Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 183
Filtrar
1.
Int J Med Inform ; 190: 105544, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39003790

RESUMEN

OBJECTIVE: To determine the incidence of patients presenting in pain to a large Australian inner-city emergency department (ED) using a clinical text deep learning algorithm. MATERIALS AND METHODS: A fine-tuned, domain-specific, transformer-based clinical text deep learning model was used to interpret free-text nursing assessments in the electronic medical records of 235,789 adult presentations to the ED over a three-year period. The model classified presentations according to whether the patient had pain on arrival at the ED. Interrupted time series analysis was used to determine the incidence of pain in patients on arrival over time. We described the changes in the population characteristics and incidence of patients with pain on arrival occurring with the start of the Covid-19 pandemic. RESULTS: 55.16% (95%CI 54.95%-55.36%) of all patients presenting to this ED had pain on arrival. There were differences in demographics and arrival and departure patterns between patients with and without pain. The Covid-19 pandemic initially precipitated a decrease followed by a sharp, sustained rise in pain on arrival, with concurrent changes to the population arriving in pain and their treatment. DISCUSSION: Applying a clinical text deep learning model has successfully identified the incidence of pain on arrival. It represents an automated, reproducible mechanism to identify pain from routinely collected medical records. The description of this population and their treatment forms the basis of intervention to improve care for patients with pain. The combination of the clinical text deep learning models and interrupted time series analysis has reported on the effects of the Covid-19 pandemic on pain care in the ED, outlining a methodology to assess the impact of significant events or interventions on pain care in the ED. CONCLUSION: Applying a novel deep learning approach to identifying pain guides methodological approaches to evaluating pain care interventions in the ED, giving previously unavailable population-level insights.

2.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38869361

RESUMEN

The apparent velocity measured by an interferometric surface velocimeter is a function of both the surface velocity and the time derivative of the refractive index along the measurement path. We employed this dual sensitivity to simultaneously measure km/s surface velocities and 1018 cm-3 average plasma densities with combined VISAR (velocity interferometer system for any reflector) and PDV (photonic Doppler velocimetry) measurements in experiments performed on the Z Pulsed Power Facility. We detail the governing equations, associated assumptions, and analysis specifics and show that the surface velocity can be extracted without knowledge of the specific plasma density profile.

3.
Emerg Med Australas ; 36(4): 659-661, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38837326

RESUMEN

Repeated intentional foreign body ingestion (RIFBI) in patients with Emotionally Unstable Personality Disorder (EUPD) is a common clinical presentation to the emergency department. The relationship between repeated foreign body ingestion and a co-existent personality disorder diagnosis is complex, making it challenging to manage. Our institution implemented a novel interdisciplinary model of care for RIFBI as a way of improving health outcomes in this cohort of patients. Our observations following the model of care are presented herein. We encourage other health networks to adopt this model of care for managing RIBFI in EUPD.


Asunto(s)
Cuerpos Extraños , Adulto , Femenino , Humanos , Masculino , Ingestión de Alimentos , Servicio de Urgencia en Hospital , Cuerpos Extraños/complicaciones , Trastornos de la Personalidad/complicaciones
4.
Mol Brain ; 17(1): 26, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778381

RESUMEN

Aggregation of misfolded α-synuclein (α-syn) is a key characteristic feature of Parkinson's disease (PD) and related synucleinopathies. The nature of these aggregates and their contribution to cellular dysfunction is still not clearly elucidated. We employed mass spectrometry-based total and phospho-proteomics to characterize the underlying molecular and biological changes due to α-syn aggregation using the M83 mouse primary neuronal model of PD. We identified gross changes in the proteome that coincided with the formation of large Lewy body-like α-syn aggregates in these neurons. We used protein-protein interaction (PPI)-based network analysis to identify key protein clusters modulating specific biological pathways that may be dysregulated and identified several mechanisms that regulate protein homeostasis (proteostasis). The observed changes in the proteome may include both homeostatic compensation and dysregulation due to α-syn aggregation and a greater understanding of both processes and their role in α-syn-related proteostasis may lead to improved therapeutic options for patients with PD and related disorders.


Asunto(s)
Neuronas , Enfermedad de Parkinson , Agregado de Proteínas , Proteómica , Proteostasis , alfa-Sinucleína , alfa-Sinucleína/metabolismo , Animales , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Neuronas/metabolismo , Neuronas/patología , Ratones , Mapas de Interacción de Proteínas , Proteoma/metabolismo
6.
J Burn Care Res ; 45(4): 1001-1008, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-38602148

RESUMEN

Burn injuries often lead to psychological distress, from depression and anxiety to adjustment concerns and posttraumatic stress. There is some evidence that the anatomical location of burn injuries (eg, head/neck, feet) has a specific negative effect on psychological functioning. The purpose of this study was to examine the associations between burn injury location and emotional distress. First, we administered self-report questionnaires to burn survivors with ≤ 5% TBSA at a single adult outpatient burn clinic. Second, we used a cross-sectional analysis of the Burn Model System National Database. The mean values of each measure of psychological distress (ie, quality of life, self-esteem, depression, posttraumatic stress, anxiety, and, for contrast, posttraumatic growth) were examined for each anatomical location for those participants with a burn in those anatomical areas against those with burn in other areas. Using Kruskal-Wallis tests to compare psychological distress, we found no significant differences in outcome measures in either sample analyzed in our study. These findings contrast with prior literature indicating the negative psychological effect of burn injuries on certain locations in the body. Further research should explore whether larger burns (ie, < 5% TBSA) affecting critical areas of the body may be associated with psychological distress.


Asunto(s)
Quemaduras , Distrés Psicológico , Calidad de Vida , Humanos , Quemaduras/psicología , Femenino , Masculino , Estudios Transversales , Adulto , Persona de Mediana Edad , Bases de Datos Factuales , Encuestas y Cuestionarios , Autoinforme , Trastornos por Estrés Postraumático/psicología , Trastornos por Estrés Postraumático/epidemiología , Ansiedad/epidemiología , Ansiedad/psicología , Autoimagen , Estrés Psicológico/psicología , Estrés Psicológico/epidemiología , Depresión/epidemiología , Depresión/psicología
7.
BMJ Open Qual ; 13(1)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38448040

RESUMEN

BACKGROUND: In general, the quality of pain care in emergency departments (ED) is poor, despite up to 80% of all ED patients presenting with pain. This may be due to the lack of well-validated patient-reported outcome measures (PROMs) of pain care in the ED setting. The American Pain Society-Patient Outcome Questionnaire-Revised Edition (APS-POQ-R), with slight modification for ED patients, is a potentially useful PROM for the adult ED, however it is yet to be completely validated. METHODS: Adult patients, who had presented with moderate to severe acute pain, were recruited at two large inner-city EDs in Australia. A modified version of the APS-POQ-R was administered at the completion of their ED care. Responses were randomly split into three groups and underwent multiple rounds of exploratory and confirmatory factor analysis with testing for construct, convergent, divergent validity and internal consistency. RESULTS: A total of 646 ED patients (55.6% female), with a median age of 48.3 years, and moderate to severe pain on arrival, completed the ED-modified APS-POQ-R. Psychometric evaluation resulted in a reduced nine-question tool, which measures three constructs (pain relief and satisfaction (α=0.891), affective distress (α=0.823) and pain interference (α=0.908)) and demonstrated construct, convergent, divergent validity, and internal consistency. CONCLUSIONS: This new tool, which we refer to as the American Pain Society-Patient Outcome Questionnaire-Revised for the ED (APS-POQ-RED), should form the basis for reporting patient-reported outcomes of ED pain care in future quality improvement and research.


Asunto(s)
Manejo del Dolor , Dolor , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Australia , Servicio de Urgencia en Hospital , Medición de Resultados Informados por el Paciente
8.
Nanomaterials (Basel) ; 14(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38470781

RESUMEN

Wear performance is integral to component longevity, minimizing industrial waste and excess energy costs in a wide variety of applications. Anodized aluminum oxide (AAO) has many beneficial properties leading to its wide use across industries as a surface treatment for many aluminum components, but the wear properties of the coating could be improved significantly. Here, we used an electrochemical method to incorporate molybdenum disulfide (MoS2), a nanomaterial used as a dry lubricant, to modify alloys of aluminum during AAO preparation. Using Raman spectroscopy and tribological scratch measurements, we thoroughly characterized the structure and wear behavior of the films. The MoS2 deposition procedure was optimal on aluminum 5052 anodized in higher acid concentrations, with friction coefficients at around 0.05 (~10× better than unmodified AAO). Changing anodization conditions to produce harder films with smaller pores led to worsened wear properties, likely because of lower MoS2 content. Studying a commercial MoS2/AAO film of a different Al alloy (7075) showed that a heat treatment step intended to fully convert all deposited MoSx species to MoS2 can adversely affect wear in some alloys. While Al 6061 and 1100 produced films with worse wear performance compared to Al 5052 or 7075, our results show evidence that acid cleaning after initial anodization likely removes residual alloying elements, affecting MoS2 incorporation. This study demonstrates a nanomaterial modified AAO film with superior wear characteristics to unmodified AAO and relates fabrication procedure, film structure, and practical performance.

9.
Br Dent J ; 236(6): 469-474, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38519683

RESUMEN

Introduction Dental guidelines recommend professional application of fluoride varnish (FV) at least twice a year for children from the age of three.Methods NHS dental claims data were reviewed for children born in 2009 for the five-year period 2015-2019 and who attended the dentist in one of three geographical areas, labelled as Bristol, Birmingham and Cardiff. Data for 14,566 children were included in the study.Results Only 3.5% of children had been provided with ten or more FV applications at the dentist in the five-year period. Children in the Cardiff region fared less well for fluoride applications than their Bristol and Birmingham counterparts, including children that were seemingly at high risk of caries for part of the time period reviewed. For all three regions, the mean number of FV applications increased with an increase in the number of fillings provided.Conclusion Awareness of the apparent lack of FV application in the dental surgery may provide an opportunity to improve child dental health.


Asunto(s)
Caries Dental , Fluoruros Tópicos , Niño , Humanos , Adolescente , Fluoruros Tópicos/uso terapéutico , Cariostáticos/uso terapéutico , Caries Dental/prevención & control , Reino Unido , Instituciones Académicas
10.
Sci Transl Med ; 16(739): eadd8936, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38507467

RESUMEN

Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti-tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; therefore, an anti-TNF antibody-drug conjugate (ADC) would be mechanistically similar, where lysosomal catabolism could release a GC receptor modulator (GRM) payload to dampen immune cell activity. Consequently, we have generated an anti-TNF-GRM ADC with the aim of inhibiting pro-inflammatory cytokine production from stimulated human immune cells. In an acute mouse model of contact hypersensitivity, a murine surrogate anti-TNF-GRM ADC inhibited inflammatory responses with minimal effect on systemic GC biomarkers. In addition, in a mouse model of collagen-induced arthritis, single-dose administration of the ADC, delivered at disease onset, was able to completely inhibit arthritis for greater than 30 days, whereas an anti-TNF monoclonal antibody only partially inhibited disease. ADC treatment at the peak of disease was also able to attenuate the arthritic phenotype. Clinical data for a human anti-TNF-GRM ADC (ABBV-3373) from a single ascending dose phase 1 study in healthy volunteers demonstrated antibody-like pharmacokinetic profiles and a lack of impact on serum cortisol concentrations at predicted therapeutic doses. These data suggest that an anti-TNF-GRM ADC may provide improved efficacy beyond anti-TNF alone in immune mediated diseases while minimizing systemic side effects associated with standard GC treatment.


Asunto(s)
Anticuerpos , Artritis Experimental , Inmunoconjugados , Esteroides , Humanos , Animales , Ratones , Preparaciones Farmacéuticas , Receptores de Glucocorticoides/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Modelos Animales de Enfermedad , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico
11.
Microb Genom ; 10(2)2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38376377

RESUMEN

Viral metagenomics has fuelled a rapid change in our understanding of global viral diversity and ecology. Long-read sequencing and hybrid assembly approaches that combine long- and short-read technologies are now being widely implemented in bacterial genomics and metagenomics. However, the use of long-read sequencing to investigate viral communities is still in its infancy. While Nanopore and PacBio technologies have been applied to viral metagenomics, it is not known to what extent different technologies will impact the reconstruction of the viral community. Thus, we constructed a mock bacteriophage community of previously sequenced phage genomes and sequenced them using Illumina, Nanopore and PacBio sequencing technologies and tested a number of different assembly approaches. When using a single sequencing technology, Illumina assemblies were the best at recovering phage genomes. Nanopore- and PacBio-only assemblies performed poorly in comparison to Illumina in both genome recovery and error rates, which both varied with the assembler used. The best Nanopore assembly had errors that manifested as SNPs and INDELs at frequencies 41 and 157 % higher than found in Illumina only assemblies, respectively. While the best PacBio assemblies had SNPs at frequencies 12 and 78 % higher than found in Illumina-only assemblies, respectively. Despite high-read coverage, long-read-only assemblies recovered a maximum of one complete genome from any assembly, unless reads were down-sampled prior to assembly. Overall the best approach was assembly by a combination of Illumina and Nanopore reads, which reduced error rates to levels comparable with short-read-only assemblies. When using a single technology, Illumina only was the best approach. The differences in genome recovery and error rates between technology and assembler had downstream impacts on gene prediction, viral prediction, and subsequent estimates of diversity within a sample. These findings will provide a starting point for others in the choice of reads and assembly algorithms for the analysis of viromes.


Asunto(s)
Bacteriófagos , Nanoporos , Benchmarking , Tecnología , Algoritmos
12.
Data Brief ; 52: 109852, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38205219

RESUMEN

The carbon footprint of a concrete structure is directly affected by the selected concrete mixture proportions. To better understand the influence of different concrete mixtures, data was collected from Environmental Product Declarations (EPDs). Data from 39,213 U.S.A. ready-mix concrete EPDs was obtained from public repositories provided by the American Society for Testing and Materials and the National Ready Mixed Concrete Association. The EPDs in .pdf format were analyzed using a custom Python script to extract useful information for building designers, sustainability practitioners, and researchers including: life cycle assessment (LCA) midpoints (Global Warming Potential, Ozone Depletion Potential, Acidification Potential, Photochemical Ozone Creation Potential, Abiotic Depletion, Total Waste Disposed, and Consumption of Freshwater), concrete strength classes, declared unit, concrete curing time, production components, concrete manufacturers' company and plant locations, and additional LCA information. Both the dataset and an example of the Python script used to extract the information from the EPDs are provided. This dataset enables users to quickly assess the environmental impacts (including the Global Warming Potential) of different concrete mixtures without the need for extensive data collection and analysis. In summary, this dataset provides environmental information about concrete mixtures to aid civil engineering and architectural researchers, sustainability consultants, building engineering practitioners, and environmental policymakers to make sustainability-informed decisions when specifying concrete in the U.S.A.

13.
Stud Health Technol Inform ; 310: 705-709, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38269900

RESUMEN

The success of deep learning in natural language processing relies on ample labelled training data. However, models in the health domain often face data inadequacy due to the high cost and difficulty of acquiring training data. Developing such models thus requires robustness and performance on new data. A generalised incremental multiphase framework is proposed for developing robust and performant clinical text deep learning classifiers. It incorporates incremental multiphases for training data size assessments, cross-validation setup to avoid test data bias, and robustness testing through inter/intra-model significance analysis. The framework's effectiveness and generalisation were confirmed by the task of identifying patients presenting in 'pain' to the emergency department.


Asunto(s)
Aprendizaje Profundo , Humanos , Servicio de Urgencia en Hospital , Procesamiento de Lenguaje Natural , Dolor , Proyectos de Investigación
14.
Emerg Med Australas ; 36(1): 39-46, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37581206

RESUMEN

OBJECTIVE: To determine the independent predictors for clinician fatigue and decline in cognitive function following a shift in the ED during early stages of the COVID-19 pandemic. METHODS: This was a prospective, quasi-experimental study conducted in a metropolitan adult tertiary-referral hospital ED over 20 weeks in 2021. The participants were ED doctors and nurses working clinical shifts in an ED isolation area or high-risk zone (HRZ) with stringent personal protective equipment (PPE). The participants' objective and subjective fatigue was measured by the Samn-Perelli fatigue score and a psychomotor vigilance 'smart game' score, respectively. Postural signs/symptoms and urine specific gravity (SG) were measured as markers of dehydration. RESULTS: Sixty-three participants provided data for 263 shifts. Median (interquartile range) age was 33 (28-38) years, 73% were female. Worsening fatigue score was associated with working afternoon shifts (afternoon vs day, adjusted odds ratio [aOR] 5.16 [95% confidence interval (CI) 1.32-20.02]) and in non-HRZ locations (HRZ vs non-HRZ, aOR 0.23 [95% CI 0.06-0.87]). Worsening cognitive function (game score) was associated with new onset postural symptoms (new vs no symptoms, aOR 4.14 [95% CI 1.34-12.51]) and afternoon shifts (afternoon vs day, aOR 3.13 [95% CI 1.16-8.44]). Working in the HRZ was not associated with declining cognitive function. Thirty-four (37%) of the 92 participants had an end of shift urine SG >1.030. CONCLUSION: Working afternoon shifts was associated with fatigue. There was no association between HRZ allocation and fatigue, but our study was limited by a low COVID workload and fluctuating PPE requirements in the non-HRZs. Workplace interventions that target the prevention of fatigue in ED clinicians working afternoon shifts should be prioritised.


Asunto(s)
Pandemias , Tolerancia al Trabajo Programado , Adulto , Humanos , Femenino , Masculino , Estudios Prospectivos , Fatiga/etiología , Fatiga/diagnóstico , Equipo de Protección Personal
15.
Cureus ; 15(8): e43476, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37711915

RESUMEN

PURPOSE: As of January 26, 2022, the United States Medical Licensing Examination (USLME) step 1 exam went from a scored test to pass-fail step 1 (PFS1). The authors were interested in surveying medical students at a community-based medical school to observe their perceptions of the importance of student research given this recent change. METHOD: A Qualtrics survey was disseminated to medical students (years 1-4) via school emails. Data were analyzed using the Mann-Whitney test to assess Likert scale scores, and narrative comments were grouped as qualitative feedback. Survey dissemination and analysis of data were both conducted at a large community-based medical school. RESULTS: The survey sampled 104 students categorized into pre-clerkship (PC) and clerkship (CL) years, with a response rate of 33%. A contradiction was found, as indicated by the higher number (p = 0.047) of clerkship students interested in Primary Care/Family medicine residency compared to pre-clerkship students at 41% and 59%, respectively. Whereas participants who indicated they are interested in pursuing a competitive specialty for residency were 51% of pre-clerkship students over 41% of clerkship students (p = 0.047). Additionally, given the assessment change to pass/fail, students did in fact believe that residencies would now view research as a higher assessed component than before (79% pre-clerkship and 72% clerkship). However, a minority of students said that they increased their research efforts (41% and 47%). Most students supported the research opportunity improvements proposed in our survey. CONCLUSIONS: Efforts to make the step 1 exam pass/fail may have alleviated some stress related to performance but may have increased the perception of the importance of other components in a student's residency application. Our survey highlights how medical students at a community-based medical school perceive this change and how it has affected their research efforts.

16.
Metabolites ; 13(7)2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37512508

RESUMEN

Dietary flavanols are known for disease preventative properties but are often poorly absorbed. Gut microbiome flavanol metabolites are more bioavailable and may exert protective activities. Using metabolite mixtures extracted from the urine of rats supplemented with flavanols and treated with or without antibiotics, we investigated their effects on INS-1 832/13 ß-cell glucose stimulated insulin secretion (GSIS) capacity. We measured insulin secretion under non-stimulatory (low) and stimulatory (high) glucose levels, insulin secretion fold induction, and total insulin content. We conducted treatment-level comparisons, individual-level dose responses, and a responder vs. non-responder predictive analysis of metabolite composition. While the first two analyses did not elucidate treatment effects, metabolites from 9 of the 28 animals demonstrated significant dose responses, regardless of treatment. Differentiation of responders vs. non-responder revealed that levels of native flavanols and valerolactones approached significance for predicting enhanced GSIS, regardless of treatment. Although treatment-level patterns were not discernable, we conclude that the high inter-individual variability shows that metabolite bioactivity on GSIS capacity is less related to flavanol supplementation or antibiotic treatment and may be more associated with the unique microbiome or metabolome of each animal. These findings suggest flavanol metabolite activities are individualized and point to the need for personalized nutrition practices.

17.
Eur J Emerg Med ; 30(5): 356-364, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37310953

RESUMEN

BACKGROUND AND IMPORTANCE: Recommended indications for emergency computed tomography (CT) brain scans are not only complex and evolving, but it is also unknown whether they are being followed in emergency departments (EDs). OBJECTIVE: To determine the CT utilization and diagnostic yield in the ED in patients with headaches across broad geographical regions. DESIGN: Secondary analysis of data from a multinational cross-sectional study of ED headache presentations over one month in 2019. SETTING AND PARTICIPANTS: Hospitals from 10 participating countries were divided into five geographical regions [Australia and New Zealand (ANZ); Colombia; Europe: Belgium, France, UK, and Romania; Hong Kong and Singapore (HKS); and Turkey). Adult patients with nontraumatic headache as the primary presenting complaint were included. Patients were identified from ED management systems. OUTCOME MEASURES AND ANALYSIS: The outcome measures were CT utilization and diagnostic yield. CT utilization was calculated using a multilevel binary logistic regression model to account for clustering of patients within hospitals and regions. Imaging data (CT requests and reports) were sourced from radiology management systems. MAIN RESULTS: The study included 5281 participants. Median (interquartile range) age was 40 (29-55) years, 66% were women. Overall mean CT utilization was 38.5% [95% confidence interval (CI), 30.4-47.4%]. Regional utilization was highest in Europe (46.0%) and lowest in Turkey (28.9%), with HKS (38.0%), ANZ (40.0%), and Colombia (40.8%) in between. Its distribution across hospitals was approximately symmetrical. There was greater variation in CT utilization between hospitals within a region than between regions (hospital variance 0.422, region variance 0.100). Overall mean CT diagnostic yield was 9.9% (95% CI, 8.7-11.3%). Its distribution across hospitals was positively skewed. Regional yield was lower in Europe (5.4%) than in other regions: Colombia (9.1%), HKS (9.7%), Turkey (10.6%), and ANZ (11.2%). There was a weak negative correlation between utilization and diagnostic yield ( r  = -0.248). CONCLUSION: In this international study, there was a high variation (28.9-46.6%) in CT utilization and diagnostic yield (5.4-11.2%) across broad geographic regions. Europe had the highest utilization and the lowest yield. The study findings provide a foundation to address variation in neuroimaging in ED headache presentations.


Asunto(s)
Cefalea , Tomografía Computarizada por Rayos X , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Transversales , Cefalea/diagnóstico por imagen , Servicio de Urgencia en Hospital , Neuroimagen , Encéfalo
18.
J Chem Inf Model ; 63(10): 2960-2974, 2023 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-37166179

RESUMEN

Over the past few years, many machine learning-based scoring functions for predicting the binding of small molecules to proteins have been developed. Their objective is to approximate the distribution which takes two molecules as input and outputs the energy of their interaction. Only a scoring function that accounts for the interatomic interactions involved in binding can accurately predict binding affinity on unseen molecules. However, many scoring functions make predictions based on data set biases rather than an understanding of the physics of binding. These scoring functions perform well when tested on similar targets to those in the training set but fail to generalize to dissimilar targets. To test what a machine learning-based scoring function has learned, input attribution, a technique for learning which features are important to a model when making a prediction on a particular data point, can be applied. If a model successfully learns something beyond data set biases, attribution should give insight into the important binding interactions that are taking place. We built a machine learning-based scoring function that aimed to avoid the influence of bias via thorough train and test data set filtering and show that it achieves comparable performance on the Comparative Assessment of Scoring Functions, 2016 (CASF-2016) benchmark to other leading methods. We then use the CASF-2016 test set to perform attribution and find that the bonds identified as important by PointVS, unlike those extracted from other scoring functions, have a high correlation with those found by a distance-based interaction profiler. We then show that attribution can be used to extract important binding pharmacophores from a given protein target when supplied with a number of bound structures. We use this information to perform fragment elaboration and see improvements in docking scores compared to using structural information from a traditional, data-based approach. This not only provides definitive proof that the scoring function has learned to identify some important binding interactions but also constitutes the first deep learning-based method for extracting structural information from a target for molecule design.


Asunto(s)
Aprendizaje Automático , Proteínas , Unión Proteica , Ligandos , Proteínas/química , Bases de Datos de Proteínas , Simulación del Acoplamiento Molecular
19.
Cureus ; 15(3): e36478, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37090328

RESUMEN

Fishhook injuries commonly occur and may present as ophthalmic surgical emergencies. Choosing the appropriate removal technique is critical and depends on the involved extra- and intra-ocular structures and hook characteristics. We describe the case of a challenging fishhook removal where a novel surgical technique was developed. An eight-year-old boy presented with a full-thickness fishhook injury to the eyelid. During removal surgery, the thickness and density of the fishhook prevented surgical tools from transecting the shank. A novel approach was deemed necessary for safe removal, termed the clamp and retract technique. To our knowledge, this is its first documented use in the literature.

20.
BMJ Open ; 13(4): e067740, 2023 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-37094888

RESUMEN

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition with a broad spectrum of injury severity, pathophysiological processes and variable outcomes. For moderate-to-severe TBI survivors, recovery is often protracted and outcomes can range from total dependence to full recovery. Despite advances in medical treatment options, prognosis remains largely unchanged. The objective of this study is to develop a machine learning predictive model for neurological outcomes at 6 months in patients with a moderate-to-severe TBI, incorporating longitudinal clinical, multimodal neuroimaging and blood biomarker predictor variables. METHODS AND ANALYSIS: A prospective, observational, cohort study will enrol 300 patients with moderate-to-severe TBI from seven Australian hospitals over 3 years. Candidate predictors including demographic and general health variables, and longitudinal clinical, neuroimaging (CT and MRI), blood biomarker and patient-reported outcome measures will be collected at multiple time points within the acute phase of injury. The predictor variables will populate novel machine learning models to predict the Glasgow Outcome Scale Extended 6 months after injury. The study will also expand on current prognostic models by including novel blood biomarkers (circulating cell-free DNA), and the results of quantitative neuroimaging such as Quantitative Susceptibility Mapping and Dynamic Contrast Enhanced MRI as predictor variables. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the Royal Brisbane and Women's Hospital Human Research Ethics Committee, Queensland. Participants or their substitute decision-maker/s will receive oral and written information about the study before providing written informed consent. Study findings will be disseminated by peer-review publications and presented at national and international conferences and clinical networks. TRIAL REGISTRATION NUMBER: ACTRN12620001360909.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Femenino , Humanos , Australia , Biomarcadores , Lesiones Traumáticas del Encéfalo/terapia , Estudios de Cohortes , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Estudios Prospectivos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA