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Article ; Online: Transfer Learning for Mortality Prediction in Non-Small Cell Lung Cancer with Low-Resolution Histopathology Slide Snapshots.

Clark, Matthew / Meyer, Christopher / Ramos-Cejudo, Jaime / Elbers, Danne C / Pierce-Murray, Karen / Fricks, Rafael / Alterovitz, Gil / Rao, Luigi / Brophy, Mary T / Do, Nhan V / Grossman, Robert L / Fillmore, Nathanael R

Studies in health technology and informatics

2024 Volume 310, Page(s) 735–739

Abstract: High-resolution whole slide image scans of histopathology slides have been widely used in recent years for prediction in cancer. However, in some cases, clinical informatics practitioners may only have access to low-resolution snapshots of histopathology ...

Abstract	High-resolution whole slide image scans of histopathology slides have been widely used in recent years for prediction in cancer. However, in some cases, clinical informatics practitioners may only have access to low-resolution snapshots of histopathology slides, not high-resolution scans. We evaluated strategies for training neural network prognostic models in non-small cell lung cancer (NSCLC) based on low-resolution snapshots, using data from the Veterans Affairs Precision Oncology Data Repository. We compared strategies without transfer learning, with transfer learning from general domain images, and with transfer learning from publicly available high-resolution histopathology scans. We found transfer learning from high-resolution scans achieved significantly better performance than other strategies. Our contribution provides a foundation for future development of prognostic models in NSCLC that incorporate data from low-resolution pathology slide snapshots alongside known clinical predictors.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging ; Lung Neoplasms/diagnostic imaging ; Precision Medicine ; Medical Informatics ; Machine Learning
Language	English
Publishing date	2024-01-25
Publishing country	Netherlands
Document type	Journal Article
ISSN	1879-8365
ISSN (online)	1879-8365
DOI	10.3233/SHTI231062
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Article ; Online: Plasma tau predicts cerebral vulnerability in aging.

Cantero, Jose L / Atienza, Mercedes / Ramos-Cejudo, Jaime / Fossati, Silvia / Wisniewski, Thomas / Osorio, Ricardo S

Aging

2020 Volume 12, Issue 21, Page(s) 21004–21022

Abstract: Identifying cerebral vulnerability in late life may help prevent or slow the progression of aging-related chronic diseases. However, non-invasive biomarkers aimed at detecting subclinical cerebral changes in the elderly are lacking. Here, we have ... ...

Abstract	Identifying cerebral vulnerability in late life may help prevent or slow the progression of aging-related chronic diseases. However, non-invasive biomarkers aimed at detecting subclinical cerebral changes in the elderly are lacking. Here, we have examined the potential of plasma total tau (t-tau) for identifying cerebral and cognitive deficits in normal elderly subjects. Patterns of cortical thickness and cortical glucose metabolism were used as outcomes of cerebral vulnerability. We found that increased plasma t-tau levels were associated with widespread reductions of cortical glucose uptake, thinning of the temporal lobe, and memory deficits. Importantly, tau-related reductions of glucose consumption in the orbitofrontal cortex emerged as a determining factor of the relationship between cortical thinning and memory loss. Together, these results support the view that plasma t-tau may serve to identify subclinical cerebral and cognitive deficits in normal aging, allowing detection of individuals at risk for developing aging-related neurodegenerative conditions.
MeSH term(s)	Age Factors ; Aged ; Aging/blood ; Aging/psychology ; Amyloid beta-Peptides/metabolism ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/metabolism ; Cognition ; Cognitive Aging ; Cognitive Dysfunction/blood ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/psychology ; Female ; Glucose/metabolism ; Humans ; Magnetic Resonance Imaging ; Male ; Memory ; Middle Aged ; Neuropsychological Tests ; Peptide Fragments/metabolism ; Positron Emission Tomography Computed Tomography ; Risk Factors ; tau Proteins/blood
Chemical Substances	Amyloid beta-Peptides ; MAPT protein, human ; Peptide Fragments ; amyloid beta-protein (1-42) ; tau Proteins ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.104057
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Article ; Online: Association of CSF sTREM2, a marker of microglia activation, with cholinergic basal forebrain volume in major depressive disorder.

Teipel, Stefan / Bruno, Davide / Plaska, Chelsea Reichert / Heslegrave, Amanda / Ramos-Cejudo, Jaime / Osorio, Ricardo S / Zetterberg, Henrik / Blennow, Kaj / Pomara, Nunzio

Journal of affective disorders

2021 Volume 293, Page(s) 429–434

Abstract: Background: Inflammatory mechanisms are believed to contribute to the manifestation of major depressive disorder (MDD). Central cholinergic activity may moderate this effect. Here, we tested if volume of the cholinergic basal forebrain is associated ... ...

Abstract	Background: Inflammatory mechanisms are believed to contribute to the manifestation of major depressive disorder (MDD). Central cholinergic activity may moderate this effect. Here, we tested if volume of the cholinergic basal forebrain is associated with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglial activation in people with late life MDD. Methods: Basal forebrain volume was determined from structural MRI scans and levels of CSF sTREM2 with immunoassay in 29 people with late-life MDD and 20 healthy older controls at baseline and 3 years follow-up. Associations were determined using Bayesian analysis of covariance. Results: We found moderate level of evidence for an association of lower CSF levels of sTREM2 at 3 years follow up with MDD (Bayes factor in favor of an effect = 7.9). This level of evidence prevailed when controlling for overall antidepressant treatment and CSF levels of markers of AD pathology, i.e., Aβ42/Aβ40, ptau Limitations: The sample size of repeated CSF examinations was relatively small. Therefore, we used Bayesian sequential analysis to assess if effects were affected by sample size. Still, the number of cases was too small to stratify effects for different antidepressive treatments. Conclusions: Our data agree with the assumption that central cholinergic system integrity may contribute to regulation of microglia activity in late-life MDD.
MeSH term(s)	Amyloid beta-Peptides ; Basal Forebrain ; Bayes Theorem ; Biomarkers ; Cholinergic Agents ; Depressive Disorder, Major/drug therapy ; Humans ; Membrane Glycoproteins/cerebrospinal fluid ; Microglia ; Receptors, Immunologic
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Cholinergic Agents ; Membrane Glycoproteins ; Receptors, Immunologic ; TREM2 protein, human
Language	English
Publishing date	2021-06-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2021.06.030
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Article ; Online: Survival Analysis in Cognitively Normal Subjects and in Patients with Mild Cognitive Impairment Using a Proportional Hazards Model with Extreme Gradient Boosting Regression.

Khajehpiri, Boshra / Moghaddam, Hamid Abrishami / Forouzanfar, Mohamad / Lashgari, Reza / Ramos-Cejudo, Jaime / Osorio, Ricardo S / Ardekani, Babak A

Journal of Alzheimer's disease : JAD

2021 Volume 85, Issue 2, Page(s) 837–850

Abstract: Background: Evaluating the risk of Alzheimer's disease (AD) in cognitively normal (CN) and patients with mild cognitive impairment (MCI) is extremely important. While MCI-to-AD progression risk has been studied extensively, few studies estimate CN-to- ... ...

Abstract	Background: Evaluating the risk of Alzheimer's disease (AD) in cognitively normal (CN) and patients with mild cognitive impairment (MCI) is extremely important. While MCI-to-AD progression risk has been studied extensively, few studies estimate CN-to-MCI conversion risk. The Cox proportional hazards (PH), a widely used survival analysis model, assumes a linear predictor-risk relationship. Generalizing the PH model to more complex predictor-risk relationships may increase risk estimation accuracy. Objective: The aim of this study was to develop a PH model using an Xgboost regressor, based on demographic, genetic, neuropsychiatric, and neuroimaging predictors to estimate risk of AD in patients with MCI, and the risk of MCI in CN subjects. Methods: We replaced the Cox PH linear model with an Xgboost regressor to capture complex interactions between predictors, and non-linear predictor-risk associations. We endeavored to limit model inputs to noninvasive and more widely available predictors in order to facilitate future applicability in a wider setting. Results: In MCI-to-AD (n = 882), the Xgboost model achieved a concordance index (C-index) of 84.5%. When the model was used for MCI risk prediction in CN (n = 100) individuals, the C-index was 73.3%. In both applications, the C-index was statistically significantly higher in the Xgboost in comparison to the Cox PH model. Conclusion: Using non-linear regressors such as Xgboost improves AD dementia risk assessment in CN and MCI. It is possible to achieve reasonable risk stratification using predictors that are relatively low-cost in terms of time, invasiveness, and availability. Future strategies for improving AD dementia risk estimation are discussed.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/epidemiology ; Cognitive Dysfunction/genetics ; Disease Progression ; Female ; Genetic Testing/methods ; Humans ; Magnetic Resonance Imaging ; Male ; Neuropsychological Tests ; Prognosis ; Proportional Hazards Models ; Risk Assessment/methods ; Survival Analysis
Language	English
Publishing date	2021-12-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-215266
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Article: The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people.

Jacobs, Tovia / Jacobson, Sean R / Fortea, Juan / Berger, Jeffrey S / Vedvyas, Alok / Marsh, Karyn / He, Tianshe / Gutierrez-Jimenez, Eugenio / Fillmore, Nathanael R / Bubu, Omonigho M / Gonzalez, Moses / Figueredo, Luisa / Gaggi, Naomi L / Plaska, Chelsea Reichert / Pomara, Nunzio / Blessing, Esther / Betensky, Rebecca / Rusinek, Henry / Zetterberg, Henrik /

Blennow, Kaj / Glodzik, Lidia / Wisniewski, Thomas M / Leon, Mony J / Osorio, Ricardo S / Ramos-Cejudo, Jaime

Research square

2024

Abstract: Background: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into ... ...

Abstract	Background: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau Results: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β=-12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ+ (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. Conclusions: We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-4076789/v1
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Article ; Online: Plasma Amyloid-β dynamics in late-life major depression: a longitudinal study.

Pomara, Nunzio / Bruno, Davide / Plaska, Chelsea Reichert / Ramos-Cejudo, Jaime / Osorio, Ricardo S / Pillai, Anilkumar / Imbimbo, Bruno P / Zetterberg, Henrik / Blennow, Kaj

Translational psychiatry

2022 Volume 12, Issue 1, Page(s) 301

Abstract: Depressed individuals are twice as likely to develop Alzheimer's disease (AD) as compared to controls. Brain amyloid-β (Aβ) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of Aβ dynamics and depression. ...

Abstract	Depressed individuals are twice as likely to develop Alzheimer's disease (AD) as compared to controls. Brain amyloid-β (Aβ) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of Aβ dynamics and depression. The aim of this study was to test if plasma Aβ levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-β
MeSH term(s)	Aged ; Alzheimer Disease ; Amyloid beta-Peptides ; Biomarkers ; Depression/complications ; Depressive Disorder, Major/complications ; Humans ; Longitudinal Studies ; Peptide Fragments
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments
Language	English
Publishing date	2022-07-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-022-02077-8
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Article ; Online: Endotyping Sleep Apnea One Breath at a Time: An Automated Approach for Separating Obstructive from Central Sleep-disordered Breathing.

Parekh, Ankit / Tolbert, Thomas M / Mooney, Anne M / Ramos-Cejudo, Jaime / Osorio, Ricardo S / Treml, Marcel / Herkenrath, Simon-Dominik / Randerath, Winfried J / Ayappa, Indu / Rapoport, David M

American journal of respiratory and critical care medicine

2021 Volume 204, Issue 12, Page(s) 1452–1462

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Adult ; Aged ; Airway Resistance ; Clinical Decision Rules ; Diagnosis, Differential ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Polysomnography ; ROC Curve ; Reproducibility of Results ; Sleep Apnea, Central/diagnosis ; Sleep Apnea, Central/physiopathology ; Sleep Apnea, Obstructive/diagnosis ; Sleep Apnea, Obstructive/physiopathology
Language	English
Publishing date	2021-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202011-4055OC
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Article ; Online: Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study.

Ramos-Cejudo, Jaime / Johnson, Andrew D / Beiser, Alexa / Seshadri, Sudha / Salinas, Joel / Berger, Jeffrey S / Fillmore, Nathanael R / Do, Nhan / Zheng, Chunlei / Kovbasyuk, Zanetta / Ardekani, Babak A / Pomara, Nunzio / Bubu, Omonigho M / Parekh, Ankit / Convit, Antonio / Betensky, Rebecca A / Wisniewski, Thomas M / Osorio, Ricardo S

Journal of the American Heart Association

2022 Volume 11, Issue 9, Page(s) e023918

Abstract: Background Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to ... ...

Abstract	Background Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. Methods and Results We examined associations of baseline platelet function with incident dementia risk in the community-based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause-specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow-up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper-responders, as well as the platelet response to 0.1 µmol/L epinephrine. Conclusions Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20-year follow-up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.
MeSH term(s)	Adenosine Diphosphate ; Alzheimer Disease/epidemiology ; Female ; Humans ; Longitudinal Studies ; Male ; Platelet Aggregation ; Platelet Function Tests ; Risk Factors
Chemical Substances	Adenosine Diphosphate (61D2G4IYVH)
Language	English
Publishing date	2022-04-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.121.023918
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Article ; Online: Evidence of upregulation of the cholinergic anti-inflammatory pathway in late-life depression.

Pomara, Nunzio / Bruno, Davide / Plaska, Chelsea Reichert / Pillai, Anilkumar / Ramos-Cejudo, Jaime / Osorio, Ricardo / Imbimbo, Bruno P / Heslegrave, Amanda / Zetterberg, Henrik / Blennow, Kaj

Journal of affective disorders

2021 Volume 286, Page(s) 275–281

Abstract: Background: Decreased cholinergic tone associated with increased proinflammatory cytokines has been observed in several human diseases associated with low-grade inflammation. We examined if this attenuated cholinergic anti-inflammatory pathway (CAP) ... ...

Abstract	Background: Decreased cholinergic tone associated with increased proinflammatory cytokines has been observed in several human diseases associated with low-grade inflammation. We examined if this attenuated cholinergic anti-inflammatory pathway (CAP) mechanism contributed to increased neuroinflammation observed in depression. Methods: We measured cerebrospinal fluid (CSF) cholinergic markers (AChE and BChE activities) in 28 individuals with longstanding late-life major depression (LLMD) and 19 controls and their relationship to central and peripheral levels of pro-inflammatory cytokines (IL-6 and IL-8). Additionally, we examined if these cholinergic indices were related to CSF markers of microglial activation and neuroinflammation (sTREM2 and complement C3). Results: Compared with controls, LLMD patients had a significant reduction in CSF BChE levels. Lower CSF BChE and AChE activities were associated with lower CSF markers of microglial and neuroinflammation (sTREM2 and C3). In addition, in LLMD patients we found an inverse relationship between peripheral marker of inflammation (plasma IL-6) and CSF BChE and AChE levels. Conclusions: Our results suggest an upregulation of the CAP mechanism in LLMD with an elevation in peripheral markers of inflammation and concomitant reduction in markers of glial activation associated with a higher cholinergic tone. Future studies should confirm these findings in a larger sample including individuals with acute and more severe depressive episodes and across all ages.
MeSH term(s)	Acetylcholinesterase/metabolism ; Cholinesterases ; Depression ; Humans ; Neuroimmunomodulation ; Up-Regulation
Chemical Substances	Acetylcholinesterase (EC 3.1.1.7) ; Cholinesterases (EC 3.1.1.8)
Language	English
Publishing date	2021-03-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2021.03.012
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Article ; Online: Development and validation of a convolutional neural network to identify blepharoptosis.

Abascal Azanza, Cristina / Barrio-Barrio, Jesús / Ramos Cejudo, Jaime / Ybarra Arróspide, Bosco / Devoto, Martín H

Scientific reports

2023 Volume 13, Issue 1, Page(s) 17585

Abstract: Blepharoptosis is a recognized cause of reversible vision loss and a non-specific indicator of neurological issues, occasionally heralding life-threatening conditions. Currently, diagnosis relies on human expertise and eyelid examination, with most ... ...

Abstract	Blepharoptosis is a recognized cause of reversible vision loss and a non-specific indicator of neurological issues, occasionally heralding life-threatening conditions. Currently, diagnosis relies on human expertise and eyelid examination, with most existing Artificial Intelligence algorithms focusing on eyelid positioning under specialized settings. This study introduces a deep learning model with convolutional neural networks to detect blepharoptosis in more realistic conditions. Our model was trained and tested using high quality periocular images from patients with blepharoptosis as well as those with other eyelid conditions. The model achieved an area under the receiver operating characteristic curve of 0.918. For validation, we compared the model's performance against nine medical experts-oculoplastic surgeons, general ophthalmologists, and general practitioners-with varied expertise. When tested on a new dataset with varied image quality, the model's performance remained statistically comparable to that of human graders. Our findings underscore the potential to enhance telemedicine services for blepharoptosis detection.
MeSH term(s)	Humans ; Artificial Intelligence ; Blepharoptosis/diagnosis ; Neural Networks, Computer ; Algorithms ; ROC Curve
Language	English
Publishing date	2023-10-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-44686-3
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