Artificial intelligence assisted patient blood and urine droplet pattern analysis for non‑invasive and accurate diagnosis of bladder cancer

Bladder cancer is one of the most common cancer types in the urinary system. Yet, current bladder cancer diagnosis and follow-up techniques are time-consuming, expensive, and invasive. In the clinical practice, the gold standard for diagnosis remains invasive biopsy followed by histopathological analysis. In recent years, costly diagnostic tests involving the use of bladder cancer biomarkers have been developed, however these tests have high false-positive and false-negative rates limiting their reliability. Hence, there is an urgent need for the development of cost-effective, and non-invasive novel diagnosis methods. To address this gap, here we propose a quick, cheap, and reliable diagnostic method. Our approach relies on an artificial intelligence (AI) model to analyze droplet patterns of blood and urine samples obtained from patients and comparing them to cancer-free control subjects.The AI-assisted model in this study uses a deep neural network, a ResNet network, pre-trained on ImageNet datasets. Recognition and classification of complex patterns formed by dried urine or blood droplets under different conditions resulted in cancer diagnosis with a high specificity and sensitivity.Our approach can be systematically applied across droplets, enabling comparisons to reveal shared spatial behaviors and underlying morphological patterns. Our results support the fact that AI-based models have a great potential for non-invasive and accurate diagnosis of malignancies, including bladder cancer

Determining the origin of synchronous multifocal bladder cancer by exome sequencing

BACKGROUND: Synchronous multifocal tumours are commonly observed in urothelial carcinomas of the bladder. The origin of these physically independent tumours has been proposed to occur by either intraluminal migration (clonal) or spontaneous transformation of multiple cells by carcinogens (field effect). It is unclear which model is correct, with several studies supporting both hypotheses. A potential cause of this uncertainty may be the small number of genetic mutations previously used to quantify the relationship between these tumours. METHODS: To better understand the genetic lineage of these tumours we conducted exome sequencing of synchronous multifocal pTa urothelial bladder cancers at a high depth, using multiple samples from three patients. RESULTS: Phylogenetic analysis of high confidence single nucleotide variants (SNV) demonstrated that the sequenced multifocal bladder cancers arose from a clonal origin in all three patients (bootstrap value 100 %). Interestingly, in two patients the most common type of tumour-associated SNVs were cytosine mutations of TpC* dinucleotides (Fisher’s exact test p < 10(−41)), likely caused by APOBEC-mediated deamination. Incorporating these results into our clonal model, we found that TpC* type mutations occurred 2-5× more often among SNVs on the ancestral branches than in the more recent private branches (p < 10(−4)) suggesting that TpC* mutations largely occurred early in the development of the tumour. CONCLUSIONS: These results demonstrate that synchronous multifocal bladder cancers frequently arise from a clonal origin. Our data also suggests that APOBEC-mediated mutations occur early in the development of the tumour and may be a driver of tumourigenesis in non-muscle invasive urothelial bladder cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1859-8) contains supplementary material, which is available to authorized users

Highly luminescent and cytocompatible cationic Ag2S NIR-emitting quantum dots for optical imaging and gene transfection

The development of non-toxic theranostic nanoparticles capable of delivering a therapeutic cargo and providing a means for diagnosis is one of the most challenging tasks in nano-biotechnology. Gene therapy is a very important mode of therapy and polyethyleneimine (PEI) is one of the most successful vehicles for gene transfection, yet poses significant toxicity. Optical imaging utilizing quantum dots is one of the newer but fast growing diagnostic modalities, which requires non-toxic, highly luminescent materials, preferentially active in the near infrared region. Ag2S NIRQDs fit to this profile perfectly. Here, we demonstrate the aqueous synthesis of cationic Ag2S NIRQDs with a mixed coating of 2-mercaptopropionic acid (2MPA) and PEI (branched, 25 kDa), which are highly luminescent in the NIR-I window (lambda(em) = 810-840 nm) as new theranostic nanoparticles. Synergistic stabilization of the QD surface via the simultaneous use of a small molecule and a polymeric material provided the highest quantum yield, 150% (with respect to LDS 798 at pH 7.4), reported in the literature for Ag2S. These cationic particles show a dramatic improvement in cytocompatibility even without PEGylation, a strong optical signal easily detected by confocal laser microscopy and effective conjugation and transfection of the green fluorescence protein plasmid (pGFP) to HeLa and MCF-7 cell lines (40% efficiency). Overall, these Ag2S NIRQDs show great potential as new theranostics

Frequency and economic burden of psychogenic non-epileptic seizures in patients applying for disability benefits due to epilepsy

Background Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures and are often misdiagnosed as epilepsy. Objective To investigate the frequency of PNES and to calculate the economic burden of the patients who admitted to video-electroencephalographicmonitoring (VEM) to obtain a diagnosis of epilepsy in order to apply for disability retirement. Methods The present retrospective study included 134 patients who required disability reports between 2013 and 2019 and had their definite diagnoses after VEM. Following VEM, the patients were divided into three groups: epilepsy, PNES, and epilepsy + PNES. Results In total, 22.4% (n = 30) of the patients were diagnosed with PNES, 21.6% (n = 29) with PNES and epilepsy, and 56% (n = 75), with epilepsy. The frequency of PNES among all patients was of 44% (n = 59). In patients with PNES alone, the annual cost of using anti-seizure medication was of 160.67 ± 94.04 dollars; for psychostimulant drugs, it was of 148.3 ± 72.48 dollars a year; and the mean direct cost for diagnostic procedures was of 582.9 ± 330.0 (range: 103.52–1601.3) dollars. Conclusions Although it is challenging to determine the qualitative and quantitative total cost in these patient groups, early diagnosis and sociopsychological support will reduce the additional financial burden on the health system and increase the quality of life of the patients

Determining the origin of synchronous multifocal bladder cancer by exome sequencing

Background: Synchronous multifocal tumours are commonly observed in urothelial carcinomas of the bladder. The origin of these physically independent tumours has been proposed to occur by either intraluminal migration (clonal) or spontaneous transformation of multiple cells by carcinogens (field effect). It is unclear which model is correct, with several studies supporting both hypotheses. A potential cause of this uncertainty may be the small number of genetic mutations previously used to quantify the relationship between these tumours.Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK)Science Academy of Turkey through the BAGEP progra

Ag2S-Based NIR-emitting Quantum Dots as New Theranostic Materials

Near Infrared (NIR) emitting semiconductor quantum dots (QDs) have attracted great interest as a new class of fluorescent probes for cellular, molecular and in-vivo imaging applications, due to their stable and size-tunable absorption range, large molar extinction coefficient, long luminescence lifetime and higher penetration depth into the tissues than visible light [1, 2]. Recently, Ag2S quantum dots emerged as promising new particles because of the lower cytotoxicity compared to previously reported NIR QDs such as PbS [3], PbSe [4], CdHgTe [5]. Variety of nanoparticles are being designed and tested for gene transfection. QDs provide both a vector basis and a means for optical detection. Therefore, there is a considerable amount of effort in developing QD based gene vectors. In this study, we report the synthesis of Ag2S based theranostic materials, discuss their physical properties and cytotoxicity and demonstrate their superior transfection efficiency

Ag2S-Based NIR-emitting Quantum Dots as New Theranostic Materials

Near Infrared (NIR) emitting semiconductor quantum dots (QDs) have attracted great interest as a new class of fluorescent probes for cellular, molecular and in-vivo imaging applications, due to their stable and size-tunable absorption range, large molar extinction coefficient, long luminescence lifetime and higher penetration depth into the tissues than visible light [1, 2]. Recently, Ag2S quantum dots emerged as promising new particles because of the lower cytotoxicity compared to previously reported NIR QDs such as PbS [3], PbSe [4], CdHgTe [5]. Variety of nanoparticles are being designed and tested for gene transfection. QDs provide both a vector basis and a means for optical detection. Therefore, there is a considerable amount of effort in developing QD based gene vectors. In this study, we report the synthesis of Ag2S based theranostic materials, discuss their physical properties and cytotoxicity and demonstrate their superior transfection efficiency