Search results for: breast cancer screening

Authors: Cláudia Moço, Maria Santos, Carlos Arsénio, Débora Mendes, Miguel Oliveira. José Paulo Da Silva

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Construction industry generates large amounts of waste all over the world. About 450 million tons of construction and demolition wastes (C&DW) are produced annually in the European Union. C&DW are highly heterogeneous materials in size and composition, which imposes strong difficulties on their management. Directive n.º 2008/98/CE, of the European Parliament and of the Council of 6 November establishes that 70 % of the C&DW have to be recycled by 2020. To evaluate possible applications of these materials, a detailed physical, chemical and environmental characterization is necessary. Multi Triagem, Lda. is a company located in Algarve (Portugal) and was supported by the European Regional Development Fund (grant QREN 30307 Multivalor) to quantify and characterize the received C&DW, in order to evaluate their possible applications. This evaluation, performed in collaboration with the University of Algarve, involves a physical, chemical and environmental detailed characterization of the received C&DW. In this work we report on the amounts, trial procedures and properties of the C&DW received over a period of fifteen month. In this period the company received C&DW coming from 393 different origins. The total amount was 32.458 tons, mostly mixtures containing concrete, masonry/mortar and soil/rock. Most of C&DW came from demodulation constructions and diggings. The organic/inert component, namely metal, glass, wood and plastics, were screened first and account for about 3 % of the received materials. The remaining materials were screened and grouped according to their origin and contents, the latter evaluated by visual inspection. Twenty five samples were prepared and submitted to a detailed physical, chemical and environmental analysis. The C&DW aggregates show lower quality properties than natural aggregates for concrete preparation and unbound layers of road pavements. However, chemical analyzes indicated that most samples are environmentally safe. A continuous monitoring of the presence of heavy metals and organic compounds is needed in order to perform a proper screening of the C&DW. C&DW aggregates provide a good alternative to natural aggregates.

Keywords: construction and demolition wastes, waste classification, waste composition, waste screening

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Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Vanessa Bennemann, Gabriela Laste, Márcia Inês Goettert

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The gestational period is a phase in which the pregnant woman undergoes constant physiological and hormonal changes, which are part of the woman’s biological cycle, the development of the fetus, childbirth, and lactation. These are factors of response to the immunological adaptation of the human reproductive process that is directly related to the pregnancy’s well-being and development. Although most pregnancies occur without complications, about 15% of pregnant women will develop potentially fatal complications, implying maternal and fetal risk. Therefore, requiring specialized care for high-risk pregnant women (HRPW) with obstetric interventions for the survival of the mother and/or fetus. Among the risk factors that characterize HRPW are the women's age, gestational diabetes mellitus (GDM), autoimmune diseases, infectious diseases such as syphilis and HIV, hypertension (SAH), preeclampsia, eclampsia, HELLP syndrome, uterine contraction abnormalities, and premature placental detachment (PPD), thyroid disorders, among others. Thus, pregnancy has an impact on the thyroid gland causing changes in the functioning of the mother's thyroid gland, altering the thyroid hormone (TH) profiles and production as pregnancy progresses. Considering, throughout the gestational period, the interpretation of the results of the tests to evaluate the thyroid functioning depends on the stage in which the pregnancy is. Thyroid disorders are directly related to adverse obstetric outcomes and in child development. Therefore, the adequate release of TH is important for a pregnancy without complications and optimal fetal growth and development. Objective: Investigate the physiological effects caused by thyroid disorders in the gestational period. Methods: A search for articles indexed in PubMed, Scielo, and MDPI databases, was performed using the term “AND”, with the descriptors: Pregnancy, Thyroid. With several combinations that included: Melatonin, Thyroidopathy, Inflammatory processes, Cytokines, Anti-inflammatory, Antioxidant, High-risk pregnancy. Subsequently, the screening was performed through the analysis of titles and/or abstracts. The criteria were: including clinical studies in general, randomized or not, in the period of 10 years prior to the research, in the English literature; excluded: experimental studies, case reports, research in the development phase. Results: In the preliminary results, a total of studies (n=183) were found, (n=57) excluded, such as studies of cancer, diabetes, obesity, and skin diseases. Conclusion: To date, it has been identified that thyroid diseases can impair the fetus’s brain development. Further research is suggested on this matter to identify new substances that may have a potential therapeutic effect to aid the gestational period with thyroid diseases.

Keywords: pregnancy, thyroid, melatonin, high-risk pregnancy

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Authors: Jindriska Svobodova, Jan Novotny

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A teacher’s attitude to creativity plays an essential role in the thinking development of his/her students. The purpose of this study is to understand if a science teacher's personal creativity can modify his/her ability to produce various kinds of questions. This research used an education activity based on cosmic sketches and pictures by K.E. Tsiolkovsky, the founder of astronautics, to explore if any relationship between individual creativity and the asking questions skill exists. As a screening instrument, which allows an assessment of the respondent's creative potential, a common test of creative thinking was used. The results of the creativity test and the diversity of the questions are mentioned.

Keywords: science education, active learning, physics teaching, religious cosmology

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Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

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Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50,oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals, stem bark extract

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Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

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Authors: Suman Som, Abhijit Maity, Sunil B. Daschakraborty, Sujit Chaudhuri, Manik Pradhan

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Background: Helicobacter pylori is a common and important human pathogen and the primary cause of peptic ulcer disease and gastric cancer. Currently H. pylori infection is detected by both invasive and non-invasive way but the diagnostic accuracy is not up to the mark. Aim: To set up an optimal diagnostic cut-off value of 13C-Urea Breath Test to detect H. pylori infection and evaluate a novel c-PDR methodology to overcome of inconclusive grey zone. Materials and Methods: All 83 subjects first underwent upper-gastrointestinal endoscopy followed by rapid urease test and histopathology and depending on these results; we classified 49 subjects as H. pylori positive and 34 negative. After an overnight, fast patients are taken 4 gm of citric acid in 200 ml water solution and 10 minute after ingestion of the test meal, a baseline exhaled breath sample was collected. Thereafter an oral dose of 75 mg 13C-Urea dissolved in 50 ml water was given and breath samples were collected upto 90 minute for 15 minute intervals and analysed by laser based high precisional cavity enhanced spectroscopy. Results: We studied the excretion kinetics of 13C isotope enrichment (expressed as δDOB13C ‰) of exhaled breath samples and found maximum enrichment around 30 minute of H. pylori positive patients, it is due to the acid mediated stimulated urease enzyme activity and maximum acidification happened within 30 minute but no such significant isotopic enrichment observed for H. pylori negative individuals. Using Receiver Operating Characteristic (ROC) curve an optimal diagnostic cut-off value, δDOB13C ‰ = 3.14 was determined at 30 minute exhibiting 89.16% accuracy. Now to overcome grey zone problem we explore percentage dose of 13C recovered per hour, i.e. 13C-PDR (%/hr) and cumulative percentage dose of 13C recovered, i.e. c-PDR (%) in exhaled breath samples for the present 13C-UBT. We further explored the diagnostic accuracy of 13C-UBT by constructing ROC curve using c-PDR (%) values and an optimal cut-off value was estimated to be c-PDR = 1.47 (%) at 60 minute, exhibiting 100 % diagnostic sensitivity , 100 % specificity and 100 % accuracy of 13C-UBT for detection of H. pylori infection. We also elucidate the gastric emptying process of present 13C-UBT for H. pylori positive patients. The maximal emptying rate found at 36 minute and half empting time of present 13C-UBT was found at 45 minute. Conclusions: The present study exhibiting the importance of c-PDR methodology to overcome of grey zone problem in 13C-UBT for accurate determination of infection without any risk of diagnostic errors and making it sufficiently robust and novel method for an accurate and fast non-invasive diagnosis of H. pylori infection for large scale screening purposes.

Keywords: 13C-Urea breath test, c-PDR methodology, grey zone, Helicobacter pylori

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Authors: Abdullah Malek, Muzn Al Khaldi, Lian Odeh, Atheer Tariq, Mohammad Al Fardan, Hiba Barqawi

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H. pylori bacterium is a known underlying agent for gastritis, peptic ulcer disease, and gastric cancer and is believed to infect half of the world’s population. Even with the ubiquity of H. pylori bacterium, there is lack of knowledge regarding its modes of transmission, associated diseases, carcinogenic effect and means of prevention; especially in the UAE. A cross sectional study of 500 participants, of which 58% (n= 289) of the respondents were female, and 42% (n=210) were male, was conducted in Sharjah to assess the knowledge, and explore the attitudes and practices among UAE residents towards Helicobacter Pylori and its associated PUD as well as its carcinogenic nature. A structured self-administered questionnaire was distributed to the target population to establish their demographic background and selected aspects of their lifestyle. General knowledge about H. Pylori was poor, only 24.6% stated they have heard of H. pylori. Attitudes towards prevention and practices were relatively poor as well. Subjects who suffered from severe symptoms (ALARM symptoms) had significantly lower habit scores than those with mild and moderate symptoms (p=0.0078**). To the authours’ knowledge, no previous studies were conducted in the United Arab Emirates regarding the epidemiology of the infection to detect the extent of H. Pylori’s impact on the public health. The results of this study can be used to draw conclusions about the average knowledge of the UAE population regarding H. pylori. It can also be a starting point to devise new education programs and campaigns that raise awareness of this health issue which could be easily avoided with early diagnosis and antibiotic treatment.

Keywords: chronic gastritis, community health, gastric cancer, Helicobacter pylori, peptic ulcers

Procedia PDF Downloads 257

Authors: Selim M. Khan, Dustin D. Pearson, Tryggve Rönnqvist, Markus E. Nielsen, Joshua M. Taron, Aaron A. Goodarzi

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Accumulation of radioactive radon gas in indoor air poses a serious risk to human health by increasing the lifetime risk of lung cancer and is classified by IARC as a category one carcinogen. Radon exposure risks are a function of geologic, geographic, design, and human behavioural variables and can change over time. Using time series and deep machine learning modelling, we analyzed long-term radon test outcomes as a function of building metrics from 25,489 Canadian and 38,596 Swedish residential properties constructed between 1945 to 2020. While Canadian and Swedish properties built between 1970 and 1980 are comparable (96–103 Bq/m³), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that 21st Century Canadian houses show 467% greater average radon (131 Bq/m³) relative to Swedish equivalents (28 Bq/m³). These trends are consistent across housing types and regions within each country. The introduction of energy efficiency measures within Canadian and Swedish building codes coincided with opposing radon level trajectories in each nation. Deep machine learning modelling predicts that, without intervention, average Canadian residential radon levels will increase to 176 Bq/m³ by 2050, emphasizing the importance and urgency of future building code intervention to achieve systemic radon reduction in Canada.

Keywords: radon health risk, time-series, deep machine learning, lung cancer, Canada, Sweden

Procedia PDF Downloads 82

Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

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A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

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Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav

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The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.

Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid

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Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

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Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

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Authors: Prasad Urvashi, Wynn Yezarni, Williams Shehan, Ravindran Arun

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Introduction: Primary health services are often the first point of contact that patients with mental illness have with the healthcare system. A number of tools have been developed to increase detection of depression in the context of primary care. However, one challenge amongst many includes utilizing these tools within the limited primary care consultation timeframe. Therefore, short questionnaires that screen for depression that are just as effective as more comprehensive diagnostic tools may be beneficial in improving detection rates of patients visiting a primary care setting. Objective: To develop and determine the sensitivity and specificity of a 2-Question Questionnaire (2-QQ) to screen for depression in in a suburban primary care clinic in Ragama, Sri Lanka. The purpose is to develop a short screening tool for depression that is culturally adapted in order to increase the detection of depression in the Sri Lankan patient population. Methods: This was a cross-sectional study involving two steps. Step one: verbal administration of 2-QQ to patients by their primary care physician. Step two: completion of the Peradeniya Depression Scale, a validated diagnostic tool for depression, the patient after their consultation with the primary care physician. The results from the PDS were then correlated to the results from the 2-QQ for each patient to determine sensitivity and specificity of the 2-QQ. Results: A score of 1/+ on the 2-QQ was most sensitive but least specific. Thus, setting the threshold at this level is effective for correctly identifying depressed patients, but also inaccurately captures patients who are not depressed. A score of 6 on the 2-QQ was most specific but least sensitive. Setting the threshold at this level is effective for correctly identifying patients without depression, but not very effective at capturing patients with depression. Discussion: In the context of primary care, it may be worthwhile setting the 2-QQ screen at a lower threshold for positivity (such as a score of 1 or above). This would generate a high test sensitivity and thus capture the majority of patients that have depression. On the other hand, by setting a low threshold for positivity, patients who do not have depression but score higher than 1 on the 2-QQ will also be falsely identified as testing positive for depression. However, the benefits of identifying patients who present with depression may outweigh the harms of falsely identifying a non-depressed patient. It is our hope that the 2-QQ will serve as a quick primary screen for depression in the primary care setting and serve as a catalyst to identify and treat individuals with depression.

Keywords: depression, primary care, screening tool, Sri Lanka

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Authors: Fang-Bo Yu, Li-Bo Guan, Sheng-Dao Shan

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Biogas slurry was mixed with six commercial fungicides and screening against 11 phytopathogens was carried out. Results showed that inhibition of biogas slurry was different for the test strains and no significant difference between treatments of Didymella bryoniae, Fusarium oxysporum f. sp. vasinfectum, Aspergillus niger, Rhizoctonia cerealis, F. graminearum and Septoria tritici was observed. However, significant differences were found among Penicillium sp., Botrytis cinerea, Alternaria sonali, F. oxysporum F. sp. melonis and Sclerotinia sclerotiorum. The approach described here presents a promising alternative to current manipulation although some issues still need further examination. This study could contribute to the development of sustainable agriculture and better utilization of biogas slurry.

Keywords: anaerobic digestion, biogas slurry, phytopathogen, sustainable agriculture

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Authors: Larisa Gheber

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Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.

Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics

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Authors: Yao Song

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Objectives: We aimed to explore the clinicodemographic characteristics and prognosis of grey zone squamous cell cancer (GZSCC) located in the overlapping or ambiguous area of the oral cavity and oropharynx and to identify valuable factors that would improve its differential diagnosis and prognosis. Methods: Information of GZSCC patients in the Surveillance, Epidemiology, and End Results (SEER) database was compared to patients with an oral cavity (OCSCC) and oropharyngeal (OPSCC) squamous cell carcinomas with corresponding HPV status, respectively. Kaplan-Meier method with log-rank test and multivariate Cox regression analysis were applied to assess associations between clinical characteristics and overall survival (OS). A predictive model integrating age, gender, marital status, HPV status, and staging variables was conducted to classify GZSCC patients into three risk groups and verified internally by 10-fold cross validation. Results: A total of 3318 GZSCC, 10792 OPSCC, and 6656 OCSCC patients were identified. HPV-positive GZSCC patients had the best 5-year OS as HPV-positive OPSCC (81% vs. 82%). However, the 5-year OS of HPV-negative/unknown GZSCC (43%/42%) was the worst among all groups, indicating that HPV status and the overlapping nature of tumors were valuable prognostic predictors in GZSCC patients. Compared with the strategy of dividing GZSCC into two groups by HPV status, the predictive model integrating more variables could additionally identify a unique high-risk GZSCC group with the lowest OS rate. Conclusions: GZSCC patients had distinct clinical characteristics and prognoses compared with OPSCC and OCSCC; integrating HPV status and other clinical factors could help distinguish GZSCC and predict their prognosis.

Keywords: GZSCC, OCSCC, OPSCC, HPV

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Authors: Sreeparna Majee, G. C. Shit

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A study on targeted drug delivery is carried out in an unsteady flow of blood infused with magnetic NPs (nanoparticles) with an aim to understand the flow pattern and nanoparticle aggregation in a diseased arterial segment having stenosis. The magnetic NPs are supervised by the magnetic field which is significant for therapeutic treatment of arterial diseases, tumor and cancer cells and removing blood clots. Coupled thermal energy have also been analyzed by considering dissipation of energy because of the application of the magnetic field and the viscosity of blood. Simulation technique used to solve the mathematical model is vorticity-stream function formulations in the diseased artery. An elevation in SLP (Specific loss power) is noted in the aortic bloodstream when the agglomeration of nanoparticles is higher. This phenomenon has potential application in the treatment of hyperthermia. The study focuses on the lowering of WSS (Wall Shear Stress) with increasing particle concentration at the downstream of the stenosis which depicts the vigorous flow circulation zone. These low shear stress regions prolong the residing time of the nanoparticles carrying drugs which soaks up the LDL (Low Density Lipoprotein) deposition. Moreover, an increase in NP concentration enhances the Nusselt number which marks the increase of heat transfer from the arterial wall to the surrounding tissues to destroy tumor and cancer cells without affecting the healthy cells. The results have a significant influence in the study of medicine, to treat arterial diseases such as atherosclerosis without the need for surgery which can minimize the expenditures on cardiovascular treatments.

Keywords: magnetic nanoparticles, blood flow, atherosclerosis, hyperthermia

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Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

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Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

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Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

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Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

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Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Chi-Ching Lee, Po-Jung Huang, Kuo-Yang Huang, Petrus Tang

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Background: Recent advances in high-throughput research technologies such as new-generation sequencing and multi-dimensional liquid chromatography makes it possible to dissect the complete transcriptome and proteome in a single run for the first time. However, it is almost impossible for many laboratories to handle and analysis these “BIG” data without the support from a bioinformatics team. We aimed to provide a web-based analysis platform for users with only limited knowledge on bio-computing to study the functional genomics and proteomics. Method: We use NCI-60 as an example dataset to demonstrate the power of the web-based analysis platform and data delivering system: C-eXpress takes a simple text file that contain the standard NCBI gene or protein ID and expression levels (rpkm or fold) as input file to generate a distribution map of gene/protein expression levels in a heatmap diagram organized by color gradients. The diagram is hyper-linked to a dynamic html table that allows the users to filter the datasets based on various gene features. A dynamic summary chart is generated automatically after each filtering process. Results: We implemented an integrated database that contain pre-defined annotations such as gene/protein properties (ID, name, length, MW, pI); pathways based on KEGG and GO biological process; subcellular localization based on GO cellular component; functional classification based on GO molecular function, kinase, peptidase and transporter. Multiple ways of sorting of column and rows is also provided for comparative analysis and visualization of multiple samples.

Keywords: cancer, visualization, database, functional annotation

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Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: Clara Luwe, Oliver Harness, Helena Meally, Kim Martin, Alexandra Harrington

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Background: The role of ‘Renal Specialist Podiatrist’ originated in 2022 due to prevailing evidence of patients with diabetes and end-stage renal disease (ESRD) on haemodialysis (HD) and active ulcerations that were at higher risk of rapid deterioration, foot-related hospital admissions, and lower limb amputations. This role started in April 2022 with the aim of screening all patients on haemodialysis and instigating preventative measures to reduce serious foot related complications. Methods: A comprehensive neurovascular foot assessment was completed to establish baseline vascular status and identify those with peripheral arterial disease (PAD) for all patients on HD. Individual’s foot risk was stratified, advice and education tailored and issued. Identifying all diabetes patients on HD as high-risk for diabetic foot complications. Major Findings: All patients screened revealed over half of the caseload had diabetes, and more than half had a clinical presentation of PAD. All those presenting with ulcerations had a diagnosis of diabetes. Of the presenting ulcerations, the majority of these ulcers predated the renal specialist post and were classified as severe >3 SINBAD Score. Since April’22, complications have been identified quicker, reducing the severity (SINBAD<3 or below), and have improved healing times, in line with the national average. During the eight months of the role being in place, we have seen a reduction in minor amputations and no major amputations. Conclusion: By screening all patients on haemodialysis and focusing on education, early recognition of complications, appropriate treatment, and timely onward referral, we can reduce the risk of foot Diabetic foot ulcerations and lower limb amputations. Having regular podiatry input to stratify and facilitate high-risk, active wound patients across different services has helped to keep these patients stable, prevent amputations, and reduce foot-related hospital admissions and mortality from foot-related disease. By improving the accessibility to a specialist podiatrist, patients felt able to raise concerns sooner. This has helped to implement treatment at the earliest possible opportunity, enabling the identification and healing of ulcers at an earlier and less complex stage (SINBAD <3), thus, preventing potential limb-threatening complications.

Keywords: renal, podiatry, haemodialysis, prevention, early detection

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Authors: M. Dasgupta, S. Banerjee

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Content Based Image Retrieval (CBIR) coupled with Case Based Reasoning (CBR) is a paradigm that is becoming increasingly popular in the diagnosis and therapy planning of medical ailments utilizing the digital content of medical images. This paper presents a survey of some of the promising approaches used in the detection of abnormalities in retina images as well in mammographic screening and detection of regions of interest in MRI scans of the brain. We also describe our proposed algorithm to detect hard exudates in fundus images of the retina of Diabetic Retinopathy patients.

Keywords: case based reasoning, exudates, retina image, similarity based retrieval

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Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

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Authors: Himali Gunasekara, Baddika Jayaratne

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Haematological abnormalities are known to cause Ischemic Stroke or Transient Ischemic Attack (TIA). The identification of haematological correlates plays an important role in a management and secondary prevention. The objective of this study was to describe haematological correlates of stroke and their association between stroke profile. The haematological correlates screened were Lupus Anticoagulant, Dysfibroginemia, Paroxysmal nocturnal haemoglobinurea (PNH), Sickle cell disease, Systemic Lupus Erythematosis (SLE) and Myeloploriferative Neoplasms (MPN). A cross sectional descriptive study was conducted in a sample of 152 stroke patients referred to haematology department of National Hospital of Sri Lanka for thrombophilia screening. Different tests were performed to assess each hematological correlate. Diluted Russels Viper Venom Test and Kaolin clotting time were done to assess Lupus anticoagulant. Full blood count (FBC), blood picture, Sickling test and High Performance Liquid Chromatography were the tests used for detection of Sickle cell disease. Paroxysmal nocturnal haemoglobinurea was assessed by FBC, blood picture, Ham test and Flowcytometry. FBC, blood picture, Janus Kinase 2 (V617F) mutation analysis, erythropoietin level and bone marrow examination were done to look for the Myeloproliferative neoplasms. Dysfibrinogenaemia was assessed by TT, fibrinogen antigen test, clot observation and clauss test. Anti nuclear antibody test was done to look for systemic lupus erythematosis. Among study sample, 134 patients had strokes and only 18 had TIA. The recurrence of stroke/TIA was observed in 13.2% of patients. The majority of patients (94.7%) have had radiological evidence of thrombotic event. One fourth of patients had past thrombotic events while 12.5% had family history of thrombosis. Out of haematological correlates screened, Lupus anticoagulant was the commonest haematological correlate (n=16 ) and dysfibrigonaemia(n=11 ) had the next high prevalence. One patient was diagnosed with Essential thrombocythaemia and one with SLE. None of the patients were positive for screening tests done for sickle cell disease and PNH. The Haematological correlates were identified in 19% of our study sample. Among stroke profile only presence of past thrombotic history was statistically significantly associated with haematological disorders (P= 0.04). Therefore, hematological disorders appear to be an important factor in etiological work-up of stroke patients particularly in patients with past thrombotic events.

Keywords: stroke, transient ischemic attack, hematological correlates, hematological disorders

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