SACM - Germany
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Item Restricted The supplementary effect of transcranial direct current stimulation during upper limb motor practice on consolidation in healthy older adults(Saudi Digital Library, 2023) Mazi, Aseel; Nieuwboer, Alice; Vandendoorent, BrittBackground: Ageing affects the consolidation of learned motor skills. Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex in conjunction with motor sequence learning (MSL) improves consolidation. However, the effects of tDCS of the primary motor cortex (M1) on consolidation are still unclear. Additionally, it seems that the conventional tDCS montage (CONV-tDCS) generates a relatively non-focal stimulation compared to high-definition tDCS (HD-tDCS). So far, it is unknown whether the effects of tDCS depends on its montage. Objective: First, to compare tDCS and sham of the M1 during MSL on dual task (DT) performance as a measure of consolidation. Second, to compare CONV-tDCS and HD-tDCS of the M1 during MSL on DT performance. We hypothesize that tDCS, particularly HD-tDCS, when added to MSL grants superior DT performance compared to sham in older adults. Methods: This study was a sham-controlled randomized double-blind trial with a crossover for tDCS montage. Fifty-two participants were allocated to the active or sham tDCS group. Two sessions of twenty minutes of 1mA tDCS or sham of the M1 were administered during a serial reaction time task (SRTT). DT performance on the SRTT (DT-SRTT) was evaluated by adding an auditory Stroop task. The primary outcome was the mean reaction time on the DT-SRTT after the intervention. Results: The linear mixed model revealed no effect of group (p=.570) or montage (p=.946) on the DT-SRTT. Nevertheless, the mean reaction time of the single task SRTT (ST-SRTT) and DT-SRTT showed a significant improvement over time (p<0.001). Conclusion: DT performance improved with practice in older adults, irrespective of applying tDCS. We conclude that tDCS of the M1 has no surplus benefit on consolidation.17 0Item Restricted Examining the methane potential of a fiberbank sediment using two-stage anaerobic digestion system.(Saudi Digital Library, 2025) ALfaraj, Ali; Isaksson, SimonPrior to the introduction of the environmental protection act by the Swedish government in 1969, the pulp and paper (P&P) industry discharged its process wastewater directly into the waterbodies, leading to an environmental impact in the form of fiberbank sediment. The fiberbank sediment consists of a high amount of biodegradable material and toxic compounds from industrial processing, posing environmental risks such as greenhouse gas (GHG) emission and the release of toxic substances into the surrounding environment. The traditional remediation methods of contaminated sediment such as dredging and landfilling are not feasible due to the potential of emission of GHG in storage. To address this issue, anaerobic digestion (AD) in two stage configurations is proposed as pre-treatment before storage. The feasibility of the proposed solution was evaluated through laboratory experiments using CSTR reactors and by co-digestion of fiber bank sediment with primary sludge from a wastewater treatment facility. In the acidogenesis stage, an 80:20 ratio of fiberbank sediment (FB) to primary sludge (PS) was found to be optimal for maximizing volatile fatty acid (VFA) production. In the methanogenesis stage, 5% of digestate from the acidogenic reactor was mixed with 95% PS on VS basis. The result showed statistically significantly higher volumetric methane production (VMP) of the test reactor (5.1 ± 0.7 L CH4 / L) compared to control reactor (4.6 ± 0.7 L CH4 / L). In contrast, the specific methane production (SMP) showed no significant difference between the test reactor (295 ± 35) compared to control reactor (306 ±37), indicating similar efficiency of biodegradability between the test reactor and control.9 0Item Restricted Comparing human fetal liver-derived mesenchymal stromal cells to human adult bone marrow-derived mesenchymal stromal cells(Saudi Digital Library, 2019) Toonsi, Mawaddah; Götherström, Cecilia; Abomaray, Fawaz; Walther Jallow, LilianBackground: Mesenchymal stromal cells (MSC) can be isolated from various tissue sources and can be derived from adult and fetal tissues. Depending on their age, MSC have different therapeutic potentials. In this study human fetal liver MSC (fMSC) were compared to adult bone marrow MSC (aMSC) regarding their phenotype and function. Methods: fMSC and aMSC were compared in terms of their size using CASY TT and their senescence using ß-galactosidase staining. Population doublings (PD) and population doubling time (PDT) were also examined. Following induction of osteogenic differentiation, calcium deposits were stained using Alizarin red S. Finally, flow cytometry was used to examine the cells’ phenotype and purity. Results: fMSC had a significantly lower peak diameter compared to aMSC. Moreover, fMSC displayed a greater number of PD and a shorter PDT in comparison to aMSC, and the percentage of fMSC undergoing senescence was significantly lower than aMSC. Furthermore, fMSC that were induced into osteoblasts deposited more calcium salts, and hence stained more positive for Alizarin red S relative to aMSC. Finally, both cell sources were positive for the MSC markers CD90 and CD73 and negative for the non-MSC markers CD45, CD31 and HLA class II. Conclusions: The results of the study demonstrate that fMSC possess a greater proliferative and osteogenic differentiation capacity compared to aMSC. Altogether, fMSC may be a more robust cell source compared to aMSC as a therapy for diseases, including those that require bone repair.13 0Item Restricted The Role of Gamma Delta T Cells in Haematopoietic Stem Cell Transplantation and Malignancies(Saudi Digital Library, 2025) Alagrafi, Faisal Sultan; Michael, Uhlin; Mikael, Sundin; supervisor, Main; Thomas, PoiretAllogeneic haematopoietic stem cell transplantation (aHCT) is a potentially curative immunotherapeutic approach for several lethal hematological disorders. However, morbidity and mortality rates remain high after aHCT due to complications such as relapse, graft-versus-host disease (GVHD), and infections. Successful aHCT requires rapid and effective immune reconstitution, particularly within the T-cell compartment, to protect against opportunistic infections and to eliminate residual tumor cells without aggravating GVHD during the immunocompromised period following transplantation. Early reconstitution of γδ T cells plays a substantial role in immune surveillance post-aHCT via mediating anti-infection and anticancer immunity, correlating with favorable clinical outcomes with less GVHD incidence. These unique features have attracted increasing attention towards harnessing γδ T cells as effector cells for cancer immunotherapy. This thesis presents three papers to bring further knowledge on the role of γδ T cells in the dimension of aHCT and their potential use in hematological malignancy therapy. Study I aimed to investigate long-term homeostatic steady-state γδ T cell reconstitution after aHCT, focusing on its associations with previous clinical outcomes. We performed an in-depth analysis of γδ T cell phenotypes, TCR-Y repertoire, and functional responses upon stimulation in 20 recipient/donor pairs using multiparametric flow cytometry and next-generation sequencing of the TCR-y chain. Results showed a comparable phenotypic profile between recipients and donors. Upon PMA/lonomycin stimulation, recipient γδ T cells secreted high levels of cytokines. Furthermore, the TRG repertoire in recipients was almost completely restored, with no significant differences in diversity, clonality, or gene segment usage compared to donors. However, we found an association between overrepresented donor-derived clonotypes and elevated HLA-DR expression in Vδ1 T cells with increased severity of chronic GVHD in some recipients. Study II focused on augmenting the antileukemic activity of expanded γδ T cells by CD34/CD3 bispecific T-cell engager (BTE) in vitro. We demonstrated that the CD34/CD3 BTE effectively activates and redirects γδ T cells (effector cells) against CD34-expressing leukemia cell lines (target cells), as evidenced by their specific cytotoxicity in a dose-dependent manner and high cytokine release. Furthermore, CD34/CD3 BTE induced γδ T cell-mediated killing of primary CD34+ AML blasts. In the presence of CD34/CD3, γδ T cells showed superior antileukemic activity compared to conventional aß T cells, while demonstrating no cytotoxic effects against CD34+ normal cells. In Study III, we aimed to further enhance the antileukemic activity of expanded yo T cells by sensitizing leukemia cells with thymoquinone (TQ) treatment. TQ is a phytochemical compound featuring epigenetic activity and immunomodulatory properties with growing evidence as a potent anticancer candidate. We observed that γδ T cells exhibited rapid and increased cytotoxicity when co-cultured with pre-treated leukemia cell lines with TQ compared to vehicle control and untreated conditions. This enhanced cytotoxicity could be attributed to the upregulated expression of NKG2D and DNAM-1 ligands on leukemia cells after TQ treatment. We also showed that TQ pretreatment in leukemia cell lines supports the condition of the γδ T cells-based CD34/CD3 approach. Altogether, this thesis investigated that long-term γδ T cell reconstitution reaches a homeostatic state with a normalized repertoire. Elevated HLA-DR expression on Vδ1 T cells in cGVHD recipients could be a potential therapeutic target, warranting further investigation. It also highlights the potential use of expanded γδ T cells in hematological malignancy therapy by targeting CD34 and sensitizing leukemia cell lines through thymoquinone for CD34/CD3 BTE treatment11 0Item Restricted Development of a phase-field model for corrosion and degradation in bioresorbable stents(Saudi Digital Library, 2022) Harban, Ibrahim Abdullah; Döring, Daniela; Karras, IngoAccording to the World Health Organization (WHO), cardiovascular diseases—particularly chronic coronary heart disease (CHD) and myocardial infarction—are the leading causes of death in industrialized countries. In 2019, an estimated nine million people died from heart diseases, with 60% of these deaths attributable to CHD. Due to demographic change, an aging population is expected, leading to an increase in degenerative diseases and greater challenges for healthcare systems. Two treatment options currently exist for CHD: coronary artery bypass grafting (CABG), which is performed surgically and in hospital settings, and percutaneous transluminal coronary angioplasty (PTCA), introduced in 1977, where a stent is placed minimally invasively without requiring extended hospitalization. Although stent-based therapy has advantages over CABG in medical and economic terms, a recent meta-analysis shows the superiority of bypass surgery in improving 10-year survival rates, partly due to side effects of PTCA. Current research therefore focuses on bioresorbable materials for stent manufacturing, aiming to provide safer, more effective, and sustainable patient care compared to conventional permanent stents. While bioresorbable stents appear promising, their degradation behavior still leads to complications, preventing them from surpassing permanent stents at present. Ongoing projects aim to better predict corrosion processes and improve the safety of bioresorbable stents, with fracture mechanics and phase-field modeling representing promising approaches. This thesis analyzes the method of percutaneous transluminal coronary angioplasty (PTCA) and stent implantation in order to evaluate its advantages and disadvantages. The focus is on addressing the following research questions: What risks occur in percutaneous transluminal coronary angioplasty, and how can they be minimized? How can future stents be designed to optimally improve patient care?6 0Item Restricted Creating a Concept and Modelling a Lean Management Simulation Game in Plant Simulation(Saudi Digital Library, 2025) Harban, Ibrahim Abdullah; Näser, Peggy; Kober, DoreenMaterial flow technology has undergone significant development over time. While production processes were initially characterized by manual individual solutions, the introduction of mass production in the early 20th century—especially through Henry Ford’s assembly line principle—revolutionized industrial manufacturing. However, this production method also led to high inventories, long throughput times, and limited flexibility. In response to these challenges, Toyota developed the Toyota Production System (TPS) in the 1950s, which laid the foundation for Lean Management. By applying principles such as waste reduction, just-in-time production, and continuous improvement (Kaizen), more efficient and flexible manufacturing became possible. Today, Lean Production represents a global standard in industrial manufacturing, aiming at resource efficiency, quality enhancement, and delivery reliability. At the same time, material flow technology plays a crucial role in optimizing production and logistics processes, reducing costs, and strengthening competitiveness. Digitalization, especially discrete-event simulation, enables detailed analysis and optimization of material flow. Using software solutions such as Tecnomatix Plant Simulation, companies can model, simulate, and improve complex material flow systems prior to physical implementation. The aim of this thesis is to analyze the theoretical foundations of Lean Production and material flow technology, as well as their practical application in a simulation game. The focus is on evaluating the effectiveness of Lean tools such as 5S, SMED, TPM, and Poka Yoke, and on examining the influence of takt, flow, and pull principles on production performance. The results of the simulation game provide a basis for practice-oriented recommendations for implementing Lean Production in real production environments. Furthermore, the thesis investigates a simulation-based training system for conveying Lean methods. Through a simulation study, the effectiveness of optimization measures in a model factory is evaluated, aiming to derive relevant insights for improving production processes and quantifying the impact of Lean methods on material flow efficiency.13 0Item Restricted Association between Physical Activity, Sedentary Behaviors, and Sleep and Cardiometabolic Health among Adults in the Kingdom of Saudi Arabia: Establishment of the Saudi ProPASS Prospective Cohort Study(Saudi Digital Library, 2025) Alaqil, Abdulrahman Ibrahim; Caserotti, PaoloBackground: Physical behaviors such as physical activity (PA), sedentary behavior (SB), andsleep are crucial indicators of health, with insufficient PA, excessive SB, and poor sleep being linked to higher incidences of non-communicable diseases (NCDs) like cardiovascular disease and diabetes. Globally, many adults do not meet recommended PA levels, and most countries are unlikely to meet global PA targets by 2030. This issue is particularly severe in Saudi Arabia, where urbanization has led to lifestyle changes characterized by low PA, increased SB, and a rising prevalence of NCDs. Despite the significance of these behaviors, there is a lack of comprehensive data on PA, SB, and sleep among Saudi adults. The World Health Organization has flagged in particular the expansion of device-based data to under-represented counties as an urgent research need to enhance understanding of the health impacts of these behaviors. In response, the Prospective Physical Activity, Sitting, and Sleep Consortium (ProPASS) was established as an international research platform to spearhead the expansion of the evidence base and transition to wearables data based global guidelines. Initially, ProPASS focused on thigh-worn and recently ProPASS has expanded to wrist-worn accelerometry devices to collect detailed data on PA, SB,sleep, and their connections to health outcomes. Based on ProPASS methodologies, this Ph.D.study seeks to address this gap by establishing a cohort in Saudi Arabia, thereby providing crucialdata to guide public health strategies in line with Saudi Vision 2030. Objectives: This thesis aimed to establish a prospective cohort that will investigative theassociations between device measured lifestyle behavior (physical activity, sedentary behavior,and sleep time) and cardiometabolic health in a sample of Saudi adults. This thesis seeks to provide preliminary evidence of feasibility and validity of ProPASS methods within Saudi Arabia context as well as initial evidence of associations between 24-hour physical behaviors and cardiometabolichealth in this population. Method: The aims were investigated in three cross-sectional studies with adults in Saudi Arabia.The study I aimed to translated and culture adaptation for three questionnaires which were Sedentary Behavior Questionnaire (SBQ), Dietary Habits Questionnaire adapted from the Surveyof Health, Aging and Retirement in Europe (SHARE), and Preclinical Mobility Limitation questionnaire. The study II aimed to assess the feasibility and acceptability of ProPASS method in Saudi Arabia, where recruitment, acceptability, suitability, of study procedures, and Resources and ability to manage and implement the study were assessed. Lastly, study III investigated the association between physical behaviors and cardiometabolic health markers. Result: The Sedentary Behavior, Dietary Habits SHARE, and Preclinical Mobility Limitation questionnaires are ready to be used in Arabic-speaking countries (Paper I). The ProPASS protocols have a requirement rate of approximately 65% and a high completion rate of about 88%, indicating they are feasible to administer in Saudi Arabia (Paper II). Preliminary results from Study III(n=845) showed that Saudi adults spend 13.07 hours sitting, 2.01 hours standing, 1.08 hour in LIPA, 0.98 hours in MVPA, and 6.85 hours sleeping (Paper III). Conclusion:This thesis successfully established a foundational understanding of physical behaviors, includingPA, SB, and sleep, within a Saudi Arabian context. The translation and cultural adaptation of key questionnaires (SBQ, SHARE Dietary Habits, and Preclinical Mobility Limitation) have made them suitable for use in Arabic-speaking populations, filling a critical gap in tools available forthis region. The feasibility study demonstrated that the ProPASS protocols, which incorporate advanced device-based measurements, are both viable and well-received among Saudi adults, withhigh completion rates. Preliminary findings from the cohort reveal significant patterns of physical behavior, such as prolonged sitting times and limited engagement in MVPA, which are concerning given their associations with cardiometabolic health risks. These results underscore the urgent need for targeted public health strategies to address the sedentary lifestyles prevalent in Saudi Arabia, in alignment with Saudi Vision 2030. The data gathered from this research not only enriches the global understanding of physical behaviors in underrepresented regions but also provides a robust foundation for future studies aimed at mitigating the rising burden of non-communicable diseases in the Kingdom.15 0Item Restricted Appraisal of Sustainable Urban Development in Shaqra City, Saudi Arabia(Eberhard Karls Universität Tübingen, 2024) Alhomaidhi, Ahmed Abdullah; Olaf, KühneThis study thoroughly explores sustainable urban development in Shaqra City, Saudi Arabia. It examines the challenges, opportunities, and solutions needed to promote sustainability in environmental, economic, and social areas. Using thematic and interpretive analyses, the study identifies key factors shaping the city. In terms of the environment, Shaqra City can enhance sustainability by improving agricultural spaces. However, issues like the lack of systematic garbage sorting in waste management reveal the need for focused solutions. In the economic dimension, the city shows potential in family-based businesses and seasonal activities like the Red Pepper Festival. However, challenges such as high fees and operational costs hinder commercial investments. Compared to neighboring regions, Shaqra City's economic growth is relatively slow, emphasizing the need for targeted economic measures. On the social front, efforts to reduce corruption and build trust in municipal institutions show progress. Opinions about gender equality vary, but community well-being is supported by initiatives like educational campaigns and local events. Despite these efforts, challenges such as limited social community initiative and proximity to larger urban centers persist. Opportunities for environmental awareness, cultural understanding, and partnerships can address these issues. The study offers recommendations to address these challenges and harness opportunities. These include environmental conservation, economic diversification, and governance reforms. With collaboration among stakeholders, Shaqra City can progress toward a more sustainable and resilient urban future.14 0Item Restricted Bridging the gaps in mortality data and healthcare access: A novel verbal autopsy application using subnational T2DM register in Saudi Arabia.(University of Gothenburg, 2025) Alyazidi, Faleh; Hussain-Alkhateeb, Laith; Petzold, Max; Shakely, DelérAbstract Background: Diabetes mellitus is an increasingly critical health concern in Saudi Arabia, often with other comorbidities and mortality causes, such as cardiovascular disease (CVD). National sociodemographic changes entail the urgent need for reliable insights on the scale and causes of mortality in order to develop appropriate healthcare policy. Where death certification is inadequate, verbal autopsy (VA) can serve as a useful tool to fill crucial gaps in vital data. This thesis aims to explore various contextual dimensions using the validated VA method. Specifically, this thesis aims to explore the community perception of causes of death, measure the circumstantial barriers (social and health system) to accessing healthcare, assess and validate the adequacy of medical certification of cause of death at population level, and investigate the clinical and demographic factors influencing out of hospital deaths among deceased individuals with specific health conditions T2DM and CVD. Methods: Studies I-IV utilized mortality data from the T2DM register at a major hospital in Makkah City, while Study V used data from the CVD registers at two major hospitals. For the first three studies, 302 VA assessments were conducted with the deceased’s next of kin. The VA data were analyzed using the computerized InterVA-5 software, which provided probable causes of death and circumstances of mortality categories (COMCATs). Study I employed Lin’s concordance correlation coefficient (CCC) to assess the concordance between verbal autopsy causes of death (VACoD) as a presumed reference standard and family-reported causes of death. Also, the study employed multiple logistic regression to identify factors influencing community perception of causes of death. Study II applied epidemiological estimations of absolute measures and Causes Specific Mortality Fractions (CSMFs), while also using numerical and graphical assessment to describe trends and patterns in the VA data. The COMCATs were ranked across the causes of death based on their derived probabilities. Study III employed Lin’s CCC to assess the concordance between physician reviewed causes of death (PRCoD) and VACoD at the population level. Study IV employed multiple logistic regression to identify factors influencing out of hospital deaths among deceased with T2DM, while Study V focused on CVD. Findings: Study I demonstrated broad community perceptions of causes of death, with notable misconceptions related to type of death and marital status. Study II found most deaths were seen as inevitable, with the COMCATs ‘recognition’ and ‘traditions’ being identified as avoidable barriers. Study III showed moderate concordance between PRCoD and VACoD, though discrepancies were apparent in the CSMFs, particularly for the most prevalent causes. Studies IV and V uncovered that cause and year of death in addition to nationality significantly influenced out of hospital deaths, with both studies illustrating decreasing trend of out of hospital mortality. Conclusion: This thesis uncovers challenges for Saudi public health policy concerning T2DM-related mortality, identifying issues in access to healthcare, community perceptions, and medical certification. Misconceptions about mortality causes of death hamper prevention strategies, while health system and sociocultural barriers heighten latent problems. The findings underscore the requirement to enhance the medical certification, as discrepancies between PRCoD and VA data suggest challenges in current practices on population level.7 0Item Restricted Investigation of the role of Kv1.3 and Kv1.6 potassium channels in retinal ganglion cell degeneration in vitro.(Eberhard-Karls-University Tübingen, 2023-12-11) Fallatah, Azdah Hamed; Paquet-Durand, François1.0. Abstract 1.1. Introduction Organotypic retinal explants are an ideal system for identifying and studying potential treatments for retinal diseases, such as inherited retinal degeneration (IRD). In the organotypic retinal explant culture procedure, retinal ganglion cells (RGCs) usually progressively die in response to optic nerve axotomy. Previous studies connected RGC death to excessive NO/cGMP/PKG signalling. Another study showed that PKG targets Kv1.3 and Kv1.6 potassium channels, which are located in the ganglion cell layer (GCL). Others showed that Kv1.3/Kv1.6 potassium channels contribute to RGC degeneration after optic nerve crush in vivo. Interestingly, recent studies showed that PKG inhibition in retinal explants restored the viability and function of RGCs in vitro. Here, we investigated whether the direct inhibition of Kv1.3 and Kv1.6 channels with 50 nM Margatoxin (MrgX) might rescue RGCs in vitro to find a possible relationship between RGCs survival, PKG inhibition, and Kv1.3/Kv1.6 channels. 1.2. Methods For this study, cultures of organotypic retinal explants derived from post-natal day (P) 12 wild type (WT) mice were treated with the Kv1.3/Kv1.6 inhibitor of MrgX until P13 (24h) or P14 (48h). The PKG inhibitor CN238 was used to treat retinal explants at P13 (24h), P14 (48h), and P24. The rate of RGC degeneration was evaluated using both TUNEL-assay, which can label dead cells, and RNA-binding protein with multiple splicing (RBPMS) staining, which is a marker for RGCs. Furthermore, Amacrine cell (AC) staining was used to determine the protective effect of MrgX and CN238. 1.3. Results RGCs survived in vitro after 48h of culture with MrgX, RBPMS-positive cells showed a 70 % increase per mm2. On the other hand, the number of TUNEL-positive cells remained below 1,000 per mm2 in both MrgX-treated and non-treated groups. The overall percent difference in cell death between the two groups was 2%. In cultures treated with CN238, the amount of TUNEL-positive cell/mm2 dropped significantly after 24h and 48h. Cultures treated with CN238 for 10 days showed a significant increase in RBPMS-positive cells/mm2 and a significant decrease in TUNEL-positive cells/mm2. 1.4. Conclusion The inhibition of the Kv1.3 and Kv1.6 channels with 50 nM MrgX protected RGCs from the induced degeneration due to optic nerve transection in WT retina in vitro. This suggests a relationship between Kv1 channels and RGC death. In addition, the CN238-mediated PKG inhibition rescued RGCs. Together these results suggest that RGC degeneration in retinal explants following the severing of the optic nerve could be triggered by a potential new putative cell death pathway, which involves the signalling along the cGMP/PKG/Kv1 pathway.11 0