIM1 (monster-opto-Stromal interaction molecule 1), an ultra-light-sensitive OptoSTIM1 variant. The monSTIM1 transgene was incorporated at the AAVS1 locus in human embryonic stem cells (hESCs) by CRISPR-Cas9-mediated genome editing. Not only were we able to elicit light-induced intracellular Ca2+ concentration ([Ca2+]i) transients from the resulting homozygous monSTIM1+/+-hESCs, but we also successfully differentiated them into pancreatic islet-like organoids (PIOs). Upon light stimulation, the ß-cells in these monSTIM1+/+-PIOs displayed reversible and reproducible [Ca2+]i transient dynamics. Furthermore, in response to photoexcitation, they secreted human insulin. Light-responsive insulin secretion was similarly observed in monSTIM1+/+-PIOs produced from neonatal diabetes (ND) patient-derived induced pluripotent stem cells (iPSCs). Under LED illumination, monSTIM1+/+-PIO-transplanted diabetic mice produced human c-peptide. Collectively, we developed a cellular model for the optogenetic control of insulin secretion using hPSCs, with the potential to be applied to the amelioration of hyperglycemic disorders.
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Diabetes Mellitus Experimental , Células Madre Pluripotentes Inducidas , Células Secretoras de Insulina , Islotes Pancreáticos , Células Madre Pluripotentes , Humanos , Ratones , Animales , Secreción de Insulina , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Islotes Pancreáticos/metabolismo , Células Madre Pluripotentes/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Organoides , Células Madre Pluripotentes Inducidas/metabolismo , Diferenciación CelularRESUMEN
In 2019, the National Evidence-based Healthcare Collaborating Agency (NECA) in Korea established a health technology reassessment (HTR) system to manage the life cycle of health technologies and develop operational measures promoting the efficient use of healthcare resources. The purpose of this study is to introduce the detailed implementation process and practical functional methods of the HTR implemented by NECA.The HTR is a structured multidisciplinary method for analyzing health technologies currently used in the healthcare system based on the latest information on parameters, such as clinical safety, effectiveness, and cost-effectiveness of optimizing the use of healthcare resources as well as social and ethical issues. All decision-making stages of the HTR are carefully reviewed and transparently managed. The HTR committee makes significant decisions, and the subcommittee decides the details related to the assessment process.Since the pilot began in 2018, 262 cases have been reassessed, of which, 126 cases (48.1 percent) were health services not covered by the National Health Insurance (NHI). Over the past 5 years, approximately 130 recommendations for the in-use technologies were determined by the HTR committee. In the near future, it will be necessary to officially develop and establish a Korean HTR system and a legal foundation to optimize the NHI system.
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Evaluación de la Tecnología Biomédica , Análisis Costo-Beneficio , Toma de Decisiones , Programas Nacionales de Salud/organización & administración , República de Corea , Evaluación de la Tecnología Biomédica/organización & administraciónRESUMEN
INTRODUCTION: Inpatients need to recognize their fall risk accurately and objectively. Nurses need to assess how patients perceive their fall risk and identify the factors that influence patients' fall risk perception. PURPOSE: This study aims to explore the congruency between nurses' fall risk assessment and patients' perception of fall risk and identify factors related to the non-congruency of fall risk. DESIGNS: A descriptive and cross-sectional design was used. The study enrolled 386 patients who were admitted to an acute care hospital. Six nurses assessed the participants' fall risk. Congruency was classified using the Morse Fall Scale for nurses and the Fall Risk Perception Questionnaire for patients. FINDINGS: The nurses' fall risk assessments and patients' fall risk perceptions were congruent in 57% of the participants. Underestimation of the patient's risk of falling was associated with gender (women), long hospitalization period, department (orthopedics), low fall efficacy, and history of falls before hospitalization. Overestimation of fall risk was associated with age group, gender (men), department, and a high health literacy score. In the multiple logistic regression, the factors related to the underestimation of fall risk were hospitalization period and department, and the factors related to the overestimation of fall risk were health literacy and department. CONCLUSIONS: Nurses should consider the patient's perception of fall risk and incorporate it into fall prevention interventions. CLINICAL RELEVANCE: Nurses need to evaluate whether patients perceive the risk of falling consistently. For patients who underestimate or overestimate their fall risk, it may be helpful to consider clinical and fall-related characteristics together when evaluating their perception of fall risk.
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Accidentes por Caídas , Humanos , Accidentes por Caídas/prevención & control , Accidentes por Caídas/estadística & datos numéricos , Femenino , Masculino , Estudios Transversales , Medición de Riesgo , Persona de Mediana Edad , Anciano , Adulto , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/psicología , Personal de Enfermería en Hospital/estadística & datos numéricos , Pacientes Internos/psicología , Pacientes Internos/estadística & datos numéricos , Anciano de 80 o más Años , PercepciónRESUMEN
An environmentally friendly oxidation system has proposed for the practical and scalable production of value-added 2,5-furandicarboxylic acid from 1â kg of 5-hydroxymethylfurfural. The system is composed of a simple base, oxygen, and a green solvent, thereby providing a sustainable and economical approach to organic synthesis. To gain insight into the mechanism of this oxidation process, NMR spectroscopic analysis and kinetic study are used for the mechanistic investigation of this environmentally friendly oxidation process.
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Cationic amphipathic structures are often utilized in natural membrane-active host-defense peptides. Negatively charged surface membranes of rapidly proliferating bacterial and cancer cells have been targeted by various synthetic peptides and peptidomimetics adopting the structural motif. Herein, we synthesized a set of conjugates composed of cationic amphipathic peptoids (i.e., oligo-N-substituted glycines) and a chlorin photosensitizer, named chlorin e6 (Ce6)-peptoid conjugates (CPCs). Among the nine CPCs, CPC 7, composed of Ce6, a PEG linker, and guanidine-rich helical amphipathic peptoids, exhibited a distinct photoresponsive inactivation of Gram-positive and Gram-negative bacteria. Subsequent studies showed that CPC 7 effectively killed various cancer cells after irradiation with red light (655 nm), suggesting the potential of CPC 7 as a dual antimicrobial and anticancer agent. Confocal laser scanning microscopy and flow cytometry data suggested that CPC 7 could induce apoptotic cell death. Our results show the potential of peptoid-based photosensitizer conjugates as a versatile platform for antimicrobial and anticancer photodynamic therapy agents and peptoid therapeutics.
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Antiinfecciosos , Antineoplásicos , Clorofilidas , Peptoides , Fotoquimioterapia , Porfirinas , Peptoides/farmacología , Peptoides/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Antibacterianos , Bacterias Gramnegativas , Bacterias Grampositivas , Fotoquimioterapia/métodos , Péptidos/química , Antiinfecciosos/química , Antineoplásicos/farmacología , Porfirinas/farmacología , Porfirinas/químicaRESUMEN
The catalytic redox activity of Cu(II) bound to the amino-terminal copper and nickel (ATCUN) binding motif (Xxx-Zzz-His, XZH) is stimulating the development of catalytic metallodrugs based on reactive oxygen species (ROS)-mediated biomolecule oxidation. However, low Cu(I) availability resulting from the strong Cu(II) binding affinity of the ATCUN motif is regarded as a limitation to efficient ROS generation. To address this, we replaced the imidazole moiety (pKa 7.0) of Gly-Gly-His-NH2 (GGHa, a canonical ATCUN peptide) with thiazole (pKa 2.7) and oxazole (pKa 0.8), yielding GGThia and GGOxa, respectively. A newly synthesized amino acid, Fmoc-3-(4-oxazolyl)-l-alanine, served as a histidine surrogate featuring an azole ring with the lowest pKa among known analogues. Despite similar square-planar Cu(II)-N4 geometries being observed for the three Cu(II)-ATCUN complexes by electron paramagnetic resonance spectroscopy and X-ray crystallography, the azole modification enabled the Cu(II)-ATCUN complexes to exhibit significant rate enhancement for ROS-mediated DNA cleavage. Further analyses based on Cu(I)/Cu(II) binding affinities, electrochemical measurements, density functional theory calculations, and X-ray absorption spectroscopy indicated that the azole modification enhanced the accessibility of the Cu(I) oxidation state during ROS generation. Our oxazole/thiazole-containing ATCUN motifs provide a new design strategy for peptide ligands with modulated N donor ability, with potential applications in the development of ROS-mediated metallodrugs.
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Cobre , Histidina , Especies Reactivas de Oxígeno/metabolismo , Cobre/química , Oxazoles/farmacología , PéptidosRESUMEN
This study aimed to evaluate the prevalence, trends, and risk factors of early chronic obstructive pulmonary disease (COPD) by using a nationally representative sample. The datasets of the Korea National Health and Nutrition Examination Survey 2010-2019 were used, where 80,860 individuals were identified; of these, 9,045 participants aged 40-49 years who underwent spirometry with no missing data were analyzed. Early COPD was defined as forced expiratory volume in 1 s /forced vital capacity ratio < the lower limit of normal (2.5th percentile) in individuals aged <50 years without a history of asthma, inhaler therapy, or persistent respiratory symptoms. The prevalence and trend of early COPD were estimated according to features such as smoking status and pack-years. Joinpoint regression analysis was used to analyze the significant annual change in the trend according to sex, smoking status, and pack-years. A complex sample multivariable-adjusted regression model was used to identify factors affecting early COPD. The estimated population size during 2010-2019 was 82,326,178. Early COPD was present in 4.5% of patients (6.5% of men and 2.3% of women). It was present in 7.7% of current smokers, followed by former and never smokers. Among smokers with ≥ 10 pack-years, early COPD was present in 8.2%, whereas it was present in 2.6% of smokers with < 10 pack-years. Joinpoint regression analyses found a recent decrease in the trend of prevalence in males who were former and current smokers. The multivariable-adjusted logistic regression model showed that being male, lower educational level, smoking status, and pack-years were factors that affected the presence of early COPD. Continued surveillance of this pre-disease condition is required, and further research are warrant.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , Femenino , Encuestas Nutricionales , Prevalencia , Factores de Riesgo , Fumar/efectos adversos , Volumen Espiratorio Forzado , Capacidad Vital , EspirometríaRESUMEN
Hepatitis B virus (HBV) infection is a serious worldwide health problem causing liver cirrhosis and hepatocellular carcinoma. The development of novel therapeutics targeting distinct steps of the HBV life cycle and combination therapy with approved drugs (i.e., nucleot(s)ides, interferon-α) are considered effective strategies for curing HBV. Among these strategies is the development of entry inhibitors that interfere with the host entry step of HBV to prevent viral infection and transmission. Herein, we generated a novel library of cyclosporin O (CsO) derivatives that incorporate peptoid side chains. Twenty-two CsO derivatives were evaluated for membrane permeability, cytotoxicity, and in vitro HBV entry inhibitory activity. The lead compound (i.e., compound 21) showed the greatest potency in the in vitro HBV entry inhibition assay (IC50 = 0.36 ± 0.01 µM) with minimal cytotoxicity. Our peptide-peptoid hybrid CsO scaffold can readily expand chemical diversity and is applicable for screening various targets requiring macrocyclic chemical entities.
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Hepatitis B , Neoplasias Hepáticas , Peptoides , Simportadores , Antivirales/farmacología , Antivirales/uso terapéutico , Ciclosporinas , Hepatitis B/tratamiento farmacológico , Virus de la Hepatitis B , Humanos , Imidazoles , Neoplasias Hepáticas/tratamiento farmacológico , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/farmacología , Transportadores de Anión Orgánico Sodio-Dependiente/uso terapéutico , Peptoides/metabolismo , Peptoides/farmacología , Sulfonamidas , Simportadores/metabolismo , Tiofenos , Internalización del VirusRESUMEN
Unlike spiral galaxies such as the Milky Way, the majority of the stars in massive elliptical galaxies were formed in a short period early in the history of the Universe. The duration of this formation period can be measured using the ratio of magnesium to iron abundance ([Mg/Fe]) in spectra, which reflects the relative enrichment by core-collapse and type Ia supernovae. For local galaxies, [Mg/Fe] probes the combined formation history of all stars currently in the galaxy, including younger and metal-poor stars that were added during late-time mergers. Therefore, to directly constrain the initial star-formation period, we must study galaxies at earlier epochs. The most distant galaxy for which [Mg/Fe] had previously been measured is at a redshift of z ≈ 1.4, with [Mg/Fe] = . A slightly earlier epoch (z ≈ 1.6) was probed by combining the spectra of 24 massive quiescent galaxies, yielding an average [Mg/Fe] = 0.31 ± 0.12 (ref. 7). However, the relatively low signal-to-noise ratio of the data and the use of index analysis techniques for both of these studies resulted in measurement errors that are too large to allow us to form strong conclusions. Deeper spectra at even earlier epochs in combination with analysis techniques based on full spectral fitting are required to precisely measure the abundance pattern shortly after the major star-forming phase (z > 2). Here we report a measurement of [Mg/Fe] for a massive quiescent galaxy at a redshift of z = 2.1, when the Universe was three billion years old. With [Mg/Fe] = 0.59 ± 0.11, this galaxy is the most Mg-enhanced massive galaxy found so far, having twice the Mg enhancement of similar-mass galaxies today. The abundance pattern of the galaxy is consistent with enrichment exclusively by core-collapse supernovae and with a star-formation timescale of 0.1 to 0.5 billion years-characteristics that are similar to population II stars in the Milky Way. With an average past star-formation rate of 600 to 3,000 solar masses per year, this galaxy was among the most vigorous star-forming galaxies in the Universe.
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AIM: To investigate the clinical characteristics and prevalence of paediatric anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis. METHOD: A total of 94 paediatric patients (46 males, 48 females, median age 9 years 5 months, range: 8 months-17 years 8 months) with autoimmune encephalitis were recruited at Seoul National University Children's Hospital. We evaluated autoantibody status and identified patients with anti-MOG antibody-associated autoimmune encephalitis. Retrospective reviews of medical records were performed to describe clinical presentations, laboratory findings, treatments, and outcomes. RESULTS: Eight patients (five males, three females, median age 11 years 9 months) with anti-MOG antibody-associated encephalitis were identified (8.5% of those with autoimmune encephalitis), one of whom was copositive for anti-N-methyl-d-aspartate receptor (NMDAR) antibodies. Anti-NMDAR antibodies were identified in 23 patients (23 out of 94, 24.5%). Unilateral or bilateral cortical involvement was identified in five patients. Focal contrast enhancement was also identified in three of the five patients with cortical lesions. All patients showed favourable response to immunotherapy with a Modified Rankin Scale ≤2 at the last follow-up. Relapse was found in one patient and clinico-radiological remission was achieved with cyclic intravenous immunoglobulin therapy. INTERPRETATION: Anti-MOG antibody-associated encephalitis accounts for a significant proportion of clinically defined paediatric patients with autoimmune encephalitis. Anti-MOG antibody-associated encephalitis should be included in the clinical spectrum of anti-MOG-associated diseases.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Encefalitis , Adolescente , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Autoanticuerpos , Niño , Encefalitis/complicaciones , Encefalitis/diagnóstico por imagen , Femenino , Enfermedad de Hashimoto , Humanos , Masculino , Glicoproteína Mielina-Oligodendrócito , Oligodendroglía , Estudios RetrospectivosRESUMEN
The amphiphilic conformation of α-helical peptides has important biological functions, such as ion transport, antifreeze, and innate immunity, which can be mimicked by alternating polyisocyanate copolymers. We synthesized poly(allyl isocyanate-alt-(S)-(-)-α-methylbenzyl isocyanate (P(AIC-alt-SMBIC)) and ammonium-containing P(AIC-alt-SMBIC) (N-P(AIC-alt-SMBIC)), ensuring the amphiphilic helical conformation. The benzyl group of SMBIC plays an important role in alternating copolymerization with its steric and electron-withdrawing effects, while AIC provides an alkene group capable of introducing a customized functional group. The P(AIC-alt-SMBIC) with predominantly alternating sequence was acquired at fSMBIC /fAIC =8 with a controlled molecular weight and narrow dispersity. N-P(AIC-alt-SMBIC)s were synthesized from thiol-ene radical addition with P(AIC-alt-SMBIC).
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Polímeros , Poliuretanos , Polimerizacion , Polímeros/química , Péptidos , Conformación MolecularRESUMEN
This study aimed to determine the prevalence and mechanism of linear vertigo reported by the patients during the attacks of benign paroxysmal positional vertigo (BPPV). We prospectively evaluated the characteristics (rotational vs. linear) of positional vertigo in 70 patients with posterior and horizontal canal BPPV using a questionnaire allowing multiple choices. In patients with linear vertigo, we further assessed the directionality of linear vertigo. We adopted the velocity-storage model to explain the occurrence and direction of linear vertigo in these patients with BPPV. Patients reported only rotational vertigo in 46 (46/70, 65.7%), only linear vertigo in 10 (14.3%), and both rotational and linear vertigo in 14 (20%). The patients experienced fear from rotational vertigo in 54 (54/70, 77.1%) and from linear vertigo in 20 (20/70, 28.6%). The direction of linear vertigo was concordant with the direction of inertial acceleration predicted by the velocity-storage model. Patients with BPPV may experience linear as well as rotational vertigo during the attacks. This linear vertigo may be ascribed to centrally estimated inertial acceleration.
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Vértigo Posicional Paroxístico Benigno/complicaciones , Vértigo Posicional Paroxístico Benigno/fisiopatología , Mareo/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
Multitarget engagement is considered an effective strategy to overcome the threat of bacterial infection, and antimicrobials with multiple mechanisms of action have been successful as natural chemical weaponry. Here, we synthesized a library of photosensitizer-peptoid conjugates (PsPCs) as novel antimicrobial photodynamic therapy (aPDT) agents. The peptoids, linkers, and photosensitizers were varied, and their structure-antimicrobial activity relationships against Escherichia coli were evaluated; PsPC 9 was indicated to be the most promising photoresponsive antimicrobial agent among the synthesized PsPCs. Spectroscopic analyses indicated that 9 generated singlet oxygen upon absorption of visible light (420 nm) while maintaining the weakly helical conformation of the peptoid. Mechanistic studies suggested that damage to the bacterial membrane and cleavage of DNA upon light irradiation were the main causes of bactericidal activity, which was supported by flow cytometry and DNA gel electrophoresis experiments. We demonstrated that the optimal combination of membrane-active peptoids and photosensitizers can generate an efficient aPDT agent that targets multiple sites of bacterial components and kills bacteria by membrane disruption and reactive oxygen species generation.
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Fármacos FotosensibilizantesRESUMEN
Long-period variable stars arise in the final stages of the asymptotic giant branch phase of stellar evolution. They have periods of up to about 1,000 days and amplitudes that can exceed a factor of three in the I-band flux. These stars pulsate predominantly in their fundamental mode, which is a function of mass and radius, and so the pulsation periods are sensitive to the age of the underlying stellar population. The overall number of long-period variables in a population is directly related to their lifetimes, which is difficult to predict from first principles because of uncertainties associated with stellar mass-loss and convective mixing. The time variability of these stars has not previously been taken into account when modelling the spectral energy distributions of galaxies. Here we construct time-dependent stellar population models that include the effects of long-period variable stars, and report the ubiquitous detection of this expected 'pixel shimmer' in the massive metal-rich galaxy M87. The pixel light curves display a variety of behaviours. The observed variation of 0.1 to 1 per cent is very well matched to the predictions of our models. The data provide a strong constraint on the properties of variable stars in an old and metal-rich stellar population, and we infer that the lifetime of long-period variables in M87 is shorter by approximately 30 per cent compared to predictions from the latest stellar evolution models.
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Using a long-term prospective longitudinal study of U.S. men and their fathers, the present study examined the extent to which the quantity (i.e., shared activities between fathers and sons) and the quality (i.e., assessors' ratings of fathers' positive behaviors toward sons and the relationship quality between fathers and sons) of father involvement during childhood influenced sons' diurnal patterns of salivary cortisol in adulthood (late 30s) directly and indirectly through substance use across the 20s. Findings indicated that the quantity of father involvement during childhood was directly associated with sons' diurnal cortisol patterns assessed almost 30 years later. Specifically, the quantity of father involvement in childhood significantly increased the intercept (i.e., upon awakening) and also led to a greater reduction in cortisol across the day, suggesting a well-regulated diurnal cortisol pattern. The quantity of father involvement significantly reduced the amount of sons' illicit drug and tobacco use across the 20s. Tobacco use across the 20s was associated with a lower cortisol intercept level (upon awakening), although the mediating path was not significant. The present study provided empirical evidence demonstrating long-term physiological and behavioral consequences of father involvement in childhood and its potency as a crucial early caregiving environment for sons.
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Relaciones Padre-Hijo , Padre , Adulto , Humanos , Estudios Longitudinales , Masculino , Núcleo Familiar , Estudios Prospectivos , Estrés FisiológicoRESUMEN
OBJECTIVES: Despite growing concerns about the heavy reliance on supplementary grandchild care in Korea, understanding of its longitudinal effects on the grandparents' mental health has been limited. This study examined whether transition patterns of grandchild care among Korean grandparents were associated with changes in the grandparents' depressive symptoms, directly or indirectly, through changes in two domains of social integration (intergenerational contact and social activities) after controlling for socioeconomic characteristics and baseline levels of depressive symptoms and social integration. METHOD: Using the Korean Longitudinal Study of Aging (N = 4,362), a nationally representative multiwave survey, we examined four possible statuses of grandchild care over a three-year period: started (n = 64), continuous (n = 73), and discontinued (n = 103) caregiving, and non-caregiving (n = 4,121). The proposed mediation model was analyzed using structural equation modeling with non-caregivers as a reference group, and Wald tests were conducted to further examine differences in the effects across the three caregiving groups. RESULTS: The direct effects of grandchild care on depressive symptoms in Korean grandparents were not significant. Rather, those who started or continuously provided caregiving had significantly reduced depressive symptoms via increased intergenerational contact compared to the non-caregiving group. CONCLUSION: These findings indicated beneficial effects of grandchild care on depressive symptoms in Korean grandparents through increased social integration within the family. Implications of the study findings were discussed.
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Depresión , Abuelos , Depresión/epidemiología , Humanos , Relaciones Intergeneracionales , Estudios Longitudinales , República de Corea/epidemiología , Integración SocialRESUMEN
AIMS AND OBJECTIVES: This study aimed to develop a fall risk perception questionnaire for patients admitted to acute care hospitals and to establish its reliability and validity. BACKGROUND: To prevent falls during patients' hospitalisation, it is essential for them to accurately perceive their risk of falling. DESIGN: This methodological study was performed to develop a fall risk perception questionnaire. METHODS: After generating a preliminary questionnaire, two rounds of content validity testing were performed with nine experts. Following a pilot test, a convenience sample of 236 participants was recruited from an acute care hospital between 2 May 2018 and 15 December 2019. Construct, convergent and known-group validity of the questionnaire was evaluated, and reliability was estimated by calculating the internal consistency reliability coefficients. The study adhered to STROBE guidelines. RESULTS: Exploratory factor analysis yielded a three-factor solution with 27 items. The questionnaire showed statistically significant positive correlation with the Korean Falls Efficacy Scale-International and the Morse Fall Scale, thus establishing convergent validity. For known-group comparison, Morse Fall Scale scores were categorised into two groups by cut-off score. The risk for falls group had a significantly higher perceived fall risk than the no risk for falls group, thus establishing known-group validity. Cronbach's alpha values indicated good to excellent reliability for the overall questionnaire with 27 items and for each of the three subfactors. CONCLUSIONS: The fall risk perception questionnaire demonstrated satisfactory reliability and validity in an acute care hospital setting. RELEVANCE TO CLINICAL PRACTICE: Because understanding patients' perceptions of their fall risk is essential for preventing falls, it is necessary to regularly assess patients' fall risk perception using tools with established reliability and validity.
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Accidentes por Caídas , Percepción , Accidentes por Caídas/prevención & control , Hospitales , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
We propose a computational workflow to design novel drug-like molecules by combining the global optimization of molecular properties and protein-ligand docking with machine learning. However, most existing methods depend heavily on experimental data, and many targets do not have sufficient data to train reliable activity prediction models. To overcome this limitation, protein-ligand docking calculations must be performed using the limited data available. Such docking calculations during molecular generation require considerable computational time, preventing extensive exploration of the chemical space. To address this problem, we trained a machine-learning-based model that predicted the docking energy using SMILES to accelerate the molecular generation process. Docking scores could be accurately predicted using only a SMILES string. We combined this docking score prediction model with the global molecular property optimization approach, MolFinder, to find novel molecules exhibiting the desired properties with high values of predicted docking scores. We named this design approach V-dock. Using V-dock, we efficiently generated many novel molecules with high docking scores for a target protein, a similarity to the reference molecule, and desirable drug-like and bespoke properties, such as QED. The predicted docking scores of the generated molecules were verified by correlating them with the actual docking scores.