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Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR [db/db (diabetes)] and leptin [ob/ob (obese)] are not identical, and the cause remains unclear. Here, we show that db/db, but not ob/ob, mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4 (angiopoietin-like protein 4), a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1+ mesenchymal cells at the HO site, thus promotes chondrogenesis and HO development. Disruption of LepR in PRRX1+ cells, or lineage ablation of LepR+ cells, or deletion of ANGPTL4 impeded chondrogenesis and HO in mice. Together, these findings identify ANGPTL4 as a ligand for LepR to regulate the formation of acquired HO.
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Leptina , Osificación Heterotópica , Animales , Ratones , Leptina/genética , Ligandos , Ratones Endogámicos C57BL , Osteogénesis , Receptores de Leptina/genética , Receptores de Leptina/metabolismoRESUMEN
CYP78A, a cytochrome P450 subfamily that includes rice (Oryza sativa L.) BIG GRAIN2 (BG2, CYP78A13) and Arabidopsis thaliana KLUH (KLU, CYP78A5), generate an unknown mobile growth signal (referred to as a CYP78A-derived signal) that increases grain (seed) size. However, the mechanism by which the CYP78A pathway increases grain size remains elusive. Here, we characterized a rice small grain mutant, small grain4 (smg4), with smaller grains than its wild type due to restricted cell expansion and cell proliferation in spikelet hulls. SMG4 encodes a multidrug and toxic compound extrusion (MATE) transporter. Loss of function of SMG4 causes smaller grains while overexpressing SMG4 results in larger grains. SMG4 is mainly localized to endoplasmic reticulum (ER) exit sites (ERESs) and partially localized to the ER and Golgi. Biochemically, SMG4 interacts with coat protein complex â ¡ (COPâ ¡) components (Sar1, Sec23, and Sec24) and CYP78As (BG2, GRAIN LENGTH 3.2 [GL3.2], and BG2-LIKE 1 [BG2L1]). Genetically, SMG4 acts, at least in part, in a common pathway with Sar1 and CYP78As to regulate grain size. In summary, our findings reveal a CYP78As-SMG4-COPâ ¡ regulatory pathway for grain size in rice, thus providing new insights into the molecular and genetic regulatory mechanism of grain size.
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Arabidopsis , Oryza , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Grano Comestible/genética , Semillas/genética , Arabidopsis/genéticaRESUMEN
Modern longitudinal studies collect multiple outcomes as the primary endpoints to understand the complex dynamics of the diseases. Oftentimes, especially in clinical trials, the joint variation among the multidimensional responses plays a significant role in assessing the differential characteristics between two or more groups, rather than drawing inferences based on a single outcome. We develop a projection-based two-sample significance test to identify the population-level difference between the multivariate profiles observed under a sparse longitudinal design. The methodology is built upon widely adopted multivariate functional principal component analysis to reduce the dimension of the infinite-dimensional multi-modal functions while preserving the dynamic correlation between the components. The test applies to a wide class of (non-stationary) covariance structures of the response, and it detects a significant group difference based on a single p-value, thereby overcoming the issue of adjusting for multiple p-values that arise due to comparing the means in each of components separately. Finite-sample numerical studies demonstrate that the test maintains the type-I error, and is powerful to detect significant group differences, compared to the state-of-the-art testing procedures. The test is carried out on two significant longitudinal studies for Alzheimer's disease and Parkinson's disease (PD) patients, namely, TOMMORROW study of individuals at high risk of mild cognitive impairment to detect differences in the cognitive test scores between the pioglitazone and the placebo groups, and Azillect study to assess the efficacy of rasagiline as a potential treatment to slow down the progression of PD.
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Micropterus salmoides rhabdovirus (MSRV) is an important pathogen of largemouth bass. Despite extensive research, the functional receptors of MSRV remained unknown. This study identified the host protein, laminin receptor (LamR), as a cellular receptor facilitating MSRV entry into host cells. Our results demonstrated that LamR directly interacts with MSRV G protein, playing a pivotal role in the attachment and internalization processes of MSRV. Knockdown of LamR with siRNA, blocking cells with LamR antibody, or incubating MSRV virions with soluble LamR protein significantly reduced MSRV entry. Notably, we found that LamR mediated MSRV entry via clathrin-mediated endocytosis. Additionally, our findings revealed that MSRV G and LamR were internalized into cells and co-localized in the early and late endosomes. These findings highlight the significance of LamR as a cellular receptor facilitating MSRV binding and entry into target cells through interaction with the MSRV G protein. IMPORTANCE: Despite the serious epidemic caused by Micropterus salmoides rhabdovirus (MSRV) in largemouth bass, the precise mechanism by which it invades host cells remains unclear. Here, we determined that laminin receptor (LamR) is a novel target of MSRV, that interacts with its G protein and is involved in viral attachment and internalization, transporting with MSRV together in early and late endosomes. This is the first report demonstrating that LamR is a cellular receptor in the MSRV life cycle, thus contributing new insights into host-pathogen interactions.
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Enfermedades de los Peces , Receptores de Laminina , Rhabdoviridae , Internalización del Virus , Animales , Receptores de Laminina/metabolismo , Rhabdoviridae/metabolismo , Rhabdoviridae/fisiología , Enfermedades de los Peces/virología , Enfermedades de los Peces/metabolismo , Lubina/virología , Lubina/metabolismo , Receptores Virales/metabolismo , Infecciones por Rhabdoviridae/virología , Infecciones por Rhabdoviridae/metabolismo , EndocitosisRESUMEN
Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development.
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Oryza , Regulación de la Expresión Génica de las Plantas , Ribonucleoproteínas Nucleares Heterogéneas , Lactonas , Mutación , Proteínas de Plantas , Precursores del ARNRESUMEN
BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. CONCLUSION: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.
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Epilepsias Parciales , Proteínas de Homeodominio , Espasmos Infantiles , Animales , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Epilepsias Parciales/genética , Epilepsias Parciales/tratamiento farmacológico , Secuenciación del Exoma , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Mutación , Espasmos Infantiles/genética , DrosophilaRESUMEN
Under the irradiation of an ultrafast intense laser, solid materials can be driven into nonequilibrium states undergoing an ultrafast solid-liquid phase transition. Understanding such nonequilibrium states is essential for scientific research and industrial applications because they exist in various processes including laser fusion and laser machining yet challenging in the sense that high resolution and single-shot capability are required for the measurements. Herein, an ultrafast diffraction technique with megaelectron-volt (MeV) electrons is used to resolve the atomic pathway over the entire laser-induced ultrafast melting process, from the initial loss of long-range order and the formation of high-density liquid to the progressive evolution of short-range order and relaxation into the metastable low-density liquid state. High-resolution measurements using electron pulse compression and a time-stamping technique reveal a coherent breathing motion of polyhedral clusters in transient liquid aluminum during the ultrafast melting process, as indicated by the oscillation of the interatomic distance between the center atom and atoms in the nearest-neighbor shell. Furthermore, contraction of interatomic distance was observed in a superheated liquid state with temperatures up to 6,000 K. The results provide an atomic view of melting accompanied with internal pressure relaxation and are critical for understanding the structures and properties of matter under extreme conditions.
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The HKT transporter plays an important role for plants in response to salt stress, but the transport property of the soybean HKT transporters at the molecular level is still unclear. Here, using Xenopus oocyte as a heterologous expression system and two-electrode voltage-clamp technique, we identified four HKT transporters, GmHKT1;1, GmHKT1;2, GmHKT1;3, and GmHKT1;4, which all belong to type I subfamily, but having distinct ion transport properties. While GmHKT1;1, GmHKT1;2 and GmHKT1;3 function as Na+ transporters, GmHKT1;1 is less selective against K+ than the two other transporters. Astonishingly, GmHKT1;4, which lacks transmembrane segments and has no ion permeability, is significantly expressed, and its gene expression pattern is different from the other three GmHKTs under salt stress. Interestingly, GmHKT1;4 reduced the Na+/K+ currents mediated by GmHKT1;1. Further study showed that the transport ability of GmHKT1;1 regulated by GmHKT1;4 was related to the structural differences in the first intracellular domain and the fourth repeat domain. Overall, we have identified one unique GmHKT member, GmHKT1;4, which modulates the Na+ and K+ transport ability of GmHKT1;1 via direct interaction. Thus, we have revealed a new type of HKTs interaction model for altering their ion transport properties.
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BACKGROUND: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS: Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).
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Trastorno del Espectro Autista/tratamiento farmacológico , Oxitocina/administración & dosificación , Conducta Social , Administración Intranasal , Adolescente , Trastorno del Espectro Autista/psicología , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Oxitocina/efectos adversos , Oxitocina/uso terapéutico , Habilidades Sociales , Insuficiencia del TratamientoRESUMEN
PURPOSE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting. METHODS: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses. RESULTS: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44]. CONCLUSION: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Terapia Neoadyuvante/efectos adversos , Modelos de Riesgos Proporcionales , Receptor ErbB-2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , PronósticoRESUMEN
IMPORTANCE: Although Micropterus salmoides rhabdovirus (MSRV) causes serious fish epidemics worldwide, the detailed mechanism of MSRV entry into host cells remains unknown. Here, we comprehensively investigated the mechanism of MSRV entry into epithelioma papulosum cyprinid (EPC) cells. This study demonstrated that MSRV enters EPC cells via a low pH, dynamin-dependent, microtubule-dependent, and clathrin-mediated endocytosis. Subsequently, MSRV transports from early endosomes to late endosomes and further into lysosomes in a microtubule-dependent manner. The characterization of MSRV entry will further advance the understanding of rhabdovirus cellular entry pathways and provide novel targets for antiviral drug against MSRV infection.
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Lubina , Rhabdoviridae , Animales , Rhabdoviridae/metabolismo , Lubina/metabolismo , Proteínas de Unión al GTP rab5/metabolismo , Endocitosis , Dinaminas/metabolismo , Microtúbulos/metabolismo , Clatrina/metabolismo , Concentración de Iones de Hidrógeno , Internalización del VirusRESUMEN
Imaging genetics provides unique insights into the pathological studies of complex brain diseases by integrating the characteristics of multi-level medical data. However, most current imaging genetics research performs incomplete data fusion. Also, there is a lack of effective deep learning methods to analyze neuroimaging and genetic data jointly. Therefore, this paper first constructs the brain region-gene networks to intuitively represent the association pattern of pathogenetic factors. Second, a novel feature information aggregation model is constructed to accurately describe the information aggregation process among brain region nodes and gene nodes. Finally, a deep learning method called feature information aggregation and diffusion generative adversarial network (FIAD-GAN) is proposed to efficiently classify samples and select features. We focus on improving the generator with the proposed convolution and deconvolution operations, with which the interpretability of the deep learning framework has been dramatically improved. The experimental results indicate that FIAD-GAN can not only achieve superior results in various disease classification tasks but also extract brain regions and genes closely related to AD. This work provides a novel method for intelligent clinical decisions. The relevant biomedical discoveries provide a reliable reference and technical basis for the clinical diagnosis, treatment and pathological analysis of disease.
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Encefalopatías , Neuroimagen , Humanos , Neuroimagen/métodos , Encéfalo/diagnóstico por imagen , Encefalopatías/diagnóstico por imagen , Encefalopatías/genéticaRESUMEN
The roles of brain regions activities and gene expressions in the development of Alzheimer's disease (AD) remain unclear. Existing imaging genetic studies usually has the problem of inefficiency and inadequate fusion of data. This study proposes a novel deep learning method to efficiently capture the development pattern of AD. First, we model the interaction between brain regions and genes as node-to-node feature aggregation in a brain region-gene network. Second, we propose a feature aggregation graph convolutional network (FAGCN) to transmit and update the node feature. Compared with the trivial graph convolutional procedure, we replace the input from the adjacency matrix with a weight matrix based on correlation analysis and consider common neighbor similarity to discover broader associations of nodes. Finally, we use a full-gradient saliency graph mechanism to score and extract the pathogenetic brain regions and risk genes. According to the results, FAGCN achieved the best performance among both traditional and cutting-edge methods and extracted AD-related brain regions and genes, providing theoretical and methodological support for the research of related diseases.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Encéfalo/diagnóstico por imagen , Diagnóstico por Imagen , HumanosRESUMEN
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease where, in advanced stages, clinical and pathologic stages do not correlate with outcome. Molecular and genomic biomarkers for HNSCC classification have shown promise for prognostic and therapeutic applications. This study utilized automated image analysis techniques in whole-slide images of HNSCC tumors to identify relationships between cytometric features and genomic phenotypes. Hematoxylin and eosin-stained slides of HNSCC tumors (N = 49) were obtained from The Cancer Imaging Archive, along with accompanying clinical, pathologic, genomic, and proteomic reports. Automated nuclear detection was performed across the entirety of slides, and cytometric feature maps were generated. Forty-one cytometric features were evaluated for associations with tumor grade, tumor stage, tumor subsite, and integrated genomic subtype. Thirty-two features demonstrated significant association with integrated genomic subtype when corrected for multiple comparisons. In particular, the basal subtype was visually distinguishable from the chromosomal instability and immune subtypes based on cytometric feature measurements. No features were significantly associated with tumor grade, stage, or subsite. This study provides preliminary evidence that features derived from tissue pathology slides could provide insights into genomic phenotypes of HNSCC.
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Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/genética , Proteómica , Genómica , Pronóstico , Biomarcadores de Tumor/genéticaRESUMEN
There is a close regulatory relationship between the circadian clock and the abscisic acid (ABA) signaling pathway in regulating many developmental processes and stress responses. However, the exact feedback regulation mechanism between them is still poorly understood. Here, we identified the rice (Oryza sativa) clock component PSEUDO-RESPONSE REGULATOR 95 (OsPRR95) as a transcriptional regulator that accelerates seed germination and seedling growth by inhibiting ABA signaling. We also found that OsPRR95 binds to the ABA receptor gene REGULATORY COMPONENTS OF ABA RECEPTORS10 (OsRCAR10) DNA and inhibits its expression. Genetic analysis showed OsRCAR10 acts downstream of OsPRR95 in mediating ABA responses. In addition, the induction of OsPRR95 by ABA partly required a functional OsRCAR10, and the ABA-responsive element-binding factor ABSCISIC ACID INSENSITIVE5 (OsABI5) bound directly to the promoter of OsPRR95 and activated its expression, thus establishing a regulatory feedback loop between OsPRR95, OsRCAR10, and OsABI5. Taken together, our results demonstrated that the OsRCAR10-OsABI5-OsPRR95 feedback loop modulates ABA signaling to fine-tune seed germination and seedling growth, thus establishing the molecular link between ABA signaling and the circadian clock.
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Arabidopsis , Relojes Circadianos , Oryza , Ácido Abscísico/metabolismo , Oryza/metabolismo , Relojes Circadianos/genética , Arabidopsis/genética , Germinación/fisiología , Plantones/metabolismo , Semillas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Phosphorus (P) has crucial roles in plant growth and development. Hydrogen sulphide (H2S) has multiple functions in plants, particularly having the ability to promote tolerance to a variety of adversity stresses. However, it is unclear whether H2S has a function when plants suffer Pi-deficiency stress. DES1, encoding L-cysteine desulfhydrase1, is a crucial source of H2S in Arabidopsis thaliana by catalysing the substrate L-cysteine. Under phosphate starvation, the des1 mutant had a significantly shorter primary root length than the wild-type Col-0, and exogenous application of H2S donor NaHS could compensate for the root growth-sensitive phenotype. In contrast, the transgenic lines DES1ox overexpressing DES1 exhibited less sensitivity to phosphate starvation in terms of longer roots compared to the Col-0. These results demonstrate that H2S is involved in the regulation of Arabidopsis root growth under phosphate starvation. Moreover, using quantitative real-time polymerase chain reaction experiments to analyse the changes in genes induced by phosphate starvation in des1 mutant and Col-0, we screened to find that the expression of the Sulfoquinovosyl diacylglycerol 1 (SQD1) gene was significantly downregulated in the des1 mutant. Consistently, exogenous H2S significantly promoted SQD1 expression levels in roots of Col-0. Taken together, we demonstrate that DES1-mediated H2S participates in alleviating root growth inhibition by promoting the expression of SQD1 under Pi starvation.
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BACKGROUND: Intensive longitudinal data (ILD) collected in near real time by mobile health devices provide a new opportunity for monitoring chronic diseases, early disease risk prediction, and disease prevention in health research. Functional data analysis, specifically functional principal component analysis, has great potential to abstract trends in ILD but has not been used extensively in mobile health research. OBJECTIVE: To introduce functional principal component analysis (fPCA) and demonstrate its potential applicability in estimating trends in ILD collected by mobile heath devices, assessing longitudinal association between ILD and health outcomes, and predicting health outcomes. METHODS: fPCA and scalar-to-function regression models were reviewed. A case study was used to illustrate the process of abstracting trends in intensively self-measured blood glucose using functional principal component analysis and then predicting future HbA1c values in patients with type 2 diabetes using a scalar-to-function regression model. RESULTS: Based on the scalar-to-function regression model results, there was a slightly increasing trend between daily blood glucose measures and HbA1c. 61% of variation in HbA1c could be predicted by the three preceding months' blood glucose values measured before breakfast (P < 0.0001, [Formula: see text]). CONCLUSIONS: Functional data analysis, specifically fPCA, offers a unique tool to capture patterns in ILD collected by mobile health devices. It is particularly useful in assessing longitudinal dynamic association between repeated measures and outcomes, and can be easily integrated in prediction models to improve prediction precision.
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Diabetes Mellitus Tipo 2 , Telemedicina , p-Cloroanfetamina/análogos & derivados , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Glucemia , Hemoglobina Glucada , Análisis de Componente Principal , Evaluación de Resultado en la Atención de SaludRESUMEN
Micropterus salmoides rhabdovirus (MSRV) is one of the main pathogens of largemouth bass, leading to serious economic losses. The G protein, as the only envelope protein present on the surface of MSRV virion, contains immune-related antigenic determinants, thereby becoming the primary target for the design of MSRV vaccines. Here, we displayed the G protein on the surface of yeast cells (named EBY100/pYD1-G) and conducted a preliminary assessment of the protective efficacy of the recombinant yeast vaccine. Upon oral vaccination, a robust immune response was observed in systemic and mucosal tissue. Remarkably, following the MSRV challenge, the relative percent survival of EBY100/pYD1-G treated largemouth bass significantly increased to 66.7 %. In addition, oral administration inhibited viral replication and alleviated the pathological symptoms of MSRV-infected largemouth bass. These results suggest that EBY100/pYD1-G could be used as a potential oral vaccine against MSRV infection.
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Lubina , Enfermedades de los Peces , Rhabdoviridae , Animales , Saccharomyces cerevisiae , Vacunación , Proteínas Fúngicas , Vacunas SintéticasRESUMEN
An excitonic insulator (EI) is an intriguing correlated electronic phase of condensed excitons. Ta2NiSe5 is a model material for investigating condensed excitonic states. Herein, femtosecond pump-probe spectroscopy is used to study the coherent phonon dynamics and associated exciton-phonon coupling in single-crystal Ta2NiSe5. The reflectivity time series consists of exponential decay due to hot carriers and damped oscillations due to the Ag phonon vibration. Given the in-plane anisotropic thermal conductivity of Ta2NiSe5, coherent phonon oscillations are stronger with perpendicular polarization to its quasi-one-dimensional chains. The 1-, 2-, and 4-THz vibration modes show coherent amplitude responses in the EI phase of Ta2NiSe5 with increasing temperature, totally different from those of normal coherent phonons (the 3- and 3.7-THz modes). The amplitude modes at higher frequencies decouple with the EI order parameter at lower temperatures, as supported by theoretical analysis with a model Hamiltonian of the exciton-phonon coupling system. Our work provides valuable insights into the character of the EI order parameter and its coupling to multiple coherent amplitude modes.
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PURPOSE: The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT. MATERIALS AND METHODS: Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free-hand, 'moving-shot' technique under US or CT guidance. For lesions invading critical structures intolerant to 'en bloc' high-temperature RFA, limited-field EBRT using 6- or 10-MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed. RESULTS: Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred. CONCLUSIONS: Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.