Cells In Smears Research Articles

CELLULAR COMPOSITION STATE AND MICROFLORA OF ORAL MUCOSAL EPITHELIUM OF PATIENTS WITH CHRONIC CEREBRAL ISCHEMIA

The cell composition and microflora of oral mucosal epithelium smearsand the hormonal composition of oral fluid in patients with chronic cerebral ischemiawere studied. We examined 54 patientsaged 45-65 years suffering from cerebral blood circulation disorders caused by atherosclerosis of cerebral vessels and under outpatient observation. In patients with chronic cerebral ischemia, a decrease in the size of the neutrophil pool and epithelial cell pool was noted in saliva smears, against the background of an increase in the number of lymphocytes (threefold) and “bare nuclei” -more than ten times, which indicates a weakening of local protection and is considered as a pathogenetically significantindicator. Smears of buccal epithelial cells revealed yeast-like fungi of the Candida genus (C.albicans), whose content reached 105CFU/ml in 61.44% of cases and averaged 82.5±6.4% of strains in CCI patients. Free progesterone increased 1.9-fold in oral fluid, whereas estradiol levels decreased 5-fold and cortisol increased 1.6-fold.Keywords: chronic cerebral ischemia, buccal cells, candidiasis, sex hormones.

MOSQUITO‐NET: A deep learning based CADx system for malaria diagnosis along with model interpretation using GradCam and class activation maps

AbstractMalaria is considered one of the deadliest diseases in today's world, which causes thousands of deaths per year. The parasites responsible for malaria are scientifically known as Plasmodium, which infects the red blood cells in human beings. Diagnosis of malaria requires identification and manual counting of parasitized cells in microscopic blood smears by medical practitioners. Its diagnostic accuracy is primarily affected by extensive scale screening due to the unavailability of resources. State of the art Computer‐Aided Diagnostic techniques based on deep learning algorithms such as CNNs, which perform an end to end feature extraction and classification, have widely contributed to various image recognition tasks. In this paper, we evaluate the performance of Mosquito‐Net, a custom made convnet to classify the infected and uninfected blood smears for malaria diagnosis. The CADx system can be deployed on IoT and mobile devices due to its fewer parameters and computation power, making it wildly preferable for diagnosis in remote and rural areas that lack medical facilities. Statistical analysis demonstrates that the proposed model achieves greater accuracy than the previous SOTA architectures for malaria diagnosis despite being 10 times lighter in parameters and inference time. Mosquito‐Net achieves an AUC of 99.009% and an F‐1 score of 96.7% on the validation set.

Adventitial Progenitor Cells of Human Great Saphenous Vein Enhance the Resolution of Venous Thrombosis via Neovascularization.

Background Vascular adventitia contains progenitor cells and is shown to participate in vascular remolding. Progenitor cells are recruited into the venous thrombi in mice to promote neovascularization. We hypothesized that the adventitial progenitor cells of human great saphenous vein (HGSV-AdPC) enhance the resolution of venous thrombosis via neovascularization. Methods Human great saphenous vein (HGSV) was harvested from the patients with great saphenous vein varicose and sectioned for immunohistochemistry, or minced for progenitor cell primary culture, or placed in sodium dodecyl sulfate solution for decellularization. Human venous thrombi were collected from patients with great saphenous vein varicose and superficial thrombophlebitis. Infrarenal abdominal aorta of New Zealand white rabbits was replaced with interposing decellularized vessel, and the patency of the grafts was confirmed by ultrasonic examination. Animal venous thrombi in the left infrarenal vena cava of mice were produced with Prolene suture ligation and ophthalmic force clipping of this portion. After HGSVs were digested by collagenase, the CD34+CD117+ HGSV-AdPC were isolated on FACS system, labelled with CM-Dil, and transplanted into the adventitia of infrarenal vena cava of nude mice. The percentage of thrombus organization area to the thrombus area was calculated as the organization rate. The thrombus cell, endothelial cells, and macrophages in the thrombi were counted in sections. Cell smears and frozen sections of human saphenous veins and venous thrombi were labeled with Sca1, CD34, CD117, Flk1, CD31, and F4/80 antibodies. The CD34+CD117+ HGSV-AdPC were cultured in endothelial growth medium with vascular endothelial growth factor (VEGF) to induce endothelial cell differentiation and analyzed with real time-PCR, Western blotting, and tube formation assays. Results Immunohistochemical staining showed that the CD34+CD117+ cells were located within the adventitia of HGSVs, and many CD34+ and CD117+ cells have emerged in the human venous thrombi. The number of progenitor cells within the marginal area of 7 days mice thrombi was shown to be Sca1+ ≈21%, CD34+ ≈12%, CD117+ ≈9%, and Flk1+ ≈5%. Many CD34+adventitial progenitor cells have migrated into the decellularized vessels. FACS showed that the number of CD34+CD117+ HGSV-AdPC in primary cultured cells as 1.2 ± 0.07%. After CD34+CD117+HGSV-AdPC were transplanted into the adventitia of nude mice vena cava with venous thrombi, the organization rate, nucleate cell count, endothelial cells, and macrophage cells of thrombi were shown to be significantly increased. The transplanted CD34+CD117+ HGSV-AdPC at the adventitia have crossed the vein wall, entered the venous thrombi, and differentiated into endothelial cells. The CD34+CD117+ HGSV-AdPC in the culture medium in the presence of VEGF-promoted gene and protein expression of endothelial cell markers in vitro and induced tube formation. Conclusions HGSV-AdPC could cross the vein wall and migrate from the adventitia into the venous thrombi. Increased HGSV-AdPC in the adventitia has enhanced the resolution of venous thrombi via differentiating into endothelial cells of neovascularization.

Analysis of diagnostic value of cytological smear method versus cell block method in body fluids with clinical and biochemical correlation: study of 150 cases

Background: Aspiration of serous cavities is a simple and relatively non-invasive technique toachieve diagnosis. Cytological evaluation of body cavity fluid is diagnostically challenging. Especiallyin malignant effusions, helps in staging, prognosis and management of the patients. Aims: Toassess the utility and sensitivity of cell block method over conventional smear technique incytodiagnosis of the serous effusions. And to assess the utility and sensitivity of cytologicalevaluation of body fluids with biochemical and clinical correlation. Methods: A total of 150 fluidspecimens were examined for conventional cytological smear (CS) and cell block method (CB). Outof 150 fluids, 96 were pleural fluid, 48 were ascitic fluid, 04 fluid from pouch of Douglas and 01 wasfrom synovial fluid. Results: In this study, the utility of the CB method in the cytodiagnosis ofmalignant effusions was found to be highly significant as compared to the CS method. The additionalyield of malignancy was 12% more as was obtained by the CB method. Conclusion: For the finalcytodiagnosis of body fluid, there is statistically significant difference between the two techniques. Inother words, CB is superior to CS method. It gives more information about the architecturalarrangement and the likely source of primary. More important is that diagnostic material in cellblocks is available for special studies for Immunohistochemistry which can further supplement ourknowledge about the primary source of metastasis.

Diagnostic value of sialyl-Tn immunocytochemistry in breast cancer presenting with pathological nipple discharge.

BackgroundMucin‐associated sialyl‐Tn (sTn) antigen is overexpressed and related with adverse outcome in breast cancer (BC). The role of sTn in BC has not been well defined in pathological nipple discharge (PND) cytology. The authors examined sTn immunocytochemistry (ICC) in PND to determine whether it could be a biomarker of malignancy or aggressive disease.MethodsPND was subjected to immunocytochemical staining for sTn antigen expression and thinprep cytology test (TCT) for enhancing the sensitivity and specificity. The examination data was compared with histological findings of subsequent biopsy specimens. Logistic regression analysis was used to determine which factors were most associated with malignant breast lesions.ResultsPND specimens were collected including 120 cases of intraductal papilloma, 24 cases of hyperplasia, 45 cases of ductal carcinoma in situ (DCIS), and 48 cases of invasive ductal carcinoma (IDC). STn ICC differentiated BC from benign intraductal lesions with a low sensitivity of 41.9% and a high specificity of 95.8%, but increased in combination with TCT to 64.5% and 100%, respectively. A high degree of concordance was observed between the results of sTn expression in cell smears and histological specimens. Moreover, the sTn expression was strongly associated with HER2‐positive IDC (p = 0.039). Multivariate logistic analysis showed that positive sTn expression (OR: 14.241, 95%CI: 2.574, 78.794, p = 0.010) and accompanying mass (OR: 3.307, 95%CI: 1.073, 10.188, p = 0.037) were statistically significant independent risk factors for malignant PND.ConclusionsMucin‐associated sTn expression in PND cytology appears to be a reliable diagnostic marker for BC patients with the chief complaint of malignant nipple discharge and indicates a more aggressive behavior in IDC.

DIAGNOSTIC ROLE AND UTILITY OF CONVENTIONAL SMEAR AND CELL BLOCK IN BODY FLUID CYTOLOGY

Aim The aim of this study was to compare the cytological features of exudative uids by conventional smear (CS) method and cell block (CB) method and also to assess the utility of the combined approach for cytodiagnosis of these effusions. Materials and Methods: One hundred cases pleural and peritoneal exudative uid samples were subjected to evaluation by both CS and CB methods over a period of 6 months between March 2019 to September 2019. Cellularity, architecture patterns, morphological features and yield for malignancy were compared, using the two methods. Along with the conventional smears, cell blocks were prepared by using 10% alcohol–formalin as xative agent. Result Cellularity and additional yield for malignancy was 5% more by the CB method. Conclusions CB produced signicantly better results while detecting malignant lesions and reducing suspicious results. CB technique denitively increased detection of malignancy in uid effusion when used as an adjunct to CSs. Also, CB provides material suitable for molecular genetic analysis for targeted therapies.

Somatic cell count in buffalo milk using fuzzy clustering and image processing techniques.

This research communication presents an automatic method for the counting of somatic cells in buffalo milk, which includes the application of a fuzzy clustering method and image processing techniques (somatic cell count with fuzzy clustering and image processing|, SCCFCI). Somatic cell count (SCC) in milk is the main biomarker for assessing milk quality and it is traditionally performed by exhaustive methods consisting of the visual observation of cells in milk smears through a microscope, which generates uncertainties associated with human interpretation. Unlike other similar works, the proposed method applies the Fuzzy C-Means (FCM) method as a preprocessing step in order to separate the images (objects) of the cells into clusters according to the color intensity. This contributes signficantly to the performance of the subsequent processing steps (thresholding, segmentation and recognition/identification). Two methods of thresholding were evaluated and the Watershed Transform was used for the identification and separation of nearby cells. A detailed statistical analysis of the results showed that the SCCFCI method is able to provide results which are consistent with those obtained by conventional counting. This method therefore represents a viable alternative for quality control in buffalo milk production.

Effect of moxibustion on Nrf2/HO-1 signaling pathway in rats with diminished ovarian reserve

To observe the effect of moxibustion on Nrf2/HO-1 signaling pathway in rats with diminished ovarian reserve (DOR), and to explore the protective mechanism of moxibustion on ovarian reserve function. Forty SD rats were randomly divided into a blank group, a model group, a moxibustion group and a hormone group, 10 rats in each group. The rats in the model group, moxibustion group and hormone group were treated with intragastric administration of tripterysium glycosides turbid liquid to prepare DOR model. The rats in the blank group were treated with intragastric administration of sodium chloride solution with the same volume, once a day for 14 days. The rats in the hormone group were treated with hormone sequential therapy for 14 days from the day of modeling; the rats in the moxibustion group were treated with moxibustion at bilateral "Shenshu" (BL 23) or "Guanyuan" (CV 4) and "Zhongwan" (CV 12) from the day of modeling, and the two groups acupoints were alternated every other day, 10 min each time, for 14 consecutive days. The estrus cycle was observed every day by vaginal exfoliated cell smear, and the estrus cycle disorder rate in each group was calculated. After the intervention, the HE staining was used to observe the histological morphology of ovaries; ELISA was used to detect the contents of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti Mullerian hormone (AMH), superoxide dismutase (SOD) and malondialdehyde (MDA); the protein levels of Nrf2 and HO-1 in ovarian tissue were detected by immunohistochemistry; real-time PCR (TaqMan probe method) was used to detect the expression of Nrf2 and HO-1 mRNA. Compared with the blank group, the rate of estrus cycle disorder in the model group was increased (P<0.01); compared with the model group, the rate of estrus cycle disorder in the moxibustion group and hormone group was decreased (P<0.01). Compared with the blank group, the serum contents of FSH, LH and MDA in the model group were increased (P<0.01), and the serum contents of E2, AMH and SOD were decreased (P<0.01). Compared with the model group, the serum contents of FSH, LH and MDA in the moxibustion group and hormone group were decreased (P<0.01, P<0.05), and the serum contents of E2, AMH and SOD were increased (P<0.01). Compared with the blank group, the protein and mRNA expression of Nrf2 and HO-1 in the model group were decreased (P<0.01); compared with the model group, the protein and mRNA expressions of Nrf2 and HO-1 in the moxibustion group and hormone group were increased (P<0.01). Moxibustion could reduce the rate of estrus cycle disorder, improve the level of serum sex hormones and antioxidant stress in DOR rats, and the mechanism may be related to the regulation of Nrf2/HO-1 signaling pathway.

Comparission of Smear Examination and Cell Block in Efussions

Comparission of Smear Examination and Cell Block in Efussions

Validation of a New Method for the Sputum Cytology Test During the COVID-19 Epidemic

Objective: To explore a new way to test sputum and alveolar lavage fluid samples that may contain pathogenic bacteria or viruses in the departments of pathology of middle and small scale hospitals, which are short of professional protection capability during COVID-19 epidemic. Methods: All pathological specimens were divided into two groups, samples of control group were conducted in the biological safety cabinet, and others were tested after put into pathological specimen storage bags and sealed with the seal strip. The sputum and alveolar lavage fluid were directly immersed and pretreated with 75% medical alcohol. After that, samples were performed by cell smears, liquid based cell slides and immunohistochemical staining. Then the cell morphology and tumor cell discrimination were analyzed and the expression of tumor markers was observed in samples of two groups. Result: We found that samples pre-treated with 75% medical alcohol showed clear cell structure and morphology. There was no significant difference on the morphological observation of tumor cells between these two groups. In addition, immunohistochemical results showed that the antigens are specifically expressed in tumor cells and the distribution and localization of tumor cells was diffuse and accurate after pretreatment with 75% medical alcohol, which were consistent with that of the control group. Conclusion: There was no significant effect on cell morphology, antigens and antibodies expression by using disinfectant. Our study provided a new method for technicians to test samples that may contain pathogenic bacteria or viruses without direct contact so that to protect themselves against virus during COVID-19 outbreak. Funding Information: This study was supported by the Sponsored by Shanghai Sailing Program (No.19YF1427600) and National Nature Science Foundation of China (No. 81900438). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: MISSING

Multinucleated Cells in PAP Smear- An Institutional Experience

Multinucleated Cells in PAP Smear- An Institutional Experience

Endothelial Cells in the Peripheral Blood Smear

Endothelial Cells in the Peripheral Blood Smear

Fuzzy-C means segmentation of lymphocytes for the identification of the differential counting of WBC

In the domain of histology, discovering the population of white blood cells (WBC) in blood smears helps to recognise destructive diseases. Standard tests performed in hematopathological laboratories by human experts on the blood samples of precarious cases such as leukaemia are time-consuming processes, less accurate and totally depending upon the expertise of the technicians. In order to get the advantage of faster analysis time and perfect partitioning at clumps, an algorithm is proposed in this paper that automatically identifies the counting of lymphocytes present in peripheral blood smear images containing acute lymphoblastic leukaemia (ALL) that performs lymphocytes segmentation by fuzzy C-means (FCM) clustering. Afterward, neighbouring and touching cells in cell clumps are individuated by the watershed transform (WT), and then morphological operators are applied to bring out the cells into an appropriate format in accordance with feature extraction. The extracted features are thresholded to eliminate the regions other than lymphocytes. The algorithm ensures 98.52% of accuracy in counting lymphocytes by examining 80 blood-smear image samples of the ALL-IDB1 dataset. The research works in showing this kind of improved accuracy facilitates in identifying leukaemia on starting stages for uncomplicated healing.

Clinical Study on Outcome of Treatment for Herpes Zoster

Introduction: Herpes Zoster (HZ) is caused by reactivation of Varicella Zoster Virus (VZV). It is characterised by occurrence of grouped vesicles on erythematous base which involves the entire dermatome innervated by a single spinal or cranial sensory ganglion and is associated with radicular pain. Antivirals (Acyclovir, Famciclovir and Valacyclovir) started within 72 hours of onset of lesions are the agents of choice. Aim: To study the clinical manifestations, comorbidities, efficacy and safety of Acyclovir, complications and sequelae associated with HZ. Materials and Methods: A 3-year longitudinal cohort study was conducted in 212 adult patients (&gt;18 years of age) suffering with HZ in the Department of Dermatology, Dhiraj General Hospital, Pipariya, Gujarat, India. In this study 212 patients with HZ were prescribed oral Acyclovir in a dose of 800 mg 5 times a day for 7 days. All patients were analysed in terms of clinical manifestations, pre-existing co-morbidities and incidence of complications. The clinical history and findings were recorded in a prestructured proforma. All patients were subjected to cytological examination (Tzanck smear) and Human immunodeficiency viruses (HIV) testing Enzyme-Linked Immunosorbent Assay (ELISA). Diagnosis was made primarily on the basis of clinical findings and presence of multinucleated giant cells in Tzanck smear. All the patients were treated with Oral Acyclovir. Cases were followed-up fortnightly for six weeks and evaluated for relief of symptoms, treatment outcome and complications/sequelae. Results: Two hundred and twelve cases were studied. One hundred and forty-two cases were in the 4th and 5th decades of life. Sixty-three cases had comorbidities like diabetes mellitus in 31, autoimmune diseases like pemphigus vulgaris, systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease in 19 and AIDS in 8 cases. Five cases had malignancy/lymphomas and were receiving chemotherapy for the same. In the majority, HZ occurred de novo without any comorbidities. The most common dermatomes involved were cervical and thoracic. Out of 212 cases Oral Acyclovir 800 mg was well tolerated by 74. Most common complication was Postherpetic Neuralgia (PHN), seen in 80 cases. Conclusion: The treatment of HZ with Oral Acyclovir 800 mg 5 times a day for 7 days is efficacious for healing of skin lesions and also reduces the chances of PHN if instituted within 72 hours.

Flow cytometry diagnosis of acute leukemia and comparison of cytomorphological diagnosis with Flow cytometry diagnosis

Introduction: Clinical, morphological, immunophenotypic, genetic and molecular characteristics are the most important diagnostic modalities in established diagnosis of acute leukemia. Immuno phenotyping flow cytometry has become a proven valuable tool for precise characterization of acute leukemia. This study was done to see various types of acute leukemia and aberrant antigen expression pattern in acute leukemia in patients and also to compare the results between microscopic morphology and flow cytometry.Materials and Methods: Total number of acute leukemia diagnosed was 103 and of all the age groups. All the new cases reported which were showing atypical cells in peripheral smear and treated cases to find out the minimal residual disease (MRD) were included in this study.Results: When the immune phenotyping of the acute lymphocytic leukemia patterns was done, most of the B-ALL showed positivity for CD79 alpha and HLA-DR followed by other markers and most of the T-ALL showed positivity for CD3 and CD7 markers followed by other markers. When the immune phenotyping patterns of acute myeloid leukemia was done, almost all the cases showed positive for CD13 and varying degrees of positivity with other markers.Conclusion: The flow cytometry immune phenotyping is a powerful tool for accurate diagnosis of acute leukemias and also help in identifying myeloid or lymphoid lineage of these leukemias and has great prognostic and therapeutic implications.

Atypical Presentation of COVID-19 as Acute Leukemia: A Case Report

In the absence of respiratory system involvement, COVID-19 patients developing ARDS can clinically mimic other diseases including acute leukemia due to presence of atypical lymphocytes in peripheral blood smear and increased serum lactate dehydrogenase and serum uric acid levels. Herein, we report a case who was initially suspected to have acute leukemia based on his atypical symptoms without any respiratory system involvement and deranged laboratory parameters and finally, diagnosed with COVID-19. Our patient presented with fever, myalgia, gum bleed, and petechiae. On clinical and laboratory evaluation, he was suspected to have acute leukemia based on markedly deranged serum lactate dehydrogenase and serum uric acid and the presence of atypical cells in peripheral blood smear and bone marrow. On day 3 of hospitalization, he developed respiratory symptoms, breathing difficulty which progressed to ARDS, and subsequently, he succumbed to his illness. His real-time reverse transcriptase-polymerase chain reaction test for severe acute respiratory syndrome coronavirus-2 yielded positive results. Also, Flow cytometry and fluorescence in situ hybridization studies for leukemia workup did not show any abnormalities. Although we are reporting the findings of only a single case, we aim to enhance and contribute further to the understanding of this novel infection.

A new automatic cell smear and laser release system for near-infrared light responsive release of nucleated red blood cells

The predecessor of China Optics was China Optics and Applied Optics Digest, which was founded in 1985. At that time, it was the only retrieval journal in the field of optics in China. At the end of 2008, China Optics and Applied Optics Digest was renamed

Classification and comparison of malignancy detection of cervical cells based on nucleus and textural features in microscopic images of uterine cervix

Cervical cancer is one of the major causes of death among women worldwide. Pap smear is the cytology based screening test which is used to detect abnormal cervical cells including pre-cancerous lesions. Accurate classification of Pap smear images is one of the challenging tasks in medical image processing and its performance can be enhanced by extracting and selecting the well-defined features and classifiers. The irregular chromatin structure is one of the prominent diagnostic features of abnormal cells. Classification is performed based on the extracted textural features and the benchmark Herlev dataset features. Radial basis function (RBF), polynomial and sigmoid SVM kernels are used for classification and comparison is performed with the features in benchmark database. Precision, recall and accuracy were calculated for all the combinations of the features. The classifier gives promising results when benchmark features are combined with textural features and also benchmark nucleus features with textural features. An effective integration of features for cervical cell classification had given good results for fast abnormal cell detection and primary Pap smear cell image classification.

Histogenesis of central lung cancer: cytological investigation.

To study the features of the bronchial mucosa lesion in relation to centrally growing lung cancer (LC) according to diagnostic fibrobronchoscopy in comparison with the results of cytomorphological data to determine the possible origin of tumor growth (histogenesis). The data of fibrobronchoscopy and cytological findings based on the materials of 75patients with a clinical diagnosis of LC were studied and compared. By the sum of the numerous cytomorphological features of epithelial cells and their components, the cells of the cylindrical epithelium and LC of various histological types were identified. The cells in bronchial smears and bronchial lavage were stained by Pappenheim and Papanicolau. Diagnostic material was examined by light microscopy. We have found that in a part of the patients (49%), the tumors with exophytic growth in the bronchus are covered with a cylindrical epithelium, which indirectly indicates the origin of cancer growth under the epithelial layer. In cytological preparations of 51% patients, cancer cells were found, which confirms the tumor invasion into the bronchial mucosa. In 48 (64%) patients, fibrobronchoscopy revealed that the examined bronchus was compressed from 50% to pinpoint width, evidencing that tumor growth develops from the outside, peribronchially. The obtained data indirectly confirm the development of central LC from type II pneumocytes, which are found in the glands of the submucous membrane of the bronchus. However, it does not exlude the development of this type of LC from the basal cell of the bronchial epithelium.

Novel defocus hologram aberration compensation method in digital holography integrated pathology microscope for label free 3-D imaging

In this paper we report successful integration of digital holography in off- axis transmission configuration into a commercially available pathology microscope (PathologyDHM), where Mach-Zehnder interferometric configuration was achieved in pathology microscope using 1 × 2 single mode fiber coupler and custom built optical modules. A smartphone/webcam positioned at the image plane of the finite conjugate microscope captures the interference pattern generated by the system. Using PathologyDHM, we have demonstrated a novel and simple method for compensation of aberration due to microscope objective (MO). The proposed method is called defocus hologram method and it is particularly useful in cases, where samples do not have specimen free or background flat region. Proper validation of the method was done by imaging a transmissive grating (commercial compact disc, CD-R), which doesn't have a flat background region and comparing phase profile of CD-R computed by our proposed method with self-reference conjugated hologram method. For reiterating its biological applications, phase profile of a biological sample, red blood cell smear (RBC smear), was computed with our defocus hologram method and compared with already established reference conjugated hologram method. Phase profiles of CD-R and RBC smear computed with defocus hologram method agree with self-reference and reference conjugated hologram methods respectively, within the phase error limits of the system. Integration of digital holography in to commercial pathology microscope enables 3D imaging, which coupled with artificial intelligence may prove useful in disease diagnostics and monitoring response of cells to treatment.