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Yousef Almoghrabi,1,2,* Hussam Daghistani,1,2,* Hanouf A Niyazi,3,* Hatoon A Niyazi,3,* Hind AbdulMajed,3,* Noha A Juma,3,* Noura Daffa,3,* Noof R Helmi,3,* Mohammed W Al-Rabia,3,4,* Jawahir A Mokhtar,3,5,6,* Bandar Hasan Saleh,3,* Dalya M Attallah,5 Maram Matar,5 Hani Ahmed Shukri,5 Shahd A Moqaddam,5 Sara Alamoudi,5 Khalil K Alkuwaity,6,7,* Turki Abujamel,6,7,* Ahmad M Sait,2,7 Mohammed Mufrrih,7,8 Ibrahim A Al-Zahrani,7,8,* Stephen O’hagan,9 Mazen A Ismail,10,* Ohood S Alharbi,11,* Hattan Jamal Momin,12,* Ibrahim Mohammed Abu,13,* Abdelbagi Alfadil,3,4,* Karem Ibrahem3 1Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Regenerative Medicine Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 3Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Centre of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Clinical Microbiology Laboratory, King Abdulaziz University Hospital, Jeddah, 21589, Saudi Arabia; 6Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 7Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 8Special Infectious Agents Unit BSL-3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 9Department of Chemistry, Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK; 10Department of Medical Education, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 11Department of Microbiology and Parasitology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 12Medical Service Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 13Department of Community Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia*These authors contributed equally to this workCorrespondence: Karem Ibrahem, Email kaibrahem@kau.edu.saBackground: This six-year retrospective study provides an in-depth analysis of the epidemiological and clinical patterns associated with Acinetobacter baumannii (A. baumannii) infections, focusing on age distribution, antibiotic resistance profiles, and specimen types.Aim: The research examines the incidence and characteristics of both non-Multi-Drug Resistant (non-MDR) and Multi-Drug Resistant (MDR) A. baumannii strains by reviewing patient records from January 2016 to December 2022.Methods: Through a statistical analysis, the study highlights the incidence rates across diverse age groups and explores the impact of antibiotic treatment regimens on infection outcomes. Additionally, it identifies the primary clinical specimen types for each strain, noting an association between non-MDR A. baumannii and midstream urine samples, while MDR A. baumannii strains were more frequently found in respiratory, wound, peripheral, and central line swaps/specimens.Results: The results indicate that in 2016, non-MDR A. baumannii infections were notably more frequent compared to MDR A. baumannii cases. However, a significant shift occurred in 2021 and 2022, with a marked decrease in non-MDR A. baumannii cases and an increase in MDR A. baumannii infections. Antibiotic susceptibility testing revealed that non-MDR strains were commonly tested against cefazolin, ceftazidime, ciprofloxacin, gentamicin, nitrofurantoin, oxacillin, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole. In contrast, MDR strains were frequently tested against amikacin, cefepime, colistin, meropenem, imipenem, and tigecycline.Conclusion: This study enhances the understanding of A. baumannii clinical behaviour and resistance patterns, offering valuable insights to support future research and inform strategies for infectious disease management and control.Keywords: Acinetobacter baumannii, MDR, the epidemiological and clinical patterns

Shaymaa A Abdalal,1 Hatoon A Niyazi,2 Soa’ad M Alsulami,3 Ala A Azhari,2 Hanouf A Niyazi,2 Jawahir A Mokhtar,2 Dalya M Attallah,3 Faten A Al Braikan,2 Moroj A Aldarmasi1 1Community Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Clinical Microbiology and Immunology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 3Clinical and Molecular Microbiology Laboratories, King Abdulaziz University Hospital, Jeddah, 21589, Saudi ArabiaCorrespondence: Shaymaa A Abdalal, Email sabdalal@kau.edu.saPurpose: Parasitic infections are a primary cause of illness worldwide and a public health problem. This study highlighted the prevalence of intestinal parasitic (IP) infections and their updated epidemiologic status from 2019 to 2023 at King Abdulaziz University Hospital, Jeddah, Saudi Arabia.Patients and Methods: A retrospective study was conducted from 2019 to 2023 at King Abdulaziz University Hospital. The laboratory results, socio-demographic information, and the year of data collection were collected from the hospital’s parasitology laboratory. The data were analyzed using SPSS version 26. Ethical approval was obtained from the National Committee of Bioethics (NCBE) - King Abdul Aziz City for Science and Technology, with an approval number of 258-22.Results: During the study period, 7673 stool samples were requested for intestinal parasite examination. The prevalence of IP infection from 2019 to 2023 was 212/7673, with a percentage of 2.8%. Infected patients had a mean (SD) age of 37.68 (17.27) years. Most infected patients were females (61%) and from Saudi Arabia (37.1%). Most stool samples were brown (79.1%), and about half were soft (51.7%). 2019 had the highest number of infected cases (28.3%), while the number of cases decreased in 2023 (8.8%), the lowest during five years. The most predominant parasite among study subjects was Blastocystis hominis (48.11%).Conclusion: The prevalence of IP infection is lower than in previous comparable surveys. Maintaining personal hygiene, conducting epidemiological surveillance, and enhancing environmental sanitation can prevent and control infections.Keywords: intestinal parasites, infection, prevalence, Saudi Arabia

Mohammed A Bazuhair,1,2 Mohammed Alsieni,1 Hani Abdullah,3 Jawahir A Mokhtar,3– 5 Dalya Attallah,4 Turki S Abujamel,5,6 Khalil K Alkuwaity,5,6 Hanouf A Niyazi,3 Hatoon A Niyazi,3 Hind AbdulMajed,3 Noha Juma,3 Mohammed W Al-Rabia,3 Abdelbagi Alfadil,2,3 Karem Ibrahem3 1Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Centre of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Clinical Microbiology Laboratory, King Abdulaziz University Hospital, Jeddah, 21589, Saudi Arabia; 5Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaCorrespondence: Karem Ibrahem, Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, P.O. Box 80205, Jeddah, 21589, Saudi Arabia, Tel +966 562525685, Email kaibrahem@kau.edu.saIntroduction: Candida is the primary cause of invasive fungal disease, candidiasis, especially in developed nations. The increasing resistance observed in multiple antibiotics, coupled with the prolonged process of creating new antibiotics from the ground up, emphasizes the urgent requirement for innovative methods and new compounds to combat Candida infections. Employing a treatment strategy that combines antibiotics can improve efficacy, broaden the spectrum of targeted fungal, and reduce the chances of resistance emergence. This approach shows potential in tackling the escalating problem of antibiotic resistance. The objective of this research is to explore the potential synergistic effects of combining 3-hydrazinoquinoxaline-2-thiol and thymoquinone against a variety of Candida isolates. This investigation aims to offer an understanding of the collective antimicrobial action of these compounds.Methods: Broth microdilution was utilized to assess the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and thymoquinone for 22 clinical Candida isolates. Following this, a checkerboard assay was employed to analyze the interaction between 3-hydrazinoquinoxaline-2-thiol and thymoquinone, with a specific focus on the Fractional Inhibitory Concentration Index (FICI).Results: The MICs of thymoquinone and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical Candida strains, with thymoquinone exhibiting MICs ranging from 64 to 8 μg/mL, and 3-hydrazinoquinoxaline-2-thiol displaying MICs varying from 64 to 8 μg/mL. Notably, the combination of 3-hydrazinoquinoxaline-2-thiol and thymoquinone resulted in a synergistic effect, leading to a significant reduction in MICs, with reductions of up to 64-fold with FICI below 0.5 against tested strains.Conclusion: The prospect of using 3-hydrazinoquinoxaline-2-thiol in combination with thymoquinone as an effective solution against Candida looks encouraging. Nevertheless, to validate its practical applicability, additional comprehensive testing and experiments are imperative.Keywords: Candida spp, antimicrobial resistance, 3-hydrazinoquinoxaline-2-thiol, thymoquinone, MIC, FICI

Introduction: Iparomlimab (QL1604) is a humanized immunoglobulin G4 mAb against programmed cell death protein 1 (PD-1). Here, we report the preliminary efficacy, safety, pharmacokinetics, and immunogenicity of iparomlimab in patients with advanced solid tumors., Methods: In this open-label, phase 1c study, patients with advanced or metastatic solid tumors, either failed or had no standard therapies available, were enrolled and received intravenous iparomlimab at 3 mg/kg once every 3 weeks. The primary efficacy endpoint was the objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1., Results: Between July 20, 2020, and September 6, 2021, 71 patients were enrolled and received at least one dose of iparomlimab. The ORR was 9.9% (7/71) and disease control rate was 36.6% (26/71). Median duration of response of all responders was 10.7 months [95% confidence interval (CI), 1.4-not estimable]. Additionally, the median time to progression, progression-free survival, and overall survival were 1.4 months (95% CI, 1.4-2.8), 1.4 months (95% CI, 1.4-2.7), and 9.7 months (95% CI, 7.2-15.3), respectively. A total of 52 (73.2%) patients experienced treatment-related adverse events (TRAEs) (grade ≥ 3, 19.7%). The most common TRAE (≥ 10%) was anemia (18.3%). A total of 20 (28.2%) experienced immune-related adverse events (grade ≥ 3, 7.0%). TRAEs leading to discontinuation of study drug occurred in 4 (5.6%) patients, including immune-mediated myocarditis (2 patients), Guillain-Barré syndrome (1 patient), and diarrhea (1 patient)., Conclusions: Iparomlimab showed preliminary clinical activity and had a manageable safety profile in patients with advanced solid tumors. These results support further investigation of iparomlimab as monotherapy or in combination therapy in advanced solid tumors., Trial Registration: ClinicalTrials.gov identifier, NCT05801094. Retrospectively registered in 2023-03-24., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Recycled concrete is a new and environmentally friendly material for future construction. When applying recycled concrete to cold and severe regions, it is necessary to consider the freeze-thaw resistance of recycled concrete. Using an indoor freeze-thaw cycle test system, the rapid freezing method was used to conduct rapid freeze-thaw tests on recycled concrete specimens under set freeze-thaw cycle conditions. Relevant parameters (such as compressive strength, quality loss rate, rebound value) were tested on recycled concrete specimens that completed the set number of freeze-thaw cycles. The influence of various factors (freeze-thaw cycle number, replacement rate of recycled aggregates) on the compressive strength, quality loss rate, and rebound value of recycled concrete was analyzed. The results indicate that with the increase of freeze-thaw cycles and recycled aggregate content, the workability, rebound value, and compressive strength of the specimens decrease, and the quality loss rate increases. The changes in workability of concrete are sharp, with a slump difference of 21 mm between concrete with 100% recycled coarse aggregate and concrete using natural coarse aggregate. The rebound value of the specimen shows a decreasing trend overall, but the rebound value varies for different measuring points on the same specimen. The attenuation of compressive strength is significant. When fully using recycled aggregates to prepare concrete, the compressive strength after 30 freeze-thaw cycles decreases by 49.42% compared to the compressive strength after 0 freeze-thaw cycles. The overall quality loss rate shows a decreasing trend, but the quality loss is not severe.

Introduction: Cardiovascular and noncardiovascular mortality and morbidity rates of hemodialysis patients are high despite improvement in dialysis delivery., Materials and Methods: Hemodialysis patients (n = 532) from 9 hemodialysis facilities were enrolled in this cohort study in September 2012. Causes of death, hospitalization, and hemodialysis exit were recorded during a 28-month follow-up period. A Cox proportional hazard model was used to predict death adjusting for case-mix variables, nutrition variables, bone mineral variables, Kt/V, vascular access, and Charlson comorbidities index., Results: Patients were 56.0 ± 15.4 years old (57% men). A total of 161 patients (30%) died (17 per 100 patient years), and the most common causes of death were cardiovascular diseases (42%) and infections (25%). Transplantation rate was 7 per 100 patient years and hospitalization frequency was 0.76 per patient year. Based on the multivariable Cox proportional hazard model, the mortality hazard ratio was 1.03 (95% confidence interval [CI], 1.01 to 1.05; P = .007) for age (years), 0.21 (95% CI, 0.11 to 0.40; P < .001) for serum albumin (g/dL), 1.21 (95% CI, 1.03 to 1.42; P = .02) for serum phosphorus (mg/dL), 1.001 (95% CI, 1.0005 to 1.002; P = .001) for serum intact parathyroid hormone (pg/mL), 1.58 (95% CI, 1.01 to 2.51; P = .047) for hemodialysis catheter (compared to arteriovenous fistula), and 1.75 (95% CI, 1.59 to 1.94; P < .001) for the Charlson score., Conclusions: Nutritional factors, comorbidities, vascular access, and abnormal mineral metabolism are the main determinants of mortality and morbidity in hemodialysis patients.

Cervical cancer is a common female malignancy of global dimensions. MicroRNAs (miRNAs) play crucial roles in the development, differentiation, proliferation, and apoptosis of tumors. The non-coding RNA MALAT1 participates in various physiological processes that are important for proper functioning of the body. Here, we analyzed the expression of miRNA-143 and MALAT1 in HeLa cells to evaluate their roles in the occurrence and metastasis of cervical cancer. HeLa cells were divided into five groups depending on the treatment conditions, namely, transfected with miRNA-143, MALAT1, miRNA-143 inhibitor and the MALAT1 inhibitor, and the untreated control. Reverse transcription-polymerase chain reaction was used to analyze the expression of miRNA-143 and MALAT1, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess proliferation, the trans-well assay to study cell invasion and migration, and western blot to analyze the levels of E-cadherin and vimentin. The proliferation of HeLa cells increased upon treatment with the miRNA-143 inhibitor and decreased when treated with the MALAT1 inhibitor, compared to the proliferation of the groups that were transfected with miRNA-143 and MALAT1, respectively (P < 0.05). Thus, miRNA-143 decreased cell invasion and migration potency, downregulated vimentin and upregulated E-cadherin expression, while MALAT1 had the opposite effects. In conclusion, the low expression of miRNA-143 and high expression of MALAT1 in cervical cancer cells could possibly potentiate cell invasion/migration and alter the levels of vimentin and E-cadherin.

The ruthenium complex [Ru(phen)(2)(dppz)](2+) (where phen is phenanthroline and dppz dipyridophenazine is known as a 'light switch' complex because its luminescence in solution is significantly enhanced in the presence of DNA. This property is poised to serve in diagnostic and therapeutic applications, but its binding mode with DNA needs to be elucidated further. Here, we describe the crystal structures of the Λ enantiomer bound to two oligonucleotide duplexes. The dppz ligand intercalates symmetrically and perpendicularly from the minor groove of the d(CCGGTACCGG)(2) duplex at the central TA/TA step, but not at the central AT/AT step of d(CCGGATCCGG)(2). In both structures, however, a second ruthenium complex links the duplexes through the combination of a shallower angled intercalation into the C(1)C(2)/G(9)G(10) step at the end of the duplex, and semi-intercalation into the G(3)G(4) step of an adjacent duplex. The TA/TA specificity of the perpendicular intercalation arises from the packing of phenanthroline ligands against the adenosine residue.