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1.
Bioinformatics ; 39(12)2023 12 01.
Article in English | MEDLINE | ID: mdl-38019945

ABSTRACT

MOTIVATION: Technical errors in sequencing or bioinformatics steps and difficulties in alignment at some genomic sites result in false positive (FP) variants. Filtering based on quality metrics is a common method for detecting FP variants, but setting thresholds to reduce FP rates may reduce the number of true positive variants by overlooking the more complex relationships between features. The goal of this study is to develop a machine learning-based model for identifying FPs that integrates quality metrics with genomic features and with the feature interpretability property to provide insights into model results. RESULTS: We propose a random forest-based model that utilizes genomic features to improve identification of FPs. Further examination of the features shows that the newly introduced features have an important impact on the prediction of variants misclassified by VEF, GATK-CNN, and GARFIELD, recently introduced FP detection systems. We applied cost-sensitive training to avoid errors in misclassification of true variants and developed a model that provides a robust mechanism against misclassification of true variants while increasing the prediction rate of FP variants. This model can be easily re-trained when factors such as experimental protocols might alter the FP distribution. In addition, it has an interpretability mechanism that allows users to understand the impact of features on the model's predictions. AVAILABILITY AND IMPLEMENTATION: The software implementation can be found at https://github.com/ideateknoloji/FPDetect.


Subject(s)
Genomics , High-Throughput Nucleotide Sequencing , High-Throughput Nucleotide Sequencing/methods , Genomics/methods , Genome , Software , Computational Biology
2.
J Cancer Res Ther ; 19(2): 253-258, 2023.
Article in English | MEDLINE | ID: mdl-37006064

ABSTRACT

Objective: The median survival time for metastatic gastric cancer that has a poor prognosis is usually shorter than 1 year. The fluorouracil, oxaliplatin, and docetaxel (FLOT) regimen is observed to be effective in the neo-adjuvant treatment of gastric cancer. However, data on the FLOT regimen in metastatic gastric cancer are limited. The current study aims to evaluate the safety and efficacy of the FLOT regimen in metastatic gastric cancer in real life. Study Design: Retrospective study. Place and Duration of Study: The study was performed in an Institute of Oncology of a university and included the patients diagnosed between January 2015 and December 2020. Methodology: In addition to the clinicopathological data of patients with human epidermal growth factor receptor 2 (HER-2)-negative metastatic gastric cancer, we retrospectively evaluated the survival and treatment-related toxicities. The FLOT regimen (Fluorouracil 2600 mg/m2 24 hours continuous intravenous infusion, leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2 on day 1) every 2 weeks was used in all patients. Results: The study included 94 patients who were followed up for a median of 11.1 (min-max: 1.5-65.8) months. The number of male patients was 60 (63.4%), and the median age was 58 (min-max: 27-78) years. The primary tumor was located in the stomach (72.3%) and gastroesophageal junction (27.7%). The objective response rate was observed in 64.8% of the patients. The median overall survival was 13.5 (95% CI: 9.2-17.8) months, whereas the progression-free survival was 7 (95% CI: 5.7-8.3) months. The 1-year survival rate was 53.6%. Complete response was detected in 7.4% of the patients. Among grade 3-4 toxicities, neutropenia (44.6%), leukopenia (27.6%), neuropathy (12.7%), and fatigue (9.5%) were the most common observed toxicities. Conclusion: FLOT is a highly active option in the first-line treatment of metastatic gastric cancer, with a favorable safety profile.


Subject(s)
Stomach Neoplasms , Humans , Male , Middle Aged , Stomach Neoplasms/pathology , Docetaxel , Leucovorin , Oxaliplatin , Retrospective Studies , Fluorouracil , Antineoplastic Combined Chemotherapy Protocols/adverse effects
3.
Int J Mol Sci ; 23(18)2022 Sep 07.
Article in English | MEDLINE | ID: mdl-36142239

ABSTRACT

In the maxillofacial area, specifically the orbital floor, injuries can cause bone deformities in the head and face that are difficult to repair or regenerate. Treatment methodologies include use of polymers, metal, ceramics on their own and in combinations mainly for repair purposes, but little attention has been paid to identify suitable materials for orbital floor regeneration. Polyurethane (PU) and hydroxyapatite (HA) micro- or nano- sized with different percentages (25%, 40% & 60%) were used to fabricate bioactive tissue engineering (TE) scaffolds using solvent casting and particulate leaching methods. Mechanical and physical characterisation of TE scaffolds was investigated by tensile tests and SEM respectively. Chemical and structural properties of PU and PU/HA scaffolds were evaluated by infrared (IR) spectroscopy and Surface properties of the bioactive scaffold were analysed using attenuated total reflectance (ATR) sampling accessory coupled with IR. Cell viability, collagen formed, VEGF protein amount and vascularisation of bioactive TE scaffold were studied. IR characterisation confirmed the integration of HA in composite scaffolds, while ATR confirmed the significant amount of HA present at the top surface of the scaffold, which was a primary objective. The SEM images confirmed the pores' interconnectivity. Increasing the content of HA up to 40% led to an improvement in mechanical properties, and the incorporation of nano-HA was more promising than that of micro-HA. Cell viability assays (using MG63) confirmed biocompatibility and CAM assays confirmed vascularization, demonstrating that HA enhances vascularization. These properties make the resulting biomaterials very useful for orbital floor repair and regeneration.


Subject(s)
Polyurethanes , Vascular Endothelial Growth Factor A , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Bone Regeneration , Collagen , Durapatite/chemistry , Polyurethanes/chemistry , Porosity , Solvents , Tissue Engineering/methods , Tissue Scaffolds/chemistry
5.
J Dermatolog Treat ; 27(3): 275-7, 2016.
Article in English | MEDLINE | ID: mdl-26368051

ABSTRACT

BACKGROUND: Non-HIV related Kaposi sarcoma (NHKS) is a rare indolent neoplasm which is more common around Mediterranean origin. Data concerning factors that influence progression-free survival (PFS) for NHKS are insufficient. The purpose of present retrospective analysis was to distinguish the factors affecting PFS in patients with NHKS. METHODS: A hundred and twenty-eight consecutive patients with NHKS who were treated or observed between 1997 and 2014 at Istanbul University Institute of Oncology were included into the study. Treatment response and progression definitions were determined according to different treatment modalities administered at first line. RESULTS: Majority of patients were male (n = 97, 75.8%). Median age of the whole group was 66 years (28-85). Of the patients, 15 patients were immunosuppressant, whereas 113 patients had no disease that caused immunosuppression. Patients were treated with local excision (n = 57, 44.5%), chemotherapy (n = 32, 25.0%) and/or radiotherapy (n = 13, 10.2%) or observed without treatment (n = 26, 20.3%). At a median follow-up of 28 months, 71 (55.5%) patients had progression, while 3 patients (2.3%) died of NHKS. On univariate analysis, patients who had hypertension (HT) had poorer PFS compared with others (19 ± 12 versus 41 ± 22 months; p = 0.03), whereas plaque formation was associated with better outcome (25 ± 9 versus 54 ± 12 months; p = 0.03). In addition, heavy smoking (≥40 pack-years) had a borderline significance regarding better PFS time (23 ± 24 versus 45 ± 38 months, p = 0.06). On multivariate analysis, none of factors evaluated had any impact on PFS. CONCLUSIONS: HT was correlated with poorer outcome among NHKS patients. Patients with plaque formation and ≥40 pack-years of smoking had better PFS than others.


Subject(s)
Sarcoma, Kaposi/epidemiology , Sarcoma, Kaposi/therapy , Adult , Aged , Aged, 80 and over , Disease Progression , Disease-Free Survival , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/radiotherapy , HIV Infections/surgery , HIV Infections/therapy , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Sarcoma, Kaposi/drug therapy , Sarcoma, Kaposi/radiotherapy , Sarcoma, Kaposi/surgery
6.
Thorac Cardiovasc Surg ; 58(4): 210-4, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20514575

ABSTRACT

BACKGROUND: Stab wounds of the heart still cause a significant number of traumatic deaths every year. The aim of this study was to assess the outcome of patients with cardiac stab wounds requiring emergency thoracotomy. PATIENTS AND METHODS: Preoperative and operative variables were reviewed for all patients treated at the Mansoura Emergency Hospital between August 1998 and July 2008. RESULTS: Seventy-three patients were treated for stab wounds of the heart. Of these 69 were male (94.5 %) and only 4 were female (5.5 %). Mean patient age was 28.5 +/- 5.8 years. The clinical status was stable in 22 patients (30.1 %) and unstable in 26 patients (35.6 %), while 10 patients were in shock (13.7 %), and 15 patients had suffered cardiac arrest prior to thoracotomy (20.6 %). Emergency room (ER) thoracotomy was performed in 18 patients (24.7 %) and operative room (OR) thoracotomy was carried out in 55 patients (75.3 %). The commonest location of stab wounds to the heart was the right ventricle in 28 patients (38.4 %) followed by the left ventricle in 25 patients (34.2 %). Mortality was 23.3 % (17 patients), and morbidity was 21.4 % (12 patients out of 56 surviving patients). Prognostic factors included clinical status (patients in shock or cardiac arrest had a mortality rate of 50 % and 60 %, respectively), cardiopulmonary resuscitation (CPR; mortality rate: 68.2 %) and ER thoracotomy (mortality rate: 66.7 %). CONCLUSION: Clinical status as shock, CPR and ER thoracotomy were prognostic of a poor outcome and associated with high mortality rates.


Subject(s)
Heart Injuries/surgery , Thoracotomy , Wounds, Stab/surgery , Adolescent , Adult , Cardiopulmonary Resuscitation , Egypt , Emergency Service, Hospital , Female , Heart Arrest/etiology , Heart Arrest/surgery , Heart Injuries/complications , Heart Injuries/mortality , Humans , Male , Middle Aged , Operating Rooms , Retrospective Studies , Risk Assessment , Risk Factors , Shock, Cardiogenic/etiology , Shock, Cardiogenic/surgery , Thoracotomy/adverse effects , Thoracotomy/mortality , Treatment Outcome , Wounds, Stab/complications , Wounds, Stab/mortality , Young Adult
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