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Article ; Online: The trade-off between bias and imprecision: Debunking the myth of bias as the primary culprit in patient result misclassification.

Çubukçu, Hikmet Can

2023

Language	English
Publishing date	2023-12-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2944-0
ISSN	1943-7722 ; 0002-9173
ISSN (online)	1943-7722
ISSN	0002-9173
DOI	10.1093/ajcp/aqad172
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Article ; Online: Machine learning-based clinical decision support using laboratory data.

Çubukçu, Hikmet Can / Topcu, Deniz İlhan / Yenice, Sedef

Clinical chemistry and laboratory medicine

2023 Volume 62, Issue 5, Page(s) 793–823

Abstract: Artificial intelligence (AI) and machine learning (ML) are becoming vital in laboratory medicine and the broader context of healthcare. In this review article, we summarized the development of ML models and how they contribute to clinical laboratory ... ...

Abstract	Artificial intelligence (AI) and machine learning (ML) are becoming vital in laboratory medicine and the broader context of healthcare. In this review article, we summarized the development of ML models and how they contribute to clinical laboratory workflow and improve patient outcomes. The process of ML model development involves data collection, data cleansing, feature engineering, model development, and optimization. These models, once finalized, are subjected to thorough performance assessments and validations. Recently, due to the complexity inherent in model development, automated ML tools were also introduced to streamline the process, enabling non-experts to create models. Clinical Decision Support Systems (CDSS) use ML techniques on large datasets to aid healthcare professionals in test result interpretation. They are revolutionizing laboratory medicine, enabling labs to work more efficiently with less human supervision across pre-analytical, analytical, and post-analytical phases. Despite contributions of the ML tools at all analytical phases, their integration presents challenges like potential model uncertainties, black-box algorithms, and deskilling of professionals. Additionally, acquiring diverse datasets is hard, and models' complexity can limit clinical use. In conclusion, ML-based CDSS in healthcare can greatly enhance clinical decision-making. However, successful adoption demands collaboration among professionals and stakeholders, utilizing hybrid intelligence, external validation, and performance assessments.
MeSH term(s)	Humans ; Decision Support Systems, Clinical ; Artificial Intelligence ; Laboratories ; Machine Learning ; Clinical Decision-Making
Language	English
Publishing date	2023-11-29
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2023-1037
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Article ; Online: False negative results and tolerance limits of SARS-CoV-2 laboratory tests.

Çubukçu, Hikmet Can / Coşkun, Abdurrahman

Pathogens and global health

2021 Volume 115, Issue 3, Page(s) 137–138

MeSH term(s)	COVID-19 ; Clinical Laboratory Techniques ; Humans ; Immunoassay ; Immunoglobulin G ; Immunoglobulin M ; Kinetics ; Luminescence ; SARS-CoV-2
Chemical Substances	Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2021-01-28
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2625162-0
ISSN	2047-7732 ; 2047-7724
ISSN (online)	2047-7732
ISSN	2047-7724
DOI	10.1080/20477724.2021.1881370
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Article ; Online: Estimation of Low-Density Lipoprotein Cholesterol Concentration Using Machine Learning.

Çubukçu, Hikmet Can / Topcu, Deniz İlhan

Laboratory medicine

2021 Volume 53, Issue 2, Page(s) 161–171

Abstract: Objective: Low-density lipoprotein cholesterol (LDL-C) can be estimated using the Friedewald and Martin-Hopkins formulas. We developed LDL-C prediction models using multiple machine learning methods and investigated the validity of the new models along ... ...

Abstract	Objective: Low-density lipoprotein cholesterol (LDL-C) can be estimated using the Friedewald and Martin-Hopkins formulas. We developed LDL-C prediction models using multiple machine learning methods and investigated the validity of the new models along with the former formulas. Methods: Laboratory data (n = 59,415) on measured LDL-C, high-density lipoprotein cholesterol, triglycerides (TG), and total cholesterol were partitioned into training and test data sets. Linear regression, gradient-boosted trees, and artificial neural network (ANN) models were formed based on the training data. Paired-group comparisons were performed using a t-test and the Wilcoxon signed-rank test. We considered P values <.001 with an effect size >.2 to be statistically significant. Results: For TG ≥177 mg/dL, the Friedewald formula underestimated and the Martin-Hopkins formula overestimated the LDL-C (P <.001), which was more significant for LDL-C <70 mg/dL. The linear regression, gradient-boosted trees, and ANN models outperformed the aforementioned formulas for TG ≥177 mg/dL and LDL-C <70 mg/dL based on a comparison with a homogeneous assay (P >.001 vs. P <.001) and classification accuracy. Conclusion: Linear regression, gradient-boosted trees, and ANN models offer more accurate alternatives to the aforementioned formulas, especially for TG 177 to 399 mg/dL and LDL-C <70 mg/dL.
MeSH term(s)	Cholesterol, HDL ; Cholesterol, LDL ; Humans ; Linear Models ; Machine Learning ; Triglycerides
Chemical Substances	Cholesterol, HDL ; Cholesterol, LDL ; Triglycerides
Language	English
Publishing date	2021-10-11
Publishing country	England
Document type	Journal Article
ZDB-ID	391758-7
ISSN	1943-7730 ; 0007-5027
ISSN (online)	1943-7730
ISSN	0007-5027
DOI	10.1093/labmed/lmab065
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Article ; Online: Optimization of patient-based real-time quality control based on the Youden index.

İlhan Topcu, Deniz / Can Çubukçu, Hikmet

Clinica chimica acta; international journal of clinical chemistry

2022 Volume 534, Page(s) 50–56

Abstract: Aim: This study sets out to investigate the utility of exponentially weighted moving average (EWMA) as patient-based real-time quality control (PBRTQC) by conducting a simulation study and subsequent real-patient data implementation to determine optimal ...

Abstract	Aim: This study sets out to investigate the utility of exponentially weighted moving average (EWMA) as patient-based real-time quality control (PBRTQC) by conducting a simulation study and subsequent real-patient data implementation to determine optimal EWMA features (weighting factors, control limits, and truncation methods) based on the Youden index. Methods: A simulation experiment was conducted in the first stage to investigate optimal EWMA features for the tests, including aspartate aminotransferase, blood urea nitrogen, and glucose, calcium, creatinine, potassium, sodium, triglycerides, thyroid - stimulating hormone (TSH), and vitamin B12 tests. In the second stage of the study, EWMA was applied to real patient data to elucidate practical utility and achieve final optimal EWMA features. Different degrees of systematic errors (SE) including total allowable error (TEa) as a maximum error level were added to both simulation and patient results, and then the EWMA performance was assessed for different EWMA features. We calculated Youden's index for each combination of EWMA features to find their optimal features to achieve minimum false positive rate (FPR) and maximum error detection rate at the SE level corresponding to TEa. Results: EWMA implementation on real patient data revealed optimal EWMA features for each test. FPR values of creatinine and glucose were 18.48% and 10.17%, respectively, which exceeded the acceptable criteria for FPR (10%). The remaining six analytes showed acceptable FPR. Conclusions: We showed the implementation of EWMA as PBRTQC, and optimization of its features based on the Youden index by conducting extensive performance evaluations and simulations in this study.
MeSH term(s)	Computer Simulation ; Creatinine ; Glucose ; Humans ; Quality Control
Chemical Substances	Creatinine (AYI8EX34EU) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-07-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2022.06.028
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Article ; Online: Validation of SMA screening kits with SMN1 gene analysis in a Turkish cohort.

Gülşen, Murat / Ceylan, Ahmet Cevdet / Bahsi, Taha / Çubukçu, Hikmet Can / Dursun, Onur Burak

Clinica chimica acta; international journal of clinical chemistry

2024 Volume 555, Page(s) 117793

Abstract: Objective: It is crucial to start early treatment in Spinal Muscular Atrophy (SMA) with available drugs to stop the progression of the disease, therefore making SMA screening preferable. This study assessed Quantitative Real-Time Polymerase Chain ... ...

Abstract	Objective: It is crucial to start early treatment in Spinal Muscular Atrophy (SMA) with available drugs to stop the progression of the disease, therefore making SMA screening preferable. This study assessed Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) compared to Multiplex Ligation-dependent Probe Amplification (MLPA) for detecting Spinal Muscular Atrophy (SMA) through SMN1 gene copy number analysis in a Turkish cohort. Methods: We analyzed 249 DNA samples, previously tested for SMN1 and SMN2 gene deletion via MLPA, using qRT-PCR kits from three different companies. Accuracy, sensitivity, and specificity of qRT-PCR in identifying deletions of SMN1 copy number variations. Results: High accuracy (96.2-98.7%) achieved with qRT-PCR for detecting homozygous deletions, heterozygous deletions, and copy number variations in the SMN1 gene. Minor discrepancies between qRT-PCR and MLPA were observed, possibly due to single nucleotide polymorphisms affecting primer binding. Conclusions: The qRT-PCR method proved to be a rapid, cost-effective, and accurate technique, aligning well with the demands of routine SMA screening, suggesting its general suitability for application in SMA screening programs. This research highlights the importance of improving molecular methodologies and the value of collaborations between government and relevant sectors to overcome rare diseases, particularly through the enhancement of screening initiatives which is the first and most effective strategy to protect the public health.
MeSH term(s)	Humans ; DNA Copy Number Variations ; Muscular Atrophy, Spinal/diagnosis ; Muscular Atrophy, Spinal/genetics ; Gene Dosage ; Real-Time Polymerase Chain Reaction/methods ; Multiplex Polymerase Chain Reaction/methods ; Survival of Motor Neuron 1 Protein/genetics
Chemical Substances	SMN1 protein, human ; Survival of Motor Neuron 1 Protein
Language	English
Publishing date	2024-02-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2024.117793
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Article ; Online: Voluntary imitation of dynamic facial expressions in attention deficit hyperactivity disorder: a facial-behavior analysis.

Yildirim Demİrdöğen, Esen / Turan, Bahadır / Gülşen, Murat / Çubukçu, Hikmet Can / Dursun, Onur Burak

Journal of clinical and experimental neuropsychology

2024 Volume 45, Issue 9, Page(s) 915–927

Abstract: Objective: The difficulties involved in social interaction among children with attention deficit hyperactivity disorder (ADHD) have been shown in many studies. Based on the knowledge that the imitation of facial expressions is a key factor in social ... ...

Abstract	Objective: The difficulties involved in social interaction among children with attention deficit hyperactivity disorder (ADHD) have been shown in many studies. Based on the knowledge that the imitation of facial expressions is a key factor in social interaction and functionality, the focus of prior studies has been on the evaluation of facial expressions in individuals with ADHD. However, little is known about voluntary facial mimicry in individuals with ADHD. In this context, we aimed to evaluate the voluntary-facial-imitation intensity of dynamic facial expressions in children with ADHD. Method: Forty-one children with ADHD and 53 typically developing children were included in the study. Participants were presented with a video of six basic emotions and neutral facial expressions selected from the EU-Emotion Stimulus Set via a screen. After each emotion, the instruction "now imitate it" was given. While the children watched the video, their faces were recorded with a webcam. The intensity of the children's voluntary facial imitations was examined with a computer vision program (Openface) that performs facial analysis on recorded videos. Results: There was no significant difference between the groups in terms of facial emotion recognition accuracy. In group comparisons of voluntary facial mimicry, children with ADHD showed a significantly higher imitation intensity after emotional expressions of sadness, surprise and fear. There was no difference between the groups after the emotions of happiness, anger and disgust. Conclusion: This non-obtrusive, noninvasive, and cost-effective method allowed us to measure the quantitative differences in facial mimicry between children with ADHD and typically developing children. Our results contribute new information to the literature by indicating which emotions can be used in the evaluation of social communication skills, as well as intervention targets for these skills, in children with ADHD.
MeSH term(s)	Child ; Humans ; Attention Deficit Disorder with Hyperactivity/psychology ; Facial Expression ; Imitative Behavior ; Emotions ; Fear ; Facial Recognition
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Journal Article
ZDB-ID	605982-x
ISSN	1744-411X ; 0168-8634 ; 1380-3395
ISSN (online)	1744-411X
ISSN	0168-8634 ; 1380-3395
DOI	10.1080/13803395.2024.2320464
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Article: Effects of cigarette smoke on oxidant–antioxidant system of lung tissue

Çubukçu, Hikmet Can / Durak, İlker

Toxicological and environmental chemistry. 2021 Mar. 16, v. 103, no. 3

2021

Abstract: The present study set out to investigate the effects of cigarette smoke on oxidant–antioxidant systems of homogenized bovine lung tissue and the possible protective effects of cigarette filters impregnated with vitamin C and lemon juice. Cigarette smoke ... ...

Abstract	The present study set out to investigate the effects of cigarette smoke on oxidant–antioxidant systems of homogenized bovine lung tissue and the possible protective effects of cigarette filters impregnated with vitamin C and lemon juice. Cigarette smoke was passed into bovine lung homogenate supernatant and malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, paraoxonase-1, nitric oxide synthase, and nitric oxide were determined. Malondialdehyde and nitric oxide levels were found to have increased as the dose of cigarette smoke increased and superoxide dismutase activity decreased with incremental doses of cigarette smoke exposure. Furthermore, the lemon juice impregnated filters scavenged nitric oxide. The cigarette smoke led to lipid peroxidation and a reduction in superoxide dismutase activity. Antioxidant-impregnated filters could not prevent oxidative stress.
Keywords	ascorbic acid ; catalase ; cattle ; cigarettes ; environmental science ; glutathione peroxidase ; lemon juice ; lipid peroxidation ; lungs ; malondialdehyde ; nitric oxide ; nitric oxide synthase ; oxidative stress ; smoke ; superoxide dismutase ; toxicology
Language	English
Dates of publication	2021-0316
Size	p. 269-278.
Publishing place	Taylor & Francis
Document type	Article
ISSN	1029-0486
DOI	10.1080/02772248.2021.1973003
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Ex vivo expansion of natural killer cells for hematological cancer immunotherapy: a systematic review and meta-analysis.

Çubukçu, Hikmet Can / Mesutoğlu, Pınar Yurdakul / Seval, Güldane Cengiz / Beksaç, Meral

Clinical and experimental medicine

2022 Volume 23, Issue 6, Page(s) 2503–2533

Abstract: The present systematic review aimed to investigate natural killer (NK) cell ex vivo expansion protocols within the scope of clinical trials targeting hematological cancer and to conduct a meta-analysis to assess the effect of NK cell infusion on survival. ...

Abstract	The present systematic review aimed to investigate natural killer (NK) cell ex vivo expansion protocols within the scope of clinical trials targeting hematological cancer and to conduct a meta-analysis to assess the effect of NK cell infusion on survival. Research articles of clinical studies in which cell products produced by ex vivo expansion, consisting of a certain amount of NK cells and infused to patients with hematological cancer, were included in the systematic review. We conducted a proportion analysis with random effects for product purity and viability values. Studies having control groups were included in the survival meta-analysis. Among 11.028 identified records, 21 were included in the systematic review. We observed statistically significant heterogeneity for viability (I2 = 97.83%, p < 0.001) and purity values (I2 = 99.95%, p < 0.001), which was attributed to the diversity among isolation and expansion protocols. In addition, the survival meta-analysis findings suggested that NK cell therapy favors disease-free survival (DFS) of patients with myeloid malignancies but limited to only two clinical studies (odds ratio = 3.40 (confidence interval:1.27-9.10), p = 0.01). While included protocols yielded cell products with acceptable viability, the utility of immunomagnetic methods; feeder cells such as K562 expressing membrane-bound IL15 and 4-1BBL or expressing membrane-bound IL21 and 4-1BBL might be preferable to achieve better purity. In conclusion, NK cell therapy has a potential to improve DFS of patients with myeloid malignancies.
MeSH term(s)	Humans ; K562 Cells ; Killer Cells, Natural ; Immunotherapy ; Feeder Cells ; Hematologic Neoplasms
Language	English
Publishing date	2022-11-04
Publishing country	Italy
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-022-00923-z
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Article ; Online: Uncertainty of measurement for 14 immunoassay analytes: application to laboratory result interpretation.

Çubukçu, Hikmet Can / Yavuz, Ömer / Devrim, Erdinç

Scandinavian journal of clinical and laboratory investigation

2019 Volume 79, Issue 1-2, Page(s) 117–122

Abstract: Laboratory tests are an integral part of clinical decision making. Therefore, measurement uncertainty comes into prominence in the context of the accuracy of the laboratory result. This study aims to investigate measurement uncertainty of 14 immunoassay ... ...

Abstract	Laboratory tests are an integral part of clinical decision making. Therefore, measurement uncertainty comes into prominence in the context of the accuracy of the laboratory result. This study aims to investigate measurement uncertainty of 14 immunoassay analytes, to compare them with different quality goals and to utilize them in the result interpretation. Measurement uncertainties of 14 immunoassay analytes were estimated by using internal and external quality control data by using Nordtest approach. Expanded uncertainties (U) were compared with allowable total error (TEa%), permissible relative deviation in the external quality assessment (PRD
MeSH term(s)	Analysis of Variance ; Biomarkers/blood ; Clinical Decision-Making/ethics ; Dehydroepiandrosterone/blood ; Diagnostic Tests, Routine/standards ; Estradiol/blood ; Folic Acid/blood ; Follicle Stimulating Hormone/blood ; Humans ; Hydrocortisone/blood ; Immunoassay/standards ; Luteinizing Hormone/blood ; Progesterone/blood ; Prolactin/blood ; Quality Control ; Reference Values ; Testosterone/blood ; Thyrotropin/blood ; Thyroxine/blood ; Uncertainty ; Vitamin B 12/blood
Chemical Substances	Biomarkers ; Testosterone (3XMK78S47O) ; Dehydroepiandrosterone (459AG36T1B) ; Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E) ; Prolactin (9002-62-4) ; Luteinizing Hormone (9002-67-9) ; Follicle Stimulating Hormone (9002-68-0) ; Thyrotropin (9002-71-5) ; Folic Acid (935E97BOY8) ; Vitamin B 12 (P6YC3EG204) ; Thyroxine (Q51BO43MG4) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2019-01-10
Publishing country	England
Document type	Journal Article
ZDB-ID	3150-1
ISSN	1502-7686 ; 0036-5513
ISSN (online)	1502-7686
ISSN	0036-5513
DOI	10.1080/00365513.2018.1550806
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