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1.
Biol Pharm Bull ; 47(3): 556-561, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432911

RESUMO

Mental illness poses a huge social burden, accounting for approximately 14% of all deaths. Depression, a major component of mental illness, affects approximately 300 million people worldwide, mainly in developed countries, and is not only a major social burden but also a cause of suicide. The social burden of depression is estimated to increase further in developing countries, and overcoming it is a pressing issue for all countries, including Japan. Although clinical evidence has demonstrated the efficacy of serotonergic neurotransmission enhancers in the treatment of depression, the full picture of their therapeutic effects has not yet been fully elucidated. In this review, we show that the hyperactivity of serotonin neurons, especially those in the dorsal raphe nucleus, is commonly induced by various antidepressants within a period corresponding to the onset of their clinical efficacy. We established quantitative prediction methods for pharmacological activity using only chemical structures to translate the biological understanding of mental disorders, including major depressive disorders, into clinically effective therapeutics. Our method exhibited better performance than the previously reported methods of quantitative prediction, while targeting a larger number of proteins. Our article suggests the importance of integrative neuropharmacology and informatics-based pharmacology studies to understand the biological basis of mental disorders and facilitate drug development for these disorders.


Assuntos
Transtorno Depressivo Maior , Transtornos Mentais , Transtornos Psicóticos , Humanos , Neurofarmacologia , Transtornos Mentais/tratamento farmacológico , Informática
2.
Mol Biol Rep ; 51(1): 419, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483683

RESUMO

BACKGROUND: A novel lytic bacteriophage (phage) was isolated with Pseudomonas mendocina strain STP12 (P. mendocina) from the untreated site of Sewage Treatment Plant of Lovely Professional University, India. P. mendocina is a Gram-negative, rod-shaped, aerobic bacterium belonging to the family Pseudomonadaceae and has been reported in fifteen (15) cases of economically important diseases worldwide. METHODS AND RESULTS: Here, a novel phage specifically infecting and killing P. mendocina strain STP12 was isolated from sewage sample using enrichment, spot test and double agar overlay (DAOL) method and was designated as vB_PmeS_STP12. The phage vB-PmeS-STP12 was viable at wide range of pH and temperature ranging from 4 to10 and - 20 to 70 °C respectively. Host range and efficiency of plating (EOP) analysis indicated that phage vB-PmeS-STP12 was capable of infecting and killing P. mendocina strain STP6 with EOP of 0.34. Phage vB_PmeS_STP12 was found to have a significant bacterial reduction (p < 0.005) at all the doses administered, particularly at optimal MOI of 1 PFU/CFU, compared to the control. Morphological analysis using high resolution transmission electron microscopy (HR-TEM) revealed an icosahedral capsid of ~ 55 nm in diameter on average with a short, non-contractile tail. The genome of vB_PmeS_STP12 is a linear, dsDNA containing 36,212 bp in size with a GC content of 58.87% harbouring 46 open reading frames (ORFs). The 46 predicted ORFs encode proteins with functional information categorized as lysis, replication, packaging, regulation, assembly, infection, immune, and hypothetical. However, the genome of vB_PmeS_STP12 appeared to be devoid of tRNAs, integrase gene, toxins genes, virulence factors, antimicrobial resistance genes (ARGs) and CRISPR arrays. The blast analysis with phylogeny revealed that vB_PmeS_STP12 is genetically similar to Pseudomonas phage PMBT14, Pseudomonas phage Almagne and Serratia phage Serbin with a highest identity of 74.00%, 74.93% and 59.48% respectively. CONCLUSIONS: Taken together, characterization, morphological analysis and genome-informatics indicated that vB_PmeS_STP12 is podovirus morphotype belonging to the class Caudoviticetes, family Zobellviridae which appeared to be devoid of integrase gene, ARGs, CRISPR arrays, virulence factors and toxins genes, exhibiting stability and infectivity at wide range of pH (4 to10) and temperature (-20 to 70 °C), thereby making vB_PmeS_STP12 suitable for phage therapy or biocontrol. Based on the bibliometric analysis and data availability with respect to sequences deposited in GenBank, this is the first report of a phage infecting Pseudomonas mendocina.


Assuntos
Bacteriófagos , Terapia por Fagos , Humanos , Bacteriófagos/genética , Pseudomonas , Esgotos , Genoma Viral , Informática , Integrases , Fatores de Virulência , Filogenia
3.
Appl Clin Inform ; 15(1): 129-144, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38354837

RESUMO

BACKGROUND: Given the inequities in access to health care resources like COVID-19 vaccination, health systems should carefully consider how to reach underrepresented groups. Reflecting on vaccine rollout efforts holds insight on the role of community engagement and informatics support in promoting health equity. OBJECTIVES: This study aimed to assess the effectiveness of four outreach strategies deployed by University of Washington (UW) Medicine in improving vaccine equity over traditional vaccine scheduling online or by phone, we report on appointment scheduling and completion of appointments (i.e., vaccine administration) through (1) automated outreach to individuals from underrepresented groups, (2) temporary "pop-up" clinics in neighborhoods highly impacted by COVID-19, (3) vulnerable population clinics, and (4) mobile vaccine vans. METHODS: We conducted a 6-month retrospective analysis of electronic health records (EHR) to describe the sociodemographic characteristics of individuals who scheduled appointments using the outreach strategies and characteristics associated with a greater likelihood of vaccine administration based on appointment completion. To help explain trends in the EHR data, we engaged 10 health system leaders and staff who spearheaded the outreach strategies in follow-up conversations to identify qualitative insights into what worked and why. RESULTS: Compared with traditional scheduling, all outreach strategies except vulnerable population clinics had higher vaccine appointment completion rates, including automated outreach (N = 3,734 [94.7%], p < 0.001), pop-up clinics (N = 4,391 [96.0%], p < 0.001), and mobile vans (N = 4,198 [99.1%], p < 0.001); and lower cancellation rates, including automated outreach (N = 166 [1.1%], p < 0.001), pop-up clinics (N = 155 [0.6%], p < 0.001), and mobile vans (N = 0 [0%], p < 0.001). Qualitative insights emphasized ongoing community partnerships and information resources in successful outreach. CONCLUSION: Vaccine equity outreach strategies improved the proportion of patients who scheduled and completed vaccination appointments among populations disproportionately impacted by COVID-19. Engaging community partners and equity-focused informatics tools can facilitate outreach. Lessons from these outreach strategies carry practical implications for health systems to amplify their health equity efforts.


Assuntos
COVID-19 , Vacinas , Humanos , Vacinas contra COVID-19 , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Informática
5.
Anesth Analg ; 138(2): 253-272, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38215706

RESUMO

The role of informatics in public health has increased over the past few decades, and the coronavirus disease 2019 (COVID-19) pandemic has underscored the critical importance of aggregated, multicenter, high-quality, near-real-time data to inform decision-making by physicians, hospital systems, and governments. Given the impact of the pandemic on perioperative and critical care services (eg, elective procedure delays; information sharing related to interventions in critically ill patients; regional bed-management under crisis conditions), anesthesiologists must recognize and advocate for improved informatic frameworks in their local environments. Most anesthesiologists receive little formal training in public health informatics (PHI) during clinical residency or through continuing medical education. The COVID-19 pandemic demonstrated that this knowledge gap represents a missed opportunity for our specialty to participate in informatics-related, public health-oriented clinical care and policy decision-making. This article briefly outlines the background of PHI, its relevance to perioperative care, and conceives intersections with PHI that could evolve over the next quarter century.


Assuntos
COVID-19 , Informática Médica , Humanos , Pandemias , Informática em Saúde Pública , Informática , Anestesiologistas
6.
Drug Discov Today ; 29(3): 103894, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266979

RESUMO

The understudied members of the druggable proteomes offer promising prospects for drug discovery efforts. While large-scale initiatives have generated valuable functional information on understudied members of the druggable gene families, translating this information into actionable knowledge for drug discovery requires specialized informatics tools and resources. Here, we review the unique informatics challenges and advances in annotating understudied members of the druggable proteome. We demonstrate the application of statistical evolutionary inference tools, knowledge graph mining approaches, and protein language models in illuminating understudied protein kinases, pseudokinases, and ion channels.


Assuntos
Informática , Proteoma
8.
Stud Health Technol Inform ; 310: 1410-1411, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38269671

RESUMO

A pragmatic informatics approach was developed to create knowledge tools for co-design of a new model of mental healthcare in cardiac surgery The real-world evidence generation leverages existing technological platforms and routine data collections plus tailored brief tools, surveys and qualitative data.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Saúde Mental , Humanos , Coração , Pacientes , Informática
9.
Stud Health Technol Inform ; 310: 1492-1494, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38269712

RESUMO

FHIR is a new standard that is rapidly being adopted in healthcare. We describe and implement a Radiology informatics platform (RIS) that is FHIR native and incorporates the ability to execute AI algorithms to aid with the interpretation of scans. Our design utilises the FHIR workflow pattern as an application programming interface with functionality provided by independent micro services thus granting flexibility and expandability.


Assuntos
Radiologia , Radiografia , Algoritmos , Instalações de Saúde , Informática
10.
Stud Health Technol Inform ; 310: 1534-1535, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38269732

RESUMO

This study classifies the nursing informatics competency requirements for nurses and healthcare leaders in the United States according to each of the four levels listed in the "Management Ladder for Hospital Nurse Managers (JNA version)" published by the Japanese Nursing Association. Computer skills were included in Level I. Fifteen informatics knowledge items and four informatic competency items that could not be classified for the levels of the management ladder for nurse managers in Japan. This list of nursing informatics competencies, categorized according to the management levels of hospital nurse managers, can be used to provide nursing informatics training to them.


Assuntos
Enfermeiras Administradoras , Informática em Enfermagem , Humanos , Japão , Informática , Hospitais
11.
Stud Health Technol Inform ; 310: 404-408, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38269834

RESUMO

In the residential aged care sector medication management has been identified as a major area of concern contributing to poor outcomes and quality of life for residents. Monitoring medication management in residential aged care in Australia has been highly reliant on small, internal audits. The introduction of electronic medication administration systems provides new opportunities to establish improved methods for ongoing, timely and efficient monitoring of a range of medication indicators, made more meaningful by linking medication data with resident characteristics and outcomes. Benchmarking contemporary medication indicators provides a further opportunity for improvement and is most effective when indicator data are adjusted to take account of confounding factors, such as residents' characteristics and health conditions. Roundtables provide a structure for sharing and discussing indicator data in a trusted and supportive environment and encourage the identification of strategies which may be effective in improving medication management. This paper describes a new project to establish, implement and evaluate a National Aged Care Medication Roundtable.


Assuntos
Informática , Qualidade de Vida , Humanos , Idoso , Assistência ao Paciente , Austrália , Benchmarking
12.
Stud Health Technol Inform ; 310: 1276-1280, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270020

RESUMO

Resilience research is attracting increasing attention as stressors such as pandemics and climate change impact normal life worldwide. Informatics tools can play an important role in enhancing resilience of people, communities, and organizations. We present Resilience Informatics as a sub-discipline of resilience research and propose a conceptual framework for Resilience Informatics to aid in the development and effective deployment of informatics systems for resilience.


Assuntos
Saúde Pública , Resiliência Psicológica , Humanos , Mudança Climática , Informática , Pandemias
13.
Stud Health Technol Inform ; 310: 1364-1365, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270045

RESUMO

Alzheimer's disease and other dementias are becoming more prevalent and placing increasing burdens on the community. The ADNeT Screening and Trials initiative aims to improve research outcomes by identifying people with an increased risk of developing these diseases and directing them to suitable clinical trials. To support the initiative, we have developed a modular informatics platform utilizing private cloud deployment to securely manage operational and research data across six clinical sites.


Assuntos
Doença de Alzheimer , Humanos , Austrália , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Informática
14.
Drug Discov Today ; 29(3): 103882, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218214

RESUMO

The Knowledge Management Center (KMC) for the Illuminating the Druggable Genome (IDG) project aims to aggregate, update, and articulate protein-centric data knowledge for the entire human proteome, with emphasis on the understudied proteins from the three IDG protein families. KMC collates and analyzes data from over 70 resources to compile the Target Central Resource Database (TCRD), which is the web-based informatics platform (Pharos). These data include experimental, computational, and text-mined information on protein structures, compound interactions, and disease and phenotype associations. Based on this knowledge, proteins are classified into different Target Development Levels (TDLs) for identification of understudied targets. Additional work by the KMC focuses on enriching target knowledge and producing DrugCentral and other data visualization tools for expanding investigation of understudied targets.


Assuntos
Genoma , Gestão do Conhecimento , Humanos , Proteoma , Bases de Dados Factuais , Informática
15.
J Nat Prod ; 87(2): 217-227, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38242544

RESUMO

The urgent need for new classes of orally available, safe, and effective antivirals─covering a breadth of emerging viruses─is evidenced by the loss of life and economic challenges created by the HIV-1 and SARS-CoV-2 pandemics. As frontline interventions, small-molecule antivirals can be deployed prophylactically or postinfection to control the initial spread of outbreaks by reducing transmissibility and symptom severity. Natural products have an impressive track record of success as prototypic antivirals and continue to provide new drugs through synthesis, medicinal chemistry, and optimization decades after discovery. Here, we demonstrate an approach using computational analysis typically used for rational drug design to identify and develop natural product-inspired antivirals. This was done with the goal of identifying natural product prototypes to aid the effort of progressing toward safe, effective, and affordable broad-spectrum inhibitors of Betacoronavirus replication by targeting the highly conserved RNA 2'-O-methyltransferase (2'-O-MTase). Machaeriols RS-1 (7) and RS-2 (8) were identified using a previously outlined informatics approach to first screen for natural product prototypes, followed by in silico-guided synthesis. Both molecules are based on a rare natural product group. The machaeriols (3-6), isolated from the genus Machaerium, endemic to Amazonia, inhibited the SARS-CoV-2 2'-O-MTase more potently than the positive control, Sinefungin (2), and in silico modeling suggests distinct molecular interactions. This report highlights the potential of computationally driven screening to leverage natural product libraries and improve the efficiency of isolation or synthetic analog development.


Assuntos
Produtos Biológicos , COVID-19 , Humanos , SARS-CoV-2 , Produtos Biológicos/farmacologia , Informática , Antivirais/farmacologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-37771233

RESUMO

A dental implant with three distinct layers, of titanium alloy at core, porous titanium alloy at the intermediate layer and titanium alloy hydroxyapatite composite at the outer layer, is designed to achieve low elastic modulus and adequate strength with bioactive surface. Artificial Neural Network (ANN) along with Rule of Mixture (ROM) is used to generate the objective functions for the Genetic Algorithm (GA) based multi-objective optimization for achieving the optimal designs, which are validated using Finite Element Analysis (FEA) simulations. The composition and processing parameters are correlated with the yield strength and elastic modulus of titanium alloy using ANN. The ANN models are generated to express the strength and effective modulus of the implant using ROM. To determine the optimal composition of titanium alloys, porous layers, and composite layers for a three-layer dental implant, multi-objective genetic algorithm is employed. The Pareto optimal solutions provide the guidelines for designing the implant. A few selected non-dominated solutions are used for studying the actual stress distribution at the bone-implant interface using FEA, and showed significant improvements compared to conventional implants.


Assuntos
Implantes Dentários , Titânio , Ligas , Interface Osso-Implante , Informática , Análise de Elementos Finitos , Estresse Mecânico
18.
J Proteome Res ; 23(1): 107-116, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38147001

RESUMO

Chemical cross-linking combined with mass spectrometry is a technique used to study protein structures and identify protein complexes. Traditionally, chemical cross-linkers contain two reactive groups, allowing them to covalently bond a pair of proximal residues, either within a protein or between two proteins. The output of a cross-linking experiment is a list of interacting site pairs that provide structural constraints for modeling of new structures and complexes. Due to the binary reactive nature of cross-linking reagents, only pairs of interacting sites can be directly observed, and assembly of higher-order structures typically requires prior knowledge of complex composition or iterative docking to produce a putative model. Here, we describe a new tetrameric cross-linker bearing four amine-reactive groups, allowing it to covalently link up to four proteins simultaneously and a real-time instrument method to facilitate the identification of these tetrameric cross-links. We applied this new cross-linker to isolated mitochondria and identified a number of higher-order cross-links in various OXPHOS complexes and ATP synthase, demonstrating its utility in characterizing complex interfaces. We also show that higher-order cross-links can be used to effectively filter models of large protein assemblies generated by using Alphafold. Higher-dimensional cross-linking provides a new avenue for characterizing multiple protein interfaces, even in complex samples such as intact mitochondria.


Assuntos
Aminas , Proteínas , Proteínas/química , Espectrometria de Massas/métodos , Informática , Reagentes de Ligações Cruzadas/química
19.
JCO Clin Cancer Inform ; 7: e2300136, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38055914

RESUMO

In August 2022, the Cancer Informatics for Cancer Centers brought together cancer informatics leaders for its biannual symposium, Precision Medicine Applications in Radiation Oncology, co-chaired by Quynh-Thu Le, MD (Stanford University), and Walter J. Curran, MD (GenesisCare). Over the course of 3 days, presenters discussed a range of topics relevant to radiation oncology and the cancer informatics community more broadly, including biomarker development, decision support algorithms, novel imaging tools, theranostics, and artificial intelligence (AI) for the radiotherapy workflow. Since the symposium, there has been an impressive shift in the promise and potential for integration of AI in clinical care, accelerated in large part by major advances in generative AI. AI is now poised more than ever to revolutionize cancer care. Radiation oncology is a field that uses and generates a large amount of digital data and is therefore likely to be one of the first fields to be transformed by AI. As experts in the collection, management, and analysis of these data, the informatics community will take a leading role in ensuring that radiation oncology is prepared to take full advantage of these technological advances. In this report, we provide highlights from the symposium, which took place in Santa Barbara, California, from August 29 to 31, 2022. We discuss lessons learned from the symposium for data acquisition, management, representation, and sharing, and put these themes into context to prepare radiation oncology for the successful and safe integration of AI and informatics technologies.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Humanos , Inteligência Artificial , Informática , Neoplasias/diagnóstico , Neoplasias/radioterapia
20.
Sci Rep ; 13(1): 22942, 2023 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-38135704

RESUMO

Gliomas with CDKN2A mutations are known to have worse prognosis but imaging features of these gliomas are unknown. Our goal is to identify CDKN2A specific qualitative imaging biomarkers in glioblastomas using a new informatics workflow that enables rapid analysis of qualitative imaging features with Visually AcceSAble Rembrandtr Images (VASARI) for large datasets in PACS. Sixty nine patients undergoing GBM resection with CDKN2A status determined by whole-exome sequencing were included. GBMs on magnetic resonance images were automatically 3D segmented using deep learning algorithms incorporated within PACS. VASARI features were assessed using FHIR forms integrated within PACS. GBMs without CDKN2A alterations were significantly larger (64 vs. 30%, p = 0.007) compared to tumors with homozygous deletion (HOMDEL) and heterozygous loss (HETLOSS). Lesions larger than 8 cm were four times more likely to have no CDKN2A alteration (OR: 4.3; 95% CI 1.5-12.1; p < 0.001). We developed a novel integrated PACS informatics platform for the assessment of GBM molecular subtypes and show that tumors with HOMDEL are more likely to have radiographic evidence of pial invasion and less likely to have deep white matter invasion or subependymal invasion. These imaging features may allow noninvasive identification of CDKN2A allele status.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/patologia , Homozigoto , Deleção de Sequência , Glioma/patologia , Proteínas Inibidoras de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Informática , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Mutação
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