World Academy of Science, Engineering and Technology

Authors: Mengesha Srahbzu Biresaw, József Vitrai, Péter Halás, Vivian Correa, Anna Szűcs

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Objective: To assess the adult Hungarian population’s knowledge about and attitude towards epilepsy and compare the present findings with previous ones in 1994 and 2000. Methods: We performed a cross-sectional survey of the Hungarian adult population from 28th February to 8th March 2023. A non-probability quota sampling with a random walk method was used. We applied the Computer-Assisted Personal Interviewing (CAPI) method and used a multi-criteria weighting procedure to correct for bias along the main socio-demographic variables. To detect changes over time, we used chi-square tests, and to analyze the effect of sociodemographic characteristics, we applied multivariate logistic regression. Results: One thousand participants (53.1% women, mean age 48.1 ±16.75 years) representing Hungary’s population were interviewed, yielding a response rate of 80.3%. 26.3% knew someone with epilepsy (55.9% in 1994 and 51.9% in 2000), and 30.8% saw an epileptic seizure (58% in 1994 and 55.3% in 2000). Compared to the young, fewer adults and elderly people knew someone with epilepsy or had seen a seizure. Alike in 1994 and 2000, 16.6% reported objection to their children’s interaction with people with epilepsy; however, in the present study, significantly fewer people opposed their children marrying or working together with epileptic people, indicating a change in attitude (P<0.0001). Rural residents had less objection to their children’s interaction with people with epilepsy (P<0.05). People with secondary education objected significantly more often than those with primary education to their children’s interaction (P=0.037) or marriage to people with epilepsy (P=0.043), or their having equal employment (P=0.008). Higher education people were as ‘permissive’ as those with primary education. Significance: Certain parameters of familiarity and attitude-markers of the Hungarian population towards epilepsy have improved. These tendencies are promising, but work is still needed; our results will hopefully evoke educational programs and campaigns against negative attitudes.

Keywords: attitude, knowledge, stigma, epilepsy, Hungary

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Authors: Anietie M. Archibong, Mfoniso I. Udonkang, Aniekan-Augusta O. Eyo, Dianabasi K. Udo

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Diabetes mellitus is a chronic disease marked by hyperglycaemia which often leads to several complications despite treatment with orthodox medicines. Medicinal plants have been shown to have anti-diabetic properties. The study aimed to investigate the effect of aqueous crude leaf extract of Sterculia tragacantha on the pancreas of Alloxan-induced diabetic Sprague dawley rats. Sixty-two male rats (150-180g weight) were used. The mean lethal dose (LD50) was determined with 32 rats using Lorke’s method. Thirty rats comprising six groups of five animals each: Group I (negative control), Group II (Alloxan-induced-diabetic-non-treated), Group III (diabetic-5mg/kg/day Glabenclamide-treated), Group IV (diabetic low dose 44.72 mg/kg), Group V (diabetic given medium dose 89.44 mg/kg), and Group VI (diabetic given high dose 134.16 mg/kg) of extract were given for 14 days orally. The fasting blood sugar levels were measured at baseline, 24/72 hours, and 7/14 days. Formalin-fixed-paraffin wax-embedded pancreases were stained with haematoxylin and eosin, Masson trichrome, and anti-insulin antibody. The LD50 was 447.21 mg/kg. The body weights (p=0.511) and pancreas weights (p=0.103) were not affected by the extract. The extract decreased the fasting blood glucose levels on day 7 (p=0.015) and day 14 (p=0.001). The pancreas in Group I and IV were normal. Groups II, III, and V had hypertrophied islets, while VI had atrophied islets with fibrosis. Group III had scanty beta cells. Aqueous leaf extract of Sterculia tragacantha had moderate toxicity, anti-diabetic properties, and minimal pathological effect on the pancreas. The low dose of the extract is safer for administration.

Keywords: Alloxan, Diabetes mellitus, pancreatic beta cells, Sterculia tragacantha

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Authors: Swapnali Sadhale, Ankita Mehendale, Jincy Rajan, Subhasis Banerji

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Research Objectives: Brain-computer interfaces are being tested in different rehabilitation setups to train cognition or to help trigger neurostimulation, robotic movement of a limb or electrical stimulation of muscle. However, we find that translation to physical recovery is limited to gross joint movement with no resolution of behavioural compensation in the brain and muscle, making co-ordinated movements, and hence independent living, difficult. The objectives of this research is to use an integrated brain-muscle-computer interface to restore cognitive and physical function in one wearable system. The EEG and EMG wearables are used to observe in real-time the instantaneous brain-muscle responses of the patient while he/she attempts to do a movement or a task. Methodology used in Research: The synergistic brain-muscle platform, Synphne, consists of a Headgear (8-channel EEG capture device) and Arm Gear (8-channel EMG capture device) and a computer software that provides integrated, real-time feedback while running video-led instructions of various movements and tasks that a patient needs to watch and attempt to follow. Subjects with severe, moderate and mild disability were recruited as case studies. All had undergone prior neurorehabilitation with limited progress in grasping ability. A task such as writing with a pen was chosen as it is highly valued by patients who have lost this ability. Writing involves an integrated execution of cognitive ability (short-term memory, sequential planning, executive function) and fine motor skill, midline crossing and trunk stability. This task was to be attempted by the stroke-affected dominant arm on which the EMG wearable was worn. The qualifying criteria were: the inability to grasp a pen with a two-finger pinch with the affected dominant hand, a minimum 10% active flexion and extension movement in fingers, 50% pain-free passive range of motion of the fingers, wrist and elbow, ability to sit for 10 min at a time and respond to instructions from a computer screen supported by a video demonstrating the task. The routine started with simple grasping and transfer training with a pen of larger diameter that was comfortable for the subject while maintaining a stable, relaxed focus in the brain state, as shown in the EEG feedback. This was to be integrated with correct muscle firing in finger flexion muscles and the stabilization of the elbow and wrist through the EMG feedback. This was followed by a simple drawing task maintaining the same brain state and relaxed antagonist muscles in the writing arm. Once the arm stabilised in drawing, the subject was introduced to writing alphabets and numbers first on tracing and then without. Main Contributions of this Research: In conventional and tech-assisted rehabilitation, the biggest challenge is the return to independent living. Recovery of fine motor skills, which are critical to independent living, remains elusive to a large segment of the stroke population. We find that the integrated training of cognition and physical function is crucial to regaining this. This novel approach shows promise in helping close that gap.

Keywords: stroke, neurorehabilitation, brain, wearables

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Authors: Sergey V. Sazonov, Anna S. Mogilenskikh, Svetlana S. Deryabina, Denis A. Demidov, Sergey M. Demidov

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The majority of breast cancer (BC) cases are estrogen receptor (ER) positive, and the most common among surrogate molecular biological subtypes is Luminal A. Despite ongoing treatment, drug resistance occurs in a significant proportion of patients, leading to disease recurrence. To determine the sensitivity of a particular tumor to therapy, it is necessary to create an in vitro model, which could then serve as a basis for the selection of personalized therapy for breast cancer. The aim is to evaluate the molecular genetic profile of tumor cells from primary cultures of the Luminal A subtype of breast cancer as a potential model for assessing resistance to therapy. Materials and methods: Primary cell cultures were obtained from a surgical sample in patients with Luminal A subtype of breast cancer when the following inclusion criteria were met: absence of previous therapy and availability of voluntary informed consent. The subtype was determined using the IHC method. Growth was maintained in a serum-free Mammocult™ environment (STEMCELL, Canada). The culture was passed after 7-10 days (p1-p5), and flow cytometry was performed on a Beckman Coulter cytometer (USA) at each passage. Antibodies to estrogen (Alexa Fluor® 647, SP1, Abcam, Canada) to HER2 (24D2, Brilliant Violet 421™, Biolegend, USA) were used for evaluation, and at least 5,000 events were analyzed.). NGS testing was performed on the same cells (Prep&Seq™ U-panel BCEv1, 63 genes). Results: Luminal A subtype includes cases with a Ki-67 threshold of less than 10% of tumor cell nuclei, no HER2 expression (level 0 to 1 points), lack of amplification of the HER2 gene, and high estrogen and/or progesterone levels. The median for RE expression was 66.5% (IQR 7.1) from p1 to p5, and this index didn´t change significantly throughout culture (p<0.001). The presence of Her2 oncoprotein was detected in 5.0% across all passages (IQR 5.2). The data obtained are consistent with the characteristics of the Luminal A subtype. NGS testing detected mutations in genes associated with breast cancer: BARD1, BRCA2, BRIP1, CASP8, CCNE1, CDH1, KEAP1, MSH3, NF1, PALB2, RAD51D, RECQL5, TP53 ZNF217, as well as in genes associated with the Luminal A subtype: PIK3CA, MAP3KI, ESR1. At all passages are detected in the MAP3K1 gene, 7 mutations (3 missenses, 3 synonymous, 1 in-frame) except p2 and p5. A mutation in 1 exon (synonymous) is added at p2 and p5, while no changes are detected in the other genes. Conclusion: Primary cell cultures during the five passages can preserve the expression of RE and the composition of mutations in genes and can be used as an in vitro model. The combination of mutation in ESR1 and MAP3K gene is a potential factor of acquired resistance to therapy in patients with Luminal A breast cancer.

Keywords: breast cancer, Luminal A subtype, primary cell culture, HER2 receptors, estrogen receptors, MAP3K1 gene, ESR1 gene

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Authors: Ling Yin

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NLRP3 inflammasome-mediated signal initiation, transduction, integration, and perception is activated in multiple cancers by pro-tumorigenic and anti-tumorigenic roles. The blockade of NLRP3 inflammasome and the induction of inflammatory response by SARS-COV-2 leads to the direct inhibition of cytokine products. NLRP3-mediated neuroinflammation contribute to the pathogenesis of neurodegenerative diseases. Therefore, inhibitors directly targeting the NLRP3 inflammasome in cancer, COVID, and neurodegenerative disease, are worth investigating further in clinical trials and drug discovery. Nuclear receptors (NR) are transcription factors that play vital roles in multiple biological processes, such as growth, development, metabolism, reproduction, and inflammation. Adeno-associated virus (AAV) is an appealing and leading gene therapy viral vector candidate for treating a variety of diseases, such as cancer, retinal diseases, blood diseases, and neurodegenerative diseases. MicroRNAs (miRNAs) play a pivotal role in the pathogenesis of chronic inflammatory diseases, such as Alzheimer's disease, atherosclerosis, and multiple sclerosis. Consequently, combined therapy of NLRP3 with NR, AAV and miRNAs will lead to the development of novel preventions and therapeutics.

Keywords: NLRP3 inflammasome, cancer, COVID, neurodegenerative diseases, personalized therapy

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Authors: Nagaveni Hegde, Priya Sharma, Anitha M.

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A vital network of two-way communication between the central nervous system (CNS) and the gastrointestinal tract, the gut-brain axis has a major impact on both health and illness. This axis revolves around the gut microbiota, a complex ecology of microbes that is essential for controlling brain activity and influencing mood, cognitive activities, and pain perception. Chronic pain and neuroinflammation are caused by microglia, the CNS's resident macrophages, which are impacted by signals from the stomach and the central nervous system. Mechanisms including immune system modulation, vagus nerve pathways, neurotransmitter modulation, and microbial metabolites further mediate this interaction. Numerous neurological problems, such as mood disorders (depression, bipolar disorder), neurodevelopmental issues (schizophrenia, autism), and neurodegenerative diseases, have been linked to dysbiosis, an imbalance in the gut microbiota. The mechanics of gut-brain communication, the factors influencing the composition of the gut microbiome, and the effects of dysbiosis on neurological health are all examined in this review. Furthermore, we discuss state-of-the-art developments in microbiome research that present promising paths for the creation of new treatments for neurological and psychiatric disorders, including microbial profiling, microbiota transplantation, and tailored therapeutics. Knowing how the stomach and brain interact dynamically creates new opportunities for tailored microbiome-based therapies that improve mental health and wellbeing.

Keywords: gut-brain axis, microbiota, dysbiosis, neurological disorders, microglia

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Authors: Ahlam Azalmad, Younes Elmaadaoui, Mohamed Hilal

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Background: This study highlights the impact of optimizing target margins by minimizing setup errors in cervical cancer radiotherapy through electronic portal imaging device, aiming to improve treatment accuracy and patient outcomes. These findings are crucial for refining treatment protocols and enhancing the safety and effectiveness of radiation oncology practices. As a groundbreaking initiative within our department, this work marks a major advancement in treatment optimization and will be disseminated to other radiotherapy centers, encouraging the adoption of consistent and improved radiotherapy practices. Materials and Methods: The study involved 20 cervical cancer patients treated between January 30 and September 30, 2024, using knee and foot fixed supports for immobilization. Treatment setups were verified with electronic portal imaging and delivered via an Elekta linear accelerator to enhance radiotherapy precision. Displacement analysis used bony landmarks to assess setup errors, guiding the calculation of safety margins based on ICRU-62 guidelines and Stroom's and Van Herk's formulas. Results: The study revealed systematic errors of up to 0.22 cm and random errors of 0.74 cm along the X-axis, 0.2 cm and 0.08 cm along the Y-axis, and 0.18 cm and 0.08 cm along the Z-axis. Based on these findings, the calculated CTV-PTV margins for the X, Y, and Z axes were 0.61 cm, 0.57 cm, and 0.51 cm, respectively, using Van Herk’s formula; 0.5 cm, 0.46 cm, and 0.42 cm with Stroom’s formula; and 0.23 cm, 0.22 cm, and 0.2 cm according to ICRU-62 guidelines. Considering these calculations, a 6 mm safety margin is recommended as optimal. Discussion: While electronic portal imaging device improves radiotherapy precision, it has limitations, including limited field of view, difficulty with soft tissue visualization, and insufficient resolution for small errors. Patient variations and setup errors occurring after imaging further complicate safety margin calculations. Time, image quality, and radiation dose concerns also pose challenges. Integrating electronic portal imaging device with advanced imaging techniques like 3D imaging can enhance treatment accuracy. Conclusion: this study highlights the significance of a 6 mm safety margin, showing that image guided verification with electronic portal imaging enhances accuracy, reduces errors, and improves the precision of pelvic radiotherapy.

Keywords: cervical cancer, precision, PTV margins, radiotherapy, setup errors

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Authors: Yixuan Zhou, Ming Zhang, Liang Qin, Fanglin Lu

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Wound healing is a vital physiological process that supports the body’s ability to repair itself. Impaired healing can lead to complications such as infections, chronic ulcers, or tissue damage. Understanding the pathogenesis of wound healing is essential for developing targeted interventions to promote optimal healing outcomes and prevent complications associated with impaired wound healing. However, the underlying mechanism remains elusive. Macrophages play a crucial role in wound healing, and their function varies with the healing stage. Two main phenotypes of macrophages, known as M1 and M2, have been identified, each with distinct functions. The transition from M1 to M2 macrophages is a process that occurs during the healing of an injury. Dysregulation of macrophage polarization can impair wound healing and lead to chronic wounds. Therefore, understanding the roles of M1 and M2 macrophages and their regulation in the wound microenvironment is important for developing therapeutic strategies to promote optimal wound healing. We evaluated the efficacy of conditioned cell-free media from mouse bone marrow macrophages (BMMs) to improve wound healing in mouse models. M1 or M2 polarizations of BMMs are assessed in vitro post-stimulations using published protocols. In vivo, efficacies are assessed in a mouse model of wound healing. Macroscopy and histological data show a consistent effect of daily treatments with cell-free media from M2 BMMs on the healing of wounds in mice. These results are illustrated by a smaller wound area size, fewer inflammatory infiltrations, and enhanced angiogenesis in the healing stage. This multi-modal investigation suggests the potential of M2 macrophages for the healing of dermal injuries.

Keywords: wound healing, bone marrow macrophages, mouse model, polarization

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Authors: Yahia Massinissa, Benhouda Afaf, Benbia Souhila, Meddour Noura, Takellalet Karima, Zeroual Amina

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The present work aims to evaluate the anti-inflammatory and hemostatic activities of the methanolic extract AHMeOH of Atriplex halimus’s leaves which belongs to the chenopodiaceae family The preliminary evaluation of the phytochemical composition of the leaves made it possible to highlight the presence of some chemical groups such as polyphenols, flavonoids and alkaloids. This was confirmed by a quantitative analysis based on the determination of total polyphenols and flavonoids. Quantitative determination of total flavonoids reveals that AHMeOH is rich in flavonoids (16 ± 0.88 μg Q / mg extract) and polyphenols (20 ± 0.20 μg AG / mg extract). For anti-inflammatory activity, the tests show that AHMeOH has a significant effect (P≤0.05) of inhibiting hypotonic-induced hemolysis with concentrations (100 and 200 μg / ml) with 77.55 and 90% respectively, and heat-induced hemolysis with percentages 81.75% and 87.44% respectively with significant difference (P ≤0.05). The obtained results with this plant reveal that the inhibition of denaturation of albumin is dose dependent. The concentration of 400 μg / ml gives denaturation inhibition of 81.00 ± 17.70% and the concentration 600 μg / ml gives an effect of 82.95 ± 17.40%. About the haemostatic activity our extract with the doses 10 mg / ml, 20 mg / ml and 30 mg / ml confer a decrease of the plasma recalcification time in the tube, these concentrations could prolong the time of coagulation significantly compared to the control (P≤0.001). This result is an interesting indication in favor of haemostatic activity of AHMeOH.

Keywords: albumin, atriplex halimus, hemostatic activity, methanolic extract

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Authors: Ranveet Saggu, Saad Bin Ahmed

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Cardiovascular Disease (CVD) is the leading cause of death worldwide. One of its main manifestations, myocardial infarction (commonly known as a heart attack), occurs about 750,000 times a year, caused by insufficient blood flow to a portion of the heart muscle. A quick and accurate diagnosis of a heart attack or heart failure is crucial in the treatment of the patient. The aim of this research project is to improve the prediction of cardiovascular diseases by automating risk assessment using binary classifiers. The methodology includes Exploratory Data Analysis (EDA), which helps to obtain information about the dataset with the help of visualizations and metrics. Additionally, Feature Engineering techniques is employed to address missing values, outliers, feature extraction, and normalizing the dataset. Subsequently, various classification machine learning algorithms are trained, and their accuracy along with other metrics are evaluated to identify the most efficient model in terms of processing time and predictive performance.

Keywords: cardiovascular disease, machine learning, deci- sion trees, logistic regression, k-nearest neighbor, xgboost, random forest, gradient boosting

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Authors: Shima Behzadi

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Context:MicroRNA expression and K-Ras gene mutations play crucial roles in the prognosis of colorectal cancer. Understanding their correlation can provide valuable insights for better diagnosis and treatment strategies. Methodology:A case-control study involving 100 Iranian patients diagnosed with colorectal cancer was conducted. The expression of miR-141 and the presence of K-Ras mutations were analyzed using real-time PCR. Findings:The study demonstrated a significant correlation between miR-141 expression and K-Ras gene mutations in colorectal cancer patients. Patients with K-Ras mutations exhibited higher levels of miR-141 expression, indicating its potential as a prognostic biomarker. Theoretical importance:This research highlights the potential utility of miR-141 as a prognostic marker in colorectal cancer, particularly in patients with K-Ras mutations. It contributes to the understanding of molecular mechanisms associated with colorectal cancer prognosis. Data collection:Tissue samples from colorectal cancer patients with and without K-Ras mutations were collected and analyzed for miR-141 expression levels. Analysis procedures:Real-time PCR was used to quantify miR-141 expression levels in tumor samples with K-Ras mutations compared to those without these mutations. Conclusion:The study confirms a significant association between miR-141 expression and K-Ras mutations in Iranian colorectal cancer patients, suggesting the potential of miR-141 as a valuable prognostic biomarker in this context.

Keywords: colorectal cancer, K-Ras gene, miR-141 marker, real time PCR, electrophoresis

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Authors: Atefeh Shahbazi, Zahra Shahravi, Melika Mirghafari

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The application of fetal membranes in chronic wounds, particularly diabetic foot ulcers (DFUs), has shown remarkable efficacy in enhancing wound healing, with a notable impact on re-epithelialization. Fetal membranes exhibit potent anti-inflammatory and anti-scarring properties, primarily due to their ability to eliminate allogeneic amniotic cells while retaining a cytokine-rich matrix during preparation. When integrated with collagen, this combination creates a unique microenvironment within the wound, fostering the expansion of epithelial cells, fibroblasts, and keratinocytes ex vivo, while preserving their normal phenotype. These cells, in turn, stimulate the release of growth factors and healing signals essential for tissue regeneration. This study aims to assess the efficacy of fetal membranes combined with collagen in the management of DFUs by comparing standard care alone with standard care supplemented with fetal membrane allograft treatment. The study involved two groups of patients: Group A: Patients received the wound dressing with fetal membranes and collagen, followed up for 3 months (15 patients).Group B: Patients were treated with only sterile gauze, with no specialized dressing, and were followed up for 3 months (15 patients). The healing progress in both groups will be evaluated, and the outcomes will provide valuable insights into the potential for further improvements in wound care strategies. Preliminary findings emphasize the significant potential of fetal membranes to enhance healing in chronic diabetic wounds, demonstrating their ability to accelerate tissue regeneration, reduce inflammation, and promote faster, more effective wound closure.

Keywords: biological scaffold, stem cells, skin damage, diabetic foot ulcers

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Authors: Izadpanh Shaghayegh, Adli Fateme

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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms, including tremors, bradykinesia, rigidity, and freezing of gait (FOG), which arise from degeneration of the basal ganglia. While pharmacological treatments, particularly dopaminergic therapies, remain the primary approach for managing PD, their long-term effectiveness diminishes due to complications such as dyskinesia and motor fluctuations. Deep brain stimulation (DBS) has emerged as an alternative for symptom management but remains invasive, costly, and associated with significant risks. In light of these challenges, non-invasive brain stimulation (NIBS) techniques are gaining attention as promising alternatives for treating PD. These methods, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and microwave brain stimulation (MBS), offer advantages such as reduced risk and non-invasiveness while providing targeted modulation of brain activity. Recent innovations, such as hemispherical antenna arrays for focused stimulation and advanced signal patterns like high-frequency prime harmonics and temporal interference (TI), have further enhanced the precision and efficacy of NIBS. These techniques have shown potential in modulating neuronal excitability, improving gait, and reducing motor symptoms in PD patients, with some approaches demonstrating effectiveness in treating FOG. Despite promising results, continued research is necessary to refine these technologies, optimize treatment protocols, and evaluate their long-term impact on PD progression. This review highlights recent advances in non-invasive brain stimulation for PD and discusses their potential as adjunctive therapies for managing motor symptoms and improving quality of life in PD patients.

Keywords: Parkinson’s disease, non-invasive brain stimulation, deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, freezing of gait, microwave brain stimulation, neuromodulation

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Authors: Shilpa Mukundaraj, Nagaraju Shivaiah

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Amyloidogenic conditions, driven by protein aggregation into insoluble fibrils, which pose significant challenges in the clinical condition of diabetes management, particularly through the amyloidogenic LVEALYL sequence in insulin B-chain. This study explores a dual therapeutic strategy involving cysteine protease enzymes such as papain and ficin and inhibitory peptides to target insulin amyloidosis. Combining in silico, in vitro, and in vivo methodologies, the research aims to inhibit amyloid formation and degrade preformed fibrils. Inhibitory peptides were designed using structure-guided approaches in Rosetta to specifically target the LVEALYL sequence. Concurrently, cysteine protease enzymes, including papain and ficin, were evaluated for their fibril disassembly potential. In vitro experiments, utilizing SDS- PAGE and spectroscopic techniques, confirmed dose-dependent degradation 50 to 300ug in vitro and 60mg/kg in vivo of amyloid aggregates by these enzymes, with significant disaggregation observed at higher concentrations 20mg. Peptide inhibitors effectively reduced fibril formation, as evidenced by reduced Thioflavin T fluorescence and circular dichroism spectroscopy. Complementary in silico analyses, including molecular docking and dynamic simulations, provided structural insights into enzyme binding interactions with amyloidogenic regions. Key residues involved in substrate recognition and cleavage were identified, with computational findings aligning strongly with experimental data. These insights confirmed the specificity of papain and ficin in targeting insulin fibrils. For translational potential, an in vivo rat model was developed, involving subcutaneous insulin amyloid injections to induce localized amyloid deposits. Over six days of enzyme treatment, a marked reduction in amyloid burden was observed through histological findings and biochemical assay superoxide dismutase can provide insights into oxidative damage due to amyloid deposition. Furthermore, inflammatory markers IL-6, TNFα were significantly attenuated in treated groups, emphasizing the dual role of enzymes in amyloid clearance and inflammation modulation. This integrative study highlights the promise of cysteine protease enzymes and inhibitory peptides as complementary therapeutic strategies for managing insulin amyloidosis. By targeting both the formation and persistence of amyloid fibrils, this dual approach offers a novel and effective avenue for amyloidosis treatment.

Keywords: insulin amyloidosis, peptide inhibitors, cysteine protease enzymes, amyloid degradation

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Authors: Mrabet S., Beghdadi C., Bensadok S., Benzoubara W., Bestani R. F., Djellakh H., Ahmed Fouatih N.

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Introduction: The notion of beauty is imposed on us by philosophers as an obvious fact that would impose it on everyone, a self-proclaimed absolute truth, a clearly readable divining intuition for each of us. Beauty is often linked to rationality or moral notions. Materials and Methods: In order to evaluate and compare the perceptions of different groups of evaluators regarding changes made to the components of a smile, an analytical cross-sectional epidemiological study was conducted. Results: The selected population included 184 patients, 152 dental students, 22 general practitioners and 42 orthodontists. The criteria studied concern the smile line, gingival exposure, dental exposure, alignment of free edges, or coincidence of interincisal points. Discussion and Conclusion: A different appreciation between laypeople and professionals was observed on several criteria for judging an attractive smile. Hence the importance of listening to the patient's complaints and defining from the outset a therapeutic strategy that aims to restore aesthetics and function. On the groups of professionals, the impact of variables such as age, sex, as well as professional experience is undeniable and seems to affect the appreciation of the smile.

Keywords: smile, orthodontics, appreciation, practitioner

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Authors: Moustafa Gabr

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Galectin-3 has been identified as a critical player in driving the neuroinflammatory responses in Alzheimer's disease (AD). A key feature of this function of galectin-3 is associated with its interaction with the triggering receptor expressed on myeloid cells-2 (TREM2). Herein, we report a high-throughput screening (HTS) platform that can be used for the identification of inhibitors of TREM2 and galectin-3 interaction. We have utilized this HTS assay to screen a focused library of compounds optimized for central nervous system (CNS)-related diseases. MG-257 was identified from this screen as the first example of a small molecule that can attenuate TREM2 signaling based on its high affinity to galectin-3 (endogenous ligand of TREM2). Remarkably, MG-257 reduced the levels of proinflammatory cytokines in activated microglial cells, which highlights its ability to inhibit the neuroinflammatory response associated with AD.

Keywords: medicinal chemistry, Alzheimer's disease, drug discovery, therapeutics

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Authors: Assane Dieng, Abass Sarr, Gora Lo, Awa Ba, Halimatou Diop Ndiaye, Makhtar Camara

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Introduction: Escherchia coli is one of the main beta-lactamase-producing bacteria. In Senegal, we are witnessing a weakness in the technical platform and a deficit in qualified personnel in laboratories, especially in rural areas. This is why there is little updated data on antibiotic bacterial resistance in rural areas. The objective is to study infections with Escherichia coli producing extended-spectrum beta-lactamase (ESBL) at the Tambacounda Regional Hospital Center (CHRT), Senegal. Methodology: Samples were taken from patients consulted at the Tambacounda Regional Hospital Center (CHRT) from January to October 2024. The search for Escherichia coli was carried out by determining morphological, biochemical and cultural characteristics. The antibiogram was performed using the Mueller-Hinton (MH) agar diffusion method following the recommendations of the Antibiogram Committee of the French Society of Microbiology (CA SFM). ESBL production was detected using the double synergy method Results: A total of 287 germs were isolated during the study period, including 96 strains of Escherichia coli, 47 of which produced a broad-spectrum beta-lactamase. ESBL-producing E. coli strains were more common in men (61.2%). The most affected age groups were [60-79 years] and [20-39 years] with respective rates of 36.7% and 27%. ESBL-producing E. coli strains were isolated mainly in non-hospitalized patients (79%). Beta-lactamase-producing E. coli strains were mainly resistant to tetracycline (95.7%), norfloxacin (91.5%) and ciprofloxacin (87.2%).Conclusion: ESBL-producing E. coli strains are also present in rural areas Thus, to have more comprehensive data, qualified personnel as well as a high-level technical platform should be available in these laboratories.

Keywords: E. coli, beta-lactamase, rural area, non hospitalized

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Authors: Farnoosh Davarian

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The present research focuses on organizing the cooperation of units constrained by demand response (DR) programs, considering ancillary services in the P-Q power market. Moreover, it provides a comprehensive exploration of the effects of demand reduction and redistribution across several predefined scenarios (in three pre-designed demand response programs, for example, ranging from 5% to 20%) on system voltage and losses in a smart distribution system (in the studied network, distributed energy resources (DERs) such as synchronous distributed generators and wind turbines offer their active and reactive power for the proposed market).GAMS, a specialized software for high-powered modeling, is used for optimizing linear, nonlinear, and integer programming challenges. GAMS modeling is separate from its solution method, which is a notable feature. Thus, by providing changes in the solver, it is possible to solve the model using various methods (linear, nonlinear, integer, etc.). Finally, the combined active and reactive market challenge in smart distribution systems, considering renewable distributed sources and demand response programs in GAMS, will be evaluated. The active and reactive power trading by the distribution company is carried out in the wholesale market. What is demanded is active power. By using the buy-back/payment program, it is possible for responsive loads or aggregators to participate in the market. The objective function of the proposed market is to minimize the price of active and reactive power for DERs and distribution companies and the penalty cost for CO2 emissions and the cost of the buy-back/payment program. In this research, the objective function is to minimize the cost of active and reactive power from distributed generation sources and distribution companies, the cost of carbon dioxide emissions, and the cost of the buy-back/payment program. The effectiveness of the proposed method has been evaluated in a case study.

Keywords: consumer behavior, demand response, pollution cost, combined active and reactive market

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Authors: Deepika Gupta, Namita Bhutani, Mithlesh Bhargav

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Objective: Breast cancer is the most commonly encountered lesion in females after non-melanoma skin malignancies. The triple assessment is an important approach in pre-operative lesions in developing countries. The objectives of the present study were to determine diagnostic accuracy and calculation of ROM along with cyto-histopathological correlation with the incorporation of a new IAC reporting system. Material and Methods: A total of 940 FNAC slides were retrieved from December 2019 to December 2020 and categorized according to the new IAC system. The diagnostic accuracy and calculation of ROM, along with cyto-histopathological correlation, were determined. Results: All the breast FNAC lesions were categorized from C1 to C5. Of the 940 cases, 358 cases had cyto-histopathological correlation. The ROM was ranging from 0% to 99%. All the statistical parameters were calculated along with diagnostic accuracy which was 97%. Conclusion: The new IAC standardized reporting system of breast FNAC evoked the utilization of rapid, accurate, and low-cost diagnostic tests and broadened the understanding and application of breast FNAC.

Keywords: accuracy, fine needle aspiration cytology, IAC, risk of malignancy, Yokohama system

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Authors: Serdar Kucuk, Redwan Alqasemi

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In this paper, the generic kinematic equations of 1-Degrees-Of-Freedom (DOF), 2-DOF, and 3-DOF above-knee prosthetic legs are derived using the mathematical tools used in science of robotics. As it is known, since the human leg performs rotational motions in the knee joint and foot-ankle joint, the axial rotational motions in the above-knee prosthetic legs are performed by using one or more revolute joints. When deriving the kinematic equations of the 1-DOF, 2-DOF, and 3-DOF above-knee prosthetic legs, the foot-ankle is treated as if there were a fixed non-rotating joint, a revolute joint, and a universal joint, respectively. The kinematic equations of the prosthetic legs presented in this article are obtained using DH method. The main advantages of this method are the easy physical interpretation of robot mechanisms and the use of 4x4 homogeneous transformation matrices, which are widely used in the literature. It is thought that the equations presented in this article contribute positively to the design, control, simulation and hence easy production of above-knee prosthetic legs.

Keywords: robotic above-knee prosthetic legs, generic kinematic equations, revolute and universal joints, DH method

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Authors: Yakubu Adamu

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The aim of this research was to assess the factors contributing to the need for optimisation of the gastric emptying protocols in nuclear medicine and molecular imaging (SNMMI) procedures. The objective is to suggest whether optimisation is possible and provide supporting evidence for the current imaging protocols of gastric emptying examination used in nuclear medicine. The research involved the use of some selected patients with 30 dynamic series for the image processing using ImageJ, and by so doing, the calculated half-time, retention fraction to the 60 x1 minute, 5 minute and 10-minute protocol, and other sampling intervals were obtained. Results from the study IDs for the gastric emptying clearance half-time were classified into normal, abnormal fast, and abnormal slow categories. In the normal category, which represents 50% of the total gastric emptying image IDs processed, their clearance half-time was within the range of 49.5 to 86.6 minutes of the mean counts. Also, under the abnormal fast category, their clearance half-time fell between 21 to 43.3 minutes of the mean counts, representing 30% of the total gastric emptying image IDs processed, and the abnormal slow category had clearance half-time within the range of 138.6 to 138.6 minutes of the mean counts, representing 20%. The results indicated that the calculated retention fraction values from the 1, 5, and 10-minute sampling curves and the measured values of gastric emptying retention fraction from sampling curves of the study IDs had a normal retention fraction of <60% and decreased exponentially with an increase in time and it was evident with low percentages of retention fraction ratios of < 10% after the 4 hours. Thus, this study does not change categories suggesting that these values could feasibly be used instead of having to acquire actual images. Findings from the study suggest that the current gastric emptying protocol can be optimized by acquiring fewer images. The study recommended that the gastric emptying studies should be performed with imaging at a minimum of 0, 1, 2, and 4 hours after meal ingestion.

Keywords: gastric emptying, retention fraction, clearance halftime, optimisation, protocol

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Authors: Laiba Amin, Rashna H. Sukhia, Mubassar Fida

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Introduction: This study evaluates the accuracy of responses from ChatGPT, Google Bard, and Microsoft Copilot regarding dentofacial orthopedic appliances. As artificial intelligence (AI) increasingly enhances various fields, including healthcare, understanding its reliability in specialized domains like orthodontics becomes crucial. By comparing the accuracy of different AI models, this study aims to shed light on their effectiveness and potential limitations in providing technical insights. Materials and Methods: A total of 110 questions focused on dentofacial orthopedic appliances were posed to each AI model. The responses were then evaluated by five experienced orthodontists using a modified 5-point Likert scale to ensure a thorough assessment of accuracy. This structured approach allowed for consistent and objective rating, facilitating a meaningful comparison between the AI systems. Results: The results revealed that Google Bard demonstrated the highest accuracy at 74%, followed by Microsoft Copilot, with an accuracy of 72.2%. In contrast, ChatGPT was found to be the least accurate, achieving only 52.2%. These results highlight significant differences in the performance of the AI models when addressing orthodontic queries. Conclusions: Our study highlights the need for caution in relying on AI for orthodontic insights. The overall accuracy of the three chatbots was 66%, with Google Bard performing best for removable Class II appliances. Microsoft Copilot was more accurate than ChatGPT, which, despite its popularity, was the least accurate. This variability emphasizes the importance of human expertise in interpreting AI-generated information. Further research is necessary to improve the reliability of AI models in specialized healthcare settings.

Keywords: artificial intelligence, large language models, orthodontics, dentofacial orthopaedic appliances, accuracy assessment.

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Authors: Leila Baghaarabani, Parvin Razzaghi, Mennatolla Magdy Mostafa, Ahmad Albaqsami, Al Warith Al Rushaidi, Masoud Al Rawahi

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Predicting the interaction between drugs and their molecular targets is pivotal for advancing drug development processes. Due to the time and cost limitations, computational approaches have emerged as an effective approach to drug-target interaction (DTI) prediction. Most of the introduced computational based approaches utilize the drug molecule and protein sequence as input. This study does not only utilize these inputs, it also introduces a protein representation developed using a masked protein language model. In this representation, for every individual amino acid residue within the protein sequence, there exists a corresponding probability distribution that indicates the likelihood of each amino acid being present at that particular position. Then, the similarity between each pair of amino-acids is computed to create similarity matrix. To encode the knowledge of the similarity matrix, Bi-Level Routing Attention (BiFormer) is utilized, which combines aspects of transformer-based models with protein sequence analysis and represents a significant advancement in the field of drug-protein interaction prediction. BiFormer has the ability to pinpoint the most effective regions of the protein sequence that are responsible for facilitating interactions between the protein and drugs, thereby enhancing the understanding of these critical interactions. Thus, it appears promising in its ability to capture the local structural relationship of the proteins by enhancing the understanding of how it contributes to drug protein interactions, thereby facilitating more accurate predictions. To evaluate the proposed method, it was tested on two widely recognized datasets: Davis and KIBA. A comprehensive series of experiments was conducted to illustrate its effectiveness in comparison to cuttingedge techniques.

Keywords: BiFormer, transformer, protein language processing, self-attention mechanism, binding affinity, drug target interaction, similarity matrix, protein masked representation, protein language model

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Authors: Arundhathi S., Poongodi R.

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Tumor-infiltrating lymphocytes (TILs) are indicative of the local immune response against tumor proliferation and metastasis. Emerging as a significant marker of immune reactivity, TILs are utilized to evaluate prognostic outcomes across various malignancies, including colon, ovarian, lung, bladder, and breast cancers. In breast cancer (BC), TILs are particularly relevant for assessing tumor response to therapy in both adjuvant and neoadjuvant settings, with a prominent role in triple-negative breast cancer (TNBC), where they have been associated with improved outcomes. As such, TILs are recognized as an independent marker of favorable prognosis in several tumor types, underscoring their potential as a tool in personalized cancer therapy.

Keywords: breast cancer, intratumoral TIL, stromal TIL, tumor infiltrating lymphocytes

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Authors: Chro Kavian

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The studies conducted show that cancer is a disease caused by populations of microbes, a notion gaining traction as the interaction between the human microbiome and the tumor microenvironment (TME) increasingly shows how environment and microbes dictate the progress and treatment of neoplastic diseases. A person’s human microbiome is defined as a collection of bacteria, fungi, viruses, and other microorganisms whose structure and composition influence biological processes like immune system modulation and nutrient metabolism, which, in turn, affect how susceptible a person is to neoplastic diseases, and response to different therapies. Recent reports demonstrated the influence specific microbiome bacterial populations have on the TME, thereby altering tumoral behaviors and the TME’s contributing factors that impact patients' lives. In addition, gut microbes and their SCFA products are important determinants of the inflammatory landscape of tumors and augment anti-tumor immunity, which can influence immunotherapy outcomes. Studies have also found that dysbiosis, or microbial imbalance, correlates with biological processes such as cancer progression, metastasis, and therapy resistance, leading scientists to explore the use of microbiome deficiencies as adjunctive approaches to chemotherapy and other, more traditional treatments. Nonetheless, mental health practitioners struggling to comprehend the existent gap between cancer patients with pronounced resolutive capabilities and the profound clinical impact Microbiome-targeted cancer therapy has been proven to possess.

Keywords: microbiome, cancer, tumor, immune system

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Authors: Joseph Mary Ssembatya, Blessing Michael Taremwa

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Background: Multiple schwannomas are typically associated with neurofibromatosis type 1 (NF1), but rare cases occur independently of neurofibromatosis. Schwannomas are benign, slow-growing tumors, primarily affecting the cervical and lumbar spine. When large, they may extend over multiple vertebral levels, posing surgical challenges. Case Presentation: A 13-year-old Ugandan Munyankore female patient, presented with a 6-year history of progressive quadriparesis, particularly in the lower limbs. Clinical examination showed hypertonia and hyperreflexia, with no indicators of neurofibromatosis or prior trauma. MRI revealed two “kissing” schwannomas extending from C2 to T2 in the cervical spine. Decompressive surgery was performed through laminoplasty and partial lesion resection, and histology confirmed schwannoma. Two weeks postoperatively, the patient experienced cerebrospinal fluid (CSF) leakage, neck pain, and headache, which required re-operation and duraplasty. Following these interventions, the patient’s neurological status stabilized, with noted improvement in lower limb strength. Discussion: “Kissing” schwannomas are most frequently documented in the cerebellopontine angle, rarely in the spine, and even more rarely in children. While multiple schwannomas are often associated with NF2, this case had no family history or clinical signs of the disorder. Giant invasive spinal schwannomas (GISS) that span multiple vertebrae demand intricate surgical approaches due to their proximity to neurovascular structures. Conclusion: This is the first reported case of kissing cervical schwannomas in a young patient from a low- to middle-income country. Surgical decompression, though challenging, is critical for neurological recovery in such advanced cases.

Keywords: kissing schwannoma, cervical spine, low resource, young, uganda

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Authors: Jessie Justice

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This is a case report of a vestibular schwannoma presenting with numbness to the left lower lip and tongue and altered taste. The aim of this case is to raise awareness of differential diagnoses for trigeminal nerve paraesthesia and, hence, prompt thorough investigation. A 65-year-old male was referred to the Oral and Maxillofacial department regarding sudden-onset of numbness to his left lower lip and left tongue, with altered taste sensation subsequently developing. The patient was simultaneously being investigated for severe hearing loss in his left ear. On examination, there was altered sensation in the distribution of the left inferior alveolar nerve and left lingual nerve. There was no palpable cervical lymphadenopathy and no intra-oral lesions or dental cause for the symptoms. Due to his hearing loss in the left ear, the patient was sent for magnetic resonance imaging of the internal auditory meatus by the Ear, Nose and Throat (ENT) department, revealing a 2.5cm mass within the left cerebellopontine angle presumed to be a vestibular schwannoma. This led to the diagnosis of trigeminal nerve compression by a medium vestibular schwannoma. Consequently, the patient was followed up by an ENT, who referred him for stereotactic radiosurgery. A literature review regarding vestibular schwannomas presenting with orofacial paraesthesia was then carried out. A review of the literature has shown the incidence of vestibular schwannoma to be 3-5 cases per 100,000. It has been reported that approximately 5% of vestibular schwannoma cases display orofacial dysaesthesia, and about 1-3% of cases exhibit trigeminal neuralgia symptoms. This is a rare case of vestibular schwannoma causing trigeminal nerve paraesthesia. The aim of this study is to raise awareness of alternative causes of trigeminal nerve paraesthesia and the available literature surrounding this.

Keywords: acoustic neuroma, orofacial dysaesthesia, trigeminal nerve paraesthesia, vestibular schwannoma

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Authors: Alejandra Ben-Aissa, Martina Moreno, Luciano Sappia, Paul Lacharmoise, Ana Moya

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Organ-on-Chip (OoC) stands out as a highly promising approach for drug testing, presenting a cost-effective and ethically superior alternative to conventional in vivo experiments. These cutting-edge devices emerge from the integration of tissue engineering and microfluidic technology, faithfully replicating the physiological conditions of targeted organs. Consequently, they offer a more precise understanding of drug responses without the ethical concerns associated with animal testing. When addressing the limitations of OoC due to conventional and time-consuming techniques, Lab-On-Chip (LoC) emerge as a disruptive technology capable of providing real-time monitoring without compromising sample integrity. This work develops LoC platforms that can be integrated within OoC platforms to monitor essential culture media parameters, including glucose, oxygen, and pH, facilitating the straightforward exchange of sensing units within a dynamic and controlled environment without disrupting cultures. This approach preserves the experimental setup, minimizes the impact on cells, and enables efficient, prolonged measurement. The LoC system is fabricated following the patented methodology protected by EU patent EP4317957A1. One of the key challenges of integrating sensors in a biocompatible, feasible, robust, and scalable manner is addressed through fully printed sensors, ensuring a customized, cost-effective, and scalable solution. With this technique, sensor reliability is enhanced, providing high sensitivity and selectivity for accurate parameter monitoring. In the present study, LoC is validated measuring a complete culture media. The oxygen sensor provided a measurement range from 0 mgO2/L to 6.3 mgO2/L. The pH sensor demonstrated a measurement range spanning 2 pH units to 9.5 pH units. Additionally, the glucose sensor achieved a measurement range from 0 mM to 11 mM. All the measures were performed with the sensors integrated in the LoC. In conclusion, this study showcases the impactful synergy of OoC technology with LoC systems using fully printed sensors, marking a significant step forward in ethical and effective biomedical research, particularly in drug development. This innovation not only meets current demands but also lays the groundwork for future advancements in precision and customization within scientific exploration. Acknowledgments: This work was financially supported by the Catalan Government through the funding grant ACCIÓ-Eurecat (Project Traça-IMPULSENS).

Keywords: organ on chip, lab on chip, real time monitoring, biosensors

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Authors: Hasanzade Nazenin, Hasanova Naila

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According to the WHO, osteoporosis is one of the most important health problems in the world and occupies the 4th place in its importance after cardiovascular pathology, oncological diseases and diabetes mellitus. The significance of osteoporosis is determined by its prevalence among the population, the severity of the course, the cause of death, disability, reduced quality of life, high economic costs for prevention and treatment. Osteoporosis is a systemic skeletal disease characterized by a decrease in bone mass and a violation of the structure of bone tissue, leading to an increase in bone fragility and the risk of fractures. Osteoporosis is manifested by low-traumatic fractures. Due to the complexity of the recovery process, the treatment of osteoporotic fractures is one of the important problems of modern traumatology. Diagnostic markers are needed to monitor the recovery period. Human cartilage glycoprotein -39, which has been studied so far in inflammatory processes in the bones, may allow the development of the correct treatment regimen, reflecting the level of metabolic processes in the bone tissue. The study was performed to examine the dynamics of human cartilage glycoprotein-39 (HCgp39) in the blood serum during osteoporosis and fracture healing. The material of the study is formed by the examination results of 68 people aged 38-83. Group I - control group consisted of 14 practically healthy people, group II - 14 patients with osteoporosis, group III - 15 patients with non-osteoporotic fractures, group IV - 25 patients with osteoporotic fractures. In groups, they were analyzed by enzyme-linked immunosorbent assay 3 times during the first month. As a result, in the first month of the recovery period, no significant difference was observed in the HCgp39 dynamics for groups II and IV (p> 0.05). However, there was a significant reduction in group III (p <0.05). As no osteoporotic changes were observed in this patient group, bone healing was rapid and it was possible to monitor the dynamics of HCgp39 changes within 1 month. Patients with osteoporosis and other bone fractures in the process of complete recovery need to study HCgp39 more as a diagnostic indicator.

Keywords: osteoporosis, osteoporotic fractures, human cartilage glycoprotein, HCgp39

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Authors: Gulnara Azizova, Naila Hasanova, Nazenin Hasanzade

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The aim of study is to investigate the role of osteoactivin as a more sensitive and modern diagnostic biomarker that has a prognostic value in metabolic and repair processes occurring in bone and cartilage tissue in osteoporosis and osteoporotic fractures. Osteoactivin (OA) is a new glycoprotein that is highly expressed during osteoblast differentiation. It was first discovered in an osteopetrotic rat model using mRNA . This study was carried out on patients between the ages of 45-83 from the Department of Traumatology and placed in 3 groups: group I - 14 patients with osteoporosis, group II - 15 patients with non-osteoporotic fractures, group III - 25 patients with osteoporotic fractures. The control group consisted of 14 healthy people. To monitor changes in osteoactivin, blood samples were taken at 3 stages: on day 1 before treatment, on day 10 of treatment, and 1 month after treatment. The concentration of OA in the blood serum was determined by ELISA method on the immunoassay analyzer “Mindray MR- 96A” using a set of reagents from the company Boster ( ELISA Kit PicoKine, USA). The statistical evaluation was performed by using SPSS 22.0 program (IBM SPSS Inc., USA). Compared to the control, osteoactivin concentration increased by 66.2% in patients with osteoporosis, 54.1% in patients with non-osteoporotic fractures, and 80.2% in patients with osteoporotic fractures, indicating that it plays an important role in the pathogenesis of osteoporotic fractures. At 1 month after treatment, osteoactivin concentration increased by 81.6% in patients with non-osteoporotic fractures. The lack of a significant change in osteoporotic fractures is explained by the late healing of these fractures. Based on the sensitivity and specificity indicators, the ROC curve was created and it was determined that osteoactivin is a test with high general diagnostic value, specificity and informativeness in the prognosis of osteoporosis and osteoporotic fractures, and can be used throughout the treatment period.

Keywords: osteoactivin, bone, osteoporosis., cartilage

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