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Abstract Despite advancements in ergonomic comfort assessments in automotive design, optimizing seat dimensions within the constrained spaces of micro-electric cars presents a substantial challenge. In this study, response surface methodology (RSM) is utilized for the ergonomics design of a micro electric car in the conceptual design phase. Specifically, five critical seat dimensions are analyzed: Seatback Angle, Seat Base Angle, Steering Wheel Height from Car Base, Distance from Seat Base to Pedals, and Distance from Seat Base to Steering Wheel. The analysis took place using a 2-level full factorial design L32 orthogonal array. The optimal dimensions are determined using RSM, such as the mean comfort level and signal-to-noise ratio are maximized, and the standard deviation for multiple drivers is minimized. Three regression models are formulated for the three responses, and their adequacy is checked using different methods. The optimal dimensions are obtained and verified through digital human modeling simulation. This research offers practical guidelines for the ergonomic seating design in micro-electric vehicles, enhancing comfort without compromising space efficiency.

Abstract In arid and semiarid zones, groundwater is a vital and indispensable natural resource. Indeed, these water resources have become extremely limited due to several factors, including climate change, salinization, and overexploitation. This study covers the hydrochemical characterization of groundwater in the Nekor-Ghiss plain which is located in northern Morocco. To achieve this objective, a set of 79 water samples was analyzed, for various physical and chemical parameters of the samples, including E.C, pH, TDS, HCO3 −, SO4 2−, Ca2+, Mg2+, Na+, K+, PO4 3−, NO3 −, NO2 − and NH4 +. Several methods were used to interpret the hydrochemical data, namely graphical methods, principal component analysis (PCA), hierarchical ascending classification, and ion exchange indices. A detailed geochemical study of groundwater is described to identify the origin of the chemical composition of groundwater. The results show that the samples studied are characterized by very high mineralization (> 1500 mg/l), with the predominance of Na+, Cl− and SO4 2− ions. The interpretation of geochemical signatures of groundwater in the Nekor-Ghiss plain shows sulfate-sodium (Na–SO4) and chloride-sodium (Na–Cl) facies. Natural geochemical processes are responsible for water regulation, while human activities exert a limited influence on this control. Marine intrusion, evaporation, and the ion exchange process largely control the chemistry of the aquifer. Using PCA to confirm controlled water chemistry processes revealed three homogeneous groups. The study contributes to a better understanding of the quality and mineralization of groundwater in the Nekor-Ghiss plain, and it will serve as a reference for other plains with similar characteristics.

ABSTRACT: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that primarily causes the growth of tumors alongnerves. Additionally, the germline mutations involved in NF1 predispose patients to develop further malignancies. The mainstay initial treatment for these malignancies is surgical removal at diagnosis, although targeted therapies are under evaluation in the relapsed setting. We report a case of malignant peripheral nerve sheath tumor (MPNST), gastrointestinal stromal tumor (GIST), and pheochromocytoma in a patient with NF1 who presented with an infected right shoulder lesion that was confirmed to be spindle cell sarcoma via biopsy. She was treated with antibiotics; however, she rapidly deteriorated and opted for hospice care. NF1 germline mutations increase the risk of patients developing various types of cancer. Recent studies have shown that there is a rolefor using MEK inhibitors such as selumetinib for treating patients with NF1.

BACKGROUND: Multiple myeloma (MM) represents the second most common hematologic malignancy (15%). Induction with bortezomib, cyclophosphamide, and dexamthasone VCd (d: low dose dexamthasone) regimen is widely used due to its high effectiveness, low toxicity and good tolerability, particularly with renal impairment. Real-world data on the use of VCD in clinical practice is lacking. OBJECTIVES: Evaluate the real-world experience of the VCD regimen DESIGN: Retrospective SETTING: Tumor registry database of tertiary cancer care center PATIENTS AND METHODS: Newly diagnosed MM patients who received VCD induction and underwent autologous stem cell transplant (ASCT) from July 2007 to July 2020 MAIN OUTCOME MEASURES: Response evaluation, progression-free survival (PFS) and overall survival (OS). SAMPLE SIZE: 87 patients RESULTS: Of 102 patients who started induction with VCd, 87 patients experienced a partial response or more overall response rate of 85%). The median age of these 87 patients at diagnosis was 52 years, of which 29.9% presented with renal impairment and 60.3% of patients had stage 2 by the Revised International Staging System (R-ISS). Patients with a standard cytogenetic risk achieved a better response compared to those with a poor cytogenetic risk (P=.044). The post-induction response rates were 6.9% stringent complete remission (sCR), 35% complete remission (CR); 41.4% very good partial response (VGPR), and 16.1% partial response (PR), respectively; the response rates became greater for sCR and CR post-transplantation at day 100 with 16.1% sCR, 35.6% CR, 32.2% VGPR and 16.1% PR, respectively. The median PFS was 49 months and 5 years OS was 84%. PFS was better in patients who achieved sCR vs PR (83 vs 35 months, P=.037). High LDH, high-risk cytogenetic and stage 3 R-ISS showed a worse median PFS and OS. CONCLUSIONS: VCD induction in newly diagnosed MM is highly effective, convenient, tolerable and affordable regimen, especially in low and middle-income countries with limited resources, also with favorable outcomes and survival. while those who did not respond successfully shifted to VRD or VTD. LIMITATIONS: The usual limitations of a retrospective analysis using registry-level data, no data on quality of life.

Abstract In this study, tin dioxide nanoparticles (SnO2 NPs) were successfully synthesized through an eco-friendly method using basil leaves extract. The fabricated SnO2 NPs demonstrated significant adsorption capabilities for phenol (PHE), p-nitrophenol (P-NP), and p-methoxyphenol (P-MP) from water matrices. Optimal conditions for maximum removal efficiency was determined for each phenolic compound, with PHE showing a remarkable 95% removal at a 3 ppm, 0.20 g of SnO2 NPs, pH 8, and 30 min of agitation at 35 °C. Molecular docking studies unveiled a potential anticancer mechanism, indicating the ability of SnO2 NPs to interact with the epidermal growth factor receptor tyrosine kinase domain and inhibit its activity. The adsorption processes followed pseudo-second order kinetics and Temkin isotherm model, revealing spontaneous, exothermic, and chemisorption-controlled mechanisms. This eco-friendly approach utilizing plant extracts was considered as a valuable tool for nano-sorbent production. The SnO2 NPs not only exhibit promise in water treatment and also demonstrate potential applications in cancer therapy. Characterization techniques including scanning electron microscopy, UV–visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction spectroscopy (XRD), and energy-dispersive X-ray spectroscopy (EDAX) provided comprehensive insights into the results.

Background: Diabetes is a metabolic disorder requiring the administration of insulin or other oral hypoglycemic medicines. Although metformin is a popular prescription for type 2 diabetes, long-term use of chemotherapy-based diabetes medications can be hazardous. As a result, novel plant medicines with a high concentration of bioactive molecules, no harmful side effects, and potent pharmacological effects must be found. Edible Boswellia sacra (B. sacra) Flueck oleo-gum resin is widely utilized to treat many clinical diseases in traditional Arab, Chinese, African, and Ayurvedic medicine. Objective: The goal of this study was to examine the possible therapeutic benefits of several B. sacra oleo-gum resin extracts on rat streptozotocin (STZ)-induced hyperglycemia (Type II). Materials and methods: For 29 days, hyperglycemic rats are given either metformin (the reference drug; 250 mg/kg body weight per day) or several B. sacra extracts (ethanol, methanol, hydrodistilled, ethyl acetate, and acetone extracts) at doses of 200 or 400 mg/kg/day. Blood glucose levels and body weights were measured before the initiation and at 7, 11, 16, 22, and 29 days after oral treatment. Furthermore, an oral glucose tolerance test (OGTT) was carried out. At the end of the study, the rats were euthanized, and blood samples were obtained to evaluate cytokines (interleukin (IL-)2 and IL-8), reduced glutathione (GSH), superoxide dismutase (SOD), and serum insulin levels. The pancreas and liver tissues were rapidly excised, washed, fixed, and kept in a 10% formalin buffer for histological examination. Results: B. sacra's ethanolic extract had the greatest concentration of total pentacyclic triterpenic acid (PTA) (391.52 mg/g) in comparison to the other extracts. The lower dose of B. sacra ethanol extract, 200 mg/kg/day, reduces blood glucose levels more efficiently than the higher dose of 400 mg/kg/day. In a 180-min OGTT, diabetic rats given ethanol extract (200 mg/kg) performed no better than control rats and even outperformed those given the reference medication metformin. Additionally, ethanol extract (200 mg/kg)- or metformin-treated diabetic rats gained weight. This was associated with a significant (p

Abstract Background The low-level laser therapy (LLLT) and low-intensity pulsed ultrasound (LIPUS) have been recently applied to control pain during orthodontic treatment. Objective To evaluate and compare the effectiveness of LLLT and LIPUS in reducing pain induced by orthodontic separation. Study design A single-blinded randomized controlled trial. Methods One hundred and fifty patients were randomly assigned into three groups; LLLT group, LIPUS group, and control group. After 5 min from the separators’ placement, the first dose of the laser or the ultrasound was applied, the second dose was applied after 24 h, and the third dose was applied after 48 h on both maxillary and mandibular first molars. The exposure of laser was for 20 s at each point (maxillary and mandibular first molars), with an 810-nm aluminum-gallium-arsenide (AlGaAs) diode laser on continuous mode. The output power set at 150 mW, the energy density of 4 J/cm2, and a laser spot diameter of 7 mm were applied. Whereas the frequency of ultrasonic toothbrush was 1.6 MHz; and average output intensity was 0.2 W/cm2. The application was for 20 min (5 min on each first molar). The control group received the separators without another intervention. A Visual Analog Scale (VAS 100 mm) was used to assess pain intensity at several time intervals during the first four days after the separators’ placement. Results A total of 145 patients were assessed. There was a significant difference in pain perception among the three groups after 5 min (P = .002). The maximum pain level was reached after 24 h. However, the laser group and the ultrasound group showed a statistically significant decrease in pain scores compared to the control group at all the assessment time points (P .05). Conclusions The LLLT and the LIPUS effectively reduce the separation pain when applied in multiple doses without differences between them. Trial registration This trial was registered with the German Clinical Trials Register (DRKS). ( https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID= DRKS00029991). Date of registration: 26/08/2022.

Takayasu arteritis (TA) is a chronic granulomatous inflammatory arteritis of large vessels. Females aged 20-40 are usually affected and the manifestations can range from asymptomatic disease to major cardiovascular and neurological abnormalities. Herein, we present a case of a 20-year-old female who had a persistent cough as the initial manifestation of an underlying TA. She had a free past medical history. The patient sought medical help multiple times and took many antibiotics with no improvement. Laboratory tests showed a marked elevation in inflammatory markers so the patient was admitted for further investigations. CT scan showed a circumferential mural thickening involving mainly the descending thoracic aorta which is highly suggestive of an underlying chronic granulomatous vasculitis behind this. Our patient was treated with a combination of corticosteroid and azathioprine and showed substantial improvement after 2 weeks. TA can present with various symptoms. Therefore, patients presenting with atypical symptoms and late-onset vascular symptoms need a high degree of suspicion with close follow-up to allow early detection of any complication.

Abstract In this study, we report the first total hemisynthesis of trans-himachalol sesquiterpene, a stereoisomer of the natural cis-himachalol isolated from Cedrus atlantica essential oils, from himachalenes mixture in five steps. Reactions conditions were optimized and structures of the obtained compounds were confirmed by IR, mass spectra, 1H, and 13C NMR. The synthesized compounds were investigated for potential activities on various isolated smooth muscles and against different neurotransmitters using molecular docking. The results show that the synthesized compounds display high affinities towards the active site of the protein 7B2W and the compounds exhibit promising activities on various isolated smooth muscles and against different neurotransmitters.

Abstract Background Many modern pharmaceutical researchers continue to focus on the discovery and evaluation of natural compounds for possible therapies for obesity, diabetes, infections, cancer, and oxidative stress. Extraction of Ocimum basilicum seed essential oil and evaluation of its antioxidant, anti-obesity, antidiabetic, antibacterial, and cytotoxic activities were the goals of the current study. Method O. basilicum seed essential oil was extracted and evaluated for its anticancer, antimicrobial, antioxidant, anti-obesity, and anti-diabetic properties utilizing standard biomedical assays. Results O. basilicum seed essential oil showed good anticancer activity against Hep3B (IC50 56.23 ± 1.32 µg/ml) and MCF-7 (80.35 ± 1.17 µg/ml) when compared with the positive control, Doxorubicin. In addition, the essential oil showed potent antibacterial (against Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Proteus mirabilis, and Pseudomonas aeruginosa) and antifungal (against Candida albicans) activities. Moreover, as for the anti-amylase test, IC50 was 74.13 ± 1.1 µg/ml, a potent effect compared with the IC50 of acarbose, which was 28.10 ± 0.7 µg/ml. On the other hand, for the anti-lipase test, the IC50 was 112.20 ± 0.7 µg/ml a moderate effect compared with the IC50 of orlistat, which was 12.30 ± 0.8 µg/ml. Finally, the oil had a potent antioxidant effect with an IC50 of 23.44 ± 0.9 µg/ml compared with trolox (IC50 was 2.7 ± 0.5 µg/ml). Conclusion This study has provided initial data that supports the importance of O. basilcum essential oil in traditional medicine. The extracted oil not only exhibited significant anticancer, antimicrobial, and antioxidant properties but also antidiabetic and anti-obesity effects, which provided a foundation for future research.

Abstract Leukemia burden is growing in the Gulf Council Cooperation (GCC) countries. Nonetheless, there is no unified protocol for managing adult acute lymphoblastic leukemia (ALL) patients in the GCC‐countries. Therefore, the GCC Adult‐ALL Treaters working group developed this consensus to address the adult‐ALL treatment protocols in the GCC‐countries and related toxicities' management. Besides, the consensus aimed to highlight the current unmet needs and treatment gaps and provide recommendations to optimize adult‐ALL care and patient‐centered communication. A three‐step modified Delphi method to develop evidence‐based recommendations through two‐voting rounds and in‐between virtual meetings are used in the manuscript development. A 12 experts' panel from five GCC‐countries and two international experts were invited to participate in this consensus. This consensus consisted of 35‐statements that highlighted the experts' recommendations to optimize ALL adults' care in the first line setting and manage pediatric or pediatric‐inspired regimens‐related toxicities. Besides, guidance was provided for future research direction and improve patient‐centered communication. In conclusion, the adult‐ALL management landscape is evolving, and the current evidence highlights better response and survival outcomes with pediatric or pediatric‐inspired regiments. Therefore, protocols are needed to optimize the adult‐ALL management in the GCC and tailored clinical‐trials findings according to the GCC patients' characteristics and local‐healthcare infrastructure.

Abstract Introduction Thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura are two well recognized syndromes that are characterized by low platelet counts. In contrast, essential thrombocythemia is a myeloproliferative disease characterized by abnormally high platelet numbers. The coexistence of thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura in a single patient has been reported in the literature on a few occasions. However, having essential thrombocythemia complicating the picture has never been reported before. Case presentation We present a case where thrombotic thrombocytopenic purpura, essential thrombocythemia, and idiopathic thrombocytopenic purpura were diagnosed in a 42-year-old African-American woman in the space of a few years; we are reporting this case with the aim of drawing attention to this undocumented occurrence, which remains under investigation. Conclusions As the three conditions have different natural histories and require different treatment modalities, it is important to recognize that these diseases may be seen sequentially. This case emphasizes the importance of reviewing peripheral blood smears for evaluation of thrombocytopenia and bone marrow aspirations for diagnosis of thrombocythemia in order to reach an accurate diagnosis and tailor therapy accordingly. Moreover, this case demonstrates the variability and complexity of platelet disorders. This occurrence of three different types of platelet disorders in one patient remains a pure observation on our part; regardless, this does raise the possibility of a common underlying, as yet undiscovered, pathophysiology that could explain the phenomenon.

Organ donation is considered a life-saving treatment for end-stage organ failure worldwide. However, the severe organ shortage in Saudi Arabia creates a gap between patients in need of transplantation and the availability of organs. In Saudi Arabia, a limited number of studies have assessed knowledge and attitudes toward organ donation, especially in Jeddah City. Thus, this study aimed to assess the knowledge, attitudes, and barriers to organ donation and to determine the factors that may hinder or facilitate organ donation. Our findings indicated that almost half of the participants (49.2%) obtained their information from online resources. Fear of the unknown (31.2%) and a lack of knowledge (28.5%) were the main barriers to organ donation. A high percentage of the participants (73%) were unaware of any local or international legislation regarding organ donation. Half of the study participants were willing to donate their organs, with insignificant differences in age, gender, occupation, and education level. Only 5.4% of the respondents had an organ donor card. The study indicated that half of the participants were willing to donate organs, but they were unaware of local and international legislation. Therefore, an intensive education program and campaigns are recommended to increase public awareness about organ donation.

Methotrexate (MTX) is potent chemotherapeutic agent, often administered intrathecally to treat or prevent central nervous system involvement in lymphomas and leukemias, particularly T-cell lymphoblastic leukemia (T-LBL). MTX has been linked to adverse neurologic effects that mimic acute stroke, including facial drooping, hemiplegia, impaired consciousness, and seizures, as well as changes on imaging—known as MTX-induced leukoencephalopathy (LE). We report a case of a 17-year-old male diagnosed with T-LBL, who had been receiving MTX chemotherapy for 4 months. After receiving his fourth dose of MTX, he presented to the emergency department with fever, facial drooping, and acute left-sided weakness. Brain magnetic resonance imaging (MRI) revealed bilateral deep white matter T2 hyperintense foci, increased on the right, with associated diffusion restriction in the right centrum semiovale—consistent with MTX-induced LE. After his symptoms resolved, he was discharged on leucovorin. Six months afterward, he was rechallenged with MTX and developed recurrence of symptoms. Repeat MRI showed well-defined T2/FLAIR hyperintensities in the right centrum semiovale without corresponding diffusion restriction. The left centrum semiovale hyperintensity became less conspicuous in comparison to the previous MRI study. We report a rare case of recurrence of LE after MTX rechallenge and discuss mechanisms, best imaging modalities, and possible treatment options for MTX-induced LE. Given the ominous presentation of MTX-induced LE, we urge clinicians to maintain a high index of suspicion for this condition. Further research is necessary to understand why only certain patients develop recurrence of LE after subsequent doses of MTX.

Negotiations are underway at the WHO for a legally binding instrument for pandemic prevention, preparedness and response. As seen in the International Health Regulations, however, countries signing up to an agreement is no guarantee of its effective implementation. We, therefore, investigated the potential design features of an accountability framework for the proposed pandemic agreement that could promote countries’ compliance with it. We reviewed the governance of a number of international institutions and conducted over 40 interviews with stakeholders and experts to investigate how the pandemic agreement could be governed.We found that enforcement mechanisms are a key feature for promoting the compliance of countries with the obligations they sign up for under international agreements but that they are inconsistently applied. It is difficult to design enforcement mechanisms that successfully avoid inflicting unintended harm and, so, we found that enforcement mechanisms generally rely on soft political levers rather than hard legal ones to promote compliance. Identifying reliable information on states’ behaviour with regard to their legal obligations requires using a diverse range of information, including civil society and intergovernmental organisations, and maintaining legal, financial, and political independence.We, therefore, propose that there should be an independent mechanism to monitor states’ compliance with and reporting on the pandemic agreement. It would mainly triangulate a diverse range of pre-existing information and have the authority to receive confidential reports and seek further information from states. It would report to a high-level political body to promote compliance with the pandemic agreement.

Abstract The spread of HIV is on the rise and has become a global issue, especially for underdeveloped and developing countries. This is due to the fact that HIV majorly occurs asymptomatically and is implausible for early diagnosis. Recent advances in research and science have enabled the investigation of a new potential treatment involving gene-based therapy, known as RNA interference (RNAi) that will direct gene silencing and further compensate for natural variants and viral mutants. Several types of small regulatory RNA are discussed in this present study, including microRNA (miRNA), small interfering RNA (siRNA), and short hairpin RNA (shRNA). This paper examines the mechanism of RNAi as a viable HIV therapy, using a minimum of four shRNAs to target both dispensable host components (CCR5) and viral genes (Gag, Env, Tat, Pol I, Pol II and Vif). Moreover, a multiplexed mechanism of shRNAs and miRNA is known to be effective in preventing viral escape due to mutation as the miRNA develops a general polycistronic platform for the expression of a large amount of shRNA-miRs. Several administration methods as well as the advantages of this RNAi treatment are also discussed in this study. The administration methods include (1) ex vivo delivery with the help of viral vectors, nanoparticles, and electroporation, (2) nonspecific in vivo delivery using non-viral carriers including liposomes, dendrimers and aptamers, as well as (3) targeted delivery that uses antibodies, modified nanoparticles, nucleic acid aptamers, and tissue-specific serotypes of AAV. Moreover, the advantages of this treatment are related to the effectiveness in silencing the HIV gene, which is more compatible compared to other gene therapy treatments, such as ZFN, TALEN, and CRISPR/Cas9.

Primary splenic or hepatic angiosarcomas are ultra-rare and aggressive malignancies associated with poor prognosis. The mainstay treatments are surgical resection and chemotherapy. We report a case of angiosarcoma in a 50-year-old woman who presented with bruising, fatigue, ecchymosis, and hepatosplenomegaly. She was treated with the multi-kinase inhibitor sunitinib for 4 weeks before developing a splenic hemorrhage and succumbing. Recent studies have demonstrated the clinical benefit of immunotherapies in angiosarcomas. Additionally, sequencing techniques have showcased the diverse molecular aberrations involved in angiosarcomas, which offer opportunities for precision-matched targeted therapies such as inhibitors of the VEGF/VEGFR axis and PI3K/Akt/mTor pathway.

Groundwater is an indispensable source of water for drinking water supply, agriculture and industry worldwide. In arid and semi-arid regions, groundwater has seriously deteriorated in recent decades due to environmental changes, anthropogenic activities and marine intrusion. A total of 79 groundwater samples from the Nekor-Ghiss plain were sampled for major chemical ion analysis. These analyzes showed that the water samples were highly mineralized (>1,500 mg/L), with hardness (83.5% of the samples were very hard) and high concentrations of chemical elements, such as Cl−, Mg2+, Na+ and SO42-. To assess the quality of water in the study area for irrigation and consumption purposes, we used the quality index (GWQI) as well as a multi-criteria analysis based on “geographic information system” by assigning a weight to the different water quality parameters. Also, Piper and Durov diagram was investigated. The results of the study were focused on the water quality parameters of the collected groundwater samples, such as the sodium adsorption rate (SAR), the percentage of soluble sodium (Na%), the Residual Sodium Carbonate (RSC) and Permeability Index (PI) Majority of water samples in the study area are suitable to be used for irrigation. Magnesium Risk (MH) and Kelley’s Ratio Kelly ratio. 51.9% unsuitable samples to 59.49% good samples for irrigation purposes. Monitoring the quality and quantity of groundwater is crucial for the effective and sustainable management of this valuable resource. According to the results obtained, it appears that 92% of all the samples are located in the domain of frequent recharge waters of limestone and dolomitic aquifers, namely, Ca-Mg-HCO3. About 8% of the samples measured have a composition of the Ca-Na-Mg-HCO3 type.

Hydroxyapatite (HAp) synthesized through a wet chemical procedure was used to adsorb lead (II) from an aqueous solution. HAp was characterized using Fourier transform infrared, X-ray diffraction, Brunauer–Emmett–Teller analysis, and scanning electron microscopy. The removal of Pb+2 was investigated using the factorial design approach to investigate the efficiency of different Pb+2 concentrations, adsorption contact time, and HAp mass. The greatest Pb+2 removal (98.94%) was obtained at a starting concentration of 50 mg/L, a contact period of 15 min, and a pH of 8. At 323 K, the isothermal adoption module was fitted to the Langmuir isotherms with a regression coefficient (R2) of 0.96. The thermodynamic calculations revealed that the adsorption process was exothermic, spontaneous, and predominantly dominated by chemisorption. Furthermore, the maximum adsorption capacity (Qmax) at equilibrium was 90.18 mg/g, and the adsorption kinetics was specified by a pseudo-second-order kinetic model. Density functional theory and theoretical studies showed that the results of the experiment were correlated by the observation of a much higher negative Eads value for the lead ion adsorbate molecules as they attached to the surface of the adsorbent.