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In this paper, the optimal approximation algorithm is proposed to simplify non-linear functions and/or discrete data as piecewise polynomials by using the constrained least squares. In time-sensitive applications or in embedded systems with limited resources, the runtime of the approximate function is as crucial as its accuracy. The proposed algorithm searches for the optimal piecewise polynomial (OPP) with the minimum computational cost while ensuring that the error is below a specified threshold. This was accomplished by using smooth piecewise polynomials with optimal order and numbers of intervals. The computational cost only depended on polynomial complexity, i.e., the order and the number of intervals at runtime function call. In previous studies, the user had to decide one or all of the orders and the number of intervals. In contrast, the OPP approximation algorithm determines both of them. For the optimal approximation, computational costs for all the possible combinations of piecewise polynomials were calculated and tabulated in ascending order for the specific target CPU off-line. Each combination was optimized through constrained least squares and the random selection method for the given sample points. Afterward, whether the approximation error was below the predetermined value was examined. When the error was permissible, the combination was selected as the optimal approximation, or the next combination was examined. To verify the performance, several representative functions were examined and analyzed.
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The objective of this study was to determine whether multi-microRNA analysis using a combination of four microRNA biomarkers (miR-1246, 202, 21, and 219B) could improve the diagnostic performance of mammography in determining breast cancer risk by age group (under 50 vs. over 50) and distinguish breast cancer from benign breast diseases and other cancers (thyroid, colon, stomach, lung, liver, and cervix cancers). To verify breast cancer classification performance of the four miRNA biomarkers and whether the model providing breast cancer risk score could distinguish between benign breast disease and other cancers, the model was verified using nonlinear support vector machine (SVM) and generalized linear model (GLM) and age and four miRNA qRT-PCR analysis values (dCt) were input to these models. Breast cancer risk scores for each Breast Imaging-Reporting and Data System (BI-RADS) category in multi-microRNA analysis were analyzed to examine the correlation between breast cancer risk scores and mammography categories. We generated two models using two classification algorithms, SVM and GLM, with a combination of four miRNA biomarkers showing high performance and sensitivities of 84.5% and 82.1%, a specificity of 85%, and areas under the curve (AUCs) of 0.967 and 0.965, respectively, which showed consistent performance across all stages of breast cancer and patient ages. The results of this study showed that this multi-microRNA analysis using the four miRNA biomarkers was effective in classifying breast cancer in patients under the age of 50, which is challenging to accurately diagnose. In addition, breast cancer and benign breast diseases can be classified, showing the possibility of helping with diagnosis by mammography. Verification of the performance of the four miRNA biomarkers confirmed that multi-microRNA analysis could be used as a new breast cancer screening aid to improve the accuracy of mammography. However, many factors must be considered for clinical use. Further validation with an appropriate screening population in large clinical trials is required. This trial is registered with (KNUCH 2022-04-036).
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Neoplasias da Mama , Doença da Mama Fibrocística , MicroRNAs , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , MicroRNAs/genética , Mamografia/métodos , Mama , BiomarcadoresRESUMO
BACKGROUND: Ciliogenesis-associated kinase 1 (CILK1) is a ciliary gene that localizes in primary cilia and regulates ciliary transport. Mutations in CILK1 cause various ciliopathies. However, the pathogenesis of CILK1-deficient kidney disease is unknown. METHODS: To examine whether CILK1 deficiency causes PKD accompanied by abnormal cilia, we generated mice with deletion of Cilk1 in cells of the renal collecting duct. A yeast two-hybrid system and coimmunoprecipitation (co-IP) were used to identify a novel regulator, kinesin light chain-3 (KLC3), of ciliary trafficking and cyst progression in the Cilk1-deficient model. Immunocytochemistry and co-IP were used to examine the effect of KLC3 on ciliary trafficking of the IFT-B complex and EGFR. We evaluated the effects of these genes on ciliary trafficking and cyst progression by modulating CILK1 and KLC3 expression levels. RESULTS: CILK1 deficiency leads to PKD accompanied by abnormal ciliary trafficking. KLC3 interacts with CILK1 at cilia bases and is increased in cyst-lining cells of CILK1-deficient mice. KLC3 overexpression promotes ciliary recruitment of IFT-B and EGFR in the CILK1 deficiency condition, which contributes to the ciliary defect in cystogenesis. Reduction in KLC3 rescued the ciliary defects and inhibited cyst progression caused by CILK1 deficiency. CONCLUSIONS: Our findings suggest that CILK1 deficiency in renal collecting ducts leads to PKD and promotes ciliary trafficking via increased KLC3.
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Doenças Renais Policísticas , Camundongos , Animais , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/metabolismo , Rim/metabolismo , Cílios/metabolismo , Mutação , Receptores ErbB/metabolismoRESUMO
Objectives: Research suggests that the death of a spouse has an adverse effect on a widow(er)'s cognition. However, little research has examined how the marital context before widowhood and gender influence this association. Guided by the social ambivalence and disease (SAD) model, this study examined the associations between spousal loss and cognition , with moderating effects of gender and pre-loss marital quality.Method: We analyzed a national longitudinal data, Midlife in the United States (MIDUS), specifically MIDUS 2 (2004-2005) and MIDUS 3 (2013-2014). The analytic sample consisted of (1) 146 participants who experienced the death of their spouse between MIDUS 2 and MIDUS 3 and (2) 144 age- and gender-matched comparison participants who did not lose their spouse during the period.Results: Adverse influence of widowhood on cognition was more pronounced among bereaved men than bereaved women. Widowed individuals whose relationships with their deceased spouse were ambivalent had poorer cognition than widowed individuals who had aversive relationships with their deceased spouse.Conclusion: Findings suggest that the influence of spousal death on cognitive functioning depends on gender and pre-loss marital quality, emphasizing the importance of considering pre-loss marital relationship and gender dynamics in developing efficient interventions for the widowed.
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Casamento , Viuvez , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Casamento/psicologia , Cognição , Cônjuges/psicologia , Afeto , Identidade de GêneroRESUMO
Vertebrate primary cilium is a Hedgehog signaling center but the extent of its involvement in other signaling systems is less well understood. This report delineates a mechanism by which fibroblast growth factor (FGF) controls primary cilia. Employing proteomic approaches to characterize proteins associated with the FGF-receptor, FGFR3, we identified the serine/threonine kinase intestinal cell kinase (ICK) as an FGFR interactor. ICK is involved in ciliogenesis and participates in control of ciliary length. FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. Activation of the FGF signaling pathway affected both primary cilia length and function in a manner consistent with cilia effects caused by inhibition of ICK activity. Moreover, knockdown and knockout of ICK rescued the FGF-mediated effect on cilia. We provide conclusive evidence that FGF signaling controls cilia via interaction with ICK.
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Cílios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Animais , Sistemas CRISPR-Cas , Fatores de Crescimento de Fibroblastos/metabolismo , Células HEK293 , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Camundongos Knockout , Modelos Animais , Simulação de Acoplamento Molecular , Células NIH 3T3 , Fosforilação , Domínios e Motivos de Interação entre Proteínas , Proteínas Serina-Treonina Quinases/genética , Proteômica , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Transdução de SinaisRESUMO
BACKGROUND: The post-colonoscopy periprosthetic joint infection (PJI) risk in patients with total prosthetic knee joints has limited research. The present study investigated the PJI risk and determined the risk factors for post-colonoscopy PJI in total knee arthroplasty (TKA) recipients. The hypothesis was that colonoscopy is associated with an increased PJI risk in patients with total prosthetic knee joints. This study can potentially help guide the decision making for prophylactic antibiotic use for colonoscopy. METHODS: This nationwide matched cohort study used claims data from the Health Insurance Review and Assessment Service database and enrolled patients who underwent unilateral TKA between 2008 and 2016. The history of diagnostic colonoscopy was investigated at least 1 year postoperatively. The propensity score was matched between colonoscopy and non-colonoscopy cohorts, and the post-colonoscopy PJI risk was compared. The PJI risk following invasive colonoscopic procedures, including biopsy, polypectomy, and mucosal or submucosal resection, was investigated, and the risk factors for post-colonoscopy PJI were determined. RESULTS: In total, 45,612 and 211,841 patients were matched in the colonoscopy and control cohorts, respectively. The colonoscopy cohort had greater 9-month and 1-year PJI risks from the index colonoscopy date than the matched controls (9 months: hazard ratio [HR] 1.836, P = .006; 1 year: HR 1.822, P = .031). Invasive colonoscopic procedures did not increase the PJI risk at any time point post-colonoscopy. The only significant risk factor for PJI was post-traumatic arthritis (adjusted HR 4.034, P = .023). CONCLUSION: Colonoscopy was associated with an increased PJI risk in TKA recipients, regardless of concomitant invasive colonoscopic procedures. LEVEL OF EVIDENCE: III, Prognostic.
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Artroplastia de Quadril , Artroplastia do Joelho , Infecções Relacionadas à Prótese , Artroplastia do Joelho/efeitos adversos , Estudos de Coortes , Colonoscopia/efeitos adversos , Humanos , Pontuação de Propensão , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
In Korean language, questions containing ambiguous wh-words may be interpreted as either wh-questions or yes-no questions. This study investigated 43 Korean three-year-olds' ability to disambiguate eight indeterminate questions using prosodic and visual cues. The intonation of each question provided a cue as to whether it should be interpreted as a wh-question or a yes-no question. The questions were presented alongside picture stimuli, which acted as either a matched (presentation of corresponding auditory-visual stimuli) or a mismatched contextual cue (presentation conflicting auditory-visual stimuli). Like adults, the children preferred to comprehend questions involving ambiguous wh-words as wh-questions, rather than yes-no questions. In addition, children were as effective as adults in disambiguating indeterminate questions using prosodic cues regardless of the visual cue. However, when confronted with conflicting auditory-visual stimuli (mismatched), the quality of children's responses was less accurate than adults' responses.
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Desenvolvimento da Linguagem , Idioma , Adulto , Criança , Sinais (Psicologia) , Humanos , República da CoreiaRESUMO
BACKGROUND: The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls. METHODS: RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA. RESULTS: Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group. CONCLUSIONS: Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes.
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Análise de Sequência de RNA/métodos , Transcriptoma , Incompetência do Colo do Útero/metabolismo , alfa-Defensinas/sangue , Adulto , Feminino , Humanos , Projetos Piloto , Gravidez , Incompetência do Colo do Útero/genéticaRESUMO
The present study investigated how single-talker and babble maskers affect auditory and lexical processing during native (L1) and non-native (L2) speech recognition. Electroencephalogram (EEG) recordings were made while L1 and L2 (Korean) English speakers listened to sentences in the presence of single-talker and babble maskers that were colocated or spatially separated from the target. The predictability of the sentences was manipulated to measure lexical-semantic processing (N400), and selective auditory processing of the target was assessed using neural tracking measures. The results demonstrate that intelligible single-talker maskers cause listeners to attend more to the semantic content of the targets (i.e., greater context-related N400 changes) than when targets are in babble, and that listeners track the acoustics of the target less accurately with single-talker maskers. L1 and L2 listeners both modulated their processing in this way, although L2 listeners had more difficulty with the materials overall (i.e., lower behavioral accuracy, less context-related N400 variation, more listening effort). The results demonstrate that auditory and lexical processing can be simultaneously assessed within a naturalistic speech listening task, and listeners can adjust lexical processing to more strongly track the meaning of a sentence in order to help ignore competing lexical content.
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Percepção da Fala , Fala , Eletroencefalografia , Potenciais Evocados , Feminino , Humanos , Idioma , Masculino , Mascaramento PerceptivoRESUMO
The short rib polydactyly syndromes (SRPS) are a group of recessively inherited, perinatal-lethal skeletal disorders primarily characterized by short ribs, shortened long bones, varying types of polydactyly and concomitant visceral abnormalities. Mutations in several genes affecting cilia function cause SRPS, revealing a role for cilia function in skeletal development. To identify additional SRPS genes and discover novel ciliary molecules required for normal skeletogenesis, we performed exome sequencing in a cohort of patients and identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one SRPS family. The p.E80K mutation abolished serine/threonine kinase activity, resulting in altered ICK subcellular and ciliary localization, increased cilia length, aberrant cartilage growth plate structure, defective Hedgehog and altered ERK signalling. These data identify ICK as an SRPS-associated gene and reveal that abnormalities in signalling pathways contribute to defective skeletogenesis.
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Anormalidades Múltiplas/genética , Proteínas Hedgehog/genética , Proteínas Serina-Treonina Quinases/genética , Síndrome de Costela Curta e Polidactilia/genética , Esqueleto/crescimento & desenvolvimento , Anormalidades Múltiplas/fisiopatologia , Cílios/genética , Cílios/patologia , Exoma/genética , Feminino , Humanos , Lactente , Sistema de Sinalização das MAP Quinases , Linhagem , Gravidez , Análise de Sequência de DNA , Síndrome de Costela Curta e Polidactilia/patologia , Transdução de Sinais , Esqueleto/anormalidadesRESUMO
In the eukaryotic circadian clock machinery, negative feedback repression of CLOCK (CLK) and BMAL1 transcriptional activity by PERIOD (PER) and CRYPTOCHROME (CRY) underlies the basis for 24 h rhythmic gene expression. Thus, precise regulation of the time-dependent nuclear entry of circadian repressors is crucial to generating normal circadian rhythms. Here, we sought to identify novel kinase(s) that regulate nuclear entry of mammalian CRY1 (mCRY1) with an unbiased screening using red fluorescent protein (RFP)-tagged human kinome expression plasmids in mammalian cells. Transient expression of human vaccinia-related kinase 3 (hVRK3) reduced the nuclear presence of mCRY1. hVRK3 expression also induced alterations in the subcellular localization of other core clock proteins, including mCRY2, mPER2, and BMAL1. In contrast, the subcellular localization of mCLK was not changed. Given that singly expressed mCLK mostly resides in the cytoplasm and that nuclear localization sequence (NLS) mutation of hVRK3 attenuated the effect of hVRK3 co-expression on subcellular localization, ectopically expressed hVRK3 presumably reduces the retention of proteins in the nucleus. Finally, downregulation of hvrk3 using siRNA reduced the amplitude and lengthened the period of the cellular bioluminescence rhythm. Taken together, these data suggest that VRK3 plays a role in setting the amplitude and period length of circadian rhythms in mammalian cells.
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Núcleo Celular/metabolismo , Ritmo Circadiano/fisiologia , Regulação da Expressão Gênica/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Frações Subcelulares/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Células HEK293 , Humanos , Camundongos , Células NIH 3T3 , Distribuição TecidualRESUMO
Endocrine-cerebro-osteodysplasia (ECO) syndrome is a recessive genetic disorder associated with multiple congenital defects in endocrine, cerebral, and skeletal systems that is caused by a missense mutation in the mitogen-activated protein kinase-like intestinal cell kinase (ICK) gene. In algae and invertebrates, ICK homologs are involved in flagellar formation and ciliogenesis, respectively. However, it is not clear whether this role of ICK is conserved in mammals and how a lack of functional ICK results in the characteristic phenotypes of human ECO syndrome. Here, we generated Ick knockout mice to elucidate the precise role of ICK in mammalian development and to examine the pathological mechanisms of ECO syndrome. Ick null mouse embryos displayed cleft palate, hydrocephalus, polydactyly, and delayed skeletal development, closely resembling ECO syndrome phenotypes. In cultured cells, down-regulation of Ick or overexpression of kinase-dead or ECO syndrome mutant ICK resulted in an elongation of primary cilia and abnormal Sonic hedgehog (Shh) signaling. Wild-type ICK proteins were generally localized in the proximal region of cilia near the basal bodies, whereas kinase-dead ICK mutant proteins accumulated in the distal part of bulged ciliary tips. Consistent with these observations in cultured cells, Ick knockout mouse embryos displayed elongated cilia and reduced Shh signaling during limb digit patterning. Taken together, these results indicate that ICK plays a crucial role in controlling ciliary length and that ciliary defects caused by a lack of functional ICK leads to abnormal Shh signaling, resulting in congenital disorders such as ECO syndrome.
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Anormalidades Múltiplas/patologia , Cílios/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Anormalidades Múltiplas/genética , Animais , Western Blotting , Padronização Corporal/genética , Padronização Corporal/fisiologia , Córtex Cerebral/embriologia , Córtex Cerebral/patologia , Cílios/genética , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/metabolismo , Embrião de Mamíferos/ultraestrutura , Sistema Endócrino/embriologia , Sistema Endócrino/patologia , Proteínas Hedgehog/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Confocal , Microscopia Eletrônica , Sistema Musculoesquelético/embriologia , Sistema Musculoesquelético/patologia , Células NIH 3T3 , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , SíndromeRESUMO
Periodontal diseases are infectious polymicrobial inflammatory diseases that lead to destruction of the periodontal ligament, gingiva, and alveolar bone. Sequential colonization of a broad range of bacteria, including Fusobacterium nucleatum and Porphyromonas gingivalis, is an important phenomenon in this disease model. F. nucleatum is a facultative anaerobic species thought to be a key mediator of dental plaque maturation due to its extensive coaggregation with other oral bacteria, while P. gingivalis is an obligate anaerobic species that induces gingival inflammation by secreting various virulence factors. The formation of a bacterial complex by these two species is central to the pathogenesis of periodontal disease. Reactive oxygen species (ROS) are produced during bacterial infections and are involved in intracellular signaling. However, the impact of oral bacteria-induced ROS on the ecology of F. nucleatum and P. gingivalis has yet to be clarified. In the present study, we investigated ROS production induced in primary human oral cells by F. nucleatum and P. gingivalis and its effect on the formation of their bacterial complexes and further host cell apoptosis. We found that in primary human gingival fibroblasts (GFs), two NADPH oxidase isoforms, NOX1 and NOX2, were activated in response to F. nucleatum infection but not P. gingivalis infection. Accordingly, increased NADPH oxidase activity and production of superoxide anion were observed in GFs after F. nucleatum infection, but not after P. gingivalis infection. Interestingly, in NOX1, NOX2, or NOX1/NOX2 knockdown cells, the number of P. gingivalis decreased when the cells were coinfected with F. nucleatum. A similar pattern of host cell apoptosis was observed. This implies that F. nucleatum contributes to attachment of P. gingivalis by triggering activation of NADPH oxidase in host cells, which may provide an environment more favorable to strict anaerobic bacteria and have a subsequent effect on apoptosis of host cells.
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Aderência Bacteriana/fisiologia , Fusobacterium nucleatum/metabolismo , Gengiva/patologia , Glicoproteínas de Membrana/metabolismo , NADPH Oxidases/metabolismo , Doenças Periodontais/patologia , Porphyromonas gingivalis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ativação Enzimática , Fibroblastos/citologia , Fibroblastos/metabolismo , Gengiva/citologia , Gengiva/metabolismo , Humanos , Glicoproteínas de Membrana/genética , NADPH Oxidase 1 , NADPH Oxidase 2 , NADPH Oxidases/genética , Doenças Periodontais/microbiologia , Porphyromonas gingivalis/fisiologia , Interferência de RNA , RNA Interferente Pequeno/genéticaRESUMO
Pushing bulging fetal membranes back into the uterine cavity effectively without rupture of fetal membranes during emergency cerclage is a concern to obstetricians. We have developed a new uniconcave balloon device for repositioning fetal membranes into the uterus during emergency cerclage. Our technique can be accomplished easily with few complications.
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Cerclagem Cervical/instrumentação , Tratamento de Emergência , Adulto , Desenho de Equipamento , Feminino , HumanosRESUMO
Adults heard recordings of two spatially separated speakers reading newspaper and magazine articles. They were asked to listen to one of them and ignore the other, and EEG was recorded to assess their neural processing. Machine learning extracted neural sources that tracked the target and distractor speakers at three levels: the acoustic envelope of speech (delta- and theta-band modulations), lexical frequency for individual words, and the contextual predictability of individual words estimated by GPT-4 and earlier lexical models. To provide a broader view of speech perception, half of the subjects completed a simultaneous visual task, and the listeners included both native and non-native English speakers. Distinct neural components were extracted for these levels of auditory and lexical processing, demonstrating that native English speakers had greater target-distractor separation compared to non-native English speakers on most measures, and that lexical processing was reduced by the visual task. Moreover, there was a novel interaction of lexical predictability and frequency with auditory processing; acoustic tracking was stronger for lexically harder words, suggesting that people listened harder to the acoustics when needed for lexical selection. This demonstrates that speech perception is not simply a feedforward process from acoustic processing to the lexicon. Rather, the adaptable context-sensitive processing long known to occur at a lexical level has broader consequences for perception, coupling with the acoustic tracking of individual speakers in noise.Significance Statement In challenging listening conditions, people use focused attention to help understand individual talkers and ignore others, which changes their neural processing for speech at auditory through lexical levels. However, lexical processing for natural materials (e.g., conversations, audiobooks) has been difficult to measure, because of limitations of tools to estimate the predictability of individual words in longer discourses. The present investigation uses a contemporary large language model, GPT-4, to estimate word predictability, and demonstrates that listeners make online adaptations to their auditory neural processing in accord with these predictions; neural activity more closely tracks the acoustics of the target talker when words are less predictable from the context.
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Purpose: Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the efficacy of AOMs has been reported, there have been no direct comparisons of these drugs. Therefore, in the present study, we aimed to compare the efficacy of all the AOMs available in Korea in a real-world setting. Patients and Methods: The body weight and composition of 205 adults treated with phentermine, phentermine/topiramate, liraglutide, naltrexone/bupropion, lorcaserin, or orlistat for at least 6 months were analyzed at 2 month intervals. The prevalence of the achievement of a ≥5% weight loss and the changes in body composition were compared between participants using each AOM at each visit. Results: A total of 132 (64.4%) participants achieved ≥5% weight loss within 6 months (prevalence of ≥5% weight loss after 6 months: phentermine, 87.2%; phentermine/topiramate, 67.7%; liraglutide, 58.1%; naltrexone/bupropion, 35.3%; lorcaserin, 75%; orlistat, 50%). At each visit, after adjustment for age, sex, and baseline body weight, phentermine use was associated with a significantly higher prevalence of ≥5% weight loss than the use of the other AOMs, except for liraglutide. There were significant differences in the body weight, body mass index and body fat mass among the AOM groups by visit (P for interaction <0.05), but not in their waist circumference, skeletal muscle mass, percentage body fat, or visceral fat area. Conclusion: All the AOMs were effective at inducing and maintaining weight loss, in the absence of significant changes in muscle mass, over a 6 month period, and the short-term use of phentermine and the long-term use of phentermine/topiramate or liraglutide would be practical choices for the treatment of obesity. However, further, large-scale studies are necessary to confirm these findings.
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Fármacos Antiobesidade , Liraglutida , Adulto , Humanos , Orlistate/uso terapêutico , Topiramato/uso terapêutico , Liraglutida/uso terapêutico , Naltrexona/uso terapêutico , Bupropiona/uso terapêutico , Frutose , Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Peso Corporal , Fentermina/efeitos adversos , Redução de PesoRESUMO
L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems.
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Background: Periprosthetic osteolysis is a prevalent complication following total ankle arthroplasty (TAA), implicating various cytokines in osteoclastogenesis as pivotal in this process. This study aimed to evaluate the relationship between osteolysis and the concentrations of osteoclastogenesis-related cytokines in synovial fluid and investigate its clinical value following TAA. Methods: Synovial fluid samples from 23 ankles that underwent revision surgery for osteolysis following TAA were analyzed as the osteolysis group. As a control group, we included synovial fluid samples obtained from 23 ankles during primary TAA for osteoarthritis. The receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in these samples was quantified using sandwich enzyme-linked immunosorbent assay techniques, and a bead-based multiplex immunoassay facilitated the detection of specific osteoclastogenesis-related cytokines. Results: RANKL levels averaged 487.9 pg/mL in 14 of 23 patients in the osteolysis group, with no detection in the control group's synovial fluid. Conversely, a significant reduction in OPG levels was observed in the osteolysis group (p = 0.002), resulting in a markedly higher mean RANKL/OPG ratio (0.23) relative to controls (p = 0.020). Moreover, the osteolysis group had increased concentrations of various osteoclastogenesis-related cytokines (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, IP-10, and monocyte chemotactic protein-1) in the synovial fluid relative to the control group. Conclusions: Our results demonstrated that periprosthetic osteolysis was associated with osteoclastogenesis activation through an elevated RANKL/OPG ratio following TAA. We assume that RANKL and other osteoclastogenesis-related cytokines in the synovial fluid have clinical value as a potential marker for the development and progression of osteolysis following TAA.
Assuntos
Artroplastia de Substituição do Tornozelo , Biomarcadores , Osteólise , Osteoprotegerina , Ligante RANK , Líquido Sinovial , Humanos , Líquido Sinovial/metabolismo , Líquido Sinovial/química , Osteólise/metabolismo , Osteólise/etiologia , Masculino , Feminino , Ligante RANK/metabolismo , Idoso , Pessoa de Meia-Idade , Artroplastia de Substituição do Tornozelo/efeitos adversos , Osteoprotegerina/metabolismo , Osteoprotegerina/análise , Biomarcadores/metabolismo , Biomarcadores/análise , Idoso de 80 Anos ou mais , Citocinas/metabolismo , Citocinas/análise , ReoperaçãoRESUMO
BACKGROUND: This study investigated the association between atherosclerosis and systemic inflammation markers, specifically the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in healthy middle-aged adults. METHODS: A retrospective cross-sectional study was conducted on a total of 1264 Korean adults aged 40-65. We assessed these inflammatory markers and carotid metrics, such as carotid intima-media thickness (cIMT), plaque number (PN), plaque stenosis score (PSS), and plaque score (PS), using linear regression, logistic regression, and receiver operating characteristic analysis. RESULTS: In males, the ESR and CRP were significantly correlated with the PN (p < 0.001 and p = 0.048, respectively). The ESR was correlated with the PN in females (p = 0.004). The NLR and PLR both correlated with the PS in males (p < 0.001 and p = 0.015, respectively) and females (p = 0.015 and p = 0.023, respectively). The odds ratio for the NLR as a risk factor for increased cIMT was 1.15 (95% confidence interval [CI], 1.03-2.15) for males and 1.05 (95% CI, 1.01-1.29) for females. The AUC for the NLR and PLR as a predictor for the PS showed significance in both men and women. CONCLUSIONS: Inflammatory markers, particularly the NLR and PLR, demonstrate a correlation with carotid atherosclerosis. Both the NLR and PLR hold potential as valuable surrogate markers for carotid atherosclerosis. To further substantiate their predictive efficacy, further prospective studies are needed.
RESUMO
Autistic individuals and their families are at risk for poor outcomes in employment and mental health and may be vulnerable to long-term effects of broader societal conditions. The aim of the current longitudinal study was to understand the impact of the Great Recession of 2007-2009 on autistic individuals and their mothers (N = 392). Hierarchical linear modeling (HLM) results indicated that problem behavior of autistic adults increased in the years following the recession. The rate at which autistic individuals moved away and lived separately from their mothers also slowed during the recession. Mothers experienced significantly higher levels of depressive symptoms postrecession, compared to prerecession. In many other respects, the autistic individuals and their mothers did not experience negative outcomes, suggesting resilience and a strong safety net. These included the physical health and vocational/employment status of the autistic adults and their mothers. Results point to specific areas of vulnerability of autistic individuals and their mothers during the economic downturn, as well as a broad pattern of resilience in these families.