Search results for: prognosis

Authors: Jenny Fairthorne, Yuka Mori, Helen Leonard

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Background: Primary care-givers of children with autism spectrum disorder (ASD) or intellectual disability (ID) have poorer health and quality of life (QoL) than primary care-givers (hereafter referred to as just care-givers) of typically developing children. We aimed to review original research which described factors impacting the health of care-givers of children with ASD or ID and to discuss how these factors might influence care-giver health. Methods: We searched Web of Knowledge, Medline, Scopus and Google Scholar using selections of words from each of three groups. The first comprised terms associated with ASD and ID and included autism, pervasive development disorder, intellectual disability, mental retardation, disability, disabled, Down and Asperger. The second included terms related to health such as depression, physical, mental, psychiatric, psychological and well-being. The third was terms related to care-givers such as mother, parent and care-giver. We included an original paper in our review if it was published between 1st January 1990 and 31st December, 2016, described original research in a peer-reviewed journal and was written in English. Additional criteria were that the research used a study population of 15 persons or more; described a risk or protective factor for the health of care-givers of a child with ASD, ID or a sub-type (such as ASD with ID or Down syndrome). Using previous research, we developed a simple and objective five-level tool to assess the strength of evidence provided by the reviewed papers. Results: We retained 33 papers. Factors impacting primary care-giver health included child behaviour, level of support, socio-economic status (SES) and diagnostic issues. Challenging child behaviour, the most commonly identified risk factor for poorer care-giver health and QoL was reported in ten of the studies. A higher level of support was associated with improved care-giver health and QoL. For example, substantial evidence indicated that family support reduced care-giver burden in families with a child with ASD and that family and neighbourhood support was associated with improved care-giver mental health. Higher socio-economic status (SES) was a protective factor for care-giver health and particularly maternal health. Diagnostic uncertainty and an unclear prognosis are factors which can cause the greatest concern to care-givers of children with ASD and those for whom a cause of their child’s ID has not been identified. We explain how each of these factors might impact caregiver health and how they might act differentially in care-givers of children with different types of ASD or ID (such as Down syndrome and ASD without ID). Conclusion: Care-givers of children with ASD may be more likely to experience many risk factors and less likely to experience the protective factors we identified for poorer mental health. Interventions to reduce risk factors and increase protective factors could pave the way for improved care-giver health. For example, workshops to train care-givers to better manage challenging child behaviours and earlier diagnosis of ASD (and particularly ASD without ID) would seem likely to improve care-giver well-being. Similarly, helping to expand support networks might reduce care-giver burden and stress leading to improved health.

Keywords: autism, caregivers, health, intellectual disability, mothers, review

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Authors: Kantha Siddhanth Gujjari, Shaani Singhal, Robert Andrew Danks, Adrian Praeger

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Background: Trigeminal neuralgia (TN) is a heterogenous pain syndrome characterised by short paroxysms of lancinating facial pain in the distribution of the trigeminal nerve, often triggered by usually innocuous stimuli. TN has a low prevalence of less than 0.1%, of which 80% to 90% is caused by compression of the trigeminal nerve from an adjacent artery or vein. The root entry zone of the trigeminal nerve is most sensitive to neurovascular conflict (NVC), causing dysmyelination. Whilst microvascular decompression (MVD) is an effective treatment for TN with NVC, all patients do not achieve long-term pain relief. Pre-operative scoring systems by Panczykowski and Hardaway have been proposed but have not been externally validated. These pre-operative scoring systems are composite scores calculated according to a subtype of TN, presence and degree of neurovascular conflict, and response to medical treatments. There is discordance in the assessment of NVC identified on pre-operative magnetic resonance imaging (MRI) between neurosurgeons and radiologists. To our best knowledge, the prognostic impact for MVD of this difference of interpretation has not previously been investigated in the form of a composite scoring system such as those suggested by Panczykowski and Hardaway. Aims: This study aims to identify prognostic factors and externally validate the proposed scoring systems by Panczykowski and Hardaway for TN. A secondary aim is to investigate the prognostic difference between a neurosurgeon's interpretation of NVC on MRI compared with a radiologist’s. Methods: This retrospective cohort study included 95 patients who underwent de novo MVD in a single neurosurgical unit in Melbourne. Data was recorded from patients’ hospital records and neurosurgeon’s correspondence from perioperative clinic reviews. Patient demographics, type of TN, distribution of TN, response to carbamazepine, neurosurgeon, and radiologist interpretation of NVC on MRI, were clearly described prospectively and preoperatively in the correspondence. Scoring systems published by Panczykowski et al. and Hardaway et al. were used to determine composite scores, which were compared with the recurrence of TN recorded during follow-up over 1-year. Categorical data analysed using Pearson chi-square testing. Independent numerical and nominal data analysed with logistical regression. Results: Logistical regression showed that a Panczykowski composite score of greater than 3 points was associated with a higher likelihood of pain-free outcome 1-year post-MVD with an OR 1.81 (95%CI 1.41-2.61, p=0.032). The composite score using neurosurgeon’s impression of NVC had an OR 2.96 (95%CI 2.28-3.31, p=0.048). A Hardaway composite score of greater than 2 points was associated with a higher likelihood of pain-free outcome 1 year post-MVD with an OR 3.41 (95%CI 2.58-4.37, p=0.028). The composite score using neurosurgeon’s impression of NVC had an OR 3.96 (95%CI 3.01-4.65, p=0.042). Conclusion: Composite scores developed by Panczykowski and Hardaway were validated for the prediction of response to MVD in TN. A composite score based on the neurosurgeon’s interpretation of NVC on MRI, when compared with the radiologist’s had a greater correlation with pain-free outcomes 1 year post-MVD.

Keywords: de novo microvascular decompression, neurovascular conflict, prognosis, trigeminal neuralgia

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Authors: Ammar Asma, Bouafia Nabiha, Dhahri Meriem, Ben Cheikh Asma, Ezzi Olfa, Chafai Rim, Njah Mansour

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Despite recent advances in treatment of the lung cancer patients, the prognosis remains poor. Information is limited regarding health related quality of life (QOL) status of advanced lung cancer patients. The purposes of this study were: to assess patient reported symptom burden, to measure their QOL, and to identify determinant factors associated with QOL. Materials/Methods: A cross sectional study of 60 patients was carried out from over the period of 03 months from February 1st to 30 April 2016. Patients were recruited in two department of health care: Pneumology department in a university hospital in Sousse and an oncology unit in a University Hospital in Kairouan. Patients with advanced stage (III and IV) of lung cancer who were hospitalized or admitted in the day hospital were recruited by convenience sampling. We used a questionnaire administrated and completed by a trained interviewer. This questionnaire is composed of three parts: demographic, clinical and therapeutic information’s, QOL measurements: based on the SF-36 questionnaire, Symptom’s burden measurement using the Lung Cancer Symptom Scale (LCSS). To assess Correlation between symptoms burden and QOL, we compared the scores of two scales two by two using the Pearson correlation. To identify factors influencing QOL in Lung cancer, a univariate statistical analysis then, a stepwise backward approach, wherein the variables with p< 0.2, were carried out to determine the association between SF-36 scores and different variables. Results: During the study period, 60 patients consented to complete symptom and quality of life questionnaires at a single point time (72% were recruited from day hospital). The majority of patients were male (88%), age ranged from 21 to 79 years with a mean of 60.5 years. Among patients, 48 (80%) were diagnosed as having non-small cell lung carcinoma (NSCLC). Approximately, 60 % (n=36) of patients were in stage IV, 25 % in stage IIIa and 15 % in stage IIIb. For symptom burden, the symptom burden index was 43.07 (Standard Deviation, 21.45). Loss of appetite and fatigue were rated as the most severe symptoms with mean scores (SD): 49.6 (25.7) and 58.2 (15.5). The average overall score of SF36 was 39.3 (SD, 15.4). The physical and emotional limitations had the lowest scores. Univariate analysis showed that factors which influence negatively QOL were: married status (p<0.03), smoking cessation after diagnosis (p<0.024), LCSS total score (p<0.001), LCSS symptom burden index (p<0.001), fatigue (p<0.001), loss of appetite (p<0.001), dyspnea (p<0.001), pain (p<0.002), and metastatic stage (p<0.01). In multivariate analysis, unemployment (p<0.014), smoking cessation after diagnosis (p<0.013), consumption of analgesic (p<0.002) and the indication of an analgesic radiotherapy (p<0.001) are revealed as independent determinants of QOL. The result of the correlation analyses between total LCSS scores and the total and individual domain SF36 scores was significant (p<0.001); the higher total LCSS score is, the poorer QOL is. Conclusion: A built in support of lung cancer patients would better control the symptoms and promote the QOL of these patients.

Keywords: quality of life, lung cancer, metastasis, symptoms burden

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Authors: Sadia Munir, Diana White, Aya Albahri, Pratiwi Hastania, Eltahir Mohamed, Mahmood Khan, Fathima Mohamed, Ayat Kadhi, Haila Saleem

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Preeclampsia is a major complication of pregnancy. Prediction and management of preeclampsia is a challenge for obstetricians. To our knowledge, no major progress has been achieved in the prevention and early detection of preeclampsia. There is very little known about the clear treatment path of this disorder. Preeclampsia puts both mother and baby at risk of several short term- and long term-health problems later in life. There is huge health service cost burden in the health care system associated with preeclampsia and its complications. Preeclampsia is divided into two different types. Early onset preeclampsia develops before 34 weeks of gestation, and late onset develops at or after 34 weeks of gestation. Different genetic and environmental factors, prognosis, heritability, biochemical and clinical features are associated with early and late onset preeclampsia. Prevalence of preeclampsia greatly varies all over the world and is dependent on ethnicity of the population and geographic region. To authors best knowledge, no published data on preeclampsia exist in Qatar. In this study, we are reporting the incidence of preeclampsia in Qatar. The purpose of this study is to compare the incidence and risk factors of both early onset and late onset preeclampsia in Qatar. This retrospective longitudinal cohort study was conducted using data from the hospital record of Women’s Hospital, Hamad Medical Corporation (HMC), from May 2014-May 2016. Data collection tool, which was approved by HMC, was a researcher made extraction sheet that included information such as blood pressure during admission, socio demographic characteristics, delivery mode, and new born details. A total of 1929 patients’ files were identified by the hospital information management when they apply codes of preeclampsia. Out of 1929 files, 878 had significant gestational hypertension without proteinuria, 365 had preeclampsia, 364 had severe preeclampsia, and 188 had preexisting hypertension with superimposed proteinuria. In this study, 78% of the data was obtained by hospital electronic system (Cerner) and the remaining 22% was from patient’s paper records. We have gone through detail data extraction from 560 files. Initial data analysis has revealed that 15.02% of pregnancies were complicated with preeclampsia from May 2014-May 2016. We have analyzed difference in the two different disease entities in the ethnicity, maternal age, severity of hypertension, mode of delivery and infant birth weight. We have identified promising differences in the risk factors of early onset and late onset preeclampsia. The data from clinical findings of preeclampsia will contribute to increased knowledge about two different disease entities, their etiology, and similarities/differences. The findings of this study can also be used in predicting health challenges, improving health care system, setting up guidelines, and providing the best care for women suffering from preeclampsia.

Keywords: preeclampsia, incidence, risk factors, maternal

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Authors: Fangfang Wang, Tianjing Wang, Leyi Fu, Feng Yun, Ningning Xie, Jue Zhou, Fan Qu

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Background: Ferroptosis, a recently discovered form of programmed cell death characterized by iron-dependent lipid peroxidation, may be linked to polycystic ovary syndrome (PCOS). Diseases marked by iron overload have been correlated with ferroptosis. Coincidently, investigations have revealed anomalies in iron metabolism among women with PCOS; however, there were inconsistencies in the evidence. Objective and Rationale: This review aimed to comprehensively explore the potential relationship between ferroptosis and PCOS by investigating the differences in iron metabolism among women with PCOS in comparison to a control group. Additionally, a narrative synthesis was provided on the past research status regarding the association between PCOS and ferroptosis. Methods: A systematic search of the literature was performed using PubMed, Embase, Web of Science from inception up to December 2022. Search terms relating to assisted PCOS, ferroptosis, and iron metabolism were used. PRISMA guidance was followed. RevMan 5.4 was utilized for conducting the meta-analysis, wherein the investigated outcomes included iron status (ferritin, iron, transferrin saturation) and a systemic iron-regulatory hormone (hepcidin). A narrative synthesis was performed to explore the correlation between PCOS and ferroptosis. Results: In the meta-analysis comprising a total of 16 studies, significant differences in serum ferritin levels between the PCOS group and the control group were observed (15 studies, standardized mean difference (SMD): 0.41, 95% CI: 0.22 to 0.59, P<0.01). This indicates elevated serum ferritin levels in PCOS patients compared to women without PCOS. The transferrin saturation in PCOS patients was significantly higher than that in the control group (3 studies, mean difference (MD): 4.39, 95% CI: 1.67 to 7.11, P<0.01). Regarding serum iron (6 studies, SMD: 0.05, 95% CI: -0.24 to 0.33, P=0.75) and serum hepcidin (4 studies, SMD: -0.44, 95% CI: -1.41 to 0.52, P=0.37), no statistically significant differences were observed between the PCOS group and the control group. Other studies have found that ferroptosis is involved in the occurrence and development of PCOS, offering valuable insights for guiding potential treatment measures and prognosis evaluation of PCOS. In addition, ferroptosis is involved in the miscarriage of PCOS-like rats; thus, controlling ferroptosis might improve pregnancy outcomes in PCOS. Conclusions: The observation of a significant elevation in serum ferritin and transferrin saturation levels in women with PCOS may suggest an underlying disturbance in iron metabolism, potentially inducing the activation of ferroptosis. Further research is imperative to elucidate the underlying pathophysiology, providing insights for potential preventive measures and therapeutic strategies. Limitation: There are some limitations as follows: First, due to limited extractable information, we excluded purely abstract publications and non-English publications. Second, the majority of original articles were case-control studies, making it difficult to determine the causal relationship between iron metabolism abnormalities and the onset of PCOS. Third, there is substantial heterogeneity in the definition of PCOS.

Keywords: polycystic ovary syndrome, ferroptosis, iron metabolism, systematic review and meta-analysis

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Authors: Shradha Parsekar, Suma Nair, Ajay Bailey, Binu V. S.

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Background: Concealing of cancer-related information is seen in many low-and-middle-income countries and may be associated with multiple factors. Comparatively, there is lack of information about, how breast cancers diagnosed women disclose cancer-related information to their social contacts and vice versa. To get more insights on the participant’s experience, opinions, expectations, and attitudes, a qualitative study is a suitable approach. Therefore, this study involving in-depth interviews was planned to lessen this gap. Methods: Interviews were conducted separately among breast cancer patients and their caregivers with semi-structured qualitative interview guide. Purposive and convenient sampling was being used to recruit patients and caregivers, respectively. Ethical clearance and permission from the tertiary hospital were obtained and participants were selected from the Udupi district, Karnataka, India. After obtaining a list of breast cancer diagnosed cases, participants were contacted in person and their willingness to take part in the study was taken. About 39 caregivers and 35 patients belonging to different breast cancer stages were recruited. Interviews were recorded with prior permission. Data was managed by Atlas.ti 8 software. The recordings were transcribed, translated and coded in two cycles. Most of the patients belonged to stage II and III cancer. Codes were grouped together into to whom breast cancer status was concealed to and underneath reason for the same. Main findings: followings are the codes and code families which emerged from the data. 1) Concealing the breast cancer status from social contacts other than close family members (such as extended family, neighbor and friends). Participants perceived the reasons as, a) to avoid questions which people probe (which doesn’t have answers), b) to avoid people paying courtesy visit (to inquire about the health as it is Indian culture to visit the sick person) making it inconvenient for patient and caregivers have to offer something and talk to them, c) to avoid people getting shocked (react as if cancer is different from other diseases) or getting emotional/sad, or getting fear of death d) to avoid getting negative suggestion or talking anything in front of patient as it may affect patient negatively, e) to avoid getting stigmatized, f) to avoid getting obstacle in child’s marriage. 2) Participant concealed the breast cancer status of young children as they perceived that it may a) affect studies, b) affect emotionally, c) children may get scared. 3) Concealing the breast cancer status from patients as the caregivers perceived that they have fear of a) worsening patient’s health, b) patient getting tensed, c) patient getting shocked, and d) patient getting scared. However, some participants stressed important in disclosing the cancer status to social contact/patient to make the people aware of the disease. Conclusion: The news of breast cancer spreads like electricity in the wire, therefore, patient or family avoid it for many reasons. Although, globally, due to physicians’ ethical obligations, there is an inclination towards more disclosure of cancer diagnosis and status of prognosis to the patient. However, it is an ongoing argument whether patient/social contacts should know the status especially in a country like India.

Keywords: breast cancer, concealing cancer status, India, qualitative study

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Authors: Andreas Stollwitzer, Lara Bettinelli, Josef Fink

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The expansion of the high-speed rail network over the past decades has resulted in new challenges for engineers, including traffic-induced resonance vibrations of railway bridges. Excessive resonance-induced speed-dependent accelerations of railway bridges during high-speed traffic can lead to negative consequences such as fatigue symptoms, distortion of the track, destabilisation of the ballast bed, and potentially even derailment. A realistic prognosis of bridge vibrations during high-speed traffic must not only rely on the right choice of an adequate calculation model for both bridge and train but first and foremost on the use of dynamic model parameters which reflect reality appropriately. However, comparisons between measured and calculated bridge vibrations are often characterised by considerable discrepancies, whereas dynamic calculations overestimate the actual responses and therefore lead to uneconomical results. This gap between measurement and calculation constitutes a complex research issue and can be traced to several causes. One major cause is found in the dynamic properties of the ballasted track, more specifically in the persisting, substantial uncertainties regarding the consideration of the ballasted track (mechanical model and input parameters) in dynamic calculations. Furthermore, the discrepancy is particularly pronounced concerning the damping values of the bridge, as conservative values have to be used in the calculations due to normative specifications and lack of knowledge. By using a large-scale test facility, the analysis of the dynamic behaviour of ballasted track has been a major research topic at the Institute of Structural Engineering/Steel Construction at TU Wien in recent years. This highly specialised test facility is designed for isolated research of the ballasted track's dynamic stiffness and damping properties – independent of the bearing structure. Several mechanical models for the ballasted track consisting of one or more continuous spring-damper elements were developed based on the knowledge gained. These mechanical models can subsequently be integrated into bridge models for dynamic calculations. Furthermore, based on measurements at the test facility, model-dependent stiffness and damping parameters were determined for these mechanical models. As a result, realistic mechanical models of the railway bridge with different levels of detail and sufficiently precise characteristic values are available for bridge engineers. Besides that, this contribution also presents another practical application of such a bridge model: Based on the bridge model, determination equations for the damping factor (as Lehr's damping factor) can be derived. This approach constitutes a first-time method that makes the damping factor of a railway bridge calculable. A comparison of this mathematical approach with measured dynamic parameters of existing railway bridges illustrates, on the one hand, the apparent deviation between normatively prescribed and in-situ measured damping factors. On the other hand, it is also shown that a new approach, which makes it possible to calculate the damping factor, provides results that are close to reality and thus raises potentials for minimising the discrepancy between measurement and calculation.

Keywords: ballasted track, bridge dynamics, damping, model design, railway bridges

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Authors: Irena Kostovska, Katerina Tosheska Trajkovska, Svetlana Cekovska, Julijana Brezovska Kavrakova, Hristina Ampova, Sonja Topuzovska, Ognen Kostovski, Goce Spasovski, Danica Labudovic

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Background: Proteinuria is an important feature of secondary nephropathies. The quantitative and qualitative analysis of proteinuria plays an important role in determining the types of proteinuria (glomerular, tubular and mixed), in the diagnosis and prognosis of secondary nephropathies. The damage of the glomerular basement membrane is responsible for a proteinuria characterized by the presence of large amounts of protein with high molecular weights such as albumin (69 kilo Daltons-kD), transferrin (78 kD) and immunoglobulin G (150 kD). An insufficiency of proximal tubular function is the cause of a proteinuria characterized by the presence of proteins with low molecular weight (LMW), such as retinol binding protein (21 kD) and α1-microglobulin (31 kD). In some renal diseases, a mixed glomerular and tubular proteinuria is frequently seen. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) is the most widely used method of analyzing urine proteins for clinical purposes. The main aim of the study is to determine the type of proteinuria in the most common secondary nephropathies such as diabetic, hypertensive nephropathy and preeclampsia. Material and methods: In this study were included 90 subjects: subjects with diabetic nephropathy (n=30), subjects with hypertensive nephropahty (n=30) and pregnant women with preeclampsia (n=30). We divided all subjects according to UM/CR into three subgroups: macroalbuminuric (UM/CR >300 mg/g), microalbuminuric (UM/CR 30-300 mg/g) and normolabuminuric (UM/CR<30 mg/g). In all subjects, we measured microalbumin and creatinine in urine with standard biochemical methods. Separation of urinary proteins was performed by SDS-PAGE, in several stages: linear gel preparation (4-22%), treatment of urinary samples before their application on the gel, electrophoresis, gel fixation, coloring with Coomassie blue, and identification of the separated protein fractions based on standards with exactly known molecular weight. Results: According to urinary microalbumin/creatinin ratio in group of subject with diabetic nephropathy, nine patients were macroalbuminuric, while 21 subject were microalbuminuric. In group of subjects with hypertensive nephropathy, we found macroalbuminuria (n=4), microalbuminuria (n=20) and normoalbuminuria (n=6). All pregnant women with preeclampsia were macroalbuminuric. Electrophoretic separation of urinary proteins showed that in macroalbuminric patients with diabetic nephropathy 56% have mixed proteinuria, 22% have glomerular proteinuria and 22% have tubular proteinuria. In subgroup of subjects with diabetic nephropathy and microalbuminuria, 52% have glomerular proteinuria, 8% have tubular proteinuria, and 40% of subjects have normal electrophoretic findings. All patients with maroalbuminuria and hypertensive nephropathy have mixed proteinuria. In subgroup of patients with microalbuminuria and hypertensive nephropathy, we found: 32% with mixed proteinuria, 27% with normal findings, 23% with tubular, and 18% with glomerular proteinuria. In all normoalbuminruic patiens with hypertensive nephropathy, we detected normal electrophoretic findings. In group of subjects pregnant women with preeclampsia, we found: 81% with mixed proteinuria, 13% with glomerular, and 8% with tubular proteinuria. Conclusion: By SDS PAGE method, we detected that in patients with secondary nephropathies the most common type of proteinuria is mixed proteinuria, indicating both loss of glomerular permeability and tubular function. We can conclude that SDS PAGE is high sensitive method for detection of renal impairment in patients with secondary nephropathies.

Keywords: diabetic nephropathy, preeclampsia, hypertensive nephropathy, SDS PAGE

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Authors: Sthanu Mahadev, Wen Chan, Melanie Lim

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Anisotropy dominated continuous-fiber composite materials have garnered attention in numerous mechanical and aerospace structural applications. Tailored mechanical properties in advanced composites can exhibit superiority in terms of stiffness-to-weight ratio, strength-to-weight ratio, low-density characteristics, coupled with significant improvements in fatigue resistance as opposed to metal structure counterparts. Extensive research has demonstrated their core potential as more than just mere lightweight substitutes to conventional materials. Prior work done by Mahadev and Chan focused on formulating a modified composite shell theory based prognosis methodology for investigating the structural response of thin-walled circular cylindrical shell type composite configurations under in-plane mechanical loads respectively. The prime motivation to develop this theory stemmed from its capability to generate simple yet accurate closed-form analytical results that can efficiently characterize circular composite shell construction. It showcased the development of a novel mathematical framework to analytically identify the location of the centroid for thin-walled, open cross-section, curved composite shells that were characterized by circumferential arc angle, thickness-to-mean radius ratio, and total laminate thickness. Ply stress variations for curved cylindrical shells were analytically examined under the application of centric tensile and bending loading. This work presents a cost-effective, small-platform experimental methodology by taking advantage of the full-field measurement capability of digital image correlation (DIC) for an accurate assessment of key mechanical parameters such as in-plane mechanical stresses and strains, centroid location etc. Mechanical property measurement of advanced composite materials can become challenging due to their anisotropy and complex failure mechanisms. Full-field displacement measurements are well suited for characterizing the mechanical properties of composite materials because of the complexity of their deformation. This work encompasses the fabrication of a set of curved cylindrical shell coupons, the design and development of a novel test-fixture design and an innovative experimental methodology that demonstrates the capability to very accurately predict the location of centroid in such curved composite cylindrical strips via employing a DIC based strain measurement technique. Error percentage difference between experimental centroid measurements and previously estimated analytical centroid results are observed to be in good agreement. The developed analytical modified-shell theory provides the capability to understand the fundamental behavior of thin-walled cylindrical shells and offers the potential to generate novel avenues to understand the physics of such structures at a laminate level.

Keywords: anisotropy, composites, curved cylindrical shells, digital image correlation

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Miroslava Cuperlovic-Culf, Lipu Wang, Ketty Boyle, Nadine Makley, Ian Burton, Anissa Belkaid, Mohamed Touaibia, Marc E. Surrette

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Metabolic changes are one of the major factors in the development of a variety of diseases in various species. Metabolism of agricultural plants is altered the following infection with pathogens sometimes contributing to resistance. At the same time, pathogens use metabolites for infection and progression. In humans, metabolism is a hallmark of cancer development for example. Quantified metabolomics data combined with other omics or clinical data and analyzed using various unsupervised and supervised methods can lead to better diagnosis and prognosis. It can also provide information about resistance as well as contribute knowledge of compounds significant for disease progression or prevention. In this work, different methods for metabolomics quantification and analysis from Nuclear Magnetic Resonance (NMR) measurements that are used for investigation of disease development in wheat and human cells will be presented. One-dimensional 1H NMR spectra are used extensively for metabolic profiling due to their high reliability, wide range of applicability, speed, trivial sample preparation and low cost. This presentation will describe a new method for metabolite quantification from NMR data that combines alignment of spectra of standards to sample spectra followed by multivariate linear regression optimization of spectra of assigned metabolites to samples’ spectra. Several different alignment methods were tested and multivariate linear regression result has been compared with other quantification methods. Quantified metabolomics data can be analyzed in the variety of ways and we will present different clustering methods used for phenotype determination, network analysis providing knowledge about the relationships between metabolites through metabolic network as well as biomarker selection providing novel markers. These analysis methods have been utilized for the investigation of fusarium head blight resistance in wheat cultivars as well as analysis of the effect of estrogen receptor and carbonic anhydrase activation and inhibition on breast cancer cell metabolism. Metabolic changes in spikelet’s of wheat cultivars FL62R1, Stettler, MuchMore and Sumai3 following fusarium graminearum infection were explored. Extensive 1D 1H and 2D NMR measurements provided information for detailed metabolite assignment and quantification leading to possible metabolic markers discriminating resistance level in wheat subtypes. Quantification data is compared to results obtained using other published methods. Fusarium infection induced metabolic changes in different wheat varieties are discussed in the context of metabolic network and resistance. Quantitative metabolomics has been used for the investigation of the effect of targeted enzyme inhibition in cancer. In this work, the effect of 17 β -estradiol and ferulic acid on metabolism of ER+ breast cancer cells has been compared to their effect on ER- control cells. The effect of the inhibitors of carbonic anhydrase on the observed metabolic changes resulting from ER activation has also been determined. Metabolic profiles were studied using 1D and 2D metabolomic NMR experiments, combined with the identification and quantification of metabolites, and the annotation of the results is provided in the context of biochemical pathways.

Keywords: metabolic biomarkers, metabolic network, metabolomics, multivariate linear regression, NMR quantification, quantified metabolomics, spectral alignment

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Authors: Meenakshi Barsaul Chauhan, Aastha Chauhan, Shilpa Hurmade, Rajeev Sen, Jyotsna Sen, Monika Dalal

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Introduction: Ovarian masses are common forms of neoplasm in women and represent 2/3rd of gynaecological malignancies. A pre-operative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic mass to a gynecological oncologist for appropriate therapy and optimized treatment, which can improve survival. In the younger age group preoperative differentiation into benign or malignant pathology can decide for conservative or radical surgery. Imaging modalities have a definite role in establishing the diagnosis. By using International Ovarian Tumor Analysis (IOTA) classification with sonography, costly radiological methods like Magnetic Resonance Imaging (MRI) / computed tomography (CT) scan can be reduced, especially in developing countries like India. Thus, this study is being undertaken to evaluate the role of clinical methods and sonography for diagnosis of the nature of the ovarian tumor. Material And Methods: This prospective observational study was conducted on 40 patients presenting with ovarian masses, in the Department of Obstetrics and Gynaecology, at a tertiary care center in northern India. Functional cysts were excluded. Ultrasonography and color Doppler were performed on all the cases.IOTA rules were applied, which take into account locularity, size, presence of solid components, acoustic shadow, dopper flow etc . Magnetic Resonance Imaging (MRI) / computed tomography (CT) scans abdomen and pelvis were done in cases where sonography was inconclusive. In inoperable cases, Fine needle aspiration cytology (FNAC) was done. The histopathology report after surgery and cytology report after FNAC was correlated statistically with the pre-operative diagnosis made clinically and sonographically using IOTA rules. Statistical Analysis: Descriptive measures were analyzed by using mean and standard deviation and the Student t-test was applied and the proportion was analyzed by applying the chi-square test. Inferential measures were analyzed by sensitivity, specificity, negative predictive value, and positive predictive value. Results: Provisional diagnosis of the benign tumor was made in 16(42.5%) and of the malignant tumor was made in 24(57.5%) patients on the basis of clinical findings. With IOTA simple rules on sonography, 15(37.5%) were found to be benign, while 23 (57.5%) were found to be malignant and findings were inconclusive in 2 patients (5%). FNAC/Histopathology reported that benign ovarian tumors were 14 (35%) and 26(65%) were malignant, which was taken as the gold standard. The clinical finding alone was found to have a sensitivity of 66.6% and a specificity of 90.9%. USG alone had a sensitivity of 86% and a specificity of 80%. When clinical findings and IOTA simple rules of sonography were combined (excluding inconclusive masses), the sensitivity and specificity were 83.3% and 92.3%, respectively. While including inconclusive masses, sensitivity came out to be 91.6% and specificity was 89.2. Conclusion: IOTA's simple sonography rules are highly sensitive and specific in the prediction of ovarian malignancy and also easy to use and easily reproducible. Thus, combining clinical examination with USG will help in the better management of patients in terms of time, cost and better prognosis. This will also avoid the need for costlier modalities like CT, and MRI.

Keywords: benign, international ovarian tumor analysis classification, malignant, ovarian tumours, sonography

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Authors: Pedro Felgueiras, Ana Miguel, Nélson Almeida, Raquel Silva

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Objective: Through the study of a clinical case of delusional somatic disorder secondary to phantogeusia, we aim to highlight the importance of considering psychosomatic conditions in differential diagnosis, as well as to emphasize the complexity of its comprehension, treatment, and respective impact on patients’ functioning. Methods: Bearing this in mind, we conducted a critical analysis of a case series based on patient observations, clinical data, and complementary diagnostic methods, as well as a non-systematic review of the literature on the subject. Results: A 61-year-old female patient with no history of psychiatric conditions. Family psychiatric history of mood disorder (depression), with psychotic features found in her mother. Medical history of many comorbidities affecting different organ systems (endocrine, gastrointestinal, genitourinary, ophthalmological). Documented neuroticism traits of personality. The patient’s family described a persistent concern about several physical symptoms across her life, with a continuous effort to obtain explanations about any sensation out of her normal perception. Since being subjected to endoscopy in 2018, she started complaints of persistent phantogeusia (acid taste) and developed excessive thoughts, feelings, and behaviors associated with this somatic symptom. The patient was evaluated by several medical specialties, and an extensive panel of medical exams was carried out, excluding any disease. Besides all the investigation and with no evidence of disease signs, acute anxiety, time, and energy dispended to this symptom culminated in severe psychosocial impairment. The patient was admitted to a psychiatric ward for investigation and treatment of this clinical picture, leading to the diagnosis of the delusional somatic disorder. In order to exclude the acute organic etiology of this psychotic disorder, an analytic panel was carried out with no abnormal results. In the context of a psychotic clinical picture, a CT scan was performed, which revealed a right cortical vascular lesion. Neuropsychological evaluation was made, with the description of cognitive functioning being globally normative. During treatment with an antipsychotic (pimozide), a complete remission of the somatic delusion was associated with the disappearance of gustative perception disturbance. In follow-up, a relapse of gustative sensation was documented, and her thoughts and speech were dominated by concerns about multiple somatic symptoms. Conclusion: In terms of abnormal bodily sensations, the oral cavity is one of the frequent sites of delusional disorder. Patients with these gustatory perception distortions complain about unusual sensations without corresponding abnormal findings in the oral area. Its pathophysiology has not been fully elucidated yet. In terms of its comprehensive psychopathology, this case was hypothesized as a paranoid development of a delusional somatic disorder triggered by a post-invasive procedure phantogeusia (which is described as a possible side effect of an endoscopy) in a patient with an anankastic personality. This case presents interesting psychopathology, reinforcing the complexity of psychosomatic disorders in terms of their etiopathogenesis, clinical treatment, and long-term prognosis.

Keywords: psychosomatics, delusional somatic disorder, phantogeusia, paranoid development

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Authors: R. Pardo, P. Menendez, MA Gil-Olarte, S. Sanchez, E. García, R. Quintana, J. Martín

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Introduction : Within oncoplastic breast techniques there is increased interest in immediate partial breast reconstruction. The volume resected is greater than that of conventional conservative techniques. Central tumours of the breast have classically been treated with a mastectomy with regard to oncological safety and cosmetic secondary effects after wide central resection of the nipple and breast tissue beneath. Oncological results for central quadrantectomy have a recurrence level, disease- free period and survival identical to mastectomy. Grissoti flap is an oncoplastic surgical technique that allows the surgeon to perform a safe central quadrantectomy with excellent cosmetic results. Material and methods: The Grissoti flap is a glandular cutaneous advancement rotation flap that can fill the defect in the central portion of the excised breast. If the inferior border is affected by tumour and further surgery is decided upon at the Multidisciplinary Team Meeting, it will be necessary to perform a mastectomy. All patients with a Grisotti flap undergoing surgery since 2009 were reviewed obtaining the following data: age, hystopathological diagnosis, size, operating time, volume of tissue resected, postoperative admission time, re-excisions due to positive margins affected by tumour, wound dehiscence, complications and recurrence. Analysis and results of sentinel node biopsy were also obtained. Results: 12 patients underwent surgery between 2009-2015. The mean age was 54 years (34-67) . All had a preoperative diagnosis of ductal infiltrative carcinoma of less than 2 cm,. Diagnosis was made with Ultrasound, Mamography or both . Magnetic resonance was used in 5 cases. No patients had preoperative positive axilla after ultrasound exploration. Mean operating time was 104 minutes (84-130). Postoperative stay was 24 hours. Mean volume resected was 159 cc (70-286). In one patient the surgical border was affected by tumour and a further procedure with resection of the affected border was performed as ambulatory surgery. The sentinel node biopsy was positive for micrometastasis in only two cases. In one case lymphadenectomy was performed in 2009. In the other, treated in 2015, no lymphadenectomy was performed as the patient had a favourable histopathological prognosis and the multidisciplinary team meeting agreed that lymphadenectomy was not required. No recurrence has been diagnosed in any of the patients who underwent surgery and they are all disease free at present. Conclusions: Conservative surgery for retroareolar central tumours of the breast results in good local control of the disease with free surgical borders, including resection of the nipple areola complex and pectoral major muscle fascia. Reconstructive surgery with the inferior Grissoti flap adequately fills the defect after central quadrantectomy with creation of a new cutaneous disc where a new nipple areola complex is reconstructed with a local flap or micropigmentation. This avoids the need for contralateral symmetrization. Sentinel Node biopsy can be performed without added morbidity. When feasible, the Grissoti flap will avoid skin-sparing mastectomy for central breast tumours that will require the use of an expander, prosthesis or myocutaneous flap, with all the complications of a more complex operation.

Keywords: Grisotti flap, oncoplastic surgery, central tumours, breast

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Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

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Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

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Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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Authors: V. Saccà, A. Sarica, F. Novellino, S. Barone, T. Tallarico, E. Filippelli, A. Granata, P. Valentino, A. Quattrone

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The work aim was to evaluate how well Random Forest (RF) and Support Vector Machine (SVM) algorithms could support the early diagnosis of Multiple Sclerosis (MS) from resting-state functional connectivity data. In particular, we wanted to explore the ability in distinguishing between controls and patients of mean signals extracted from ICA components corresponding to 15 well-known networks. Eighteen patients with early-MS (mean-age 37.42±8.11, 9 females) were recruited according to McDonald and Polman, and matched for demographic variables with 19 healthy controls (mean-age 37.55±14.76, 10 females). MRI was acquired by a 3T scanner with 8-channel head coil: (a)whole-brain T1-weighted; (b)conventional T2-weighted; (c)resting-state functional MRI (rsFMRI), 200 volumes. Estimated total lesion load (ml) and number of lesions were calculated using LST-toolbox from the corrected T1 and FLAIR. All rsFMRIs were pre-processed using tools from the FMRIB's Software Library as follows: (1) discarding of the first 5 volumes to remove T1 equilibrium effects, (2) skull-stripping of images, (3) motion and slice-time correction, (4) denoising with high-pass temporal filter (128s), (5) spatial smoothing with a Gaussian kernel of FWHM 8mm. No statistical significant differences (t-test, p < 0.05) were found between the two groups in the mean Euclidian distance and the mean Euler angle. WM and CSF signal together with 6 motion parameters were regressed out from the time series. We applied an independent component analysis (ICA) with the GIFT-toolbox using the Infomax approach with number of components=21. Fifteen mean components were visually identified by two experts. The resulting z-score maps were thresholded and binarized to extract the mean signal of the 15 networks for each subject. Statistical and machine learning analysis were then conducted on this dataset composed of 37 rows (subjects) and 15 features (mean signal in the network) with R language. The dataset was randomly splitted into training (75%) and test sets and two different classifiers were trained: RF and RBF-SVM. We used the intrinsic feature selection of RF, based on the Gini index, and recursive feature elimination (rfe) for the SVM, to obtain a rank of the most predictive variables. Thus, we built two new classifiers only on the most important features and we evaluated the accuracies (with and without feature selection) on test-set. The classifiers, trained on all the features, showed very poor accuracies on training (RF:58.62%, SVM:65.52%) and test sets (RF:62.5%, SVM:50%). Interestingly, when feature selection by RF and rfe-SVM were performed, the most important variable was the sensori-motor network I in both cases. Indeed, with only this network, RF and SVM classifiers reached an accuracy of 87.5% on test-set. More interestingly, the only misclassified patient resulted to have the lowest value of lesion volume. We showed that, with two different classification algorithms and feature selection approaches, the best discriminant network between controls and early MS, was the sensori-motor I. Similar importance values were obtained for the sensori-motor II, cerebellum and working memory networks. These findings, in according to the early manifestation of motor/sensorial deficits in MS, could represent an encouraging step toward the translation to the clinical diagnosis and prognosis.

Keywords: feature selection, machine learning, multiple sclerosis, random forest, support vector machine

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Authors: Chandu Rathnayake, Isuri Anuradha

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Early detection and accurate diagnosis of lung diseases play a crucial role in improving patient prognosis. However, conventional diagnostic methods heavily rely on subjective symptom assessments and medical imaging, often causing delays in diagnosis and treatment. To overcome this challenge, we propose a novel lung disease prediction system that integrates patient symptoms and X-ray images to provide a comprehensive and reliable diagnosis.In this project, develop a mobile application specifically designed for detecting lung diseases. Our application leverages both patient symptoms and X-ray images to facilitate diagnosis. By combining these two sources of information, our application delivers a more accurate and comprehensive assessment of the patient's condition, minimizing the risk of misdiagnosis. Our primary aim is to create a user-friendly and accessible tool, particularly important given the current circumstances where many patients face limitations in visiting healthcare facilities. To achieve this, we employ several state-of-the-art algorithms. Firstly, the Decision Tree algorithm is utilized for efficient symptom-based classification. It analyzes patient symptoms and creates a tree-like model to predict the presence of specific lung diseases. Secondly, we employ the Random Forest algorithm, which enhances predictive power by aggregating multiple decision trees. This ensemble technique improves the accuracy and robustness of the diagnosis. Furthermore, we incorporate a deep learning model using Convolutional Neural Network (CNN) with the RestNet50 pre-trained model. CNNs are well-suited for image analysis and feature extraction. By training CNN on a large dataset of X-ray images, it learns to identify patterns and features indicative of lung diseases. The RestNet50 architecture, known for its excellent performance in image recognition tasks, enhances the efficiency and accuracy of our deep learning model. By combining the outputs of the decision tree-based algorithms and the deep learning model, our mobile application generates a comprehensive lung disease prediction. The application provides users with an intuitive interface to input their symptoms and upload X-ray images for analysis. The prediction generated by the system offers valuable insights into the likelihood of various lung diseases, enabling individuals to take appropriate actions and seek timely medical attention. Our proposed mobile application has significant potential to address the rising prevalence of lung diseases, particularly among young individuals with smoking addictions. By providing a quick and user-friendly approach to assessing lung health, our application empowers individuals to monitor their well-being conveniently. This solution also offers immense value in the context of limited access to healthcare facilities, enabling timely detection and intervention. In conclusion, our research presents a comprehensive lung disease prediction system that combines patient symptoms and X-ray images using advanced algorithms. By developing a mobile application, we provide an accessible tool for individuals to assess their lung health conveniently. This solution has the potential to make a significant impact on the early detection and management of lung diseases, benefiting both patients and healthcare providers.

Keywords: CNN, random forest, decision tree, machine learning, deep learning

Procedia PDF Downloads 51

Authors: Areti Okalidou, Paul D. Hatzigiannakoglou, Aikaterini Vatou, George Kyriafinis

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Young children are nowadays adept at using technology. Hence, computer-based auditory training programs (CBATPs) have become increasingly popular in aural rehabilitation for children with hearing loss and/or with cochlear implants (CI). Yet, their clinical utility for prognostic, diagnostic, and monitoring purposes has not been explored. The purposes of the study were: a) to develop an updated version of the auditory rehabilitation tool for Greek-speaking children with cochlear implants, b) to develop a database for behavioral responses, and c) to compare accuracy rates and reaction times in children differing in hearing status and other medical and demographic characteristics, in order to assess the tool’s clinical utility in prognosis, diagnosis, and progress monitoring. The updated version of the auditory rehabilitation tool was developed on a tablet, retaining the User-Centered Design approach and the elements of the Virtual Reality (VR) serious game. The visual stimuli were farm animals acting in simple game scenarios designed to trigger children’s responses to animal sounds, names, and relevant sentences. Based on an extended version of Erber’s auditory development model, the VR game consisted of six stages, i.e., sound detection, sound discrimination, word discrimination, identification, comprehension of words in a carrier phrase, and comprehension of sentences. A familiarization stage (learning) was set prior to the game. Children’s tactile responses were recorded as correct, false, or impulsive, following a child-dependent set up of a valid delay time after stimulus offset for valid responses. Reaction times were also recorded, and the database was in Εxcel format. The tablet version of the auditory rehabilitation tool was piloted in 22 preschool children with Νormal Ηearing (ΝΗ), which led to improvements. The study took place in clinical settings or at children’s homes. Fifteen children with CI, aged 5;7-12;3 years with post-implantation 0;11-5;1 years used the auditory rehabilitation tool. Eight children with CI were monolingual, two were bilingual and five had additional disabilities. The control groups consisted of 13 children with ΝΗ, aged 2;6-9;11 years. A comparison of both accuracy rates, as percent correct, and reaction times (in sec) was made at each stage, across hearing status, age, and also, within the CI group, based on presence of additional disability and bilingualism. Both monolingual Greek-speaking children with CI with no additional disabilities and hearing peers showed high accuracy rates at all stages, with performances falling above the 3rd quartile. However, children with normal hearing scored higher than the children with CI, especially in the detection and word discrimination tasks. The reaction time differences between the two groups decreased in language-based tasks. Results for children with CI with additional disability or bilingualism varied. Finally, older children scored higher than younger ones in both groups (CI, NH), but larger differences occurred in children with CI. The interactions between familiarization of the software, age, hearing status and demographic characteristics are discussed. Overall, the VR game is a promising tool for tracking the development of auditory skills, as it provides multi-level longitudinal empirical data. Acknowledgment: This work is part of a project that has received funding from the Research Committee of the University of Macedonia under the Basic Research 2020-21 funding programme.

Keywords: VR serious games, auditory rehabilitation, auditory training, children with cochlear implants

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Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

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Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

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Authors: Jia H. Wong, Jingli Zhang, Habsah Mohamad, Iswatun H. Abdullah Ripain, Muhammad Bilal, Amelia J. Lloyd, Abdul A. Mohamed Yusoff, Jafri M. Abdullah

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Epilepsy is one of the most common neurological diseases affecting more than 50 million of people worldwide. Epilepsy is a state of recurrent, spontaneous seizures with multiple syndromes and symptoms of different causes of brain dysfunction, prognosis, and treatments; characterized by transient, occasional and stereotyped interruptions of behavior whereby the excitatory-inhibitory activities within the central nervous system (CNS) are thrown out of balance due to various kinds of interferences. The goal of antiepileptic treatment is to enable patients to be free from seizures or to achieve control of seizures through surgical treatment and/or pharmacotherapy. Pharmacotherapy through AED plays an important role especially in countries with epilepsy treatment gap due to costs and availability of health facilities, skills and resources, yet there are about one-third of the people with epilepsy have drug-resistant seizures. Hence, this poses considerable challenges to the healthcare system and the effort in providing cost-effective treatment as well as the search for alternatives to treatment and management of epilepsy. Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission is one of the key mechanisms of actions of antiepileptic drugs. GABA type > a receptors (GABAAR) are ligand-gated ion channels that mediate rapid inhibitory neurotransmission upon the binding of GABA with a heteropentameric structure forming a central pore that is permeable to the influx of chloride ions in its activated state. The major isoform of GABAA receptors consists of two α1, two β2, and one γ2 subunit. It is the most abundantly expressed combinations in the brain and the most commonly researched through Xenopus laevis oocytes. With the advancing studies on ethnomedicine and traditional treatments using medicinal plants, increasing evidence reveal that spice and herb plants with medicinal properties play an important role in the treatment of ailments within communities across different cultures. Capsaicin is the primary natural capsaicinoid in hot peppers of plant genus Capsicum, consist of an aromatic ring, an amide linkage and a hydrophobic side chain. The study showed that capsaicins conferred neuroprotection in status epilepticus mouse models through anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic actions in a dose-dependent manner. In this study, five capsaicin derivatives were tested for their ability to increase the GABA-induced chloride current on α1β2γ2S of GABAAR expressed on Xenopus laevis oocytes using the method of two-microelectrode voltage clamp. Two of the capsaicin derivatives, IS5 (N-(4-hydroxy-3-methoxybenzyl)-3-methylbutyramide) and IS10 (N-(4-hydroxy-3-methoxybenzyl)-decanamide) at a concentration of 30µM were able to significantly increase the GABA-induced chloride current with p=0.002 and p=0.026 respectively. This study were able to show the enhancement effect of two capsaicin derivatives with moderate length of hydrocarbon chain on this receptor subtype, revealing the promising inhibitory activity of capsaicin derivatives through enhancement of GABA-induced chloride current and further investigations should be carried out to verify its antiepileptic effects in animal models.

Keywords: α1β2γ2 GABAA receptors, α1β2γ2S, antiepileptic, capsaicin derivatives, two-microelectrode voltage clamp, Xenopus laevis oocytes

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Authors: Hilary Modir, Kyle Dutton, Michelle Swab, Shabnam Asghari

Abstract:

Since its emergence, the cutaneous manifestations of COVID-19 have been documented in the literature. However, the majority are case reports with significant limitations in appraisal quality, thus leaving the role of dermatological manifestations of COVID-19 erroneously underexplored. The primary aim of this review was to systematically examine clinical patterns of dermatological manifestations as reported in the literature. This study was designed as a systematic review of case reports. The inclusion criteria consisted of all published reports and articles regarding COVID-19 in English, from September 1st, 2019, until June 22nd, 2020. The population consisted of confirmed cases of COVID-19 with associated cutaneous signs and symptoms. Exclusion criteria included research in planning stages, protocols, book reviews, news articles, review studies, and policy analyses. With the collaboration of a librarian, a search strategy was created consisting of a mixture of keyword terms and controlled vocabulary. Electronic databases searched were MEDLINE via PubMed, EMBASE, CINAHL, Web of Science, LILACS, PsycINFO, WHO Global Literature on Coronavirus Disease, Cochrane Library, Campbell Collaboration, Prospero, WHO International Clinical Trials Registry Platform, Australian and New Zealand Clinical Trials Registry, U.S. Institutes of Health Ongoing Trials Register, AAD Registry, OSF preprints, SSRN, MedRxiV and BioRxiV. The study selection featured an initial pre-screening of titles and abstracts by one independent reviewer. Results were verified by re-examining a random sample of 1% of excluded articles. Eligible studies progressed for full-text review by two calibrated independent reviewers. Covidence was used to store and extract data, such as citation information and findings pertaining to COVID-19 and cutaneous signs and symptoms. Data analysis and summarization methodology reflect the framework proposed by PRISMA and recommendations set out by Cochrane and Joanna Brigg’s Institute for conducting systematic reviews. The Oxford Centre for Evidence-Based Medicine’s level of evidence was used to appraise the quality of individual studies. The literature search revealed a total of 1221 articles. After the abstract and full-text screening, only 95 studies met the eligibility criteria, proceeding to data extraction. Studies were divided into 58% case reports and 42% series. A total of 833 manifestations were reported in 723 confirmed COVID-19 cases. The most frequent lesions were 23% maculopapular, 15% urticarial and 13% pseudo-chilblains, with 46% of lesions reporting pruritus, 16% erythema, 14% pain, 12% burning sensation, and 4% edema. The most common lesion locations were 20% trunk, 19.5% lower limbs, and 17.7% upper limbs. The time to resolution of lesions was between one and twenty-one days. In conclusion, over half of the reported cutaneous presentations in COVID-19 positive patients were maculopapular, urticarial and pseudo-chilblains, with the majority of lesions distributed to the extremities and trunk. As this review’s sample size only contained COVID-19 confirmed cases with skin presentations, it becomes difficult to deduce the direct relationship between skin findings and COVID-19. However, it can be correlated that acute onset of skin lesions, such as chilblains-like, may be associated with or may warrant consideration of COVID-19 as part of the differential diagnosis.

Keywords: COVID-19, cutaneous manifestations, cutaneous signs, general dermatology, medical dermatology, Sars-Cov-2, skin and infectious disease, skin findings, skin manifestations

Procedia PDF Downloads 156

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

Procedia PDF Downloads 361