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Abstract Citrobacter koseri causes infection in people who are immunocompromised. Without effective antibiotics, these infections can become severe and life-threatening, so effective drugs are essential to treat these infections. Utilizing subtractive genomics, 2699 ORFs were predicted and translated into amino acid sequences. Metabolic pathway analysis and subcellular localization helped define the roles of key bacterial proteins. Two druggable proteins, WP_012000829.1 and WP_275157394.1, were discovered as promising targets. Alpha Fold provided 3D structures, and a library of 1600 echinoderm metabolites was docked against these proteins, with Ampicillin, Levofloxacin, and Doxycycline as controls. Notably, CMNPD13085 and CMNPD15632 exhibited the highest binding affinities for WP_012000829.1 and WP_275157394.1, respectively. Molecular dynamics simulations and MM-GBSA binding free energy complemented docking results. However, acknowledging the reliance on computational validations, the study emphasizes the need for essential in-vitro research to transform these potential inhibitors into therapeutic drugs.

Abstract The use of natural fibers has seen a significant rise in the composites sector, resulting in the creation of polymer composites with exceptional strength. These environmentally-friendly alternatives offer a compelling substitute for synthetic composites. This study explores the use of date palm waste as reinforcement for the fabrication of polyvinyl chloride (PVC) composites. A surface modification method was essential for improving the binding interaction between palm fibers and PVC composites. The two-hour benzoyl chloride treatment at 140 °C played a crucial role. The study examined the effects of hydrothermal aging on mechanical properties of composites, using various techniques such as surface morphology analysis, Fourier Transform Infrared spectroscopy, and Thermogravimetric Analysis, on composites made of untreated fibers and those treated with benzoyl chloride. Although the treatment of palm fiber-reinforced composites with benzoyl chloride improved their mechanical properties, it is crucial to note that hydrothermal aging reduced their tensile strength by 10%. Despite this, these composites prove to be well-suited for applications requiring moderate strength and stiffness in mild environmental conditions. These composites, while utilizing benzoyl chloride for surface treatment, still represent a more sustainable alternative to traditional synthetic composites by incorporating renewable date palm waste and enhancing mechanical properties, which potentially reduces overall environmental impact.

Abstract The preclinical study of atherosclerosis has traditionally centred around the use of small animal models, translating to large animal models, prior to first-in-man studies. We propose to disrupt this paradigm by designing an ex vivo pump perfused human limb model. The novel model consists of taking a freshly amputated limb and incorporating it into an ex situ pump-perfused bypass system (akin to extracorporeal membrane oxygenation), circulating warmed, oxygenated blood. The circuit incorporates an introducer sheath and guiding catheter for intravascular imaging and X-ray angiography. Regular monitoring is performed using blood gas analysis, aiming for physiological parameters. The model maintains oxygen saturations > 99% for the length of perfusion (up to 6-h). Clinical grade X-ray angiography, intravascular ultrasound and optical coherence tomography have been successfully performed. Indocyanine green, a near-infrared fluorescent dye that localises to atherosclerotic plaque, has been injected into the system and left to circulate for 90-min. Fluorescence reflectance imaging of the dissected arterial bed confirmed uptake in areas of calcific atherosclerotic plaque on intravascular imaging. This is the first demonstration of an ex vivo pump-perfused “living” limb experimental model of atherosclerosis, which shows promise for future studies in translational interventional imaging and molecular targeting.

Abstract National consensus recommendations have recently been developed to standardize colorectal tumour localization and documentation during colonoscopy. In this qualitative semi-structured interview study, we identified and contrast the perceived barriers and facilitators to using these new recommendations according to gastroenterologists and surgeons in a large central Canadian city. Interviews were analyzed according to the Consolidated Framework for Implementation Research (CFIR) through directed content analysis. Solutions were categorized using the Expert Recommendations for Implementing Change (ERIC) framework. Eleven gastroenterologists and ten surgeons participated. Both specialty groups felt that the new recommendations were clearly written, adequately addressed current care practice tensions, and offered a relative advantage versus existing practices. The new recommendations appeared appropriately complex, applicable to most participants, and could be trialed and adapted prior to full implementation. Major barriers included a lack of relevant external or internal organizational incentives, non-existing formal feedback processes, and a lack of individual familiarity with the evidence behind some recommendations. With application of the ERIC framework, common barriers could be addressed through accessing new funding, altering incentive structures, changing record systems, educational interventions, identifying champions, promoting adaptability, and employing audit/feedback processes. Future research is needed to test strategies for feasibility and effectiveness.

Abstract This study determined the prevalence and the associated factors with meeting the recommended amount of physical activity among type 2 diabetes mellitus (T2DM) patients receiving care in resource-limited settings of the West Bank of Palestine. Physical activity was assessed using the World Health Organization’s Global Physical Activity Questionnaire. Associations were examined using multivariate logistic regression. Of the 302 patients included, 117 (38.7%) met the recommended amount of physical activity. Being younger than 58 years [aOR = 2.1 (95% CI 1.0–4.3], were employed [aOR = 2.3 (95% CI 1.1–4.9)], had high income [aOR = 3.9 (95% CI 1.3–11.9)], had thought that physical activity was crucial for T2DM patients [aOR = 32.7 (95% CI 3.9–275.5)], did not have comorbidities [aOR = 2.2 (95% CI 1.1–4.4)], had normal weight [aOR = 2.8 (95% CI 1.3–6.0)], and those who were overweight [aOR = 2.6 (95% CI 1.1–6.0)] were more likely to meet the recommended amount of physical activity compared to the patients who were 58 years or older, had low income, did not think that physical activity was crucial for T2DM patients, had comorbidities, and were obese, respectively. There is a need to increase physical activity among T2DM patients in resource limited settings.

Abstract This research aims to study the chemical content (moisture, ash, fat, protein, fiber and carbohydrate), phenolic compounds, and antioxidant activity of the fruit bodies resulting from the cultivation of six edible Syrian wild mushroom strains of the Agaricus genus. These strains were collected from the western countryside of Homs governorate in Syria (Agaricus bispours BR5, Agaricus bispours B.R.9, Agaricus sinodeliciosus BR17, Agaricus qilianensis BR22, Agaricus sinodeliciosus BR42 and Agaricus qilianensis BR47) and were compared to the commercially cultivated Agaricus bisporus strain Sylvan A15 as a control. The results showed that wild strains had a good chemical composition. The BR47 had the highest protein content among the studied strains (29.52%), which was close to the content of the control (28.55%). All strains recorded higher carbohydrate content compared to the control (p

Abstract Acute myeloid leukemia (AML) is one of the most prevalent leukemia in adults. Among the various NK receptors, killer immunoglobulin-like receptors (KIRs) carry out indispensable roles in NK cell development and function through engaging with class I human leukocyte antigens (HLA-I) as their ligands. Besides divergent KIR and HLA loci, KIR/HLA-I combinations have a significant effect on NK cell response. In this case–control study, we aimed to verify the association of KIR/HLA-I combinations with susceptibility to AML in the Southwestern Iranian population. KIR and HLA genotyping was performed with PCR-SSP by some novel primers for 181 patients with AML and 181 healthy controls. According to our results, the frequencies of KIR3DS1 (p = 0.0001, OR = 2.32, 95% CI 1.51–3.58), KIR2DS4fl (p = 0.02, OR = 1.53, 95% CI 1.05–2.21), CxT4 genotypes (p = 0.03, OR = 2.0, 95% CI 1.05–3.82), and T4 gene cluster (p = 0.01, OR = 1.99, 95% CI 1.17–3.41) were significantly higher in patients than controls, while C1/C2 genotype (p = 0.00002, OR = 0.39, 95% CI 0.25–0.61), HLA-A Bw4 (p = 0.02, OR = 0.6, 95% CI 0.38–0.94), and HLA-A*11 (p = 0.03, OR = 0.57, 95% CI 0.34–0.95) alleles were more frequent in controls. In addition, inhibitory (i)KIR/HLA-I combinations analysis revealed higher frequencies of KIR2DL1( +)/HLA-C2( +), KIR2DL2/3( +)/HLA-C1( +), KIR3DL1( +)/HLA-A Bw4( +), and KIR3DL2( +)/HLA-A*03/11( +) in the control group (p = 0.002, OR = 0.49, 95% CI 0.3–0.78; p = 0.04, OR = 0.62, 95% CI 0.39–0.99; p = 0.04, OR = 0.63, 95% CI 0.4–0.99; and p = 0.03, OR = 0.62, 95% CI 0.4–0.95, respectively). Overall, the number of iKIR/HLA-I combinations was more in the control group. Moreover, KIR3DS1( +)/HLA-B Bw4Ile80( +) and the sum of HLA-B Bw4/A Bw4 combined with KIR3DS1 as activating KIR/HLA-I combinations were more frequent among patients than controls (p = 0.01, OR = 1.99, 95% CI 1.14–3.49 and p = 0.005, OR = 1.97, 95% CI 1.22–3.19, respectively). In conclusion, our results postulate that inhibitory combinations play a protective role against AML by developing potent NK cells during education. It is noteworthy that KIR/HLA-I combination studies can be applicable in donor selection for allogeneic NK cell therapy in hematological malignancies.

Abstract Obesity is a complex disease that increases an individual’s risk of developing other diseases and health-related problems. A common feature is dyslipidemia characterized by increased levels of plasma lipids, which include non-esterified fatty acids (NEFAs). The role of NEFAs in obesity-related morbidity is interesting as NEFAs constitute a reservoir of metabolic energy, are principal components of cell membranes and are precursors for signalling molecules. Bariatric surgery promotes sustained weight loss in severely obese patients, reducing the incidence and severity of co-morbidities. In this study we measure changes in circulating NEFA species in plasma samples taken from 25 obese individuals before and 9 months after Roux-en-Y gastric bypass surgery. The mean weight of the cohort reduced by 29.2% from 149.0 ± 25.1 kg pre-surgery to 105.5 ± 19.8 kg post-surgery and the BMI by 28.2% from 51.8 ± 6.3 kg/m2 pre-surgery to 37.2 ± 5.4 kg/m2. Mean glycated haemoglobin (HbA1c) reduced from 6.5 ± 1.3 to 5.5 ± 0.5%, consistent with the intervention leading to improved glycaemic control, particularly in those who were dysglycemic prior to surgery. Total and LDL cholesterol concentrations were markedly reduced following surgery. Concentrations of seven NEFAs were found to decrease 9 months after surgery compared to pre-surgery levels: myristate, palmitoleate, palmitate, linoleate, oleate, stearate and arachidonate. Bariatric surgery led to increased lipogenesis and elongase activity and decreased stearoyl-CoA desaturase 1 activity. This study therefore highlights metabolic changes that take place following gastric bypass surgery in severely obese patients.

Abstract The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) was met with rapid development of robust molecular-based detection assays. Many SARS-CoV-2 molecular tests target multiple genetic regions of the virus to maximize detection and protect against diagnostic escape. Despite the relatively moderate mutational rate of SARS-CoV-2, numerous mutations with known negative impact on diagnostic assays have been identified. In early 2021, we identified four samples positive for SARS-CoV-2 with a nucleocapsid (N) gene drop out on Cepheid Xpert® Xpress SARS-CoV-2 assay. Sequencing revealed a single common mutation in the N gene C29200T. Spatiotemporal analysis showed that the mutation was found in at least six different Canadian provinces from May 2020 until May 2021. Phylogenetic analysis showed that this mutation arose multiple times in Canadian samples and is present in six different variants of interest and of concern. The Cepheid testing platform is commonly used in Canada including in remote regions. As such, the existence of N gene mutation dropouts required further investigation. While commercial SARS-CoV-2 molecular detection assays have contributed immensely to the response effort, many vendors are reluctant to make primer/probe sequences publicly available. Proprietary primer/probe sequences create diagnostic ‘blind spots’ for global SARS-CoV-2 sequence monitoring and limits the ability to detect and track the presence and prevalence of diagnostic escape mutations. We hope that our industry partners will seriously consider making primer/probe sequences available, so that diagnostic escape mutants can be identified promptly and responded to appropriately to maintain diagnostic accuracy.

Abstract The quality of life (QoL) of men with optimal outcomes after robot-assisted radical prostatectomy (RARP) is largely unexplored. Thus we assessed meaningful changes of QoL measured with the EORTC QLQ-C30 24 months after RARP according to postsurgical Cancer of the Prostate Risk Assessment score (CAPRA-S) and pentafecta criteria. 2871 prostate cancer (PCa) patients with completed EORTC QLQ-C30 were stratified according to CAPRA-S, pentafecta (erectile function recovery, urinary continence recovery, biochemical-recurrence-free survival (BFS), negative surgical margins) and 90-day Clavien–Dindo-complications (CDC) ≤ 3a. Multivariable logistic regression analyses (LRM) aimed to predict improvement of EORTC QoL. Mean preoperative QoL values did not significantly differ between CAPRA-S low- (LR) vs. high-risk (HR, 75.7 vs. 75.2; p = 0.7) and pentafecta vs. non-pentafecta groups (75.6 vs. 75.2; p = 0.6). After RARP, stable QoL rates for CAPRA-S LR vs. HR and pentafecta were 30, 26 and 30%, respectively. Corresponding improved QoL rates were 44, 32 and 47%. In LRM, CAPRA-S and pentafecta criteria were independent predictors of improved QoL. We conclude that most favourable combined outcomes after RARP might confer stable or even improved QoL but up to one third of patients might experience deterioration. This warrants further investigation how to capture the underlying cause and to address and potentially solve these perceived negative effects despite successful RARP.

Abstract The aim of this study was to assess clinically meaningful differences of preoperative lower urinary tract symptoms (LUTS) and quality of life (QoL) before and after robot-assisted radical prostatectomy (RARP). Therefore we identified 5506 RARP patients from 2007 to 2018 with completed International Prostate Symptom Score (IPSS) and -QoL questionnaires before and 12 months after RARP in our institution. Marked clinically important difference (MCID) was defined by using the strictest IPSS-difference of − 8 points. Multivariable logistic regression analyses (LRM) aimed to predict ∆IPSS ≤ − 8 and were restricted to RARP patients with preoperatively moderate (IPSS 8–19) vs. severe (IPSS 20–35) LUTS burden (n = 2305). Preoperative LUTS was categorized as moderate and severe in 37% (n = 2014) and 5.3% of the complete cohort (n = 291), respectively. Here, a postoperative ∆IPSS ≤ − 8, was reported in 38% vs. 90%. In LRM, younger age (OR 0.98, 95%CI 0.97–0.99; p = 0.007), lower BMI (OR 0.94, 95%CI 0.92–0.97; p