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1.
J Clin Microbiol ; 62(2): e0083623, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38206000

RESUMO

HIV is an ongoing global epidemic with estimates of more than a million new infections occurring annually. To combat viral spread, continuous innovations in areas including testing and treatment are necessary. In the United States, the Centers for Disease Control and Prevention recommend that laboratories follow an HIV testing algorithm that first uses a US Food and Drug Administration approved immunoassay to detect antibodies to HIV-1 or HIV-2 as well as HIV-1 p24 antigen in serum or plasma samples. An initially reactive specimen is tested by a supplemental assay for confirmation and to differentiate antibodies to HIV-1 or HIV-2. There are few Food and Drug Administration (FDA)-approved supplemental differentiation tests currently available. A multicenter investigation was conducted to determine the clinical performance for two independent versions of the Avioq VioOne HIV Profile Supplemental Assay (Avioq, Inc., Research Triangle Park, NC). The performance of both assay versions compared favorably with the performance parameters for the Geenius HIV 1/2 Supplemental Assay as published in that assay package insert (Bio-Rad Laboratories, Hercules, CA), the current gold standard for HIV supplemental testing. When comparing the two VioOne assays, version 2 (lacking HIV-2 p27 antibody detection) demonstrated improved reproducibility, specificity, and sensitivity as compared to its predecessor. IMPORTANCE We evaluated the reproducibility, sensitivity, and specificity data for two versions of the VioOne HIV Profile Supplemental Assay and compared these results back to similar results for the Geenius HIV 1/2 Supplemental Assay that are publicly available. Our study concluded that the VioOne HIV Profile Supplemental Assay compared favorably with the Geenius HIV 1/2 Supplemental Assay, thus providing an additional option for clinical laboratories to improve and expand their HIV testing capabilities.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Estados Unidos , Reprodutibilidade dos Testes , Anticorpos Anti-HIV , Algoritmos , HIV-2 , Proteína do Núcleo p24 do HIV , Sensibilidade e Especificidade
2.
Proc Biol Sci ; 291(2017): 20232011, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38412967

RESUMO

Polarization raises concerns for democracy and society, which have expanded in the internet era where (mis)information has become ubiquitous, its transmission faster than ever, and the freedom and means of opinion expressions are expanding. The origin of polarization however remains unclear, with multiple social and emotional factors and individual reasoning biases likely to explain its current forms. In the present work, we adopt a principled approach and show that polarization tendencies can take root in biased reward processing of new information in favour of choice confirmatory evidence. Through agent-based simulations, we show that confirmation bias in individual learning is an independent mechanism and could be sufficient for creating polarization at group level independently of any additional assumptions about the opinions themselves, a priori beliefs about them, information transmission mechanisms or the structure of social relationship between individuals. This generative process can interact with polarization mechanisms described elsewhere, but constitutes an entrenched biological tendency that helps explain the extraordinary resilience of polarization against mitigating efforts such as dramatic informational change in the environment.


Assuntos
Emoções , Aprendizagem , Humanos , Relações Interpessoais , Resolução de Problemas , Recompensa
3.
J Theor Biol ; 580: 111715, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38154522

RESUMO

Indirect reciprocity is a reputational mechanism through which cooperative behavior can be promoted amongst a group of individuals. However, in order for this mechanism to effectively do so, cheating must be appropriately punished and cooperating appropriately rewarded. Errors in assessments and actions can hinder this process. In such a setting, individuals might try to reason about evidence to assign reputations given the possibility of errors. Here, we consider a well-established theory of reasoning used to combine evidence, abductive reasoning, as a possible means by which such errors can be circumvented. Specifically, we use Dempster-Shafer theory to model individuals who account for possible errors by combining information about their beliefs about the status of the population and the errors rates and then choose the simplest scenario that could explain their observations in the context of these beliefs. We investigate the effectiveness of abductive reasoning at promoting cooperation for five social norms: Scoring, Shunning, Simple Standing, Staying, and Stern Judging. We find that, generally, abductive reasoning can outperform non-reasoning models at ameliorating the effects of the aforementioned challenges and promote higher levels of cooperation under low-error conditions. However, for high-error conditions, we find that abductive reasoning can undermine cooperation. Furthermore, we also find that a degree of bias towards believing previously held reputations can help sustain cooperation.


Assuntos
Modelos Psicológicos , Normas Sociais , Humanos , Comportamento Cooperativo , Evolução Biológica
4.
Vox Sang ; 119(10): 1116-1121, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39048113

RESUMO

BACKGROUND AND OBJECTIVES: There is a growing infectious syphilis outbreak in Western Canada. Although blood donors are screened for syphilis risks, some blood donors will still be confirmed test-positive for syphilis. This study compares the characteristics of confirmed test-positive syphilis donations in both Western Canada and Eastern Canada, November 2022-August 2023. MATERIALS AND METHODS: Donors were defined as Western or Eastern Canadian. Blood donations were tested for syphilis using the PK-TP assay (Beckman Coulter PK7300 Automated Microplate System). Confirmatory Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR) assays were performed by one of two reference laboratories. An RPR titre ≥1:8 was used as a proxy for possible infectious syphilis. RESULTS: Rates of laboratory-confirmed syphilis were higher in Western (n = 43, 13.4/100,000 donations) versus Eastern donors (n = 19, 4.7/100,000 donations; Fisher's exact test, two-sided, p ≤ 0.0001). Most syphilis confirmations were in first-time donors (Western Canada n = 31/43, 72.1%, Eastern Canada 12/19, 63.2%). CONCLUSION: Although rates of laboratory-confirmed syphilis were higher in Western versus Eastern donors, Western donors did not have higher rates of infectious syphilis. Further studies might assess whether donors with laboratory-confirmed syphilis understood pre-donation screening questions or were completely unaware of a past infection.


Assuntos
Doadores de Sangue , Sífilis , Humanos , Sífilis/epidemiologia , Sífilis/sangue , Canadá/epidemiologia , Masculino , Feminino , Adulto , Treponema pallidum , Pessoa de Meia-Idade , Sorodiagnóstico da Sífilis/métodos
5.
Helicobacter ; 29(4): e13112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39085988

RESUMO

BACKGROUND AND AIM: Helicobacter pylori infections have become resistant to many previously highly effective antimicrobial regimens resulting in clarithromycin, metronidazole, or fluoroquinolone-containing therapies becoming unsuccessful. Pretreatment susceptibility testing is only widely available in the United States but is still rarely done. Here, we propose a framework to monitor H. pylori eradication in small clinical settings by routinely assessing the effectiveness of therapy. METHODS: Because of the small sample size in individual practice's, we assume an acceptable cure rate of ≥80% (preferred cure rate ≥85%) in adherent patients, with a dichotomous outcome (cured vs. failed) and consecutive patient enrollment. To obtain results (feedback) in a timely manner, for individual practices, cure rates can be estimated after 10 patients. Large practices which acquire patients more rapidly can delay analysis until a total of 104 H. pylori-infected patients, assuming a baseline cure rate of at least 85% with the preferred regimen. RESULTS: We show how data from individual practices can be utilized to improve the effectiveness of H. pylori treatment decisions. The method consists of recording and accumulating the confirmation of cure data for successive small groups of patients. These data are then analyzed as binary outcomes (pass-fail) and serve as the basis for studying and improving the effectiveness of H. pylori treatment decisions. CONCLUSION: A simple actuarial method can serve outpatient clinics to ensure a reliable test-to-cure method and avoid futile Hp regimens.


Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Humanos , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Resultado do Tratamento
6.
Naturwissenschaften ; 111(3): 27, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652309

RESUMO

Re-evaluation of photographs of the tropical butterfly Morpho helenor from a previous study (Pignataro et al. 2023) revealed that its conclusion regarding increased wing fluctuating asymmetry in forest edge habitats compared to forest interior habitats could not be replicated. This discrepancy likely arises from (i) original measurements not being conducted blindly, (ii) insufficient photograph quality hindering accurate landmark selection, and (iii) a lack of detailed description of the measurement protocol. The likelihood of false positive discoveries within the published data concerning the impacts of environmental stress on the fluctuating asymmetry of plants and animals is probably higher than previously assumed.


Assuntos
Borboletas , Florestas , Borboletas/fisiologia , Borboletas/anatomia & histologia , Animais , Asas de Animais/anatomia & histologia , Asas de Animais/fisiologia , Ecossistema , Clima Tropical
7.
Tetrahedron ; 1622024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39006909

RESUMO

Ciguatera poisoning occurs throughout subtropical and tropical regions globally. The Virgin Islands in the Caribbean Sea is a known hyperendemic region for ciguatera and has been associated with Caribbean ciguatoxin (C-CTX) contamination in fish. An algal C-CTX (C-CTX5) was identified in Gambierdiscus silvae and G. caribeaus isolated from benthic algal samples collected in waters south St. Thomas, US Virgin Islands. The highest CTX-producing isolate, G. silvae 1602 SH-6, was grown at large-scale to isolate sufficient C-CTX5 for structural confirmation by NMR spectroscopy. A series of orthogonal extraction and fractionation procedures resulted in purification of approximately 40 µg of C-CTX5, as estimated by quantitative NMR. A suite of 1D and 2D NMR experiments were acquired that verified the structure originally proposed for C-CTX5. The structural confirmation and successful isolation of C-CTX5 opens the way for work on the stability, toxicology and biotransformation of C-CTXs, as well as for the production of quantitative reference materials for analytical method development and validation. The strategies developed for purification of C-CTX5 may also apply to isolation and purification of CTXs from the Pacific Ocean and other regions.

8.
BMC Public Health ; 24(1): 2630, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334161

RESUMO

BACKGROUND: Online healthcare platforms (OHPs) promote the accessibility of health services while integrating online and offline service delivery. Continuous adoption of these platforms can reduce the information asymmetry between patients and healthcare providers. However, existing study has rarely focused on how the network externalities of these platforms influence patients' continuous adoption. Expectation Confirmation Model (ECM) explains the continuous behavior after initial adoption and reveal the factors influencing satisfaction and continuous adoption intention. Few studies have integrated network externalities with the ECM to understand patients' continuous adoption of OHPs. OBJECTIVE: This study aims to explore what factors affect the continuous adoption of OHPs based on an extension to the ECM and network externalities. We propose a comprehensive model for the continuous adoption of OHPs by patients with chronic diseases. We extend the conceptual framework by incorporating constructs related to perceived value, habits, and switching costs. METHODS: This study utilized a web-based survey to collect data from participants in China. We selected a sample of individuals who had experience with OHPs using a random sampling method. This method ensured that participants was randomly chosen from a pool of patients without any regional bias. A total of 568 questionnaires were collected and 518 valid questionnaires were obtained. Structural equation modeling was applied to assess the relationships among the constructs. Hierarchical regression analysis was utilized to examine the moderating effects, while the mediating effects were investigated using the bootstrapping approach. RESULTS: Direct network externality had significant positive impacts on the confirmation (ß = 0.232, p < 0.001) and perceived value (ß = 0.167, p < 0.010). Cross network externality had significant positive impacts on confirmation (ß = 0.307, p < 0.001) and perceived value (ß = 0.120, p < 0.05). Indirect network externality had significant positive impacts on confirmation (ß = 0.169, p < 0.010) and perceived value (ß = 0.270, p < 0.001). Confirmation had a significant positive impact on perceived value (ß = 0.205, p < 0.001) and satisfaction (ß = 0.508, p < 0.001). In addition, satisfaction had a significant positive impact on continuous adoption intention (ß = 0.579, p < 0.001). Continuous adoption intention had a significant positive impact on continuous adoption behavior (ß = 0.547, p < 0.001). Confirmation and perceived value significantly mediate the relationship between network externalities and satisfaction. Moreover, both confirmation and perceived value enhance continuous adoption intention by positively influencing satisfaction, which serves as a mediator. Additionally, confirmation directly influences satisfaction through the mediating role of perceived value. Habits and switching costs positively moderate the relationship between continuous adoption intention and behavior. CONCLUSIONS: This study contributes by expanding the incorporation of network externalities into the ECM. Results enrich the existing literature on the continuous adoption of professional online platforms.


Assuntos
Internet , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , China , Inquéritos e Questionários , Telemedicina , Satisfação do Paciente/estatística & dados numéricos , Adulto Jovem , Modelos Teóricos
9.
Biochem Genet ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003435

RESUMO

Bovicola caprae is an important obligate ectoparasite of goats worldwide including India. The present study aimed at the molecular confirmation, phylogenetics and population structure analyses of B. caprae infesting goats of three different agro-climatic locations in India, by targeting the mitochondrial cytochrome C oxidase subunit 1 (cox1) genetic marker. The phylogenetic tree exhibited the presence of two different lineages of B. caprae. The sequences generated herein clustered in lineage 2 along with the GenBank™ archived sequences from China and Iran. The sequences generated herein also showed the circulation of sub-lineages of B. caprae in India based on the analysis of pairwise genetic distances between sequences and median-joining haplotype network. The population structure analyses revealed low nucleotide (0.00353 ± 0.00291 and 0.02694 ± 0.00363) and high haplotype (0.667 ± 0.314 and 0.618 ± 0.104) diversities for the present study isolates as well as for the complete dataset, respectively, which evinced a recent demographic expansion. High genetic differentiation (FST value = 0.97826) and low gene flow (Nm = 0.00556) were also recorded in the different lineages/populations. In conclusion, the present study addressed the research gap and provided the first insight into the phylogenetics of the goat louse B. caprae and highlighted the circulation of sub-lineages of the ectoparasite in India.

10.
BMC Biol ; 21(1): 48, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36882836

RESUMO

BACKGROUND: The brain uses recent history when forming perceptual decisions. This results in carryover effects in perception. Although separate sensory and decisional carryover effects have been shown in many perceptual tasks, their existence and nature in temporal processing are unclear. Here, we investigated whether and how previous stimuli and previous choices affect subsequent duration perception, in vision and audition. RESULTS: In a series of three experiments, participants were asked to classify visual or auditory stimuli into "shorter" or "longer" duration categories. In experiment 1, visual and auditory stimuli were presented in separate blocks. Results showed that current duration estimates were repelled away from the previous trial's stimulus duration, but attracted towards the previous choice, in both vision and audition. In experiment 2, visual and auditory stimuli were pseudorandomly presented in one block. We found that sensory and decisional carryover effects occurred only when previous and current stimuli were from the same modality. Experiment 3 further investigated the stimulus dependence of carryover effects within each modality. In this experiment, visual stimuli with different shape topologies (or auditory stimuli with different audio frequencies) were pseudorandomly presented in one visual (or auditory) block. Results demonstrated sensory carryover (within each modality) despite task-irrelevant differences in visual shape topology or audio frequency. By contrast, decisional carryover was reduced (but still present) across different visual topologies and completely absent across different audio frequencies. CONCLUSIONS: These results suggest that serial dependence in duration perception is modality-specific. Moreover, repulsive sensory carryover effects generalize within each modality, whereas attractive decisional carryover effects are contingent on contextual details.


Assuntos
Percepção Auditiva , Encéfalo , Humanos , Audição
11.
Camb Q Healthc Ethics ; 33(2): 174-184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37332165

RESUMO

Pragmatism gained considerable attention in bioethical discussions in the early 21st century. However, some dimensions and contributions of pragmatism to bioethics remain underexplored in both research and practice. It is argued that pragmatism can make a distinctive contribution to bioethics through its concept, developed by Charles S. Peirce and John Dewey, that ethical issues can be resolved through experimental inquiry. Dewey's proposal that policies can be confirmed or disconfirmed through experimentation is developed by comparing it to the confirmation of scientific hypotheses, with a focus on the objection that the consequences of following a moral view or policy do not provide guidance on choosing among competing ethical perspectives. As confirmation of scientific hypotheses typically relies on evidence gathered from observation, the possibility of ethically relevant observation is then explored based on Peirce's views on feelings as emotional interpretants. Finally, the connection between Dewey's experimental ethics and democracy is outlined and compared to unfettered ethical progressivism.


Assuntos
Bioética , Humanos , Princípios Morais
12.
Shokuhin Eiseigaku Zasshi ; 65(4): 89-94, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-39443102

RESUMO

Although the safety of genome-edited foods in Japan has been confirmed through pre-submission consultation under the notification process, public perception of safety confirmation methodology has not been investigated to date. Therefore, we created three media to provide information on the safety assurance of genome-edited foods and surveyed the perception of current safety confirmation. In addition, we examined the opinions of researchers in health science on current safety confirmation methods. As a result, 62% of general consumers and 68% of researchers in health science recognized that safety is ensured. Acceptance of genome-edited foods improved when they realized that safety was ensured. Researchers in health science who felt that safety confirmation was insufficient were concerned about the third-party verification. Therefore, it was suggested that in order to boost public understanding of genome-edited foods, it would be useful to inform the public by communicating in an easy-to-understand way the safety assurance approaches being made in pre-submission consultation.


Assuntos
Inocuidade dos Alimentos , Alimentos Geneticamente Modificados , Humanos , Japão , Inquéritos e Questionários , Edição de Genes , Masculino , Feminino , Conscientização , Adulto , Pessoa de Meia-Idade , Meios de Comunicação de Massa , Adulto Jovem
13.
Entropy (Basel) ; 26(1)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38248179

RESUMO

An effective post-processing algorithm is essential for achieving high rates of secret key generation in quantum key distribution. This work introduces an approach to quantum key distribution post-processing by integrating the three main steps into a unified procedure: syndrome-based error estimation, rate-adaptive reconciliation, and subblock confirmation. The proposed scheme employs low-density parity-check codes to estimate the quantum bit error rate using the syndrome information, and to optimize the channel coding rates based on the Slepian-Wolf coding scheme for the rate-adaptive method. Additionally, this scheme incorporates polynomial-based hash verification in the subblock confirmation process. The numerical results show that the syndrome-based estimation significantly enhances the accuracy and consistency of the estimated quantum bit error rate, enabling effective code rate optimization for rate-adaptive reconciliation. The unified approach, which integrates rate-adaptive reconciliation with syndrome-based estimation and subblock confirmation, exhibits superior efficiency, minimizes practical information leakage, reduces communication rounds, and guarantees convergence to the identical key. Furthermore, the simulations indicate that the secret key throughput of this approach achieves the theoretical limit in the context of a BB84 quantum key distribution system.

14.
Entropy (Basel) ; 26(10)2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39451936

RESUMO

Empirical Bayes-based Methods (EBM) is an increasingly popular form of Objective Bayesianism (OB). It is identified in particular with the statistician Bradley Efron. The main aims of this paper are, first, to describe and illustrate its main features and, second, to locate its role by comparing it with two other statistical paradigms, Subjective Bayesianism (SB) and Evidentialism. EBM's main formal features are illustrated in some detail by schematic examples. The comparison between what Efron calls their underlying "philosophies" is by way of a distinction made between confirmation and evidence. Although this distinction is sometimes made in the statistical literature, it is relatively rare and never to the same point as here. That is, the distinction is invariably spelled out intra- and not inter-paradigmatically solely in terms of one or the other accounts. The distinction made in this paper between confirmation and evidence is illustrated by two well-known statistical paradoxes: the base-rate fallacy and Popper's paradox of ideal evidence. The general conclusion reached is that each of the paradigms has a basic role to play and all are required by an adequate account of statistical inference from a technically informed and fine-grained philosophical perspective.

15.
J Infect Dis ; 228(7): 840-850, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37015894

RESUMO

An association exists between severe respiratory syncytial virus (RSV)-bronchiolitis and a subsequent increased risk of recurrent wheezing (RW) and asthma. However, a causal relationship remains unproven. Using a retrospective population-based cohort study (339 814 children), bronchiolitis during the first 2 years of life (regardless of etiology and severity) was associated with at least a 3-fold increased risk of RW/asthma at 2-4 years and an increased prevalence of asthma at ≥5 years of age. The risk was similar in children with mild bronchiolitis as in those with hospitalized RSV-bronchiolitis and was higher in children with hospitalized non-RSV-bronchiolitis. The rate of RW/asthma was higher when bronchiolitis occurred after the first 6 months of life. Our results seem to support the hypothesis of a shared predisposition to bronchiolitis (irrespective of etiology) and RW/asthma. However, 60% of hospitalized bronchiolitis cases in our setting are due to RSV, which should be paramount in decision-making on imminent RSV prevention strategies.


Assuntos
Asma , Bronquiolite , Infecções por Vírus Respiratório Sincicial , Criança , Humanos , Lactente , Estudos de Coortes , Estudos Retrospectivos , Asma/etiologia , Asma/complicações , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/epidemiologia , Sons Respiratórios/etiologia
16.
Stud Hist Philos Sci ; 104: 68-77, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479234

RESUMO

Predictivism is the thesis that evidence successfully predicted by a scientific theory counts more (or ought to count more) in the confirmation of that theory than already known evidence would. One rationale that has been proposed for predictivism is that predictive success guards against ad hoc hypotheses. Despite the intuitive attraction of predictivism, there is historical evidence that speaks against it. As valuable as the historical evidence may be, however, it is largely indirect evidence for the epistemic attitudes of individual - albeit prominent - scientists. This paper presents the results of an empirical study of scientists' attitudes toward predictivism and ad hoc-ness (n = 492), which will put the debate on a more robust empirical footing. The paper also draws attention to a tension between the ad hoc-ness avoidance rationale of predictivism and the ways philosophers have spelled out the notion of ad hoc-ness.


Assuntos
Perciformes , Médicos , Animais , Humanos , Pesquisa Empírica , Intuição , Nestina
17.
Erkenntnis ; 89(1): 367-409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38303980

RESUMO

Some authors claim that minimal models have limited epistemic value (Fumagalli, 2016; Grüne-Yanoff, 2009a). Others defend the epistemic benefits of modelling by invoking the role of robustness analysis for hypothesis confirmation (see, e.g., Levins, 1966; Kuorikoski et al., 2010) but such arguments find much resistance (see, e.g., Odenbaugh & Alexandrova, 2011). In this paper, we offer a Bayesian rationalization and defence of the view that robustness analysis can play a confirmatory role, and thereby shed light on the potential of minimal models for hypothesis confirmation. We illustrate our argument by reference to a case study from macroeconomics. At the same time, we also show that there are cases in which robustness analysis is detrimental to confirmation. We characterize these cases and link them to recent investigations on evidential variety (Landes, 2020b, 2021; Osimani and Landes, forthcoming). We conclude that robustness analysis over minimal models can confirm, but its confirmatory value depends on concrete circumstances.

18.
J Biol Chem ; 298(5): 101898, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35378126

RESUMO

Protein-protein interactions drive various biological processes in healthy as well as disease states. The transcription factor c-Myc plays a crucial role in maintaining cellular homeostasis, and its deregulated expression is linked to various human cancers; therefore, it can be considered a viable target for cancer therapeutics. However, the structural heterogeneity of c-Myc due to its disordered nature poses a major challenge to drug discovery. In the present study, we used an in silico alanine scanning mutagenesis approach to identify "hot spot" residues within the c-Myc/Myc-associated factor X interface, which is highly disordered and has not yet been systematically analyzed for potential small molecule binding sites. We then used the information gained from this analysis to screen potential inhibitors using a conformation ensemble approach. The fluorescence-based biophysical experiments showed that the identified hit molecules displayed noncovalent interactions with these hot spot residues, and further cell-based experiments showed substantial in vitro potency against diverse c-Myc-expressing cancer/stem cells by deregulating c-Myc activity. These biophysical and computational studies demonstrated stable binding of the hit compounds with the disordered c-Myc protein. Collectively, our data indicated effective drug targeting of the disordered c-Myc protein via the determination of hot spot residues in the c-Myc/Myc-associated factor X heterodimer.


Assuntos
Descoberta de Drogas , Fator X , Técnicas Genéticas , Proteínas Proto-Oncogênicas c-myc , Fator X/metabolismo , Humanos , Conformação Molecular , Mutagênese , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas Proto-Oncogênicas c-myc/química
19.
J Clin Microbiol ; 61(8): e0061923, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37458587

RESUMO

Immunoblots remain the gold standard for HIV-1/HIV-2 infection confirmation. However, their ability to differentiate HIV-1 from HIV-2 infection on an antigenically diversified HIV-1 and HIV-2 panel remain uncommon. We performed a multicenter study on 116 serum samples accounting for most of the diversity of HIV-1 (9 different subtypes in group M, 17 circulating recombinant forms (CRFs), and 3 group O) and HIV-2 (groups A and B), evaluating seven confirmatory assays (six commercially available assays and one in-house assay) with genotyping as the reference. The assays were INNO-LIA HIV I/II score, HIV-2 blot 1.2, HIV blot 2.2, New Lav blot I and II, Geenius, and an in-house serotyping enzyme-linked immunosorbent assay (ELISA). Among the HIV-1 samples, INNO-LIA, HIV blot 2.2, New Lav blot I, Geenius, and serotyping had comparable high sensitivities, from 98% to 100%, whereas HIV-2 blot 1.2 and New Lav blot II had high rates of "undetermined" results (85% and 95%, respectively). HIV-2 blot 1.2 and New Lav blot II misclassified 7% and 5% of HIV-1 samples as HIV-2, respectively, and HIV-2 blot 1.2 had an 8% false-negative rate. Among the HIV-2 samples, INNO-LIA, New Lav blot II, HIV-2 blot 1.2, and serotyping had high sensitivities, from 96% to 100%. HIV blot 2.2 misclassified 17% of HIV-2 samples as HIV-1/HIV-2 dual infections. New Lav blot I misclassified 19% of HIV-2 samples as HIV-1 with a high (81%) undetermined rate, and Geenius misclassified 2% as HIV-1 and 7% as untypeable HIV positive. For HIV-1/HIV-2 dual infection, the results were less sensitive, with at most 87.5% for INNO-LIA and Geenius and 75% for HIV blot 2.2 and serotyping. Overall, confirmatory assays remain useful for most cases, with the exception of HIV-1/HIV-2 dual-infection suspicion.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-2/genética , Sensibilidade e Especificidade , Infecções por HIV/diagnóstico , Anticorpos Anti-HIV
20.
BMC Infect Dis ; 23(1): 273, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37131164

RESUMO

BACKGROUND: Certain bacterial infectious diseases are categorized as notifiable infectious diseases in China. Understanding the time-varying epidemiology of bacterial infections diseases can provide scientific evidence to inform prevention and control measures. METHODS: Yearly incidence data for all 17 major notifiable bacterial infectious diseases (BIDs) at the province level were obtained from the National Notifiable Infectious Disease Reporting Information System in China between 2004 and 2019. Of them 16 BIDs are divided into four categories, respiratory transmitted diseases (RTDs, 6 diseases), direct contact/fecal-oral transmitted diseases (DCFTDs, 3 diseases), blood-borne/sexually transmitted diseases (BSTDs, 2 diseases), and zoonotic and vector-borne diseases (ZVDs, 5 diseases), and neonatal tetanus is excluded in the analysis. We characterized the demographic, temporal, and geographical features of the BIDs and examined their changing trends using a joinpoint regression analysis. RESULTS: During 2004‒2019, 28 779 thousand cases of BIDs were reported, with an annualized incidence rate of 134.00 per 100 000. RTDs were the most commonly reported BIDs, accounting for 57.02% of the cases (16 410 639/28 779 000). Average annual percent changes (AAPC) in incidence were - 1.98% for RTDs, - 11.66% for DCFTDs, 4.74% for BSTDs, and 4.46% for ZVDs. Females had a higher incidence of syphilis than males, and other BIDs were more commonly reported in males. Among 0-5-year-olds, the diseases with the largest increases in incidence were pertussis (15.17% AAPC) and scarlet fever (12.05%). Children and students had the highest incidence rates of scarlet fever, pertussis, meningococcal meningitis, and bacillary dysentery. Northwest China had the highest incidence of RTDs, while South and East China had the highest incidences of BSTDs. Laboratory confirmation of BIDs increased from 43.80 to 64.04% during the study period. CONCLUSIONS: RTDs and DCFTDs decreased from 2004 to 2019 in China, while BSTDs and ZVDs increased during the same period. Great attention should be paid to BSTDs and ZVDs, active surveillance should be strengthened, and timely control measures should be adopted to reduce the incidence.


Assuntos
Doenças Transmissíveis , Escarlatina , Coqueluche , Masculino , Criança , Feminino , Recém-Nascido , Humanos , Pré-Escolar , Incidência , Escarlatina/epidemiologia , Doenças Transmissíveis/epidemiologia , China/epidemiologia
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