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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15537-e15537
    Abstract: e15537 Background: During hospitalization for colectomy patients with colon cancer may be at risk for mortality due to several reasons including underlying cancer, other comorbidities or age. Our aim was to develop a machine learning algorithm to predict end of admission mortality in patients undergoing colectomy for their cancer. We hypothesized that machine learning could be applied to patients undergoing open colectomy as part of their colon cancer treatment. Methods: All adult patients ( 〉 18 years) for the National in-patient Services (NIS) database 2014 was used to develop our algorithm. We extracted all patients with a diagnosis of cancer using the ICD-9 codes and all patients that underwent colectomy. We conducted a multivariate analysis to look at the risk factors that dictate mortality in these patients. We also developed a linear regression model and a deep learning algorithm to predict mortality in these patients. Results: We identified a total of 4120 patients that underwent open colectomy with colon cancer in the NIS 2014. We observed that several clinical and lab-based parameters were statistically significant for multivariate analyses while others were not. With most significant being all patients refined diagnosis related groups (APRDRG) risk mortality (HR = 6.20, 95%CI = 4.10-9.36), APRDRG severity (HR = 4.78, 95%CI = 3.27-7.00), chronic anemia (HR = 0.61, 95%CI = 0.40-0.94), coagulation disorders (HR = 2.32, 95%CI = 1.31-4.10), chronic electrolytes disorders (HR = 2.12, 95%CI = 1.39-3.24), neurological disorders (HR = 1.92, 95%CI = 1.11-3.32), underweight (low BMI) (HR = 2.40, 95%CI = 1.05-5.48), Hyperkalemia (HR = 2.40, 95%CI = 1.28-4.50), Acidosis (HR = 4.04, 95%CI = 2.64-6.19). In the machine learning analysis, we found out that our proposed DNN outperformed the RF with test set accuracy of 91.1%, sensitivity of 88.5%, specificity 91.2%, PPV of 24.7, NPV of 99.5% and AUROC of 0.968 [95%CI = 0.08-.014] . Conclusions: Our novel DNN model outperformed RF classifier models. The model is easy to implement, user friendly and with good accuracy. However, further external validation of the model is required.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4_Supplement ( 2020-02-15), p. P3-08-12-P3-08-12
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P3-08-12-P3-08-12
    Abstract: Background: The presence of high TILs (tumor infiltrating lymphocytes) have been shown to be predictive of response to chemotherapy and is also a prognostic factor associated with better outcome in breast cancer, especially in early stage triple-negative (TNBC) and HER2-positive breast cancers. TIL assessment, while now more standardized due to the efforts of Salgado and the International TIL Working Group (https://www.tilsinbreastcancer.org/), are still a subjective test with variability in evaluation that has prevented broad adoption. Given the advances in application of artificial intelligence to pathology images, we believe the next step for TILs is to make them automated and objective and to identify a standardized and meaning TIL cut-point. The aim of this study is to build an open source, H & E image-based automated TIL assessment algorithm for breast cancer that allows global standardization of TILs for prognostic value. Materials and methods: Using QuPath open source software, we first built a neural network classifier for image-based, automated assessment of TILs. It distinguishes tumor cells, lymphocytes, stromal cells and other cells on hematoxylin-eosin (H & E) stained sections. We then defined “eTILs%” calculated as follows for the percentage of machine defined TILs: (TILs/TILs+Tumor cells) *100. A retrospective collection of 63 TNBC cases was used as the training set (Set A) and then tested for cell classifier accuracy and the optimal “eTILs%” cut point. The validation sets were a retrospective collection of 354 TNBC patients comprised of three independent validation subsets (Set B; N=87, Set C; N=183, and Set D; N=83) in both tissue microarray (TMA) and whole tissue section (WTS) format. Results: Using an optimal cut point (30%) derived from TNBC cohort training set A, patients with high eTILs% displayed an overall survival benefit (HR 0.4, p=0.0150). This algorithm was then applied in other three TNBC validation sets (Set B: HR=0.42, p=0.0033; Set C: HR=0.42, p=0.0127; Set D in TMA format: HR=0.39, p=0.0089). For Set D, we also tested WTS format which showed HR=0.23, (p=0.0155). The validation sets were combined to assess independence from clinical status in a multi-variable analysis where eTILs% was independently associated with improved overall survival (HR=0.35, p & lt;0.0001). Conclusion: We have constructed a single institutional algorithm built from open source QuPath software that is a robust and independent prognostic factor. With further validation in tissues from other institutions and larger cohorts, this algorithm could be potentially useful as a broadly applicable, standardized and globally available method for assessment of TILs in triple negative breast cancer patients. Citation Format: Yalai Bai, Balazs Acs, Jon Zugazagoitia, Sandra Martinez-Morilla, Fahad Shabbir Ahmed, David L. Rimm. An open source, automated tumor infiltrating lymphocyte algorithm for prognosis in triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-12.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-03-09)
    Abstract: CD40, a TNF receptor family member, is expressed by a variety of immune cells and is involved in the activation of both adaptive and innate immune responses. Here, we used quantitative immunofluorescence (QIF) to evaluate CD40 expression on the tumor epithelium of solid tumors in large patient cohorts of lung, ovarian, and pancreatic cancers. Methods Tissue samples from nine different solid tumors (bladder, breast, colon, gastric, head and neck, non-small cell lung cancer (NSCLC), ovarian, pancreatic and renal cell carcinoma), constructed in tissue microarray format, were initially assessed for CD40 expression by QIF. CD40 expression was then evaluated on the large available patient cohorts for three of the tumor types demonstrating high CD40 positivity rate; NSCLC, ovarian and pancreatic cancer. The prognostic impact of CD40 expression on tumor cells was also investigated. Results CD40 expression on tumor cells was found to be common, with 80% of the NSCLC population, 40% of the ovarian cancer population, and 68% of the pancreatic adenocarcinoma population displaying some degree of CD40 expression on cancer cells. All of three of these cancer types displayed considerable intra-tumoral heterogeneity of CD40 expression, as well as partial correlation between expression of CD40 on tumor cells and on surrounding stromal cells. CD40 was not found to be prognostic for overall survival in NSCLC, ovarian cancer, or pancreatic adenocarcinoma. Conclusions The high percentage of tumor cells expressing CD40 in each of these solid tumors should be considered in the development of therapeutic agents designed to target CD40.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041352-X
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  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 592-592
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 592-592
    Abstract: 592 Background: The objective of the current analysis of the I-SPY 2 data from multiple breast cancer clinical trials for stages II and III cancers was to look at the possibility of developing a machine learning algorithm to predict pathological complete response using multimodal data. Methods: Imagining, clinical and biomarkers data form the I-SPY 2 trial was used in this analysis. Four different experiments were designed for to assess different data pre-processing and machine learning methods mainly deep neural networks (DNN) and random forest (RF) classifiers. Experiment 1 and 3 use DNNs while Experiment 2 and 4 used RFs; more over the first two experiments used data that was continuous in nature from the point of view of pre-performed imaging analysis while in later two experiments we had binarized all the variables using a median cutoff for high vs low values. The variables used were treatment recieved, HER2/neu receptor status, hormone receptor status, age, ethnicity, gynecological history, MRI feature data. All models were evaluated using robust testing methods that included sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), accuracies (training and test sets), area-under the receiver-operator curve and F1-Score. Results: From a total of 985 patients with clinical data we used 384 that had multi-feature MRI data. Time series data for the initial scan (T0) and a scan 3 weeks later (T1). The final comparative analysis showed the best model among the 4 experiment the best performing algorithms for this analysis was random forests using median cutoffs with a best F1-score (0.43), specificity (86.4%), PPV (47.8%), accuracies (train sets, 100%; test sets, 75%), and AUROCs (0.78, 0.56-0.73). Conclusions: The use of machine learning to predict pathological complete response using multimodal data shows good potential as a digital biomarker. However, these results need further validation before a clinical tool is available for the clinicians. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Case Reports in Neurological Medicine, Hindawi Limited, Vol. 2018 ( 2018-10-04), p. 1-5
    Abstract: Methamphetamine or “meth” is a sympathomimetic amine of the amphetamine-type substances (ATS) class with an extremely high potential for abuse. Illicitly abused neurostimulants like cocaine and meth predispose patients to the aneurysmal formation with reported rupture at a younger age and in much smaller sized aneurysms. However, very rapid growth of aneurysm within less than 2 weeks with methamphetamine abuse is very rarely observed or reported. In this report, we present a patient with repeated and recurrent meth abuse who demonstrated rapid growth of a pericallosal aneurysm over the period of less than two weeks. The pathophysiology of stroke related to meth and ATS abuse is multifactorial with hypertension, tachycardia, and vascular disease postulated as major mechanisms. The rapid growth of an aneurysm has a high risk of aneurysmal rupture and SAH, which is a neurosurgical emergency and therefore warrants careful consideration and close monitoring. This case confirms the dynamic temporal effects of methamphetamine use on intracranial vessels and this specific neurostimulants association to rapid aneurysmal formation. In light of vascular pathologies the possibility of drug-induced pseudoaneurysm should also be considered in young patients with history of meth abuse.
    Type of Medium: Online Resource
    ISSN: 2090-6668 , 2090-6676
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2629909-4
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-8-30)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-8-30)
    Abstract: Lymphoma-associated macrophages (LAMs) are key components in the lymphoma microenvironment, which may impact disease progression and response to therapy. There are two major subtypes of LAMs, CD68+ M1 and CD163+ M2. M2 LAMs can be transformed from M1 LAMs, particularly in certain diffuse large B-cell lymphomas (DLBCL). While mantle cell lymphoma (MCL) is well-known to contain frequent epithelioid macrophages, LAM characterization within MCL has not been fully described. Herein we evaluate the immunophenotypic subclassification, the expression of immune checkpoint molecule PD-L1, and the prognostic impact of LAMs in MCL. Materials and Methods A total of 82 MCL cases were collected and a tissue microarray block was constructed. Immunohistochemical staining was performed using CD68 and CD163, and the positive cells were recorded manually in four representative 400× fields for each case. Multiplexed quantitative immunofluorescence assays were carried out to determine PD-L1 expression on CD68+ M1 LAMs and CD163+ M2 LAMs. In addition, we assessed Ki67 proliferation rate of MCL by an automated method using the QuPath digital imaging analysis. The cut-off points of optimal separation of overall survival (OS) were analyzed using the X-Tile software, the SPSS version 26 was used to construct survival curves, and the log-rank test was performed to calculate the p -values. Results MCL had a much higher count of M1 LAMs than M2 LAMs with a CD68:CD163 ratio of 3:1. Both M1 and M2 LAMs were increased in MCL cases with high Ki67 proliferation rates ( & gt;30%), in contrast to those with low Ki67 ( & lt;30%). Increased number of M1 or M2 LAMs in MCL was associated with an inferior OS. Moreover, high expression of PD-L1 on M1 LAMs had a slightly better OS than the cases with low PD-L1 expression, whereas low expression of PD-L1 on M2 LAMs had a slightly improved OS, although both were not statistically significant. Conclusions In contrast to DLBCL, MCL had a significantly lower rate of M1 to M2 polarization, and the high levels of M1 and M2 LAMs were associated with poor OS. Furthermore, differential PD-L1 expressions on LAMs may partially explain the different functions of tumor-suppressing or tumor-promoting of M1 and M2 LAMs, respectively.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 7
    In: Journal of Global Health, International Society of Global Health, Vol. 13 ( 2023-05-5)
    Type of Medium: Online Resource
    ISSN: 2047-2978 , 2047-2986
    Language: English
    Publisher: International Society of Global Health
    Publication Date: 2023
    detail.hit.zdb_id: 2741629-X
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  • 8
    Online Resource
    Online Resource
    NIBD Journal of Health Sciences ; 2016
    In:  National Journal of Health Sciences Vol. 1, No. 1 ( 2016-10-01), p. 25-29
    In: National Journal of Health Sciences, NIBD Journal of Health Sciences, Vol. 1, No. 1 ( 2016-10-01), p. 25-29
    Type of Medium: Online Resource
    ISSN: 2519-7053 , 2519-7878
    URL: Issue
    Language: Unknown
    Publisher: NIBD Journal of Health Sciences
    Publication Date: 2016
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2011
    In:  Journal of Ethnopharmacology Vol. 135, No. 3 ( 2011-06), p. 654-661
    In: Journal of Ethnopharmacology, Elsevier BV, Vol. 135, No. 3 ( 2011-06), p. 654-661
    Type of Medium: Online Resource
    ISSN: 0378-8741
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 1491279-X
    SSG: 15,3
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  • 10
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5043-5043
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5043-5043
    Abstract: Introduction: Cancer staging can take essential time and expenses away from patients, both of which should be patients’ management. In this current study, we aim to develop a machine learning-based early TNM staging model. Methods: Normalized ribonucleic acid sequencing (RNA-seq) counts data for melanoma patients was extracted from The Cancer Genome Atlas (TCGA). Six different experiments were run to produce machine learning algorithms for nodal metastasis, distant metastasis, combine (nodal or distant) metastasis, and higher vs lower tumor stage (T4/T3 vs T2/T1/Tis). All datasets were split using 80/20 for training and test sets. Synthetic Minority Oversampling Technique (SMOTE) was used to address the imbalanced distribution of the outcome. The algorithm accuracies were determined by a percent of sensitivity, specificity, predictive values (positive and negative: PPV and NPV), and area under the receiver-operator curve (AUROC). Results: The best model for nodal metastasis was a random forest classifier (RF) with targeted gene expression (TE) showed higher sensitivity (98), specificity (100), PPV (100), NPV (94), and AUROC (1.00, 95%CI 0.91-0.99). TE for distant metastasis with RF, showed sensitivity (0), specificity (100), PPV (0), NPV (100), and AUROC (1.00, 95%CI 0.91-1.00). While TE for combined metastasis (nodal or distant) staging algorithm; Nodal or Distant Metastasis (TE) RF, showed sensitivity (98), specificity (100), PPV (100), NPV (99), and AUROC (1.00, 95%CI 0.88-0.98). The tumor staging (DEG and predicting higher stage i.e stage 3 or higher) algorithm; Tumor Staging (TE) RF, showed sensitivity (100), specificity (100), PPV (100), NPV (100), and AUROC (1.00, 95%CI 0.69-0.89) (Table 1). Conclusion: Our machine learning models can predict tumor staging including higher vs lower stage tumor, nodal metastasis, and combined metastasis with high accuracy. However, these results need to be further validated. Table 1. Machine learning models Experiment Sensitivity Specificity PPV NPV AUROC 95%CI Test Set Accuracy N Nodal Metastasis (Pan-Expression) DNN 66.22 16.98 52.69 26.47 0.495 0.25-0.47 54.55 479 Nodal Metastasis (Targeted Expression) DNN 81.13 100.0 100.0 88.10 0.982 0.62-0.83 90.21 479 Nodal Metastasis (Targeted Expression) RF 97.89 100.00 100.00 94 1.00 0.91-0.99 96.74 458 Distant Metastasis (Targeted Expression) RF 0.00 100.00 0.00 100 1.00 0.91-1.00 94.44 450* Nodal or Distant Metastasis (Targeted Expression) RF 97.56 100.00 100.00 98.56 1.00 0.88-0.98 98.91 458 Tumor Staging (Targeted Expression) RF 100.00 100.00 100.00 100.00 1.00 0.69-0.89 100.00 395 *27 cases with distant metastasis Citation Format: Fahad Shabbir Ahmed, Furqan Bin Irfan. Predicting melanoma staging using targeted RNA sequencing data using machine learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5043.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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