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1.
Biochem Biophys Res Commun ; 619: 15-21, 2022 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-35728279

RESUMEN

In the absence of a sensitive and specific diagnostic modality capable of detecting all forms of tuberculosis (TB), proteomics may identify specific Mycobacterium tuberculosis (M.tb) proteins in urine, with a potential as biomarkers. To identify candidate biomarkers for TB, proteome profile of urine from pulmonary TB patients was compared with non-disease controls (NDC) and disease controls (DC, Streptococcus pneumonia infected patients) using a combination of two-dimensional difference gel electrophoresis (2D-DIGE) and liquid chromatography tandem mass spectrometry (LCMS/MS). Eleven differentially expressed host proteins and Eighteen high abundant M.tb proteins were identified. Protein-protein interactome (PPI) and functional enrichment analyses like Gene Ontologies, Reactome pathway etc. demonstrated that the human proteins mainly belong to extracellular space and show physiological pathways for immune response and hematological disorders. Whereas, M.tb proteins belong to the cell periphery, plasma membrane and cell wall, and demonstrated catalytic, nucleotide binding and ATPase activities along with other functional processes. The study findings provide valuable inputs about the biomarkers of TB and shed light on the probable disease consequences as an outcome of the bacterial pathogenicity.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Biomarcadores/metabolismo , Humanos , Mycobacterium tuberculosis/metabolismo , Proteómica/métodos , Espectrometría de Masas en Tándem/métodos , Tuberculosis/microbiología , Tuberculosis Pulmonar/diagnóstico , Electroforesis Bidimensional Diferencial en Gel
2.
Ann Surg ; 273(2): 258-268, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-32482979

RESUMEN

OBJECTIVE: This review assimilates and critically evaluates available literature regarding the use of metabolomic profiling in surgical decision-making. BACKGROUND: Metabolomic profiling is performed by nuclear magnetic resonance spectroscopy or mass spectrometry of biofluids and tissues to quantify biomarkers (ie, sugars, amino acids, and lipids), producing diagnostic and prognostic information that has been applied among patients with cardiovascular disease, inflammatory bowel disease, cancer, and solid organ transplants. METHODS: PubMed was searched from 1995 to 2019 to identify studies investigating metabolomic profiling of surgical patients. Articles were included and assimilated into relevant categories per PRISMA-ScR guidelines. Results were summarized with descriptive analytical methods. RESULTS: Forty-seven studies were included, most of which were retrospective studies with small sample sizes using various combinations of analytic techniques and types of biofluids and tissues. Results suggest that metabolomic profiling has the potential to effectively screen for surgical diseases, suggest diagnoses, and predict outcomes such as postoperative complications and disease recurrence. Major barriers to clinical adoption include a lack of high-level evidence from prospective studies, heterogeneity in study design regarding tissue and biofluid procurement and analytical methods, and the absence of large, multicenter metabolome databases to facilitate systematic investigation of the efficacy, reproducibility, and generalizability of metabolomic profiling diagnoses and prognoses. CONCLUSIONS: Metabolomic profiling research would benefit from standardization of study design and analytic approaches. As technologies improve and knowledge garnered from research accumulates, metabolomic profiling has the potential to provide personalized diagnostic and prognostic information to support surgical decision-making from preoperative to postdischarge phases of care.


Asunto(s)
Toma de Decisiones Clínicas , Metabolómica , Procedimientos Quirúrgicos Operativos , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Pronóstico
3.
Inorg Chem ; 60(2): 597-605, 2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33411526

RESUMEN

Reactions requiring controlled delivery of protons and electrons are important in storage of energy in small molecules. While control over proton transfer can be achieved by installing appropriate chemical functionality in the catalyst, control of electron-transfer (ET) rates can be achieved by utilizing self-assembled monolayers (SAMs) on electrodes. Thus, a deeper understanding of the ET through SAM to an immobilized or covalently attached redox-active species is desirable. Long-range ET across several SAM-covered Au electrodes to covalently attached ferrocene is investigated using protonated and deuterated thiols (R-SH/R-SD). The rate of tunneling is measured using both chronoamperometry and cyclic voltammetry, and it shows a prominent kinetic isotope effect (KIE). The KIE is ∼2 (normal) for medium-chain-length thiols but ∼0.47 (inverse) for long-chain thiols. These results imply substantial contribution from the classical modes at the Au-(H)SR interface, which shifts substantially upon deuteration of the thiols, to the ET process. The underlying H/D KIE of these exchangeable thiol protons should be considered when analyzing solvent isotope effects in catalysis utilizing SAM.

4.
Int Ophthalmol ; 38(1): 241-249, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28160192

RESUMEN

PURPOSE: To compare aqueous angiogenic and inflammatory cytokine concentrations in different patterns of diabetic macular edema (DME) based on optical coherence tomography (OCT). METHODS: This prospective study was conducted between July 1, 2015, and March 31, 2016, for 9 months. Aqueous samples were obtained from 52 consecutive DME patients and 16 controls. DME patients were divided according to OCT patterns into diffuse retinal thickening (DRT; n = 17), cystoid macular edema (CME; n = 20) and serous retinal detachment (SRD; n = 15) groups. Interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) levels were measured by RayBio(R) Human ELISA Kit. RESULTS: IL-6, IL-8 and VEGF levels differed significantly between three DME groups (p < 0.001 in all cases), but the differences in TNF-α levels were not significant (p = 0.226). VEGF and IL-6 levels correlated with central foveal thickness in DRT and SRD groups, respectively. CONCLUSION: Aqueous cytokine levels vary with different morphological patterns of DME though the role of TNF-α needs to be studied further, and both anti-angiogenic and anti-inflammatory agents are required simultaneously for treatment of DME.


Asunto(s)
Humor Acuoso/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/complicaciones , Edema Macular/metabolismo , Tomografía de Coherencia Óptica/métodos , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Fóvea Central/patología , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Edema Macular/diagnóstico , Edema Macular/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Agudeza Visual
5.
Int Ophthalmol ; 36(3): 313-8, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26286756

RESUMEN

The objective of this study is to evaluate contrast sensitivity function (CSF) after clear, yellow- and orange-tinted intraocular lens (IOL) implantation. This was a prospective randomized study of 98 patients with senile cataract for a period of 6 months from day 1 of August 2014 to day 31 of January 2015. After phacoemulsification, 33 patients were implanted with clear IOLs (AcrySof UV-filtering IOL, SA60AT), 32 patients were implanted with yellow coloured IOLs (AcrySof Natural blue-light-attenuating and UV-filtering IOL, SN60AT with IMPRUV(®) filter) and 33 patients were implanted with orange-tinted blue-filtering IOLs (PC440Y Optech). After 1 month, monocular CSF was done under photopic (85 cd/m(2)) and mesopic (3 cd/m(2)) illumination condition with CSV-1000 test. The best corrected visual acuity (BCVA) after 1 month was 0.021 ± 0.058 logMAR for clear lens, 0.022 ± 0.059 logMAR for yellow lens and 0.019 ± 0.065 logMAR for orange lens (p = 0.989). Uniocular average photopic contrast sensitivity was 1.36 ± 0.19, 1.43 ± 0.18 and 1.46 ± 0.15 log units for clear lens, yellow lens and orange lens, respectively (statistically not significant; p = 0.076). Average mesopic contrast sensitivity was 1.02 ± 0.21 log units for clear lens, 1.00 ± 0.17 log units for yellow lens and 0.99 ± 0.15 log units for orange lens (statistically not significant; p = 0.771). Yellow or orange coloured blue-filtering IOLs are comparable to clear IOLs in terms of photopic and mesopic contrast sensitivity.


Asunto(s)
Visión de Colores/fisiología , Sensibilidad de Contraste/fisiología , Implantación de Lentes Intraoculares , Lentes Intraoculares , Diseño de Prótesis , Anciano , Extracción de Catarata , Femenino , Humanos , Implantación de Lentes Intraoculares/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Agudeza Visual/fisiología
6.
Phys Chem Chem Phys ; 17(38): 24866-73, 2015 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-26343998

RESUMEN

The protonation state of thiols in self-assembled monolayers (SAMs) on Ag and Au surfaces and nanoparticles (NPs) has been an issue of contestation. It has been recently demonstrated that deuterating the thiol proton produces ostentatious changes in the Raman spectra of thiols and can be used to detect the presence of the thiol functional group. Surface enhanced Raman spectroscopy (SERS) of H/D substituted aliphatic thiols on Ag surfaces clearly shows the presence of S-H vibration between 2150-2200 cm(-1) which shifts by 400 cm(-1) upon deuteration and a simultaneous >20 cm(-1) shift in the C-S vibration of thiol deuteration. Large shifts (>15 cm(-1)) in the C-S vibration are also observed for alkyl thiol SAMs on Au surfaces. Alternatively, neither the S-H vibration nor the H/D isotope effect on the C-S vibration is observed for alkyl thiol SAMs on Ag/Au NPs. XPS data on Ag/Au surfaces bearing aliphatic thiol SAMs show the presence of both protonated and deprotonated thiols while on Ag/Au NPs only deprotonated thiols are detected. These data suggest that aliphatic thiol SAMs on Au/Ag surfaces are partially protonated whereas they are totally deprotonated on Au/Ag NPs. Aromatic PhSH SAMs on Ag/Au surfaces and Ag/Au NPs do not show these vibrations or H/D shifts as well indicating that the thiols are deprotonated at these interfaces.


Asunto(s)
Oro/química , Nanopartículas/química , Plata/química , Compuestos de Sulfhidrilo/química , Deuterio/química , Espectroscopía de Fotoelectrones , Espectrometría Raman , Propiedades de Superficie
7.
Analyst ; 139(9): 2118-21, 2014 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-24634910

RESUMEN

Raman spectra of several thiols (amino acids, peptides and organic) show that the C-S-H bending mode (ßCSH) shifts from ∼850 cm(-1) to ∼620 cm(-1) on deuteration of the thiol proton by simply dissolving them in D2O and CD3OD where detection by (1)H NMR is not possible. A nondestructive analytical tool for the detection of thiols in solid/neat and in solution is developed.


Asunto(s)
Espectrometría Raman/métodos , Compuestos de Sulfhidrilo/análisis , Isótopos
8.
Inorg Chem ; 53(19): 10150-8, 2014 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-25238648

RESUMEN

Using a combination of self-assembly and synthesis, bioinspired electrodes having dilute iron porphyrin active sites bound to axial thiolate and imidazole axial ligands are created atop self-assembled monolayers (SAMs). Resonance Raman data indicate that a picket fence architecture results in a high-spin (HS) ground state (GS) in these complexes and a hydrogen-bonding triazole architecture results in a low-spin (LS) ground state. The reorganization energies (λ) of these thiolate- and imidazole-bound iron porphyrin sites for both HS and LS states are experimentally determined. The λ of 5C HS imidazole and thiolate-bound iron porphyrin active sites are 10-16 kJ/mol, which are lower than their 6C LS counterparts. Density functional theory (DFT) calculations reproduce these data and indicate that the presence of significant electronic relaxation from the ligand system lowers the geometric relaxation and results in very low λ in these 5C HS active sites. These calculations indicate that loss of one-half a π bond during redox in a LS thiolate bound active site is responsible for its higher λ relative to a σ-donor ligand-like imidazole. Hydrogen bonding to the axial ligand leads to a significant increase in λ irrespective of the spin state of the iron center. The results suggest that while the hydrogen bonding to the thiolate in the 5C HS thiolate bound active site of cytochrome P450 (cyp450) shifts the potential up, resulting in a negative ΔG, it also increases λ resulting in an overall low barrier for the electron transfer process.


Asunto(s)
Sistema Enzimático del Citocromo P-450/química , Imidazoles/química , Compuestos de Sulfhidrilo/química , Sistema Enzimático del Citocromo P-450/metabolismo , Electrodos , Enlace de Hidrógeno , Imidazoles/metabolismo , Hierro/química , Hierro/metabolismo , Ligandos , Metaloporfirinas/química , Metaloporfirinas/metabolismo , Modelos Moleculares , Estructura Molecular , Teoría Cuántica , Compuestos de Sulfhidrilo/metabolismo , Termodinámica
9.
Artif Intell Med ; 154: 102900, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38878555

RESUMEN

With Artificial Intelligence (AI) increasingly permeating various aspects of society, including healthcare, the adoption of the Transformers neural network architecture is rapidly changing many applications. Transformer is a type of deep learning architecture initially developed to solve general-purpose Natural Language Processing (NLP) tasks and has subsequently been adapted in many fields, including healthcare. In this survey paper, we provide an overview of how this architecture has been adopted to analyze various forms of healthcare data, including clinical NLP, medical imaging, structured Electronic Health Records (EHR), social media, bio-physiological signals, biomolecular sequences. Furthermore, which have also include the articles that used the transformer architecture for generating surgical instructions and predicting adverse outcomes after surgeries under the umbrella of critical care. Under diverse settings, these models have been used for clinical diagnosis, report generation, data reconstruction, and drug/protein synthesis. Finally, we also discuss the benefits and limitations of using transformers in healthcare and examine issues such as computational cost, model interpretability, fairness, alignment with human values, ethical implications, and environmental impact.

10.
Assessment ; : 10731911241236336, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38494894

RESUMEN

Graphomotor and time-based variables from the digital Clock Drawing Test (dCDT) characterize cognitive functions. However, no prior publications have quantified the strength of the associations between digital clock variables as they are produced. We hypothesized that analysis of the production of clock features and their interrelationships, as suggested, will differ between the command and copy test conditions. Older adults aged 65+ completed a digital clock drawing to command and copy conditions. Using a Bayesian hill-climbing algorithm and bootstrapping (10,000 samples), we derived directed acyclic graphs (DAGs) to examine network structure for command and copy dCDT variables. Although the command condition showed moderate associations between variables (µ|ßz|= 0.34) relative to the copy condition (µ|ßz| = 0.25), the copy condition network had more connections (18/18 versus 15/18 command). Network connectivity across command and copy was most influenced by five of the 18 variables. The direction of dependencies followed the order of instructions better in the command condition network. Digitally acquired clock variables relate to one another but differ in network structure when derived from command or copy conditions. Continued analyses of clock drawing production should improve understanding of quintessential normal features to aid in early neurodegenerative disease detection.

11.
Front Neurol ; 15: 1386728, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38784909

RESUMEN

Acuity assessments are vital for timely interventions and fair resource allocation in critical care settings. Conventional acuity scoring systems heavily depend on subjective patient assessments, leaving room for implicit bias and errors. These assessments are often manual, time-consuming, intermittent, and challenging to interpret accurately, especially for healthcare providers. This risk of bias and error is likely most pronounced in time-constrained and high-stakes environments, such as critical care settings. Furthermore, such scores do not incorporate other information, such as patients' mobility level, which can indicate recovery or deterioration in the intensive care unit (ICU), especially at a granular level. We hypothesized that wearable sensor data could assist in assessing patient acuity granularly, especially in conjunction with clinical data from electronic health records (EHR). In this prospective study, we evaluated the impact of integrating mobility data collected from wrist-worn accelerometers with clinical data obtained from EHR for estimating acuity. Accelerometry data were collected from 87 patients wearing accelerometers on their wrists in an academic hospital setting. The data was evaluated using five deep neural network models: VGG, ResNet, MobileNet, SqueezeNet, and a custom Transformer network. These models outperformed a rule-based clinical score (Sequential Organ Failure Assessment, SOFA) used as a baseline when predicting acuity state (for ground truth we labeled as unstable patients if they needed life-supporting therapies, and as stable otherwise), particularly regarding the precision, sensitivity, and F1 score. The results demonstrate that integrating accelerometer data with demographics and clinical variables improves predictive performance compared to traditional scoring systems in healthcare. Deep learning models consistently outperformed the SOFA score baseline across various scenarios, showing notable enhancements in metrics such as the area under the receiver operating characteristic (ROC) Curve (AUC), precision, sensitivity, specificity, and F1 score. The most comprehensive scenario, leveraging accelerometer, demographics, and clinical data, achieved the highest AUC of 0.73, compared to 0.53 when using SOFA score as the baseline, with significant improvements in precision (0.80 vs. 0.23), specificity (0.79 vs. 0.73), and F1 score (0.77 vs. 0.66). This study demonstrates a novel approach beyond the simplistic differentiation between stable and unstable conditions. By incorporating mobility and comprehensive patient information, we distinguish between these states in critically ill patients and capture essential nuances in physiology and functional status. Unlike rudimentary definitions, such as equating low blood pressure with instability, our methodology delves deeper, offering a more holistic understanding and potentially valuable insights for acuity assessment.

12.
Inorg Chem ; 52(4): 2000-14, 2013 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-23356644

RESUMEN

Electrodes bearing thiolate and imidazole coordinated iron porphyrin catalysts are constructed and characterized using resonance Raman spectroscopy, absorption spectroscopy, and electrochemistry. The cyclic voltammetry data and their pH dependences are used to establish the nature of the exchangeable trans ligands in both of these cases. In situ monitoring of partially reduced oxygen species (PROS) produced during O(2) reduction using rotating ring disc electrochemistry (RRDE) experiments provide direct insight into the "push-effect" of the thiolate ligand. The thiolate bound iron porphyrin electrode generates highly oxidizing species on the electrode during electrocatalytic O(2) reductions which are very reactive. These surfaces can utilize these oxidants to catalytically hydroxylate strong C-H bonds using molecular O(2) with turnover numbers as high as 200.


Asunto(s)
Sistema Enzimático del Citocromo P-450/química , Técnicas Electroquímicas , Compuestos Férricos/química , Imidazoles/química , Metaloporfirinas/química , Compuestos de Sulfhidrilo/química , Catálisis , Sistema Enzimático del Citocromo P-450/metabolismo , Electrodos , Concentración de Iones de Hidrógeno , Modelos Moleculares , Estructura Molecular , Oxidación-Reducción , Oxígeno/química , Espectrometría Raman
13.
Biochem Biophys Rep ; 35: 101493, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37304132

RESUMEN

SARS-CoV-2 causes substantial extrapulmonary manifestations in addition to pulmonary disease. Some of the major organs affected are cardiovascular, hematological and thrombotic, renal, neurological, and digestive systems. These types of muti-organ dysfunctions make it difficult and challenging for clinicians to manage and treat COVID-19 patients. The article focuses to identify potential protein biomarkers that can flag various organ systems affected in COVID-19. Publicly reposited high throughput proteomic data from human serum (HS), HEK293T/17 (HEK) and Vero E6 (VE) kidney cell culture were downloaded from ProteomeXchange consortium. The raw data was analyzed in Proteome Discoverer 2.4 to delineate the complete list of proteins in the three studies. These proteins were analyzed in Ingenuity Pathway Analysis (IPA) to associate them to various organ diseases. The shortlisted proteins were analyzed in MetaboAnalyst 5.0 to shortlist potential biomarker proteins. These were then assessed for disease-gene association in DisGeNET and validated by Protein-protein interactome (PPI) and functional enrichment studies (GO_BP, KEGG and Reactome pathways) in STRING. Protein profiling resulted in shortlisting 20 proteins in 7 organ systems. Of these 15 proteins showed at least 1.25-fold changes with a sensitivity and specificity of 70%. Association analysis further shortlisted 10 proteins with a potential association with 4 organ diseases. Validation studies established possible interacting networks and pathways affected, confirmingh the ability of 6 of these proteins to flag 4 different organ systems affected in COVID-19 disease. This study helps to establish a platform to seek protein signatures in different clinical phenotypes of COVID-19. The potential biomarker candidates that can flag organ systems involved are: (a) Vitamin K-dependent protein S and Antithrombin-III for hematological disorders; (b) Voltage-dependent anion-selective channel protein 1 for neurological disorders; (c) Filamin-A for cardiovascular disorder and, (d) Peptidyl-prolyl cis-trans isomerase A and Peptidyl-prolyl cis-trans isomerase FKBP1A for digestive disorders.

14.
Dis Markers ; 2023: 1329061, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36776920

RESUMEN

Oral squamous cell carcinomas are mostly preceded by precancerous lesions such as leukoplakia and erythroplakia. Our study is aimed at identifying potential biomarker proteins in precancerous lesions of leukoplakia and erythroplakia that can flag their transformation to oral cancer. Four biological replicate samples from clinical phenotypes of healthy control, leukoplakia, erythroplakia, and oral carcinoma were annotated based on clinical screening and histopathological evaluation of buccal mucosa tissue. Differentially expressed proteins were delineated using a label-free quantitative proteomic experiment done on an Orbitrap Fusion Tribrid mass spectrometer in three technical replicate sets of samples. Raw files were processed using MaxQuant version 2.0.1.0, and downstream analysis was done via Perseus version 1.6.15.0. Validation included functional annotation based on biological processes and pathways using the ClueGO plug-in of Cytoscape. Hierarchical clustering and principal component analysis were performed using the ClustVis tool. Across control, leukoplakia, and cancer, L-lactate dehydrogenase A chain, plectin, and WD repeat-containing protein 1 were upregulated, whereas thioredoxin 1 and spectrin alpha chain, nonerythrocytic 1 were downregulated. Across control, erythroplakia, and cancer, L-lactate dehydrogenase A chain was upregulated whereas aldehyde dehydrogenase 2, peroxiredoxin 1, heat shock 70 kDa protein 1B, and spectrin alpha chain, nonerythrocytic 1 were downregulated. We found that proteins involved in leukoplakia were associated with alteration in cytoskeletal disruption and glycolysis, while in erythroplakia, they were associated with alteration in response to oxidative stress and glycolysis across phenotypes. Hierarchical clustering subgrouped half of precancerous samples under the main branch of the control and the remaining half under carcinoma. Similarly, principal component analysis identified segregated clusters of control, precancerous lesions, and cancer, but erythroplakia phenotypes, in particular, overlapped more with the cancer cluster. Qualitative and quantitative protein signatures across control, precancer, and cancer phenotypes explain possible functional outcomes that dictate malignant transformation to oral carcinoma.


Asunto(s)
Carcinoma de Células Escamosas , Eritroplasia , Neoplasias de la Boca , Lesiones Precancerosas , Humanos , Mucosa Bucal/patología , Leucoplasia Bucal/genética , Leucoplasia Bucal/diagnóstico , Leucoplasia Bucal/patología , Proteómica , L-Lactato Deshidrogenasa , Espectrina , Lesiones Precancerosas/patología , Neoplasias de la Boca/patología , Eritroplasia/diagnóstico , Eritroplasia/patología , Carcinoma de Células Escamosas/genética , Biomarcadores
15.
Sci Rep ; 13(1): 7384, 2023 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-37149670

RESUMEN

The clock drawing test is a simple and inexpensive method to screen for cognitive frailties, including dementia. In this study, we used the relevance factor variational autoencoder (RF-VAE), a deep generative neural network, to represent digitized clock drawings from multiple institutions using an optimal number of disentangled latent factors. The model identified unique constructional features of clock drawings in a completely unsupervised manner. These factors were examined by domain experts to be novel and not extensively examined in prior research. The features were informative, as they distinguished dementia from non-dementia patients with an area under receiver operating characteristic (AUC) of 0.86 singly, and 0.96 when combined with participants' demographics. The correlation network of the features depicted the "typical dementia clock" as having a small size, a non-circular or "avocado-like" shape, and incorrectly placed hands. In summary, we report a RF-VAE network whose latent space encoded novel constructional features of clocks that classify dementia from non-dementia patients with high performance.


Asunto(s)
Aprendizaje Profundo , Persea , Humanos , Redes Neurales de la Computación , Aprendizaje Automático Supervisado , Pruebas Neuropsicológicas
16.
Res Sq ; 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37886534

RESUMEN

The clock drawing test (CDT) is a neuropsychological assessment tool to evaluate a patient's cognitive ability. In this study, we developed a Fair and Interpretable Representation of Clock drawing tests (FaIRClocks) to evaluate and mitigate bias against people with lower education while predicting their cognitive status. We represented clock drawings with a 10-dimensional latent embedding using Relevance Factor Variational Autoencoder (RF-VAE) network pretrained on publicly available clock drawings from the National Health and Aging Trends Study (NHATS) dataset. These embeddings were later fine-tuned for predicting three cognitive scores: the Mini-Mental State Examination (MMSE) total score, attention composite z-score (ATT-C), and memory composite z-score (MEM-C). The classifiers were initially tested to see their relative performance in patients with low education (<= 8 years) versus patients with higher education (> 8 years). Results indicated that the initial unweighted classifiers confounded lower education with cognitive impairment, resulting in a 100% type I error rate for this group. Thereby, the samples were re-weighted using multiple fairness metrics to achieve balanced performance. In summary, we report the FaIRClocks model, which a) can identify attention and memory deficits using clock drawings and b) exhibits identical performance between people with higher and lower education levels.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38585187

RESUMEN

Delirium is a syndrome of acute brain failure which is prevalent amongst older adults in the Intensive Care Unit (ICU). Incidence of delirium can significantly worsen prognosis and increase mortality, therefore necessitating its rapid and continual assessment in the ICU. Currently, the common approach for delirium assessment is manual and sporadic. Hence, there exists a critical need for a robust and automated system for predicting delirium in the ICU. In this work, we develop a machine learning (ML) system for real-time prediction of delirium using Electronic Health Record (EHR) data. Unlike prior approaches which provide one delirium prediction label per entire ICU stay, our approach provides predictions every 12 hours. We use the latest 12 hours of ICU data, along with patient demographic and medical history data, to predict delirium risk in the next 12-hour window. This enables delirium risk prediction as soon as 12 hours after ICU admission. We train and test four ML classification algorithms on longitudinal EHR data pertaining to 16,327 ICU stays of 13,395 patients covering a total of 56,297 12-hour windows in the ICU to predict the dynamic incidence of delirium. The best performing algorithm was Categorical Boosting which achieved an area under receiver operating characteristic curve (AUROC) of 0.87 (95% Confidence Interval; C.I, 0.86-0.87). The deployment of this ML system in ICUs can enable early identification of delirium, thereby reducing its deleterious impact on long-term adverse outcomes, such as ICU cost, length of stay and mortality.

18.
Sci Rep ; 13(1): 21021, 2023 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-38030709

RESUMEN

Pancreatic Neuroendocrine tumors (PanNET) are challenging to diagnose and often detected at advanced stages due to a lack of specific and sensitive biomarkers. This study utilized proteomics as a valuable approach for cancer biomarker discovery; therefore, mass spectrometry-based proteomic profiling was conducted on plasma samples from 12 subjects (3 controls; 5 Grade I, 4 Grade II PanNET patients) to identify potential proteins capable of effectively distinguishing PanNET from healthy controls. Data are available via ProteomeXchange with the identifier PXD045045. 13.2% of proteins were uniquely identified in PanNET, while 60% were commonly expressed in PanNET and controls. 17 proteins exhibiting significant differential expression between PanNET and controls were identified with downstream analysis. Further, 5 proteins (C1QA, COMP, HSP90B1, ITGA2B, and FN1) were selected by pathway analysis and were validated using Western blot analysis. Significant downregulation of C1QA (p = 0.001: within groups, 0.03: control vs. grade I, 0.0013: grade I vs. grade II) and COMP (p = 0.011: within groups, 0.019: control vs grade I) were observed in PanNET Grade I & II than in controls. Subsequently, ELISA on 38 samples revealed significant downregulation of C1QA and COMP with increasing disease severity. This study shows the potential of C1QA and COMP in the early detection of PanNET, highlighting their role in the search for early-stage (Grade-I and Grade-II) diagnostic markers and therapeutic targets for PanNET.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Proteómica , Detección Precoz del Cáncer , Biomarcadores de Tumor/análisis
19.
IEEE Int Conf Bioinform Biomed Workshops ; 2023: 2207-2212, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38463539

RESUMEN

Quantifying pain in patients admitted to intensive care units (ICUs) is challenging due to the increased prevalence of communication barriers in this patient population. Previous research has posited a positive correlation between pain and physical activity in critically ill patients. In this study, we advance this hypothesis by building machine learning classifiers to examine the ability of accelerometer data collected from daily wearables to predict self-reported pain levels experienced by patients in the ICU. We trained multiple Machine Learning (ML) models, including Logistic Regression, CatBoost, and XG-Boost, on statistical features extracted from the accelerometer data combined with previous pain measurements and patient demographics. Following previous studies that showed a change in pain sensitivity in ICU patients at night, we performed the task of pain classification separately for daytime and nighttime pain reports. In the pain versus no-pain classification setting, logistic regression gave the best classifier in daytime (AUC: 0.72, F1-score: 0.72), and CatBoost gave the best classifier at nighttime (AUC: 0.82, F1-score: 0.82). Performance of logistic regression dropped to 0.61 AUC, 0.62 F1-score (mild vs. moderate pain, nighttime), and CatBoost's performance was similarly affected with 0.61 AUC, 0.60 F1-score (moderate vs. severe pain, daytime). The inclusion of analgesic information benefited the classification between moderate and severe pain. SHAP analysis was conducted to find the most significant features in each setting. It assigned the highest importance to accelerometer-related features on all evaluated settings but also showed the contribution of the other features such as age and medications in specific contexts. In conclusion, accelerometer data combined with patient demographics and previous pain measurements can be used to screen painful from painless episodes in the ICU and can be combined with analgesic information to provide moderate classification between painful episodes of different severities.

20.
Indian J Public Health ; 56(4): 293-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23354141

RESUMEN

Eye diseases in childhood are important causes of medical consultation and it affects learning ability, adjustment in school and personality. To determine the pattern of ocular morbidity a cross-sectional observational study was conducted among 714 children, attending Ophthalmology department at a tertiary eye care center in Kolkata, West Bengal. All the children less than 15 years of age, attending in Unit II outpatient department were selected by complete enumeration method for duration of one year (January-December 2010). Distribution of association was analyzed by Chi-square test and difference between two proportions was calculated by z test for proportions. The common ocular morbidity were refractive errors (23.67%) followed by allergic conjunctivitis (17.23%), infection of the eye and adnexa (15.13%), ocular trauma (12.74%), and congenital eye diseases (13.59%). Majority of ocular morbidity is treatable and need early attention through eye screening cum intervention program beginning right from the childhood.


Asunto(s)
Oftalmopatías/epidemiología , Adolescente , Distribución de Chi-Cuadrado , Niño , Preescolar , Estudios Transversales , Oftalmopatías/clasificación , Oftalmopatías/diagnóstico , Femenino , Humanos , India/epidemiología , Lactante , Recién Nacido , Masculino , Centros de Atención Terciaria/estadística & datos numéricos
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