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1.
Artigo em Inglês | MEDLINE | ID: mdl-38847554

RESUMO

The aim of the present study was to determine the associations between the MICB genetic variability and the expression and the risk of development of post-transplant complications after allogeneic hematopoietic stem cell transplantation (HSCT). HSCT recipients and their donors were genotyped for two MICB polymorphisms (rs1065075, rs3828903). Moreover, the expression of a soluble form of MICB was determined in the recipients' serum samples after transplantation using the Luminex assay. Our results revealed a favorable role of the MICB rs1065075 G allele. Recipients with donors carrying this genetic variant were less prone to developing chronic graft-versus-host disease (cGvHD) when compared to recipients without any symptoms of this disease (41.41% vs. 65.38%, p = 0.046). Moreover, the MICB rs1065075 G allele was associated with a lower incidence of cytomegalovirus (CMV) reactivation, both as a donor (p = 0.015) and as a recipient allele (p = 0.039). The MICB rs1065075 G variant was also found to be associated with decreased serum soluble MICB (sMICB) levels, whereas serum sMICB levels were significantly higher in recipients diagnosed with CMV infection (p = 0.0386) and cGvHD (p = 0.0008) compared to recipients without those complications. A protective role of the G allele was also observed for the rs3828903 polymorphism, as it was more frequently detected among donors of recipients without cGvHD (89.90% vs. 69.23%; p = 0.013). MICB genetic variants, as well as serum levels of sMICB, may serve as prognostic factors for the risk of developing cGvHD and CMV infection after allogeneic HSCT.


Assuntos
Infecções por Citomegalovirus , Predisposição Genética para Doença , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade Menor , Transplante Homólogo , Humanos , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/etiologia , Infecções por Citomegalovirus/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Transplante Homólogo/efeitos adversos , Adulto , Pessoa de Meia-Idade , Doença Crônica , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Classe I/genética , Polimorfismo de Nucleotídeo Único , Alelos , Genótipo , Adulto Jovem , Citomegalovirus/fisiologia , Adolescente , Risco , Fatores de Risco
3.
Science ; 384(6701): 1159-1160, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38870298

RESUMO

New studies include health data collected from space tourists on first privately funded orbital mission.


Assuntos
Astronautas , Voo Espacial , Humanos , Risco
4.
Clin Nucl Med ; 49(7): 621-629, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38769643

RESUMO

PURPOSE: This pilot study investigates the efficacy and safety profile as well as predictive biomarkers of 225 Ac-PSMA-617-augmented 177 Lu-PSMA-617 radioligand therapy (RLT) in a cohort of high-risk patients with metastatic castration-resistant prostate cancer (mCRPC), enrolled in a prospective registry (NCT04833517). PATIENTS AND METHODS: A group of n = 33 high-risk mCRPC patients received 177 Lu-PSMA-617 RLT, augmented by 1 or more cycles of 225 Ac-PSMA-617. Response was assessed by prostate-specific antigen (PSA) serum value after 2 cycles of treatment. Overall survival (OS) and PSA-based progression-free survival were evaluated using Kaplan-Meier analysis. To assess the side effect profile, Common Terminology Criteria for Adverse Events were applied. In total, 12 potential pretherapeutic biomarkers were tested for association with OS. RESULTS: The median decrease in serum PSA value was -49.1%, and 16/33 (48.5%) patients experienced a partial response after 2 cycles RLT. The median PSA-based progression-free survival and median OS was 7.2 and 14.8 months, respectively. Alkaline phosphatase ( P < 0.001), lactate dehydrogenase ( P = 0.035), Eastern European Oncology Group Performance Score ( P = 0.037), and the presence of visceral metastases ( P = 0.029) revealed significant association with OS in Kaplan-Meier analysis (log-rank test). Most of the recorded adverse events were rated as mild or moderate. Higher-grade adverse events were very limited with only 1 case (3.0%) of grade 3 anemia. Treatment-related mild xerostomia was recorded in 6/33 (18.2%) patients. CONCLUSIONS: 225 Ac-PSMA-617 augmentation in high-risk mCRPC undergoing 177 Lu-PSMA-617 RLT appears to be an effective treatment option with a favorable safety profile. The pretherapeutic values of alkaline phosphatase, lactate dehydrogenase, the Eastern European Oncology Group Performance Score, and the presence of visceral metastases may be appropriate biomarkers predicting survival outcome of this treatment regimen.


Assuntos
Compostos Heterocíclicos com 1 Anel , Lutécio , Neoplasias de Próstata Resistentes à Castração , Sistema de Registros , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Projetos Piloto , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Dipeptídeos/uso terapêutico , Dipeptídeos/efeitos adversos , Idoso de 80 Anos ou mais , Ligantes , Resultado do Tratamento , Risco , Actínio , Radioisótopos
5.
Psychiatry Res ; 337: 115961, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754253

RESUMO

Bodily self-disturbances including anomalous embodiment of emotions are observed in psychosis-spectrum conditions. Psychosis is also associated with trauma exposure but the relationship between altered bodily experiences and trauma has not been extensively investigated in individuals at risk for psychosis (HR). We implemented a mapping task to localize felt sensations associated with trauma. Results show that trauma experiences were always localized in the body. HR reported increased rates of traumatic experiences than low-risk group (LR). HR reported sensations associated with trauma across widespread body areas. Further research is needed to elucidate how trauma might lead to psychotic-like experiences via bodily self-disturbances.


Assuntos
Trauma Psicológico , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/etiologia , Feminino , Masculino , Adulto , Adulto Jovem , Trauma Psicológico/psicologia , Adolescente , Risco , Emoções/fisiologia , Imagem Corporal/psicologia
7.
PLoS One ; 19(5): e0301802, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38758805

RESUMO

Major product safety incidents often cause widespread concern among consumers, and these product safety incidents will stimulate consumers' psychology, change their risk perception, and affect the demand for products and services of risk consumers. The change in consumer demand will eventually lead to a change in firm innovation decisions. Using Chinese firm-level data, this paper employs the news reporting of the Bawang event as a quasi-natural experiment to study the impact of risk perception changes on innovation. The empirical results of this study show that increasing consumers' risk perception caused by the negative news coverage of defective products motivates firms to increase their innovation. The effects are heterogeneous, where firms with private ownership and in developed regions are more likely to increase innovation activities. This study suggests that the relationship between consumers' risk perception and firm innovation is primarily driven by market demand. Moreover, the positive effects of risk perception on innovation are more prominent for downstream firms and those having a smaller technological distance.


Assuntos
Comportamento do Consumidor , China , Humanos , Percepção , Medição de Risco , Comércio , Risco , Invenções
8.
Schizophr Res ; 269: 79-85, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754312

RESUMO

It is unclear what types of stigma youth at clinical high risk for psychosis (CHR) experience, and the relationship between them and symptomatology. 94 CHR youth, and a control group of 45 youth with no psychosis spectrum symptoms (NP) were rated for perceived devaluation (i.e. negative views from others) and internalized mental health stigma (i.e. the extent to which they would agree with said views) as well as positive and mood symptomatology. CHR youth reported stigma more frequently than the NP group (χ2(1) = 53.55, p < .001) and at higher levels (perceived devaluation: t (137) = 8.54, p < .001; internalized stigma: t (137) = 7.48, p < .001). Surprisingly, in the CHR group, positive symptoms held no significant relationship to stigma measures. However, ratings of perceived devaluation stigma were associated with depressive symptomatology (ß = 0.27, t = 2.68, p = .0087) and depression scores were conversely associated with perceived devaluation stigma (ß = 0.30, t = 2.05, p = .043). These findings speak to the relationship between depressive symptomatology and perceived devaluation stigma in CHR youth. Perceived devaluation stigma showed greater clinical significance and could have different mechanisms than internalized stigma in CHR youth. It is also noteworthy that while positive symptoms play a central role in defining the CHR syndrome, they seem less relevant to the experience of stigma than mood symptoms. These findings highlight the importance of interventions aimed at ameliorating youth's exposure to negative views about mental health as those managing depressive symptomatology.


Assuntos
Depressão , Transtornos Psicóticos , Estigma Social , Humanos , Transtornos Psicóticos/psicologia , Masculino , Feminino , Adolescente , Depressão/psicologia , Adulto Jovem , Escalas de Graduação Psiquiátrica , Risco
9.
JAMA ; 331(23): 1985-1986, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38709521

RESUMO

This Viewpoint discusses how data gaps in published research impede clinicians' ability to clearly discuss the risks and benefits of amyloid-lowering drugs for treating Alzheimer disease.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Doença de Alzheimer/tratamento farmacológico , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Risco
15.
Biometrics ; 80(2)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38742906

RESUMO

Semicompeting risks refer to the phenomenon that the terminal event (such as death) can censor the nonterminal event (such as disease progression) but not vice versa. The treatment effect on the terminal event can be delivered either directly following the treatment or indirectly through the nonterminal event. We consider 2 strategies to decompose the total effect into a direct effect and an indirect effect under the framework of mediation analysis in completely randomized experiments by adjusting the prevalence and hazard of nonterminal events, respectively. They require slightly different assumptions on cross-world quantities to achieve identifiability. We establish asymptotic properties for the estimated counterfactual cumulative incidences and decomposed treatment effects. We illustrate the subtle difference between these 2 decompositions through simulation studies and two real-data applications in the Supplementary Materials.


Assuntos
Simulação por Computador , Humanos , Modelos Estatísticos , Risco , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Análise de Mediação , Resultado do Tratamento , Biometria/métodos
17.
PLoS One ; 19(5): e0301977, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768172

RESUMO

Based on panel data from 2009 to 2021, covering 30 provinces in China, we have been constructed the Rural Financial Risk Index using the objective entropy weighting method to study rural financial risk in China systematically from the perspective of spatial distribution. Specifically, we discuss the spatial distribution, regional differences and dynamic evolution of rural financial risk across Chinese four different regions divided into the Northeast, East, Central and West. It's found that Local government debt and Land transfer income are the two primary determinants influencing the level of rural financial risk in China. Furthermore, we conclude the ranking value of rural financial risk across four regions that the central exhibits the highest level, followed by the West, the East, and finally the Northeast, where the reasons for such ranking results as follows. Firstly, although the highest level of risk among provinces in the West is equivalent to that in the Central, there exists a smaller minimum rural financial risk in the former compared to the latter. Then, it should be noted that there's a low-low agglomeration of rural financial risk in the Northeast, while it demonstrates a high-high agglomeration in the Central according to the Moran Index test analysis. Again, there's a declining trend in rural financial risk disparity within the region and an upward trend is observed when comparing different regions (except the East vs West), especially increase largely between the Northeast and Central in past two years after analyzing the decomposition of Dagum Gini coefficient. Moreover, we study the absolute differences and dynamic evolution in different four regions through three-dimensional diagram of kernel density estimation, and it's found that the change of rural financial risk in four regions moved to the right as a whole, while the tail distribution remains inconspicuous. The absolute difference is diminishing in the Northeast, and the two-level differentiation characteristics tend to weaken as a whole in the Central, with a disordered wave peak height observed in both the East and West. Finally, the article presents pertinent policy implications but limitations according to the research findings.


Assuntos
População Rural , China , Humanos , Renda , Risco , Fatores Socioeconômicos
18.
Sci Rep ; 14(1): 10460, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714713

RESUMO

While autonomous artificial agents are assumed to perfectly execute the strategies they are programmed with, humans who design them may make mistakes. These mistakes may lead to a misalignment between the humans' intended goals and their agents' observed behavior, a problem of value alignment. Such an alignment problem may have particularly strong consequences when these autonomous systems are used in social contexts that involve some form of collective risk. By means of an evolutionary game theoretical model, we investigate whether errors in the configuration of artificial agents change the outcome of a collective-risk dilemma, in comparison to a scenario with no delegation. Delegation is here distinguished from no-delegation simply by the moment at which a mistake occurs: either when programming/choosing the agent (in case of delegation) or when executing the actions at each round of the game (in case of no-delegation). We find that, while errors decrease success rate, it is better to delegate and commit to a somewhat flawed strategy, perfectly executed by an autonomous agent, than to commit execution errors directly. Our model also shows that in the long-term, delegation strategies should be favored over no-delegation, if given the choice.


Assuntos
Teoria dos Jogos , Humanos , Modelos Teóricos , Risco
19.
Biom J ; 66(4): e2300147, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38785217

RESUMO

Time-to-event analysis often relies on prior parametric assumptions, or, if a semiparametric approach is chosen, Cox's model. This is inherently tied to the assumption of proportional hazards, with the analysis potentially invalidated if this assumption is not fulfilled. In addition, most interpretations focus on the hazard ratio, that is often misinterpreted as the relative risk (RR), the ratio of the cumulative distribution functions. In this paper, we introduce an alternative to current methodology for assessing a treatment effect in a two-group situation, not relying on the proportional hazards assumption but assuming proportional risks. Precisely, we propose a new nonparametric model to directly estimate the RR of two groups to experience an event under the assumption that the risk ratio is constant over time. In addition to this relative measure, our model allows for calculating the number needed to treat as an absolute measure, providing the possibility of an easy and holistic interpretation of the data. We demonstrate the validity of the approach by means of a simulation study and present an application to data from a large randomized controlled trial investigating the effect of dapagliflozin on all-cause mortality.


Assuntos
Biometria , Modelos de Riscos Proporcionais , Humanos , Biometria/métodos , Estatísticas não Paramétricas , Compostos Benzidrílicos/uso terapêutico , Modelos Estatísticos , Fatores de Tempo , Risco , Resultado do Tratamento , Glucosídeos
20.
Science ; 384(6695): 584-590, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38696583

RESUMO

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl, one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22 , Meningomielocele , Animais , Feminino , Humanos , Masculino , Camundongos , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Sequenciamento do Exoma , Ácido Fólico/administração & dosagem , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/genética , Meningomielocele/epidemiologia , Meningomielocele/genética , Penetrância , Disrafismo Espinal/genética , Risco , Proteínas Adaptadoras de Transdução de Sinal/genética
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