Search results for: tail gas treatment unit

Authors: M. Aguilar, D. L. Araujo, A. L. Avendaño, D. C. Flores, I. Lascurain, R. A. Molina, M. Romero

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This work presents an application of social robotics, specifically the use of a NAO Robot as a tool for therapists in the treatment of Autism Spectrum Disorder (ASD). According to this, therapies approved by specialist psychologists have been developed and implemented, focusing on creating a triangulation between the robot, the child, and the therapist, aiming to improve their social and language skills, as well as communication skills and joint attention. In addition, quantitative and qualitative analysis tools have been developed and applied to prove the acceptance and the impact of the robot in the treatment of ASD.

Keywords: autism spectrum disorder, NAO robot, social and language skills, therapy

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Authors: Alyaa Ahmed Farid, Aida Ismail, Ibrahim Rabia, Azza Fahmy, Azza El Amir

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This study was designed for assessment of 3 types of Cysteine protease inhibitors (CPIs) fluromethylketone (FMK), vinyl sulfone (VS) and sodium nitro prussid (SNP), to define which of them is the best? The experiments aimed to define the protective power of each inhibitor alone or combined with PZQ for curing S. mansoni infection in mice. In vitro, treated S. mansoni adult worms recorded a mortality rate after 1 hr of exposure to 500 ppm of FMK, VS and SNP as 75, 70 and 60%, while, treated cercaria recorded 75, 60 and 50%, respectively. FMK+PZQ treatment recorded the maximum reduction in worm burden (97.2% at 5 wk PI). VS treatment alone or combined with PZQ increases IgM, total IgG, IgG2 and IgG4 levels. In EM study of worm tegument, while only detachment of spines was observed in PZQ treated group, the completely implanted spines were reported in the degenerated tegument of adult worms in all groups treated with CPIs. Treatment with VS+PZQ increased Igs levels but, its effect was different on worm reduction. So, it is not enough to eliminate the infection and FMK+PZQ considered the antischistosomicidal drug of choice.

Keywords: praziquantel, fluromethylketone, vinyl sulfone, worm burden, immunoglobulin pattern

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Authors: Shivani Dhande, Sanjiv Choudhary, Adarshlata Singh

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Introduction: Early age of onset of baldness has marked psychological impact on personality. Combination therapies have better efficacy than monotherapy in androgenetic alopecia. Although medical, surgical treatment and cosmetic aids are available for treatment of pattern baldness, medical is first preferred the line of treatment. Although only 5% topical minoxidil is USFDA approved, 10% is available in India since 2007. Efficacy of tablet finasteride is well established in male pattern baldness. 5% topical minoxidil is effective and safe in female pattern baldness. There is a role of saw palmetto in regrowth of scalp hair. With this background research was undertaken to study efficacy and safety of topical minoxidil 10% + tab. Finesteride (1mg) + dermaroller in male pattern baldness and topical minoxidil 5% + cap. Saw palmetto (320 mg) + dermaroller in female pattern baldness. Methods and Materials: It was a randomized uncontrolled evaluator blind study consisting of total 21 patients, 15 of male pattern baldness and 6 of female pattern baldness within 20-35 yrs of age were enrolled. Male patients had Hamilton grade 2-4 MPB and females had Ludwig grade 2 FPB. Male patients were treated with Tab Finesteride 1mg once daily + 10% topical Minoxidil 1ml twice daily for 6 months. Female patients were treated with Cap. Saw palmetto 320 mg once daily + 5% topical Minoxidil twice daily for 6 months. In both male & female patients dermaroller therapy was used once in 10 days for 4 sittings followed by once in 15 days for next 5 months. Blood pressure and possible side effects were monitored in every follow up visits. Pre and post treatment photographs were taken. Assessment of hair growth was done at baseline and at the end of 6 months. Patients satisfactory grading scale and Physician assessment of hair growth scale were used to assessing the results. Trichoscan was done for assessment of hair-shaft diameter and density. Pre and post treatment photographs and Trichoscan hair growth analysis (by diameter and density) was done by physician (dermatologist) not directly involved in this study (evaluator blind). Result: This combination therapy showed moderate response in female pattern alopecia and good to excellent results in male pattern alopecia at the end of 6 months. During therapy none of the patients showed side effects like hypotension, headache and loss of libido, hirsuitism. Mild irritation due to crystal deposition was noted by 3 patients. Conclusion: Effective and early treatment using combination therapy with higher percent of Minoxidil for rapid hair growth is necessary in initial period since it will boost up the self-confidence in patients leading to better treatment compliance. Subsequent maintenance of hair growth can be done with lower concentration. No significant side effects with treatment are observed in both group of patients.

Keywords: androgenetic alopecia, dermaroller, finasteride, minoxidil, saw palmetto

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Authors: R. Berrached, H. Ait Mahamed, A. Iddou

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Water pollution is nowadays a serious problem, due to the increasing scarcity of water and thus to the impact induced by such pollution on the human health. Various techniques are made use of to deal with water pollution. Among the most used ones, some can be enumerated: the bacterian bed, the activated mud, the Lagunage as biological processes and coagulation-floculation as a physic-chemical process. These processes are very expensive and an treatment efficiency which decreases along with the increase of the initial pollutants’ concentration. This is the reason why research has been reoriented towards the use of a process by adsorption as an alternative solution instead of the other traditional processes. In our study, we have tempted to exploit the characteristics of two metallic hydroxides Al and Fe to purify contaminated water by two industrial dyes SBL blue and SRL-150 orange. Results have shown the efficiency of the two materials on the blue SBL dye.

Keywords: metallic hydroxydes, industrial dyes, purificatıon,

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Authors: Ibrahim Turfanda, Soniya Rai, Karan Vadher

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Objectives— The study aims to compare real-world adherence to and persistence with dulaglutide and liraglutide in patients with type 2 diabetes (T2D) initiating treatment in UAE. Methods— This was a retrospective, non-interventional study (observation period: 01 March 2017–31 August 2019) using the UAE Dubai e-Claims database. Included: adult patients initiating dulaglutide/liraglutide 01 September 2017–31 August 2018 (index period) with: ≥1 claim for T2D in the 6 months before index date (ID); ≥1 claim for dulaglutide/liraglutide during index period; and continuous medical enrolment for ≥6 months before and ≥12 months after ID. Key endpoints, assessed 3/6/12 months after ID: adherence to treatment (proportion of days covered [PDC; PDC ≥80% considered ‘adherent’], per-group mean±standard deviation [SD] PDC); and persistence (number of continuous therapy days from ID until discontinuation [i.e., >45 days gap] or end of observation period). Patients initiating dulaglutide/liraglutide were propensity score matched (1:1) based on baseline characteristics. Between-group comparison of adherence was analysed using the McNemar test (α=0.025). Persistence was analysed using Kaplan–Meier estimates with log-rank tests (α=0.025) for between-group comparisons. This study presents 12-month outcomes. Results— Following propensity score matching, 263 patients were included in each group. Mean±SD PDC for all patients at 12 months was significantly higher in the dulaglutide versus the liraglutide group (dulaglutide=0.48±0.30, liraglutide=0.39±0.28, p=0.0002). The proportion of adherent patients favored dulaglutide (dulaglutide=20.2%, liraglutide=12.9%, p=0.0302), as did the probability of being adherent to treatment (odds ratio [97.5% CI]: 1.70 [0.99, 2.91]; p=0.03). Proportion of persistent patients also favoured dulaglutide (dulaglutide=15.2%, liraglutide=9.1%, p=0.0528), as did the probability of discontinuing treatment 12 months after ID (p=0.027). Conclusions— Based on the UAE Dubai e-Claims database data, dulaglutide initiators exhibited significantly greater adherence in terms of mean PDC versus liraglutide initiators. The proportion of adherent patients and the probability of being adherent favored the dulaglutide group, as did treatment persistence.

Keywords: adherence, dulaglutide, effectiveness, liraglutide, persistence

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Authors: Vasiliki Markantoni, Eftychia Platsidaki, Georgios Chaidemenos, Georgios Kontochristopoulos

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Introduction: Bromhidrosis, also known as osmidrosis, is a common distressing condition with a significant negative effect on patient’s quality of life. Its etiology is multifactorial. It usually affects axilla, genital skin, breasts and soles, areas where apocrine glands are mostly distributed. Therapeutic treatments include topical antibacterial agents, antiperspirants and neuromuscular blocker agents-toxins. In this study, we aimed to evaluate the efficacy and possible complications of topical glycopyrrolate, an anticholinergic agent, for treatment of bromhidrosis. Glycopyrrolate, applied topically as a cream, solution or spray at concentrations between 0,5% and 4%, has been successfully used to treat different forms of focal hyperhidrosis. Materials and Methods: Twenty patients, six males and fourteen females, meeting the criteria for bromhidrosis were treated with topical glycopyrrolate for two months. The average age was 36. Eleven patients had bromhidrosis located to the axillae, four to the soles, four to both axillae and soles and one to the genital folds. Glycopyrrolate was applied topically as a cream at concentration 2%, formulated in Fitalite. During the first month, patients were using the cream every night and thereafter twice daily. The degree of malodor was assessed subjectively by patients and scaled averagely as ‘none’, ‘mild’, ‘moderate’, and ‘severe’ with corresponding scores of 0, 1, 2, and 3, respectively. The modified Dermatology Life Quality Index (DLQI) was used to assess the quality of life. The clinical efficacy was graded by the patient scale of excellent, good, fair and poor. In the end, patients were given the power to evaluate whether they were totally satisfied with, partially satisfied or unsatisfied and possible side effects during the treatment were recorded. Results: All patients were satisfied at the end of the treatment. No patient defined the response as no improvement. The subjectively assessed score level of bromhidrosis was remarkably improved after the first month of treatment and improved slightly more after the second month. DLQI score was also improved to all patients. Adverse effects were reported in 2 patients. In the first case, topical irritation was reported. This was classed as mild (erythema and desquamation), appeared during the second month of treatment and was treated with low-potency topical corticosteroids. In the second case, mydriasis was reported, that recovered without specific treatment, as soon as we insisted to the importance of careful hygiene after cream application so as not to contaminate the periocular skin or ocular surface. Conclusions: Dermatologists often encounter patients with bromhidrosis, therefore should be aware of treatment options. To the best of our knowledge, this is the first study to evaluate the use of topical glycopyrrolate as a therapeutic approach for bromhidrosis. Our findings suggest that topical glycopyrrolate has an excellent safety profile and demonstrate encouraging results for the management of this distressful condition.

Keywords: Bromhidrosis, glycopyrrolate, topical treatment, osmidrosis

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Authors: Ayman A. Al Hayek, Asirvatham A. Robert, Mohamed A. Al Dawish, Rim B. Braham, Hanouf S. Goudeh, Fahad S. Al Sabaan

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Introduction: The aim of this study was to explore the impact of insulin pump therapy on diabetes treatment satisfaction and glycemic control among patients with type 1 diabetes mellitus (T1DM) in Saudi Arabia. Methods: A 6-month, prospective study was conducted among 47 patients (aged17–24 years) with T1DM who attended the Insulin Pump Clinic at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between April 2014 and November 2014. The respondents were purposively and conveniently selected and were interviewed using the Arabic version of the Diabetes Treatment Satisfaction Questionnaire at baseline, 3, and 6 months. Demographics and clinical variables including hemoglobin A1c (HbA1c) were also collected. Results: The mean (±standard deviation) age of the study cohort was 19.1 ± 1.93 years. Seventeen patients were male (36.2%) and 30 were female (63.8%). Compared to baseline, significant positive differences were found in treatment satisfaction among female patients and patients with long-standing T1DM at 6 months. Frequency of hyperglycemia and hypoglycemia declined significantly in female patient’s at 6 months and in patients who had a shorter duration of T1DM. Furthermore, significant positive differences were found in HbA1c levels among female patients and among those who had a shorter duration of T1DM compared to baseline. Both female and male patients and those with a shorter duration of T1DM showed significant decline in insulin necessity at6months when compared to baseline. Conclusion: Although multiple daily injections is a feasible preference for insulin supply, insulin pumps should also be considered for patients with T1DM as it appears to increase patients’ treatment satisfaction, decrease the frequency of hypoglycemia, hyperglycemia, and reduce HbA1c levels.

Keywords: type 1 diabetes, insulin pump, Saudi Arabia, T1DM

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Authors: J. Wozniak-Holecka, T. Holecki, P. Romaniuk

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Spa facilities are being perceived as the ways of healing treatment in Poland and are guaranteed within the public financing. The universal health insurance (National Health Fund, NFZ), and the disability prevention programme held by Social Insurance Institution (ZUS) are the main sources of financing spa facilities. The dominant public payer of spa services is the NFZ. The Social Insurance Institution covers the cost of health treatment realized in spa facilities as medical rehabilitation, in the field of disability prevention. Health services delivered in the spa resorts are characterized by complexity, and the combination of various methods, typical for health prevention, education, balneotherapy, and physiotherapy. Healing with natural methods, believed to enhance the therapeutic effect, is also involved in health spa treatment. Regardless of the type of facility, each form of spa treatment includes health promotion, health education, prevention at all levels, including rehabilitation. The aim of the study was to determine the optimal organization of health education process. Its efficiency strongly depends on the type of service provider and the funding institution (NFZ vs ZUS). It results from the use of different measures of the effectiveness, the quality and the evaluation of the process being assessed by funding institutions. The methods of the study include a comparative and descriptive quantitative and qualitative analysis. In the empirical part, a questionnaire had been developed. It was then distributed among spa personnel, responsible directly for the health promotion, and among patients who are beneficiaries of health services in spa centers. The quantitative part of the study was based on interviews carried with the use of the online survey (CAWI: Computer-Assisted Web Interview), telephone survey (CATI: Computer-Assisted Telephone Interview) and a conventional questionnaire (PAPI: Paper over Pencil Interview). As a result of the conducted research, it was found that the effectiveness of health education activities in spa resort facilities in Poland is higher when the services are organized using structured tools for managerial control. This applies to formalized procedures implemented by one of the dominant payers covering costs of services (ZUS) and involves the application of health education as one of the mandatory elements of treatment, subjected to the process of control during the course of spa therapy and evaluation after it is completed.

Keywords: effectiveness, health education, public health system, spa treatment

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Authors: Zhaoguo Liu, Cunsi Shen, Yin Lu

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Growing evidence has shown that menthol has potent anticancer activity in various human cancers. However, its effect on skin cancer remains largely unknown. In the present study, we investigated the chemopreventive potential of menthol against 7, 12-dimethylbenz[a] anthracene(DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin tumorigenesis in ICR mice. Our results showed that menthol significantly inhibited TPA-induced inflammatory responses and pro-inflammatory cytokine release. We also found that menthol treatment significantly inhibited TPA-induced lipid peroxidation (LPO), mouse UDP-glucumno-syltransferase (UGT), mouse NADH Dehydrogenase, Quinone 1 (NQO1) release. Furthermore, we found menthol treatment significantly inhibited the tumor incidence and number of tumors (P < 0.001). Interestingly, we observed that menthol treatment significantly inhibited TPA-induced altered activity of NF-κB in skin tumor. Consistently, menthol-treated tumors also showed significantly suppressed the Ras-Raf-ERK signaling pathway. Thus, our results suggest that menthol inhibits DMBA/TPA-induced skin tumorigenesis by attenuating the Ras and inhibiting NF-κB activity via inhibition of inflammation responses and pro-inflammatory cytokine release.

Keywords: DMBA/TPA, NF-κB, Ras-Raf-ERK, skin tumorigenesis

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Authors: Pooja Mongia Raj, Rakesh Raj, Alpana Ram

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Background: The use of multiparticulate drug delivery systems in preference to single unit dosage forms for colon targeting purposes dates back to 1985 when Hardy and co-workers showed that multiparticulate systems enabled the drug to reach the colon quickly and were retained in the ascending colon for a relatively long period of time. Methods: Site-specific colonic drug delivery system (nanoparticles) of 5-ASA were prepared and coated with pH sensitive polymer. Chitosan nanoparticles (CTNP) bearing 5-Amino salicylic acid (5-ASA) were prepared, by ionotropic gelation method. Nanoparticulate dosage form consisting of a hydrophobic core enteric coated with pH-dependent polymer Eudragit S-100 by solvent evaporation method, for the effective delivery of drug to the colon for treatment of ulcerative colitis. Results: The mean diameter of CTNP and ECTNP formulations were 159 and 661 nm, respectively. Also optimum value of polydispersity index was found to be 0.249 [count rate (kcps) was 251.2] and 0.170 [count rate (kcps) was 173.9] was obtained for both the formulations respectively. Conclusion: CTNP and Eudragit chitosan nanoparticles (ECTNP) was characterized for shape and surface morphology by scanning electron microscopy (SEM) appeared to be spherical in shape. The in vitro drug release was investigated using USP dissolution test apparatus in different simulated GIT fluids showed promising release. In vivo experiments are in further proceeding for fruitful results.

Keywords: colon targeting, nanoparticles, polymer, 5-amino salicylic acid, edragit

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Authors: Louise Penzenstadler, Tiphaine Robet, Radu Iuga, Daniele Zullino

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Context: The outpatient clinic of the psychiatric addiction service of Geneva University Hospital has been providing support to individuals affected by various narcotics for 30 years. However, the increasing consumption of crack cocaine in Geneva has presented a new challenge for the healthcare system. Research Aim: The aim of this research is to evaluate the impact of an outreach intervention on crack cocaine addiction in users with co-occurring opioid use disorder. Methodology: The research utilizes a combination of quantitative and qualitative retrospective data analysis to evaluate the effectiveness of the outreach intervention. Findings: The data collected from October 2023 to December 2023 show that the outreach program successfully made 1,071 contacts with drug users and led to 15 new requests for care and enrollment in treatment. Patients expressed high satisfaction with the intervention, citing easy and rapid access to treatment and social support. Theoretical Importance: This research contributes to the understanding of the challenges and specific needs of a complex group of drug users who face severe health problems. It highlights the importance of outreach interventions in establishing trust, connecting users with care, and facilitating medication-assisted treatment for opioid addiction. Data Collection: Data was collected through the outreach program's interactions with drug users, including street outreach interventions and presence at locations frequented by users. Patient satisfaction surveys were also utilized. Analysis Procedures: The collected data was analyzed using both quantitative and qualitative methods. The quantitative analysis involved examining the number of contacts made, new requests for care, and treatment enrollment. The qualitative analysis focused on patient satisfaction and their perceptions of the intervention. Questions Addressed: The research addresses the following questions: What is the impact of an outreach intervention on crack cocaine addiction in users with co-occurring opioid use disorder? How effective is the outreach program in connecting drug users with care and initiating medication-assisted treatment? Conclusion: The outreach program has proven to be an effective intervention in establishing trust with crack users, connecting them with care, and initiating medication-assisted treatment for opioid addiction. It has also highlighted the importance of addressing the specific challenges faced by this group of drug users.

Keywords: crack addiction, outreach treatment, peer intervention, polydrug use

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Authors: Xuan Li, Xiaobing Cui, Nan Meng, Shuangshuang Guo, Lingling Wang

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Objective: To investigate the influence of Paeonol on diabetic nephropathy progression in streptozocin (STZ) -induced diabetic rats. Method Male Wistar rats were injected STZ 30mg.kg-1 combined with Freund's complete adjuvant (CFA) 0.1mL/rat once a week for three weeks. The diabetic rats were treated with Paenol for 13 weeks. At the end of the experiments, the rats were anesthetized. Serum and the kidney were collected. Serum superoxide dismutase (SOD) activity, malondialdehyde (MDA), blood urea nitrogen (BUN), creatinine (Cr) and total cholesterol (Chol) level were detected; kidney paraffin sections were prepared and HE and PAS staining sections were used to evaluate the pathology changes of the kidney. Immunohistochemical analysis was used to observe the expression of VEGF and fibernectin expression in the kidney. Result The blood glucose level remained over 16mmol. L-1 for 13 weeks and the ECM accumulated in the diabetic kidney apparently. Paeonol treatment increased serum SOD activity, however, MDA, BUN, Cr, and Chol level was decreased by paeonol treatment. VEGF and fibernectin expression were increased significantly in the DN rats and paeonol treatment ameliorated the overexpression. Conclusion: paeonol prevented the progression of DN.

Keywords: paeonol, STZ, diabetic nephropathy, fibernectin expression, kidney paraffin sections

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Authors: K. Digheche, K. Saadi, Z. Boumerzoug

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Welding is one of the most important technological processes used in many branches of industry such as industrial engineering, shipbuilding, pipeline fabrication among others. Generally, welding is the preferred joining method and most common steels are weldable. This investigation is a contribution to scientific work of welding of low carbon steel. This work presents the results of the isothermal heat treatment effect at 200, 400 and 600 °C on microstructural evolution in weld region of X70 pipeline steel. The welding process has been realized in three passes by industrial arc welding. We have found that the heat treatments cause grain growth reaction.

Keywords: heat treatments, low carbon steel, microstructures, welding

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Authors: Batoul Mohamed Abdullatif, Nouf Ali Asiri

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O. basilicum plant was subjected to deficit irrigation using four treatments viz. control, irrigated with 70% of soil water capacity (SWC), Treatment 1, irrigated with 50% SWC, Treatment 2, irrigated with 30% SWC and Treatment 3, irrigated with 10 % SWC. Photosynthesis pigments viz. chlorophyll a, b, and the carotenoids, proline accumulation, and oil quantity were investigated under these irrigation treatments. The results indicate that photosynthesis pigments and oil content of deficit irrigation treatments did not significantly reduced than that of the full irrigation control. Photosynthesis pigments were affected by the stage of growth and not by irrigation treatments. They were high during flowering stage and low during seed formation stage for all treatments. The lowest irrigation plants (10 % SWC) achieved, during flowering stage, 0.72 mg\g\fresh weight of chlorophyll a, compared to 0.43 mg\g\fresh weight in control plant, 0.40 mg\g\fresh weight of chlorophyll b, compared to 0.19 mg\g\fresh weight in control plants and 0.29 mg\g\fresh weight of carotenoids, compared to 0.21 mg\g\fresh weight in control plants. It has been shown that reduced irrigation rates tend to enhance O. basilicum to have high oil quantity reaching a value of 63.37 % in a very low irrigation rate (10 % SWC) compared to 45.38 of control in seeds. Proline was shown to be accumulated in roots to almost double the amount in shoot during flowering stage in treatment 3. This accumulation seems to have a pronounce effect on O. basilicum acclimation to deficit irrigation.

Keywords: deficit irrigation, photosynthesis pigments, proline accumulation, oil quantity, sweet basil flowering formation, seed formation

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Authors: Shanaka Gunasekara, Maleen Jayasuriya, Nalin Harischandra, Lilantha Samaranayake, Gamini Dissanayake

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One serious facet of the worsening Human-Elephant conflict (HEC) in nations such as Sri Lanka involves elephant-train collisions. Endangered Asian elephants are maimed or killed during such accidents, which also often result in orphaned or disabled elephants, contributing to the phenomenon of lone elephants. These lone elephants are found to be more likely to attack villages and showcase aggressive behaviour, which further exacerbates the overall HEC. Furthermore, Railway Services incur significant financial losses and disruptions to services annually due to such accidents. Most elephant-train collisions occur due to a lack of adequate reaction time. This is due to the significant stopping distance requirements of trains, as the full braking force needs to be avoided to minimise the risk of derailment. Thus, poor driver visibility at sharp turns, nighttime operation, and poor weather conditions are often contributing factors to this problem. Initial investigations also indicate that most collisions occur in localised “hotspots” where elephant pathways/corridors intersect with railway tracks that border grazing land and watering holes. Taking these factors into consideration, this work proposes the leveraging of recent developments in Convolutional Neural Network (CNN) technology to detect elephants using an RGB/infrared capable camera around known hotspots along the railway track. The CNN was trained using a curated dataset of elephants collected on field visits to elephant sanctuaries and wildlife parks in Sri Lanka. With this vision-based detection system at its core, a prototype unit of an early warning system was designed and tested. This weatherised and waterproofed unit consists of a Reolink security camera which provides a wide field of view and range, an Nvidia Jetson Xavier computing unit, a rechargeable battery, and a solar panel for self-sufficient functioning. The prototype unit was designed to be a low-cost, low-power and small footprint device that can be mounted on infrastructures such as poles or trees. If an elephant is detected, an early warning message is communicated to the train driver using the GSM network. A mobile app for this purpose was also designed to ensure that the warning is clearly communicated. A centralized control station manages and communicates all information through the train station network to ensure coordination among important stakeholders. Initial results indicate that detection accuracy is sufficient under varying lighting situations, provided comprehensive training datasets that represent a wide range of challenging conditions are available. The overall hardware prototype was shown to be robust and reliable. We envision a network of such units may help contribute to reducing the problem of elephant-train collisions and has the potential to act as an important surveillance mechanism in dealing with the broader issue of human-elephant conflicts.

Keywords: computer vision, deep learning, human-elephant conflict, wildlife early warning technology

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Authors: William G. "Gus" Simmons

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Municipal and industrial wastewater plants across our country utilize anaerobic digestion as either primary treatment or as a means of waste sludge treatment and reduction. The emphasis on renewable energy and clean energy over the past several years, coupled with increasing electricity costs and increasing consumer demands for efficient utility operations has led to closer examination of the potential for harvesting the energy value of the biogas produced by anaerobic digestion. Although some facilities may have already come to the belief that harvesting this energy value is not practical or a top priority as compared to other capital needs and initiatives at the wastewater plant, we see that many are seeing biogas, and an opportunity for additional revenues, go up in flames as they continue to flare. Conversely, few wastewater plants under progressive and visionary leadership have demonstrated that harvesting the energy value from anaerobic digestion is more than “smoke and hot air”. From providing thermal energy to adjacent or on-campus operations to generating electricity and/or transportation fuels, these facilities are proving that energy harvesting can not only be profitable, but sustainable. This paper explores ways in which wastewater treatment plants can increase their value and import to the communities they serve through the generation of clean, renewable energy; also presented the processes in which these facilities moved from energy and cost sinks to sparks of innovation and pride in the communities in which they operate.

Keywords: anaerobic digestion, harvesting energy, biogas, renewable energy, sustainability

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Authors: Jin-Hui Lee, Myung-Min Oh

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The application of temporary abiotic stresses before crop harvest is a potential strategy to enhance phytochemical content. The objective of this study was to determine the effect of various UV-A LED lights on the growth and content of bioactive compounds in kale (Brassica oleracea var. acephala). Fourteen-day-old kale seedlings were cultivated in a plant factory with artificial lighting (air temperature of 20℃, relative humidity of 60%, photosynthesis photon flux density (PPFD) of 125 µmol·m⁻²·s⁻¹) for 3 weeks. Kale plants were irradiated by four types of UV-A LEDs (peak wavelength; 365, 375, 385, and 395 nm) with 30 W/m² for 7 days. As a result, image chlorophyll fluorescence (Fv/Fm) value of kale leaves was lower as the UV-A LEDs peak wavelength was shorter. Fresh and dry weights of shoots and roots of kale plants were significantly higher in the plants under UV-A than the control at 7 days of treatment. In particular, the growth was significantly increased with a longer peak wavelength of the UV-A LEDs. The results of leaf area and specific leaf weight showed a similar pattern with those of growth characteristics. Chlorophyll content was highest in kale leaves subjected to UV-A LEDs with the peak wavelength of 395 nm at 3 days of treatment compared with the control. Total phenolic contents of UV-A LEDs with the peak wavelength of 395 nm at 5 and 6 days of treatment were 44% and 47% higher than those of the control, respectively. Antioxidant capacity showed almost the same pattern as the results of total phenol content. The activity of phenylalanine ammonia-lyase was approximately 11% and 8% higher in the UV-A LEDs with the peak wavelength of 395 nm compared to the control at 5 and 6 days of treatment, respectively. Our results imply that the UV-A LEDs with relative longer peak wavelength were effective to improve growth as well as the content of bioactive compounds of kale plants.

Keywords: bioactive compounds, growth, Kale, UV-A LEDs

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Authors: M. Yadegari, M. Nourbakhsh, N. Arbabzadeh

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The skeletal system injuries are of major importance. In addition, it is recommended to use materials for hard tissue repair in open or closed fractures. It is important to use complex minerals with a beneficial effect on hard tissue repair, stimulating cell growth in the bone. Materials that could help avoid bone fracture inflammatory reaction and speed up bone fracture repair are of utmost importance in the treatment of bone fractures. Similar to minerals, the inner eggshell membrane consists of carbohydrates, lipids, proteins with the high pH, high calcium absorptive capacity and with faster bone fracture repair ability. In the present radiographic survey, eggshell-derived bone graft substitutes were used for bone defect repair in 8 dog tibia, measuring bone density on the day of implant placement and 30 and 60 days after placement. In fact, the result of this study shows the difference in bone growth and misshapen bones between treatment and control sites. Cell growth was adequate in treatment sites and misshapen bones were less frequent here than in control sites.

Keywords: bone repair, eggshell powder, implant, radiography

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Authors: Justina I. Reamen

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The study examined the influence of rational emotive therapy on the treatment of substance abuse among Senior Secondary School Students in Makurdi metropolis Benue State Nigeria. This research adopted youth self report scale which was distributed to 1,690 SSS Students drawn from Government day Secondary School Makurdi and Government Model College Makurdi. Afterwards, 200 who were identified to indulge in substance abuse were selected for the study, 100 each from the two schools. 100 were taken as the control group and 100 as the experimental group, (50 of each group from each school). The Rational Emotive Behavior Therapy (REBT) intervention program was presented to the experimental group for seven (7) weeks. The students were taught how to apply REBT’s cognitive, Emotive and Behavioral techniques on their problems. After which post test was conducted to find out the impact of REBT on the treatment of adolescent students with substance abuse problem. GLM repeated measures of ANOVA were used to analyze the data from the study. The study reveals that REBT has positive impact on the treatment of adolescent students that abuse substances in the study area. Between pretest to post-test scores, a significant difference was observed (F=26.939; P=000) in substance abuse where a decrease of 1.12 (pre-10.91, post-9.79) scores was noticed irrespective of the groups. However, when the decrease in substance abuse were analyzed group wise, (experimental control) again significant F value (F=38.782; P=000) was obtained. From the mean scores it is evident that experimental group decreased it means by 2.56 (Pre-10.04 - Post-8.83) scores compared to control group, which changed its scores by only 0.32 scores (pre 11.04 - Post 11.36). Recommendations were made based on the findings of the research.

Keywords: abuse, influence, substance, therapy, treatment

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Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

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Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

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Authors: Kadir Mokrane, Souag Doudja

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In Algeria, one of the Mediterranean countries, water resources are limited and unevenly distributed in space and in time. Boumerdes, coastal town of Algeria, known for its farming and fishing activities. The region is also known for its semi-arid climate and a large water deficit. In order to preserve the quality of water bodies and to reduce withdrawals in the natural environment, it is necessary to seek alternative supplies. The reuse of treated wastewater seems to be a good alternative, especially for irrigation. In the framework of sustainable development, it is imperative to rationalize the use of water resources conventional and unconventional. That is why the re-use agricultural of by-products of the treatment is an alternative expected to preserve the environment and promotion of the agricultural sector. The present work aims, to search for the possibility of reuse of treated wastewater, and sludge resulting from treatment plant of the city of Boumerdes in agriculture, through the analysis of physical, chemical and bacteriological on the samples, and the continuous monitoring of the evolution of several elements during the period of study extended over 12 months, and then, the comparison of these test results to standards and guidelines established in the framework of irrigation and land application.

Keywords: treated water, sewage sludge, recycling, agriculture

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Authors: Anan Jarab, Riham Almrayat, Salam Alqudah, Maher Khdour, Tareq Mukattash, Sharell Pinto

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Background: The prevalence of diabetes in Jordan is among the highest in the world, making it a particularly alarming health problem there. It has been indicated that poor adherence to the prescribed therapy lead to poor glycemic control and enhance the development of diabetes complications and unnecessary hospitalization. Purpose: To explore factors associated with medication non-adherence in patients with type 2 diabetes in Jordan. Materials and Methods: Variables including socio-demographics, disease and therapy factors, diabetes knowledge, and health-related quality of life in addition to adherence assessment were collected for 171 patients with type 2 diabetes using custom-designed and validated questionnaires. Logistic regression was performed to develop a model with variables that best predicted medication non-adherence in patients with type 2 diabetes in Jordan. Results: The majority of the patients (72.5%) were non-adherent. Patients were found four times less likely to adhere to their medications with each unit increase in the number of prescribed medications (OR = 0.244, CI = 0.08-0.63) and nine times less likely to adhere to their medications with each unit increase in the frequency of administration of diabetic medication (OR = 0.111, CI = 0.04-2.01). Patients in the present study were also approximately three times less likely (OR = 0.362, CI = 0.24-0.87) to adhere to their medications if they reported having concerns about side effects and twice more likely to adhere to medications (OR = 0.493, CI = 0.08-1.16) if they had one or more micro-vascular complication. Conclusion: The current study revealed low adherence rate to the prescribed therapy among Jordanians with type 2 diabetes. Simplifying dosage regimen, selecting treatments with lower side effects along with an emphasis on diabetes complications should be taken into account when developing care plans for patients with type 2 diabetes.

Keywords: type 2 diabetes, adherence, glycemic control, clinical pharmacist, Jordan

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Authors: Hanan Al-Khalaifah, Afaf Al-Nasser

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Probiotics and prebiotics claimed to serve as effective alternatives to antibiotics in the poultry. This study aims to investigate the effect of different probiotics and prebiotics on the economic impact analysis of the use of probiotics and prebiotics in broiler feed. The study involved four broiler cycles, two during winter and two during summer. In the first two cycles (summer and winter), different types of prebiotics and probiotics were used. The probiotics were Bacillus coagulans (1 g/kg dried culture) and Lactobacillus (1 g/kg dried culture of 12 commercial strains), and prebiotics included fructo-oligosaccharides (FOS) (5 g/kg) and mannan-oligosaccharide (MOS) derived from Saccharomyces cerevisiae (5 g/kg). Based on the results obtained, the best treatment was chosen to be FOS, from which different ratios were used in the last two cycles during winter and summer. The levels of FOS chosen were 0.3, 0.5, and 0.7% of the diet. From an economic point of view, it was generally concluded that in all dietary treatments, food was consumed less in cycle 1 than in cycle 2, the total body weight gain was more in cycle 1 than cycle 2, and the average feed efficiency was less in cycle l than cycle 2. This indicates that the weather condition affected better in cycle 1. Also, there were very small differences between the dietary treatments in each cycle. In cycle 1, the best total feed consumption was for the FOS treatment, the highest total body weight gain and average feed efficiency were for B. coagulans. In cycle 2, all performance was better in FOS treatment. FOS significantly reduced the Salmonella sp. counts in the intestine, where the environment was driven towards acidity. FOS was the best on the average taste panel study of the produced meat. Accordingly, FOS prebiotic was chosen to be the best treatment to be used in cycles 3 and 4. The economic impact analysis generally revealed that there were no big differences between the treatments in all of the studied indicators, but there was a difference between the cycles.

Keywords: antibiotic, economic impact, prebiotic, probiotic, broiler

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Authors: E. A. Kiridi, A. O. Ogunlela

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The control of ammonia build-up and its by-product is a limiting factor for a successful commercial aquaculture in a developing country like Nigeria. The technology for an advanced treatment of fish tank effluent is uneconomical to local fish farmers which have led to indiscriminate disposal of aquaculture wastewater, thereby increasing the concentrations of these nitrogenous compound and other contaminants in surface and groundwater above the permissible level. Phytoremediation using water lettuce could offer cheaper and sustainable alternative. On the first day of experimentation, approximately 100 g of water lettuce were replicated in four hydroponic units containing aquaculture effluents. The water quality parameters measured were concentration of ammonium–nitrogen (NH₄⁺-N), nitrite-nitrogen (NO₂^--N), nitrate-nitrogen (NO₃^--N), and phosphate–phosphorus (PO₄^3--P). Others were total suspended solids (TSS), pH, electrical conductivity (EC), and biomass value. At phytoremediation intervals of 7, 14, 21 and 28 days, the biomass recorded were 361.2 g, 498.7 g, 561.2 g, and 623.7 g. Water lettuce was able to reduce the pollutant concentration of all the selected parameter. The percentage reduction of pH ranged from 3.9% to 14.4%, EC from 49.8% to 96.2%, TDS from 50.4% to 96.2%, TSS from 38.3% to 81.7%, NH₄⁺-N from 38.9% to 90.7%, NO₂^--N from 0% to 74.9%, NO₃^--N from 63.2% to 95.9% and PO₄^3--P from 0% to 76.3%. At 95% confidence level, the analysis of variance shows that F(critical) is less than F(cal) and p < 0.05; therefore, it can be concluded statistically that the inequality between the pre-treatment and post-treatment values are significant. This suggests the potency of water lettuce for remediation of aquaculture effluent.

Keywords: aquaculture effluent, nitrification, phytoremediation, water lettuce

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Authors: Deirdre Mc Grath, Joanne Reid

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Background: Ovarian cancer is the leading cause of mortality among gynaecologic cancers in developed countries and the seventh most common cancer worldwide, with nearly 240,000 women diagnosed each year. Although it is recognized engaging in exercise results in positive health care outcomes, women with ovarian cancer are reluctant to participate. No evidence currently exists focusing on how to successfully implement an exercise intervention program for patients with ovarian cancer, using a realist approach. There is a requirement for the implementation of exercise programmes within the oncology health care setting as engagement in such interventions has positive health care outcomes for women with ovarian cancer both during and following treatment. Aim: To co-design the implementation of an exercise intervention for women following treatment for ovarian cancer. Methods: This study is a realist evaluation using quantitative and qualitative methods of data collection and analysis. Realist evaluation is well-established within the health and social care setting and has, in relation to this study, enabled a flexible approach to investigate how to optimise implementation of an exercise intervention for this patient population. This single centre study incorporates three stages in order to identify the underlying contexts and mechanisms which lead to the successful implementation of an exercise intervention for women who have had treatment for ovarian cancer. Stage 1 - A realist literature review. Stage 2 -Co-design of the implementation of an exercise intervention with women following treatment for ovarian cancer, their carer’s, and health care professionals. Stage 3 –Implementation of an exercise intervention with women following treatment for ovarian cancer. Evaluation of the implementation of the intervention from the perspectives of the women who participated in the intervention, their informal carers, and health care professionals. The underlying programme theory initially conceptualised before and during the realist review was developed further during the co-design stage. The evolving programme theory in relation to how to successfully implement an exercise for these women is currently been refined and tested during the final stage of this realist evaluation which is the implementation and evaluation stage. Results: This realist evaluation highlights key issues in relation to the implementation of an exercise intervention within this patient population. The underlying contexts and mechanisms which influence recruitment, adherence, and retention rates of participants are identified. Conclusions: This study will inform future research on the implementation of exercise interventions for this patient population. It is anticipated that this intervention will be implemented into practice as part of standard care for this group of patients.

Keywords: exercise, ovarian cancer, co-design, implementation

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Authors: Laila Niklasson

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The aim of the study is to critically discuss how partner schools are engaged during Initial teacher education, ITE. The background is an experiment in Sweden where the practicum organization is reorganized due to a need to enhance quality during practicum. It is a national initiative from the government, supported by the National Agency of Education and lasts 2014-2019. The main features are concentration of students to school with a certain amount of mentors, mentors who have a mentor education and teachers with relevant subject areas and where there could be a mentor team with a leader at the school. An expected outcome is for example that the student teachers should be engaged in peer-learning. The schools should be supported by extra lectures from university teachers during practicum and also extra research projects where the schools should be engaged. A case study of one university based ITE was carried out to explore the consequences for the schools not selected. The result showed that from engaging x schools in a region, x was engaged. The schools are both in urban and rural areas, mainly in the latter. There is also a tendency that private schools are not engaged. On a unit level recruitment is perceived as harder for schools not engaged. In addition they cannot market themselves as ´selected school´ which can affect parent´s selection of school for their children. Also, on unit level, but with consequences for professional development, they are not selected for research project and thereby are not fully supported during school development. The conclusion is that from an earlier inclusive approach concerning professions where all teachers were perceived as possible mentors, there is a change to an exclusive approach where selected schools and selected teachers should be engaged. The change could be perceived as a change in governance mentality, but also in how professions are perceived, and development work is pursued.

Keywords: initial teacher education, practicum schools, profession, quality development

Procedia PDF Downloads 142

Authors: Dalila Hammiche, Lisa Klaai, Amar Boukerrou

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Following this trend, natural fiber reinforcements have been gaining importance in the composites sector. The effectiveness of natural fiber–reinforced PLA composite as an alternative material to substitute the non-renewable petroleum-based materials has been examined by researchers. In this study, we investigated the physicochemical, particle size and distribution, and thermal behavior of prickly pear seed flour (PPSF). Then, composites were manufactured with 20% in PPSF. Thermal, morphological, and mechanical properties have been studied, and water absorption tests as well. The characterization of this fiber has shown that cellulose is the majority constituent (30%), followed by hemicellulose (27%). To improve the fiber-matrix adhesion, the PPS was chemically treated with alkali treatment. The addition of PPSF decreases the thermal properties, and the study of the mechanical properties showed that the increase in the fiber content from 0 to 20% increased Young’s modulus. According to the results, the mechanical and thermal behaviors of composites are improved after fiber treatment. However, there is an increase in water absorption of composites compared to the PLA matrix. The moisture sensitivity of natural fiber composites limits their use in structural applications. Degradation of the fiber-matrix interface is likely to occur when the material is subjected to variable moisture conditions.

Keywords: biopolymer, composites, alcali treatment, mechanical properties

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Authors: Chih-Rong Shyr, Chi-Ping Huang

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Intravesical BCG is the gold-standard therapy for high risk non-muscle invasive bladder cancer (NMIBC) after TURBT, but if not responsive to BCG, these BCG unresponsive patients face cystectomy that causes morbidity and comes with a morality risk. To provide the bladder sparing options for patients with BCG-unresponsive NMIBC, several new treatments have been developed to salvage the bladders and prevent progression to muscle invasive or metastatic, but however, most approved or developed treatments still fail in a significant proportion of patients without long term success. Thus more treatment options and the combination of different therapeutic modalities are urgently needed to change the outcomes. Xenogeneic rejection has been proposed to a mechanism of action to induce anti-tumor immunity for the treatment of cancers due to the similarities between rejection mechanism to xenoantigens (proteins, glycans and lipids) and anti-tumor immunities to tumor specific antigens (neoantigens, tumor associated carbohydrates and lipids). Xenogeneic urothelial cells (XUC) of porcine origin have been shown to induce anti-tumor immune responses to inhibit bladder tumor progression in mouse bladder cancer models. To further demonstrate the efficacy of the distinct intravesical XUC treatment in NMIBC, and the combined effects with chemotherapy and immune checkpoint inhibitors (ICIs) as a alternate therapeutic option, this study investigated the therapeutic effects and mechanisms of intravesical XUC immunotherapy in an orthotopic mouse immune competent model of NMIBC, generated from a mouse bladder cancer cell line. We found that the tumor progression was inhibited by intravescial XUC treatment and there was a synergy between intravesical XUC with intravesical chemotherapeutic agent, gemcitabine or systemic ICI, anti-PD1 antibody treatment. The cancer cell proliferation was decreased but the cell death was increased by the intravecisal XUC treatment. Most importantly, the mechanisms of action of intravesical XUC immunotherapy were found to be linked to enhanced infiltration of CD4+ and CD8+ T-cell as well as NK cells, but decreased presence of myeloid immunosuppressive cells in XUC treated tumors. The increased stimulation of immune cells of XUC treated mice to xenogeneic urothelial cells and mouse bladder cancer cells in immune cell proliferation and cytokine secretion were observed both as a monotherapy and in combination with intravesical gemcitabine or systemic anti PD-L1 treatment. In sum, we identified the effects of intravesical XUC treatment in monotherapy and combined therapy on tumor progression and its cellular and molecular events related to immune activation to understand the anti-tumoral mechanisms behind intravesical XUC immunotherapy for NMIBC. These results contribute to the understanding of the mechanisms behind successful xenogeneic cell immunotherapy against NMIBC and characterize a novel therapeutic approach with a new xenogeneic cell modality for BCG-unresponsive NMIBC.

Keywords: xenoantigen, neoantigen, rejection, immunity

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Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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