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1.
JMIR Public Health Surveill ; 10: e55011, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39041282

RESUMO

Background: In South Korea, the cancer incidence rate has increased by 56.5% from 2001 to 2021. Nevertheless, the 5-year cancer survival rate from 2017 to 2021 increased by 17.9% compared with that from 2001 to 2005. Cancer survival rates tend to decline with lower socioeconomic status, and variations exist in the survival rates among different cancer types. Analyzing socioeconomic patterns in the survival of patients with cancer can help identify high-risk groups and ensure that they benefit from interventions. Objective: The aim of this study was to analyze differences in survival rates among patients diagnosed with six types of cancer-stomach, colorectal, liver, breast, cervical, and lung cancers-based on socioeconomic status using Korean nationwide data. Methods: This study used the Korea Central Cancer Registry database linked to the National Health Information Database to follow up with patients diagnosed with cancer between 2014 and 2018 until December 31, 2021. Kaplan-Meier curves stratified by income status were generated, and log-rank tests were conducted for each cancer type to assess statistical significance. Hazard ratios with 95% CIs for any cause of overall survival were calculated using Cox proportional hazards regression models with the time since diagnosis. Results: The survival rates for the six different types of cancer were as follows: stomach cancer, 69.6% (96,404/138,462); colorectal cancer, 66.6% (83,406/125,156); liver cancer, 33.7% (23,860/70,712); lung cancer, 30.4% (33,203/109,116); breast cancer, 91.5% (90,730/99,159); and cervical cancer, 78% (12,930/16,580). When comparing the medical aid group to the highest income group, the hazard ratios were 1.72 (95% CI 1.66-1.79) for stomach cancer, 1.60 (95% CI 1.54-1.56) for colorectal cancer, 1.51 (95% CI 1.45-1.56) for liver cancer, 1.56 (95% CI 1.51-1.59) for lung cancer, 2.19 (95% CI 2.01-2.38) for breast cancer, and 1.65 (95% CI 1.46-1.87) for cervical cancer. A higher deprivation index and advanced diagnostic stage were associated with an increased risk of mortality. Conclusions: Socioeconomic status significantly mediates disparities in cancer survival in several cancer types. This effect is particularly pronounced in less fatal cancers such as breast cancer. Therefore, considering the type of cancer and socioeconomic factors, social and medical interventions such as early cancer detection and appropriate treatment are necessary for vulnerable populations.


Assuntos
Neoplasias , Humanos , República da Coreia/epidemiologia , Feminino , Neoplasias/mortalidade , Neoplasias/epidemiologia , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Taxa de Sobrevida/tendências , Disparidades nos Níveis de Saúde , Fatores Socioeconômicos , Estudos de Coortes , Sistema de Registros , Classe Social , Disparidades Socioeconômicas em Saúde
2.
Immune Netw ; 24(3): e27, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38974209

RESUMO

The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1ß, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFß, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

4.
Sci Rep ; 14(1): 17070, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048623

RESUMO

The Ferromagnetic Resonance (FMR) phenomenon, marked by the selective absorption of microwave radiation by magnetic materials in the presence of a magnetic field, plays a pivotal role in the development of radar absorbing materials, high speed magnetic storage, and magnetic sensors. This process is integral for technologies requiring precise control over microwave absorption frequencies. We explored how variations in resonance fields can be effectively modulated by adjusting both the shape and stress anisotropies of magnetic materials on a flexible substrate. Utilizing polyethylene-naphthalate (PEN) as the substrate and Permalloy (Ni79Fe21, noted for its positive magnetostriction coefficient) as the magnetic component, we demonstrated that modifications in the aspect ratio and bending repetitions can significantly alter the resonance field. The results, consistent with Kittel's equation and the predictions of a uniaxial magnetic anisotropy model, underscore the potential for flexible substrates in enhancing the sensitivity and versatility of RF-based magnetic devices.

5.
Geriatr Nurs ; 58: 506-511, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38996477

RESUMO

INTRODUCTION: This study aimed to examine the association between physical activity one month post discharge and mortality over the first-year post discharge among recently hospitalized older adults with dementia. METHODS: For this descriptive sub-study, among 42 participants, we obtained physical activity data via accelerometry at one month post discharge and death status via phone call at 6 months and 1 year post discharge. We performed logistic regression. RESULTS: We found that participants' amount of time spent in physical activity one month post hospital discharge was not statistically significantly associated with mortality within the first-year post hospital discharge (OR=.996, CI=.992,1.000; p=.053). However, we did observe a strong trend. CONCLUSIONS: Given the small sample of participants, this trend is salient and should be examined in a larger sample. The results highlight a specific patient profile, recently hospitalized older adults with dementia, that would greatly benefit from physical activity interventions.


Assuntos
Acelerometria , Demência , Exercício Físico , Hospitalização , Humanos , Demência/mortalidade , Masculino , Feminino , Idoso de 80 Anos ou mais , Idoso , Alta do Paciente
6.
Br J Pharmacol ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38852992

RESUMO

BACKGROUND AND PURPOSE: Only limited therapeutic agents have been developed for non-alcoholic steatohepatitis (NASH). Glabridin, a promising anti-obesity candidate, has only limited druggability due to its low in vivo chemical stability and bioavailability. Therefore, we developed vutiglabridin (VUTI), which is based on a glabridin backbone, and investigated its mechanism of action in treating NASH in animal models. EXPERIMENTAL APPROACH: Anti-NASH effects of VUTI were determined in in vitro fatty liver models, spheroids of primary human hepatocytes and L02 normal liver cell lines. To identify VUTI possible cellular target/s, biotin-labelled VUTI was synthesized and underwent chemical proteomic analysis. Further, the evaluation of VUTI therapeutic efficacy was carried out using an amylin-NASH and high-fat (HF) diet-induced obese (DIO) mouse models. This was carried out using transcriptomic, lipidomic and proteomic analyses of the livers from the amylin-NASH mouse model. KEY RESULTS: VUTI treatment markedly reduces hepatic steatosis, fibrosis and inflammation by promoting lipid catabolism, activating autophagy and improving mitochondrial dysfunction, all of which are hallmarks of effective NASH treatment. The cellular target of VUTI was identified as paraoxonase 2 (PON2), a newly proposed protein target for the treatment of NASH, VUTI enhanced PON2 activity. The results using PON2 knockdown cells demonstrated that PON2 is important for VUTI- activation of autophagy, promoting mitochondrial function, decreasing oxidative stress and alleviating lipid accumulation under lipotoxic condition. CONCLUSION AND IMPLICATIONS: Our data demonstrated that VUTI is a promising therapeutic for NASH. Targeting PON2 may be important for improving liver function in various immune-metabolic diseases including NASH.

7.
Cancer Epidemiol ; 91: 102594, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38870624

RESUMO

BACKGROUND: We analyzed trends in cancer incidence and regional disparities of eight major types of cancer in Korea. METHODS: This retrospective cohort study used the data of 17 cities/provinces from the Korea Central Cancer Registry (1999-2020) in South Korea. Age-standardized incidence rates (per 100,000 person-years), between-group variance (per 100,000 person-years)2, and annual percentage changes ( %) were calculated for the eight most common malignancies. Joinpoint regression was utilized to identify the points at which significant changes occur in cancer incidence or regional disparity trends over time to characterize these trends. RESULTS: The incidence of stomach cancer decreased as regional disparity decreased and that of colorectal cancer initially increased but recently declined, showing fluctuations in regional disparity. The incidence and regional disparity in liver cancer decreased. The incidence of lung cancer remained stable, with reduced regional disparities. The incidence of breast cancer rose with increasing regional disparity, whereas the incidence of cervical cancer decreased, accompanied by decreased regional disparity. A significant increase in prostate cancer was found, with initially reduced regional disparities but later showed a resurgence. The incidence of thyroid cancer fluctuated alongside variations in regional disparities. CONCLUSION: This study revealed cancer incidence and regional variations in each cancer type in Korea. More studies are needed to understand the underlying factors and potential interventions for reducing cancer incidence and addressing regional disparity.


Assuntos
Neoplasias , Sistema de Registros , Humanos , República da Coreia/epidemiologia , Estudos Retrospectivos , Incidência , Masculino , Feminino , Neoplasias/epidemiologia , Sistema de Registros/estatística & dados numéricos , Pessoa de Meia-Idade , Disparidades nos Níveis de Saúde , Idoso , Adulto
8.
Rehabil Nurs ; 49(4): 115-124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904657

RESUMO

ABSTRACT: The purpose of this secondary data analysis was to describe physical activity and the factors associated with physical activity among older adults living with dementia on medical units in acute care settings. Measures included accelerometry data from the MotionWatch 8, behavioral and psychological symptoms associated with dementia, use of psychotropic medications, subjective reports of activities of daily living and other types of physical activity (e.g., walking to the bathroom, participating in therapy), delirium severity, and medications. The majority of the 204 participants were White (70%) and female (62%), with a mean age of 83 years. Over 24 hours of assessment, participants engaged in 15 ( SD = 46) minutes of vigorous activity, 43 ( SD = 54) minutes of moderate activity, 2 hours 50 ( SD = 2) minutes of low-level activity, and 20 ( SD = 3) hours of sedentary activity. Subjective walking activities, toileting, evidence of disinhibition, delirium severity, agitation, and use of psychotropic medications were associated with increased physical activity based on the MotionWatch 8. The findings provide information for rehabilitation nurses regarding factors associated with physical activity among patients with dementia admitted to acute care settings as well as some of the challenges associated with measurement of physical activity. Future research needs to continue to explore the impact of behavioral symptoms associated with dementia on physical activity and increase participation in activities that are functionally relevant.


Assuntos
Acelerometria , Demência , Exercício Físico , Humanos , Feminino , Masculino , Idoso de 80 Anos ou mais , Demência/psicologia , Demência/complicações , Idoso , Exercício Físico/psicologia , Acelerometria/métodos , Hospitalização/estatística & dados numéricos , Atividades Cotidianas/psicologia
9.
J Clin Oncol ; : JCO2302374, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38843479

RESUMO

PURPOSE: Current studies of the efficacy of scalp cooling are limited by short-term duration. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of scalp cooling in reducing persistent chemotherapy-induced alopecia (PCIA) 6 months after chemotherapy. METHODS: We conducted an open-label randomized controlled trial comparing scalp cooling versus control in newly diagnosed patients with breast cancer stages I-III scheduled to receive neoadjuvant or adjuvant chemotherapy with curative intent between December 2020 and August 2021. Patients were randomly assigned (2:1 ratio) to scalp cooling or usual clinical practice. The primary outcome was PCIA 6 months after chemotherapy. Hair thickness and density were measured using Folliscope 5.0. CIA-related distress was assessed using the CIA distress scale (CADS), with a higher score reflecting higher stress. RESULTS: The proportion of patients with PCIA at 6 months was 13.5% (12/89) in the scalp-cooling group and 52.0% (26/50) in the control group. The average difference in the change in hair thickness from baseline between the scalp-cooling and control groups was 9.0 µm in favor of the intervention group. The average difference in the change in hair density between intervention and control at the end of the study was -3.3 hairs/cm2. At 6 months after chemotherapy, the average difference in the change in CADS score between the intervention and control groups was -3.2 points, reflecting reduced CIA-related stress in the intervention group. CONCLUSION: Scalp cooling reduced the incidence of PCIA, primarily by increasing hair thickness compared with control. Scalp cooling is helpful in promoting qualitative hair regrowth. Yet, further research is necessary to observe longer-term benefits of scalp cooling.

10.
Exp Mol Med ; 56(7): 1501-1512, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38945961

RESUMO

Recent substantial evidence implicating commensal bacteria in human diseases has given rise to a new domain in biomedical research: microbiome medicine. This emerging field aims to understand and leverage the human microbiota and derivative molecules for disease prevention and treatment. Despite the complex and hierarchical organization of this ecosystem, most research over the years has relied on 16S amplicon sequencing, a legacy of bacterial phylogeny and taxonomy. Although advanced sequencing technologies have enabled cost-effective analysis of entire microbiota, translating the relatively short nucleotide information into the functional and taxonomic organization of the microbiome has posed challenges until recently. In the last decade, genome-resolved metagenomics, which aims to reconstruct microbial genomes directly from whole-metagenome sequencing data, has made significant strides and continues to unveil the mysteries of various human-associated microbial communities. There has been a rapid increase in the volume of whole metagenome sequencing data and in the compilation of novel metagenome-assembled genomes and protein sequences in public depositories. This review provides an overview of the capabilities and methods of genome-resolved metagenomics for studying the human microbiome, with a focus on investigating the prokaryotic microbiota of the human gut. Just as decoding the human genome and its variations marked the beginning of the genomic medicine era, unraveling the genomes of commensal microbes and their sequence variations is ushering us into the era of microbiome medicine. Genome-resolved metagenomics stands as a pivotal tool in this transition and can accelerate our journey toward achieving these scientific and medical milestones.


Assuntos
Metagenoma , Metagenômica , Microbiota , Humanos , Metagenômica/métodos , Microbiota/genética , Bactérias/genética , Bactérias/classificação , Animais , Genoma Bacteriano , Microbioma Gastrointestinal/genética
11.
Clin Mol Hepatol ; 30(3): 539-560, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38741238

RESUMO

BACKGROUND/AIMS: The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells. METHODS: Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively. RESULTS: We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function. CONCLUSION: Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.


Assuntos
Vírus da Hepatite B , Hepatócitos , Proteínas Nucleares , Transativadores , Replicação Viral , Vírus da Hepatite B/fisiologia , Humanos , Transativadores/metabolismo , Transativadores/genética , Animais , Camundongos , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Hepatócitos/metabolismo , Hepatócitos/citologia , Hepatócitos/virologia , Células Hep G2 , Hepatite B/metabolismo , Interferon gama/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , DNA Viral/metabolismo , Proteínas Virais Reguladoras e Acessórias
12.
Geriatr Nurs ; 57: 117-122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640645

RESUMO

Effective staff-patient communication is critical in acute care settings, particularly for patients with dementia. Limited work has examined the impact of quality of staff-patient care interactions on patient engagement. The purpose of this study was to determine whether the quality of staff-patient care interactions were associated with active patient engagement during the interaction after controlling for relevant covariates. The study was a secondary data analysis using baseline data from the Function Focused Care for Acute Care intervention study, with a total sample of 286 patients. Descriptive statistics and a generalized linear mixed model were used. The findings indicated that there was a significant relationship between the quality of care interactions and patient engagement such that receiving positive care interactions resulted in higher odds of active patient engagement. These findings can inform future interventions and training for acute care staff to improve quality of care interactions and patient engagement.


Assuntos
Demência , Participação do Paciente , Qualidade da Assistência à Saúde , Humanos , Demência/enfermagem , Masculino , Feminino , Idoso , Comunicação , Idoso de 80 Anos ou mais , Relações Profissional-Paciente
13.
J Behav Health Serv Res ; 51(3): 451-461, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38514477

RESUMO

Integrated health care (IHC) is efficacious, cost-effective, and more attractive to some consumers than traditional standalone psychotherapy, but the specific characteristics of IHC that drive this enhanced attraction have yet to be explored among potential future mental health consumers. As such, this brief report documents the results of a survey of 428 US adults who were asked to rank order the relative personal importance of seven characteristics (e.g., self-stigma mitigation, prompt appointment, saving money). These seven characteristics have been characterized in the IHC literature as potential beneficial elements of seeking mental health care from a provider in certain integrated health care settings. Getting sufficient information about one's health and treatment from one's provider was rated as most important, whereas co-location of mental/medical care and treatment privacy were rated as least important. The authors found evidence for select hypothesized demographic effects (e.g., interprovider communication rated more important for older adults) on how these factors were ranked. Professionals invested in developing and improving mental health care systems that are attractive and accessible to consumers in need of mental health care can consider the present findings when making decisions about which characteristics (e.g., getting sufficient information) should be maximized in the design and marketing of such systems. Future research, particularly longitudinal studies that assess prospective treatment seeking behavior, can build on the present study by examining the degree to which these attributes attract consumers to IHC settings.


Assuntos
Prestação Integrada de Cuidados de Saúde , Transtornos Mentais , Serviços de Saúde Mental , Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Transtornos Mentais/terapia , Estados Unidos , Idoso , Adulto Jovem , Adolescente
14.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542316

RESUMO

Nardostachys jatamansi is widely used as a traditional medicine in Asian countries. Numerous recent studies have reported the biological activities of its secondary metabolites and extracts. In this study, a total of 14 components were isolated, including cycloolivil and 2-(3'-hydroxy-5'-ethoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5-carboxylic acid, which were first discovered in N. jatamansi. The isolated compounds were investigated for their anti-inflammatory effects on HaCaT keratinocytes and their potential to alleviate skin inflammation. The results of the screening revealed that cycloolivil and 4ß-hydroxy-8ß-methoxy-10-methylene-2,9-dioxatricyclo[4.3.1.03,7]decane reduced the production of inflammatory cytokines induced by TNF-α/IFN-γ, such as IL-6, IL-8, and RANTES, in keratinocytes. This study focused on exploring the biological effects of cycloolivil, and the results suggested that cycloolivil inhibits the expression of COX-2 proteins. Further mechanistic evaluations confirmed that the anti-inflammatory effects of cycloolivil were mediated by blockage of the NF-κB and JAK/STAT signaling pathways. These results suggest that cycloolivil isolated from N. jatamansi could be used to treat skin inflammatory diseases.


Assuntos
NF-kappa B , Nardostachys , Fenóis , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Nardostachys/metabolismo , Interferon gama/metabolismo , Queratinócitos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo
15.
Nano Converg ; 11(1): 9, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38416323

RESUMO

Artificial neural networks (ANNs), inspired by the human brain's network of neurons and synapses, enable computing machines and systems to execute cognitive tasks, thus embodying artificial intelligence (AI). Since the performance of ANNs generally improves with the expansion of the network size, and also most of the computation time is spent for matrix operations, AI computation have been performed not only using the general-purpose central processing unit (CPU) but also architectures that facilitate parallel computation, such as graphic processing units (GPUs) and custom-designed application-specific integrated circuits (ASICs). Nevertheless, the substantial energy consumption stemming from frequent data transfers between processing units and memory has remained a persistent challenge. In response, a novel approach has emerged: an in-memory computing architecture harnessing analog memory elements. This innovation promises a notable advancement in energy efficiency. The core of this analog AI hardware accelerator lies in expansive arrays of non-volatile memory devices, known as resistive processing units (RPUs). These RPUs facilitate massively parallel matrix operations, leading to significant enhancements in both performance and energy efficiency. Electrochemical random-access memory (ECRAM), leveraging ion dynamics in secondary-ion battery materials, has emerged as a promising candidate for RPUs. ECRAM achieves over 1000 memory states through precise ion movement control, prompting early-stage research into material stacks such as mobile ion species and electrolyte materials. Crucially, the analog states in ECRAMs update symmetrically with pulse number (or voltage polarity), contributing to high network performance. Recent strides in device engineering in planar and three-dimensional structures and the understanding of ECRAM operation physics have marked significant progress in a short research period. This paper aims to review ECRAM material advancements through literature surveys, offering a systematic discussion on engineering assessments for ion control and a physical understanding of array-level demonstrations. Finally, the review outlines future directions for improvements, co-optimization, and multidisciplinary collaboration in circuits, algorithms, and applications to develop energy-efficient, next-generation AI hardware systems.

16.
Sci Rep ; 14(1): 5030, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424356

RESUMO

Synaptic transistors (STs) with a gate/electrolyte/channel stack, where mobile ions are electrically driven across the solid electrolyte, have been considered as analog weight elements for neuromorphic computing. The current (ID) between the source and drain in the ST is analogously updated by gate voltage (VG) pulses, enabling high pattern recognition accuracy in neuromorphic systems; however, the governing physical mechanisms of the ST are not fully understood yet. Our previous physics-based simulation study showed that ion movement in the electrolyte, rather than the electrochemical reactions that occur in the channel, plays an important role in switching. In this study, we experimentally explore the properties of the HfOx electrolyte and show that by tuning the density of oxygen vacancies, it can assume the dual role of electrolyte and channel. We demonstrate analog synaptic behavior using a novel ST with a two-layer stack of CuOx/HfOx, where the CuOx is the gate and Cu ion reservoir, and the HfOx is the electrolyte and channel. To improve state retention and linearity, we introduce a Cu ion transport barrier in the form of a dense and stoichiometric Al2O3 layer. The CuOx/Al2O3/HfOx exhibits excellent state retention and improved potentiation and depression response. Energy dispersive spectroscopy mapping following potentiation confirms the role of the Al2O3 layer in confining the Cu ions in the HfOx layer. We also show that a two-step programming scheme can further enhance synaptic response and demonstrate high recognition accuracy on the Fashion-MNIST dataset in simulation.

17.
bioRxiv ; 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38405704

RESUMO

Neural networks have emerged as immensely powerful tools in predicting functional genomic regions, notably evidenced by recent successes in deciphering gene regulatory logic. However, a systematic evaluation of how model architectures and training strategies impact genomics model performance is lacking. To address this gap, we held a DREAM Challenge where competitors trained models on a dataset of millions of random promoter DNA sequences and corresponding expression levels, experimentally determined in yeast, to best capture the relationship between regulatory DNA and gene expression. For a robust evaluation of the models, we designed a comprehensive suite of benchmarks encompassing various sequence types. While some benchmarks produced similar results across the top-performing models, others differed substantially. All top-performing models used neural networks, but diverged in architectures and novel training strategies, tailored to genomics sequence data. To dissect how architectural and training choices impact performance, we developed the Prix Fixe framework to divide any given model into logically equivalent building blocks. We tested all possible combinations for the top three models and observed performance improvements for each. The DREAM Challenge models not only achieved state-of-the-art results on our comprehensive yeast dataset but also consistently surpassed existing benchmarks on Drosophila and human genomic datasets. Overall, we demonstrate that high-quality gold-standard genomics datasets can drive significant progress in model development.

18.
Qual Life Res ; 33(5): 1287-1295, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38321193

RESUMO

PURPOSE: This study evaluated the association between social support during the re-entry period and long-term health-related quality of life (HRQoL) in breast cancer survivors using a longitudinal cohort study. METHODS: This is a prospective cohort study with 275 breast cancer survivors who reported HRQoL at 5 and 10 years after diagnosis. Social support for the re-entry period was measured 3 years after diagnosis using the Medical Outcome Study Social Support Survey (MOS-SSS). HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Breast Cancer-Specific Module (BR-23). Multivariable linear regression analysis was performed to evaluate HRQoL at 5 and 10 years after diagnosis by level of social support during the re-entry period. RESULTS: The mean (SD) of social support during re-entry period was 68.5. The low social support (LSS, score < 55) group during the re-entry period had a significantly lower HRQoL (mean difference = - 12.93) compared to moderate or high social support (MHSS, score ≥ 55) group. 5 and 10 years after diagnosis, the LSS group continued to demonstrate lower HRQoL (5 years: - 7.17; 10 years: - 7.85) compared to the MHSS group. The LSS group were more likely to have lower role and social function scores, and higher fatigue, pain, and financial problems compared to the MHSS group at 10 years after diagnosis. CONCLUSIONS: Breast cancer survivors who received lower social support during the re-entry period were more likely to experience poorer HRQoL in the long term than those who did not.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Qualidade de Vida , Apoio Social , Humanos , Qualidade de Vida/psicologia , Feminino , Neoplasias da Mama/psicologia , Pessoa de Meia-Idade , Estudos Longitudinais , Sobreviventes de Câncer/psicologia , Estudos Prospectivos , Inquéritos e Questionários , Adulto , Idoso
20.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338851

RESUMO

The most commonly used chemotherapy for colorectal cancer (CRC) is the application of 5-fluorouracil (5-FU). Inhibition of thymidylate synthase (TYMS) expression appears to be a promising strategy to overcome the decreased sensitivity to 5-FU caused by high expression of TYMS, which can be induced by 5-FU treatment. Several compounds have been shown to potentially inhibit the expression of TYMS, but it is unclear whether short-chain fatty acids (SCFAs), which are naturally produced by bacteria in the human intestine, can regulate the expression of TYMS. Sodium butyrate (NaB) is the most widely known SCFA for its beneficial effects. Therefore, we investigated the enhancing effects on inhibition of cell viability and induction of apoptosis after co-treatment of NaB with 5-FU in two CRC cell lines, HCT116 and LoVo. This study suggests that the effect of NaB in improving therapeutic sensitivity to 5-FU in CRC cells may result from a mechanism that strongly inhibits the expression of TYMS. This study also shows that NaB inhibits the migration of CRC cells and can cause cell cycle arrest in the G2/M phase. These results suggest that NaB could be developed as a potential therapeutic adjuvant to improve the therapeutic effect of 5-FU in CRC.


Assuntos
Neoplasias Colorretais , Timidilato Sintase , Humanos , Ácido Butírico/farmacologia , Timidilato Sintase/genética , Timidilato Sintase/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Apoptose
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