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1.
Cell ; 170(1): 114-126.e15, 2017 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-28666113

RESUMO

Rice feeds half the world's population, and rice blast is often a destructive disease that results in significant crop loss. Non-race-specific resistance has been more effective in controlling crop diseases than race-specific resistance because of its broad spectrum and durability. Through a genome-wide association study, we report the identification of a natural allele of a C2H2-type transcription factor in rice that confers non-race-specific resistance to blast. A survey of 3,000 sequenced rice genomes reveals that this allele exists in 10% of rice, suggesting that this favorable trait has been selected through breeding. This allele causes a single nucleotide change in the promoter of the bsr-d1 gene, which results in reduced expression of the gene through the binding of the repressive MYB transcription factor and, consequently, an inhibition of H2O2 degradation and enhanced disease resistance. Our discovery highlights this novel allele as a strategy for breeding durable resistance in rice.


Assuntos
Oryza/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Sequência de Bases , Cruzamento , Resistência à Doença , Técnicas de Inativação de Genes , Genoma de Planta , Estudo de Associação Genômica Ampla , Doenças das Plantas , Regiões Promotoras Genéticas
2.
BMC Genomics ; 25(1): 421, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684979

RESUMO

BACKGROUND: Herpetospermum pedunculosum (Ser.) C. B. Clarke is a traditional Chinese herbal medicine that heavily relies on the lignans found in its dried ripe seeds (Herpetospermum caudigerum), which have antioxidant and hepatoprotective functions. However, little is known regarding the lignan biosynthesis in H. pedunculosum. In this study, we used metabolomic (non-targeted UHPLC-MS/MS) and transcriptome (RNA-Seq) analyses to identify key metabolites and genes (both structural and regulatory) associated with lignan production during the green mature (GM) and yellow mature (YM) stages of H. pedunculosum. RESULTS: The contents of 26 lignan-related metabolites and the expression of 30 genes involved in the lignan pathway differed considerably between the GM and YM stages; most of them were more highly expressed in YM than in GM. UPLC-Q-TOF/MS confirmed that three Herpetospermum-specific lignans (including herpetrione, herpetotriol, and herpetin) were found in YM, but were not detected in GM. In addition, we proposed a lignan biosynthesis pathway for H. pedunculosum based on the fundamental principles of chemistry and biosynthesis. An integrated study of the transcriptome and metabolome identified several transcription factors, including HpGAF1, HpHSFB3, and HpWOX1, that were highly correlated with the metabolism of lignan compounds during seed ripening. Furthermore, functional validation assays revealed that the enzyme 4-Coumarate: CoA ligase (4CL) catalyzes the synthesis of hydroxycinnamate CoA esters. CONCLUSION: These results will deepen our understanding of seed lignan biosynthesis and establish a theoretical basis for molecular breeding of H. pedunculosum.


Assuntos
Cucurbitaceae , Lignanas , Metaboloma , Transcriptoma , Lignanas/metabolismo , Lignanas/biossíntese , Cucurbitaceae/genética , Cucurbitaceae/metabolismo , Regulação da Expressão Gênica de Plantas , Sementes/metabolismo , Sementes/genética , Perfilação da Expressão Gênica , Espectrometria de Massas em Tandem
3.
Opt Express ; 32(8): 13986-13997, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859356

RESUMO

The inverse design of meta-optics has received much attention in recent years. In this paper, we propose a GPU-friendly inverse design framework based on improved eigendecomposition-free rigorous diffraction interface theory, which offers up to 16.2 × speedup over the traditional inverse design based on rigorous coupled-wave analysis. We further improve the framework's flexibility by introducing a hybrid parameterization combining neural-implicit and traditional shape optimization. We demonstrate the effectiveness of our framework through intricate tasks, including the inverse design of reconfigurable free-form meta-atoms.

4.
Environ Res ; 250: 118539, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401684

RESUMO

The relationship of exposure to benzo[a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-year median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer cases. The baseline concentrations of benzo[a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI)=0.77 (0.66, 0.91) per SD increment in ln-transformed Zn]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to the highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer.


Assuntos
Benzo(a)pireno , Neoplasias Pulmonares , Zinco , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Benzo(a)pireno/toxicidade , Zinco/sangue , Pessoa de Meia-Idade , Masculino , China/epidemiologia , Feminino , Estudos Prospectivos , Idoso , Exposição Ambiental/efeitos adversos , Predisposição Genética para Doença , Fatores de Risco , Estudos de Casos e Controles , Adulto , Estratificação de Risco Genético , População do Leste Asiático
5.
AAPS PharmSciTech ; 25(2): 35, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332223

RESUMO

Currently, the marketed ophthalmic preparations of pranoprofen (PF) are mainly eye drops, but due to the special clearance mechanism of the eye and corneal reflex, the contact time between the drug and the focal site is short, most of the drug is lost, and the bioavailability is less than 5%. In the present study, an in situ gel eye drop containing no bacteriostatic agent and sensitive to temperature and ions was designed for delivery of PF. It was demonstrated to meet the criteria for ophthalmic preparations by characterization such as appearance content sterility. Ocular irritation tests showed a favorable safety profile. In vivo ocular retention time experiments showed that the ocular retention time of the pranoprofen gel was 4.41 times longer than that of commercially available drops (Pranopulin®), and the nasal tear excretion of the pranoprofen gel was lower than that of Pranopulin®, which suggests that the drug loss was reduced relative to that of the drops. The efficacy of the pranoprofen gel against tincture of cayenne pepper-induced corneal and conjunctival inflammation was examined using Pranopulin® as a control and in conjunction with inflammation scores, H&E slice results, and levels of IL-1ß, IL-6, and TNF-α. The results showed that pranoprofen gel and Pranololin® had significant efficacy in the treatment of corneal and conjunctival inflammation, and the anti-inflammatory effect of pranoprofen gel was superior to that of Pranololin®. This study provides a new option for the treatment of corneal and conjunctival inflammation.


Assuntos
Benzopiranos , Córnea , Propionatos , Humanos , Preparações de Ação Retardada/farmacologia , Inflamação/tratamento farmacológico , Soluções Oftálmicas
6.
Hum Genet ; 142(3): 431-443, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36445456

RESUMO

Pain often occurs in parallel with neuropsychiatric disorders. However, the underlying mechanisms and potential causality have not been well studied. We collected the genome-wide association study (GWAS) summary statistics of 26 common pain and neuropsychiatric disorders with sample size ranging from 17,310 to 482,730 in European population. The genetic correlation between pair of pain and neuropsychiatric disorders, as well as the relevant cell types were investigated by linkage disequilibrium (LD) score regression analyses. Then, transcriptome-wide association study (TWAS) was applied to identify the potential shared genes by integrating the gene expression information and GWAS. In addition, Mendelian randomization (MR) analyses were conducted to infer the potential causality between pain and neuropsychiatric disorders. Among the 169 pairwise pain and neuropsychiatric disorders, 55 pairs showed positive correlations (median rg = 0.43) and 9 pairs showed negative correlations (median rg = -0.31). Using MR analyses, 26 likely causal associations were identified, including that neuroticism and insomnia were risk factors for most of short-term pain, and multisite chronic pain was risk factor for neuroticism, insomnia, major depressive disorder and attention deficit/hyperactivity disorder, and vice versa. The signals of pain and neuropsychiatric disorders tended to be enriched in the functional regions of cell types from central nervous system (CNS). A total of 19 genes shared in at least one pain and neuropsychiatric disorder pair were identified by TWAS, including AMT, NCOA6, and UNC45A, which involved in glycine degradation, insulin secretion, and cell proliferation, respectively. Our findings provided the evidence of shared genetic structure, causality and potential shared pathogenic mechanisms between pain and neuropsychiatric disorders, and enhanced our understanding of the comorbidities of pain and neuropsychiatric disorders.


Assuntos
Transtorno Depressivo Maior , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/complicações , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Causalidade , Dor/complicações , Análise da Randomização Mendeliana , Peptídeos e Proteínas de Sinalização Intracelular/genética
7.
Mol Phylogenet Evol ; 186: 107860, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37329932

RESUMO

Species richness is spatially heterogeneous even in the hyperdiverse tropical floras. The main cause of uneven species richness among the four tropical regions are hot debated. To date, higher net diversification rates and/or longer colonization time have been usually proposed to contribute to this pattern. However, there are few studies to clarify the species richness patterns in tropical terrestrial floras. The terrestrial tribe Collabieae (Orchidaceae) unevenly distributes in the tropical regions with a diverse and endemic center in Asia. Twenty-one genera 127 species of Collabieae and 26 DNA regions were used to reconstruct the phylogeny and infer the biogeographical processes. We compared the topologies, diversification rates and niche evolutionary rates of Collabieae and regional lineages on empirical samplings and different simulated samplings fractions respectively. Our results suggested that the Collabieae originated in Asia at the earliest Oligocene, and then independently spread to Africa, Central America, and Oceania since the Miocene via long-distance dispersal. These results based on empirical data and simulated data were similar. BAMM, GeoSSE and niche analyses inferred that the Asian lineages had higher net diversification and niche evolutionary rates than those of Oceanian and African lineages on the empirical and simulated analyses. Precipitation is the most important factor for Collabieae, and the Asian lineage has experienced more stable and humid climate, which may promote the higher net diversification rate. Besides, the longer colonization time may also be associated with the Asian lineages' diversity. These findings provided a better understanding of the regional diversity heterogeneity in tropical terrestrial herbaceous floras.


Assuntos
Orchidaceae , Filogenia , Orchidaceae/genética , Filogeografia , Clima Tropical
8.
Opt Express ; 31(16): 26054-26068, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710475

RESUMO

We present a fully differentiable framework for seamlessly integrating wave optical components with geometrical lenses, offering an approach to enhance the performance of large-scale end-to-end optical systems. In this study, we focus on the integration of a metalens, a geometrical lens, and image data. Through the use of gradient-based optimization techniques, we demonstrate the design of nonparaxial imaging systems and the correction of aberrations inherent in geometrical optics. Our framework enables efficient and effective optimization of the entire optical system, leading to improved overall performance.

9.
Microb Pathog ; 184: 106335, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37673353

RESUMO

BACKGROUND: Increasing studies have shown that the imbalance of the respiratory microbial flora is related to the occurrence of COPD, the severity and frequency of exacerbations and mortality.However, it remains unclear how the sputum microbial flora differs during exacerbations in COPD patients manifesting emphysema phenotype, chronic bronchitis with emphysema phenotype and asthma-COPD overlap phenotype. METHODS: Sputum samples were obtained from 29 COPD patients experiencing acute exacerbations who had not received antibiotics or systemic corticosteroids within the past four weeks.Patients were divided into three groups;emphysema phenotype(E);chronic bronchitis with emphysema phenotype(B+E) and asthma-COPD overlap phenotype(ACO).We utilized metagenomic Next Generation Sequencing (mNGS) technology to analyze the sputum microbial flora in COPD patients with different phenotypes during exacerbations. RESULTS: There was no significant difference in alpha diversity and beta diversity among three groups.The microbial flora composition was similar in all three groups during exacerbations except for a significant increase in Streptococcus mitis in ACO.Through network analysis,we found Candidatus Saccharibacteria oral taxon TM7x and Fusobacterium necrophorum were the core nodes of the co-occurrence network in ACO and E respectively.They were positively correlated with some species and play a synergistic role.In B+E,Haemophilus pittmaniae and Klebsiella pneumoniae had a synergistic effect.Besides,some species among the three groups play a synergistic or antagonistic role.Through Spearman analysis,we found the relative abundance of Streptococcus mitis was negatively correlated with the number of hospitalizations in the past year(r = -0.410,P = 0.027).We also observed that the relative abundance of Prevotella and Prevotella melaninogenica was negatively correlated with age(r = -0.534,P = 0.003;r = -0.567,P = 0.001),while the relative abundance of Streptococcus oralis and Actinomyces odontolyticus was positively correlated with age(r = 0.570,P = 0.001;r = 0.480,P = 0.008).In addition,the relative abundance of Prevotella melaninogenica was negatively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio(r = -0.479,P = 0.009;r = -0.555,P = 0.002),while the relative abundance of Streptococcus sanguinis was positively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio (r = 0.450,P = 0.014;r = 0.501,P = 0.006).There was also a significant positive correlation between Oribacterium and blood eosinophil counts(r = 0.491,P = 0.007). CONCLUSION: Overall,we analyzed the sputum microbiota of COPD patients with different phenotypes and its relationship with clinical indicators, and explored the relationships between microbiota and inflammation in COPD.We hope to alter the prognosis of patients by inhibiting specific bacterial taxa related to inflammation and using guide individualized treatment in the future research.


Assuntos
Asma , Bronquite Crônica , Enfisema , Doença Pulmonar Obstrutiva Crônica , Humanos , Escarro , Fenótipo , Inflamação
10.
Ann Plast Surg ; 90(5): 409-414, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36913561

RESUMO

BACKGROUND: Secondary blepharoplasty to correct a high crease is considered challenging for most surgeons, especially in patients who show overly excessive removal of eyelid tissue in Asians. Therefore, we define a typical difficult secondary blepharoplasty as when patients present too high eyelid fold with excessive tissue resection and preaponeurotic fat deficiency. This study provides the technique of retro-orbicularis oculi fat (ROOF) transferring and volume augmentation to reconstruct eyelid anatomical structure on the base of a series of difficult secondary blepharoplasty cases in Asians and assess the effectiveness of the method in the meanwhile. METHOD: This was a secondary blepharoplasty cases-based retrospective observational study. From October 2016 to May 2021, a total of 206 cases were performed blepharoplasty revision surgery to correct high folds. Among them, a total of 58 cases (6 men, 52 women) diagnosed with difficult blepharoplasty were applied ROOF transferring and volume augmentation to correct high folds and were followed up on time. Depending on the distribution of ROOF of different thicknesses, we designed 3 different methods of harvesting and transferring ROOF flaps. The mean follow-up for patients in our study was 9 months, a range of 6 to 18 months. The postoperative results were reviewed, graded, and analyzed. RESULT: Most patients (89.66%) were satisfied. No postoperative complications were observed, such as infection, dehiscence of incision, tissue necrosis, levator dysfunction, or multiple creases. The mean height of the mid, medial, and lateral eyelid folds decreased from 8.96 ± 0.43, 8.21 ± 0.58, and 7.96 ± 0.53 mm to 6.77 ± 0.55, 6.27 ± 0.57, and 6.65 ± 0.61 mm, respectively. CONCLUSIONS: Retro-orbicularis oculi fat transposition or/and its enhancement contributes significantly to the reconstruction of the physiology of the eyelid structure and provides an available surgical option for the correction of too high folds in blepharoplasty.

11.
Int J Mol Sci ; 24(12)2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37372930

RESUMO

Maize, one of the world's major food crops, is facing the challenge of rising temperature. Leaf senescence is the most significant phenotypic change of maize under heat stress at the seedling stage, but the underlying molecular mechanism is still unknown. Here, we screened for three inbred lines (PH4CV, B73, and SH19B) that showed differentially senescing phenotypes under heat stress. Among them, PH4CV showed no obviously senescing phenotype under heat stress, while SH19B demonstrated a severely senescing phenotype, with B73 being between the two extremes. Subsequently, transcriptome sequencing showed that differentially expressed genes (DEGs) were generally enriched in response to heat stress, reactive oxygen species (ROS), and photosynthesis in the three inbred lines under heat treatment. Notably, ATP synthesis and oxidative phosphorylation pathway genes were only significantly enriched in SH19B. Then, the expression differences of oxidative phosphorylation pathways, antioxidant enzymes, and senescence-related genes in response to heat stress were analyzed in the three inbred lines. In addition, we demonstrated that silencing ZmbHLH51 by virus-induced gene silencing (VIGS) inhibits the heat-stress-induced senescence of maize leaves. This study helps to further elucidate the molecular mechanisms of heat-stress-induced leaf senescence at the seedling stage of maize.


Assuntos
Transcriptoma , Zea mays , Zea mays/metabolismo , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Genes de Plantas , Regulação da Expressão Gênica de Plantas
12.
Int J Mol Sci ; 24(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38139164

RESUMO

Glycyrol (GC) is one natural active product. Imiquimod-induced psoriasis-like Balb/c mouse models were established. The model mice were intraperitoneally injected with cyclosporine A (CsA) and GC for 8 days followed by a series of biological detections. GC had little toxicity according to the levels of peripheral blood cells, hemoglobin, blood urea nitrogen (BUN), and serum creatinine (CRE), while CsA significantly increased the levels of BUN and CRE. GC decreased the splenic index and reduced the expressions of IL-6, IL-23, and CXCL-3 in the model mice and IL-6, CXCL-1, and CXCL-2 in the inflammatory HaCaT cells. The half inhibition concentration (IC50) of GC on HaCaT cells was 29.72 µmol/L, resulting in improved apoptosis, enhanced expressions of p21, BAX, and BIK, and reduced expressions of BCL-2. GC is an immunosuppressive agent against psoriasis-like symptoms by anti-inflammatory effects, which provides a strategy for the discovery of anti-psoriatic natural products.


Assuntos
Dermatite , Psoríase , Camundongos , Animais , Interleucina-6/metabolismo , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Dermatite/metabolismo , Anti-Inflamatórios/efeitos adversos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Imunossupressores/efeitos adversos , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Pele/metabolismo , Citocinas/metabolismo
13.
J Integr Plant Biol ; 65(2): 444-467, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36479615

RESUMO

Precise replacement of an allele with an elite allele controlling an important agronomic trait in a predefined manner by gene editing technologies is highly desirable in crop improvement. Base editing and prime editing are two newly developed precision gene editing systems which can introduce the substitution of a single base and install the desired short indels to the target loci in the absence of double-strand breaks and donor repair templates, respectively. Since their discoveries, various strategies have been attempted to optimize both base editor (BE) and prime editor (PE) in order to improve the precise editing efficacy, specificity, and expand the targeting scopes. Here, we summarize the latest development of various BEs and PEs, as well as their applications in plants. Based on these progresses, we recommend the appropriate BEs and PEs for both basic plant research and crop improvement. Moreover, we propose the perspectives for further optimization of these two editors. We envision that both BEs and PEs will become the routine and customized precise gene editing tools for both plant biological research and crop improvement in the near future.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Plantas/genética , Alelos
14.
J Environ Sci (China) ; 127: 495-507, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36522080

RESUMO

Copper (Cu) exists in a variety of forms in different aquatic environments, and affects their bioavailability. In this study we provide a systematic review on toxicity of Cu which focuses on identifying evidence in the mechanisms of Cu toxicity, and apply an adverse outcome pathway (AOP) analysis to identify multiple potential mechanisms and their interactions of Cu toxicity to fish. This analysis process included the mechanisms of behavior toxicant, oxidative toxicant, ion regulation disruption toxicity, as well as endocrine disruption toxicity. It was found that at low levels of Cu exposure, swimming, avoid predators, locating prey and other sensory functions will be impaired, and the organism will suffer from metabolic alkalosis and respiratory acidosis following the inhibition of the carbonic anhydrase active. The main pathway of acute toxicity of Cu to fish is the inhibition of the Na+/K+-ATPase enzyme, and lead to reduced intracellular sodium absorption, as well as Cu-induced increased cell permeability, in turn resulting in increased sodium ion loss, leading to cardiovascular collapse and respiratory insufficiency. The endocrine disruption toxicity of Cu to fish caused growth inhibition and reproductive reduction. In addition, there are several key pathways of Cu toxicity that are affected by hardness (e.g., Ca2+) and intracellular DOC concentrations, including inhibiting Cu-induction, improving branchial gas exchange, altering membrane transport functions, decreasing Na+ loss, and increasing Na+ uptake. The results of the AOP analysis will provide a robust framework for future directed research on the mechanisms of Cu toxicity.


Assuntos
Rotas de Resultados Adversos , Poluentes Químicos da Água , Animais , Cobre/toxicidade , Cobre/análise , Disponibilidade Biológica , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Sódio , Peixes/metabolismo , Íons
15.
Zhongguo Zhong Yao Za Zhi ; 48(24): 6545-6550, 2023 Dec.
Artigo em Zh | MEDLINE | ID: mdl-38212015

RESUMO

Rhein, which is one of the main active components of Rheum palmatum, has a range of pharmacological activities such as the regulation of the metabolism of glucose and lipids, anti-inflammatory, anti-tumor, anti-fibrosis, etc. Epigenetics refers to the heritable variation of gene expression without altering the DNA sequence. It is involved in the emergence and development of inflammation, renal fibrosis, diabetes, cancer, atherosclerosis, and other diseases, thus becoming a new strategy for the treatment of many di-seases. A series of studies have shown that epigenetic modification may be a common molecular mechanism of various pharmacological effects of rhein. This paper summarized the effects of rhein on the regulation of epigenetic modification and its underlying mechanisms, which involve the regulation of DNA methylation, protein acetylation, and RNA methylation, so as to provide a basis for the development and application of rhein.


Assuntos
Antraquinonas , Neoplasias , Humanos , Antraquinonas/farmacologia , Metilação de DNA , Epigênese Genética , Neoplasias/tratamento farmacológico , Fibrose
16.
Cancer ; 128(7): 1513-1522, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34985771

RESUMO

BACKGROUND: Despite significant sexual dysfunction and distress after localized prostate cancer treatment, patients typically receive only physiologic erectile dysfunction management. The authors performed a randomized controlled trial of an online intervention supporting couples' posttreatment recovery of sexual intimacy. METHODS: Patients treated with surgery, radiation, or combined radiation and androgen deprivation therapy who had partners were recruited and randomized to an online intervention or a control group. The intervention, tailored to treatment type and sexual orientation, comprised 6 modules addressing expectations for sexual and emotional sequelae of treatment, rehabilitation, and guidance toward sexual intimacy recovery. Couples, recruited from 6 sites nationally, completed validated measures at the baseline and 3 and 6 months after treatment. Primary outcome group differences were assessed with t tests for individual outcomes. RESULTS: Among 142 randomized couples, 105 patients (mostly surgery) and 87 partners completed the 6-month survey; this reflected challenges with recruitment and attrition. There were no differences between the intervention and control arms in Patient-Reported Outcomes Measurement Information System Global Satisfaction With Sex Life scores 6 months after treatment (the primary outcome). Three months after treatment, intervention patients and partners reported more engagement in penetrative and nonpenetrative sexual activities than controls. More than 73% of the intervention participants reported high or moderate satisfaction with module content; more than 85% would recommend the intervention to other couples. CONCLUSIONS: Online psychosexual support for couples can help couples to connect and experience sexual pleasure early after treatment despite patients' sexual dysfunction. Participants' high endorsement of the intervention reflects the importance of sexual health support to couples after prostate cancer treatment. LAY SUMMARY: This study tested a web-based program supporting couples' sexual recovery of sexual intimacy after prostate cancer treatment. One hundred forty-two couples were recruited and randomly assigned to the program (n = 60) or to a control group (n = 82). The program did not result in improvements in participants' satisfaction with their sex life 6 months after treatment, but couples in the intervention group engaged in sexual activity sooner after treatment than couples in the control group. Couples evaluated the program positively and would recommend it to others facing prostate cancer treatment.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Adaptação Psicológica , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Comportamento Sexual/psicologia , Parceiros Sexuais/psicologia
17.
J R Stat Soc Series B Stat Methodol ; 84(5): 2000-2031, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37065873

RESUMO

We study the problem of high-dimensional Principal Component Analysis (PCA) with missing observations. In a simple, homogeneous observation model, we show that an existing observed-proportion weighted (OPW) estimator of the leading principal components can (nearly) attain the minimax optimal rate of convergence, which exhibits an interesting phase transition. However, deeper investigation reveals that, particularly in more realistic settings where the observation probabilities are heterogeneous, the empirical performance of the OPW estimator can be unsatisfactory; moreover, in the noiseless case, it fails to provide exact recovery of the principal components. Our main contribution, then, is to introduce a new method, which we call primePCA, that is designed to cope with situations where observations may be missing in a heterogeneous manner. Starting from the OPW estimator, primePCA iteratively projects the observed entries of the data matrix onto the column space of our current estimate to impute the missing entries, and then updates our estimate by computing the leading right singular space of the imputed data matrix. We prove that the error of primePCA converges to zero at a geometric rate in the noiseless case, and when the signal strength is not too small. An important feature of our theoretical guarantees is that they depend on average, as opposed to worst-case, properties of the missingness mechanism. Our numerical studies on both simulated and real data reveal that primePCA exhibits very encouraging performance across a wide range of scenarios, including settings where the data are not Missing Completely At Random.

18.
J Nucl Cardiol ; 29(6): 3352-3365, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35415825

RESUMO

BACKGROUND: 18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD). METHODS: Patients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries. RESULTS: 100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors. CONCLUSIONS: Coronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.


Assuntos
Aterosclerose , Calcinose , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluoreto de Sódio , Aterosclerose/diagnóstico por imagem , Aorta , Radioisótopos de Flúor
19.
J Nucl Cardiol ; 29(2): 476-488, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-32691347

RESUMO

BACKGROUND: To evaluate the cerebral metabolism in patients with heart failure (HF). METHODS: One hundred and two HF patients were prospectively enrolled, who underwent gated 99mTc-sestamibi single photon emission computed tomography (SPECT)/CT, cardiac and cerebral 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Fifteen healthy volunteers served as controls. Patients were stratified by extent of hibernating myocardium (HM) and left ventricular ejection fraction (LVEF) into 4 groups where Group1: HM < 10% (n = 33); Group2: HM ≥ 10%, LVEF < 25% (n = 34); Group3: HM ≥ 10%, 25% ≤ LVEF ≤ 40% (n = 16) and Group 4: LVEF > 40% (n = 19). The standardized uptake value (SUV) in the whole brain (SUVwhole-brain) and the SUV ratios (SUVR) in 24 cognition-related brain regions were determined. SUVwhole-brain and SUVRs were compared between the 4 patient groups and the healthy controls. RESULTS: SUVwhole-brain (r = 0.245, P = 0.013) and SUVRs in frontal areas, hippocampus, and para-hippocampus (r: 0.213 to 0.308, all P < 0.05) were correlated with HM. SUVwhole-brain differed between four patient groups and the healthy volunteers (P = 0.016) and SUVwhole-brain in Group 1 was lower than that in healthy volunteers (P < 0.05). SUVRs of Group 3 in frontal areas were the highest among four patient subgroups (P < 0.05). CONCLUSIONS: Cerebral metabolism in the whole brain was reduced but maintained in cognition-related frontal areas in HF patients with HM and moderately impaired global left ventricular function.


Assuntos
Fluordesoxiglucose F18 , Insuficiência Cardíaca , Glucose , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Volume Sistólico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Função Ventricular Esquerda
20.
IEEE Trans Circuits Syst Video Technol ; 32(5): 2535-2549, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35937181

RESUMO

The outbreak of coronavirus disease (COVID-19) has been a nightmare to citizens, hospitals, healthcare practitioners, and the economy in 2020. The overwhelming number of confirmed cases and suspected cases put forward an unprecedented challenge to the hospital's capacity of management and medical resource distribution. To reduce the possibility of cross-infection and attend a patient according to his severity level, expertly diagnosis and sophisticated medical examinations are often required but hard to fulfil during a pandemic. To facilitate the assessment of a patient's severity, this paper proposes a multi-modality feature learning and fusion model for end-to-end covid patient severity prediction using the blood test supported electronic medical record (EMR) and chest computerized tomography (CT) scan images. To evaluate a patient's severity by the co-occurrence of salient clinical features, the High-order Factorization Network (HoFN) is proposed to learn the impact of a set of clinical features without tedious feature engineering. On the other hand, an attention-based deep convolutional neural network (CNN) using pre-trained parameters are used to process the lung CT images. Finally, to achieve cohesion of cross-modality representation, we design a loss function to shift deep features of both-modality into the same feature space which improves the model's performance and robustness when one modality is absent. Experimental results demonstrate that the proposed multi-modality feature learning and fusion model achieves high performance in an authentic scenario.

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