Miracle-dz/UniFAR-FTUs huggingface dataset:
Post-Translational Modification Networks of Contractile and Cellular Stress Response Proteins in Bladder Ischemia

Molecular mechanisms underlying bladder dysfunction in ischemia, particularly at the protein and protein modification levels and downstream pathways, remain largely unknown. Here we describe a comparison of protein sequence variations in the ischemic and normal bladder tissues by measuring the mass differences of the coding amino acids and actual residues crossing the proteome. A large number of nonzero delta masses (11,056) were detected, spanning over 1295 protein residues. Clustering analysis identified 12 delta mass clusters that were significantly dysregulated, involving 30 upregulated (R2 > 0.5, ratio > 2, p < 0.05) and 33 downregulated (R2 > 0.5, ratio < −2, p < 0.05) proteins in bladder ischemia. These protein residues had different mass weights from those of the standard coding amino acids, suggesting the formation of non-coded amino acid (ncAA) residues in bladder ischemia. Pathway, gene ontology, and protein–protein interaction network analyses of these ischemia-associated delta-mass containing proteins indicated that ischemia provoked several amino acid variations, potentially post-translational modifications, in the contractile proteins and stress response molecules in the bladder. Accumulation of ncAAs may be a novel biomarker of smooth muscle dysfunction, with diagnostic potential for bladder dysfunction. Our data suggest that systematic assessment of global protein modifications may be crucial to the characterization of ischemic conditions in general and the pathomechanism of bladder dysfunction in ischemia.
A New Outlook on the Ability to Accumulate an Iodine Contrast Agent in Solid Lung Tumors Based on Virtual Monochromatic Images in Dual Energy Computed Tomography (DECT): Analysis in Two Phases of Contrast Enhancement

For some time, dual energy computed tomography (DECT) has been an established method used in a vast array of clinical applications, including lung nodule assessment. The aim of this study was to analyze (using monochromatic DECT images) how the X-ray absorption of solitary pulmonary nodules (SPNs) depends on the iodine contrast agent and when X-ray absorption is no longer dependent on the accumulated contrast agent. Sixty-six patients with diagnosed solid lung tumors underwent DECT scans in the late arterial phase (AP) and venous phase (VP) between January 2017 and June 2018. Statistically significant correlations (p ≤ 0.001) of the iodine contrast concentration were found in the energy range of 40–90 keV in the AP phase and in the range of 40–80 keV in the VP phase. The strongest correlation was found between the concentrations of the contrast agent and the scanning energy of 40 keV. At the higher scanning energy, no significant correlations were found. We concluded that it is most useful to evaluate lung lesions in DECT virtual monochromatic images (VMIs) in the energy range of 40–80 keV. We recommend assessing SPNs in only one phase of contrast enhancement to reduce the absorbed radiation dose.
Multiresidue determination of antibiotics in ready-to-eat duck eggs marketed through e-commerce stores in China and subsequent assessment of dietary risks to consumers.

In this work, the occurrence of 34 common antibiotic (15 sulfonamides and 19 quinolones) residues were evaluated in 236 ready-to-eat duck eggs (salted and preserved duck eggs) marketed through e-commerce stores by ultra-performance liquid chromatography coupled to tandem mass spectrometry, and subsequent dietary risk assessments for Chinese consumers were conducted. Among violated positives in duck egg samples, 11 analytes were found including sulfamethazine, sulfaquinoxaline, sulfamethoxazole, sulfadiazine, sulfamonomethoxine, ciprofloxacin, enrofloxacin, ofloxacin, flumequine, sarafloxacin, and nalidixic acid. A higher number of antibiotics were detected in salted duck eggs (five sulfonamides and six quinolones) than in preserved duck eggs (one sulfonamide and two quinolones). The maximum contamination of sulfonamides and quniolones was 448.0 µg/kg (sulfaquinoxaline) and 563.7 µg/kg (enrofloxacin) in salted duck eggs, respectively. Dietary exposure was evaluated through the estimated daily intake (EDI) of risky antibiotics (sulfamethazine, ciprofloxacin, and enrofloxacin) and hazard quotients (HQs). The results showed that EDIs and HQs were in the range of 0.0004 to 0.0099 µg/kg bw/day and 0.0009 to 0.1594%, respectively. The risk was low since HQs obtained were less than 100%. However, a special attention should be paid to ready-to-eat duck egg products high percentile consumers with the prosperity of e-commerce market in China. PRACTICAL APPLICATION: The present analytical method could be used for multiresidue determination of antibiotics in ready-to-eat duck eggs, and dietary risk assessments of risky antibiotics provided a support for the work of regulatory bodies to conduct surveillance programs regarding food safety evaluation of ready-to-eat foods.
Fostering Mindfulness in Continuing Pharmacy Education Using a Board Game: Initial Experiences and Perceptions

Introduction: Expansion of pharmacists' scope of practice creates a need to optimize learning within continuing professional development (CPD) that can simultaneously promote mindfulness and enhance clinical decision-making. An educational board game embracing the principles of situated learning was developed with the purpose of promoting clinical reasoning skills and mindfulness. Methods: Iter Vitae was used in a national pharmacy meeting CPD session. An evaluation was conducted by a voluntary survey to gather perceptions of game-based instruction. Results: Ninety of 115 session-attendees completed the anonymous survey. Participants strongly agreed that Iter Vitae is an effective learning tool of appropriate complexity for CPD sessions. Participant perceptions suggest that playing Iter Vitae may enhance clinical knowledge, foster critical thinking, and influence provider empathy. Open-ended responses revealed appreciation of collaborative learning within authentic case scenarios. Discussion: This game-based CPD session gave participants an opportunity to develop elements of mindful practice embedded within authentic case scenarios. Further research on game-based instruction is needed to determine its effects on knowledge and skill acquisition, retention, and impact on clinical practice.
Dynamic remodeling of host membranes by self-organizing bacterial effectors

Bacterial effectors manipulate membranes Many pathogenic bacteria use molecular syringes to translocate proteins called effectors into the host cell to hijack the cellular machinery for their proliferation. Legionella pneumophila, the causative bacteria of Legionnaires' disease, uses a large effector arsenal and harnesses the host membrane system to establish a specialized vacuole where it replicates. Hsieh et al. show that, within this effector arsenal, the phospholipid kinase MavQ and the phosphatase SidP work together and self-organize on the intracellular membrane network of its eukaryotic host to promote membrane remodeling. The interactions between MavQ and SidP constitute positive and negative feedback loops, respectively, that orchestrate their spatiotemporal oscillation during infection. Science, aay8118, this issue p. 935 Legionella bacteria translocate a kinase-phosphatase duo, which self-organizes on the endoplasmic reticulum, into the host cell. During infection, intracellular bacterial pathogens translocate a variety of effectors into host cells that modify host membrane trafficking for their benefit. We found a self-organizing system consisting of a bacterial phosphoinositide kinase and its opposing phosphatase that formed spatiotemporal patterns, including traveling waves, to remodel host cellular membranes. The Legionella effector MavQ, a phosphatidylinositol (PI) 3-kinase, was targeted to the endoplasmic reticulum (ER). MavQ and the Legionella PI 3-phosphatase SidP, even in the absence of other bacterial components, drove rapid PI 3-phosphate turnover on the ER and spontaneously formed traveling waves that spread along ER subdomains inducing vesicle and tubule budding. Thus, bacteria can exploit a self-organizing membrane-targeting mechanism to hijack host cellular structures for survival.
A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response

The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and β-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small β-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The β-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the β-annulus peptide for vaccine design.
Blend Structure and n-Type Thermoelectric Performance of PA6/SAN and PA6/PMMA Blends Filled with Singlewalled Carbon Nanotubes

The present study investigates how the formation of melt-mixed immiscible blends based on PA6/SAN and PA6/PMMA filled with single walled nanotubes (SWCNTs) affects the thermoelectric (TE) properties. In addition to the detailed investigation of the blend morphology with compositions between 100/0 wt. % and 50/50 wt. %, the thermoelectric properties are investigated on blends with different SWCNT concentrations (0.25–3.0 wt.%). Both PA6 and the blend composites with the used type of SWCNTs showed negative Seebeck coefficients. It was shown that the PA6 matrix polymer, in which the SWCNTs are localized, mainly influenced the thermoelectric properties of blends with high SWCNT contents. By varying the blend composition, an increase in the absolute Seebeck coefficient, power factor (PF), and figure of merit (ZT) was achieved compared to the PA6 composite which is mainly related to the selective localization and enrichment of SWCNTs in the PA6 matrix at constant SWCNT loading. The maximum PFs achieved were 0.22 µW/m·K2 for PA6/SAN/SWCNT 70/30/3 wt. % and 0.13 µW/m·K2 for PA6/PMMA/SWCNT 60/40/3 wt. % compared to 0.09 µW/m·K2 for PA6/3 wt. % SWCNT which represent increases to 244% and 144%, respectively. At higher PMMA or SAN concentration, the change from matrix-droplet to a co-continuous morphology started, which, despite higher SWCNT enrichment in the PA6 matrix, disturbed the electrical conductivity, resulting in reduced PFs with still increasing Seebeck coefficients. At SWCNT contents between 0.5 and 3 wt. % the increase in the absolute Seebeck coefficient was compensated by lower electrical conductivity resulting in lower PF and ZT as compared to the PA6 composites.
Enhanced Cytotoxic Activity of Docetaxel-Loaded Silk Fibroin Nanoparticles against Breast Cancer Cells

Despite decades of research, breast cancer therapy remains a great challenge. Docetaxel is an antimicrotubule agent that is effectively used for the treatment of breast cancer. However, its clinical use is significantly hampered by its low water solubility and systemic toxicity. The current study was designed to prepare docetaxel (DXL)-loaded silk-fibroin-based nanoparticles (SF-NPs) and to screen their potential antitumor activity against breast cancer cell lines. DXL-loaded SF-NPs were prepared using a nanoprecipitation technique and were evaluated for particle size, zeta potential, entrapment efficiency, and in vitro release profile. In addition, DXL-loaded SF-NPs were screened for in vitro cytotoxicity, cellular uptake, and apoptotic potential against MCF-7 and MDA-MB-231 breast cancer cell lines. The prepared DXL-loaded SF-NPs were 178 to 198 nm in diameter with a net negative surface charge and entrapment efficiency ranging from 56% to 72%. In vitro release studies exhibited a biphasic release profile of DXL from SF-NPs with sustained drug release for 72 h. In vitro cell studies revealed that entrapment of DXL within SF-NPs significantly improved cytotoxic potential against breast cancer cell lines, compared to the free drug, and enhanced cellular uptake of DXL by breast cancer cells. Furthermore, the accumulation in the G2/M phase was significantly higher in cells treated with DXL-loaded SF-NPs than in cells treated with free DXL. Collectively, the superior antitumor activities of DXL-loaded SF-NPs against breast cancer cells, compared to free DXL, could be ascribed to improved apoptosis and cell cycle arrest. Our results highlighted the feasibility of using silk fibroin nanoparticles as a nontoxic biocompatible delivery vehicle for enhanced therapeutic outcomes in breast cancer.
Solid Organ Transplantation and Survival among Individuals with a History of Cancer

Background: The success of immunotherapy highlights a possible role for immunity in controlling cancer during remission for patients with cancer in the general population. A prior cancer diagnosis is common among solid organ transplant candidates, and immunosuppressive medications administered to transplant recipients may increase recurrence risk. Methods: Using linked data from the United States solid organ transplant registry and 13 cancer registries, we compared overall and cancer-specific survival among patients with cancer who did versus did not receive subsequent transplantation. We used Cox regression in cohort and matched analyses, controlling for demographic factors, cancer stage, and time since cancer diagnosis. Results: The study included 10,524,326 patients with cancer, with 17 cancer types; 5,425 (0.05%) subsequently underwent solid organ transplantation. The median time from cancer diagnosis to transplantation was 5.7 years. Transplantation was associated with reduced overall survival for most cancers, especially cervical, testicular, and thyroid cancers [adjusted hazard ratios (aHR) for overall mortality, 3.43–4.88]. In contrast, transplantation was not associated with decreased cancer-specific survival for any cancer site, and we observed inverse associations for patients with breast cancer (aHRs for cancer-specific mortality, 0.65–0.67), non-Hodgkin lymphoma (0.50–0.51), and myeloma (0.39–0.42). Conclusions: Among U.S. patients with cancer, subsequent organ transplantation was associated with reduced overall survival, likely due to end-stage organ disease and transplant-related complications. However, we did not observe adverse associations with cancer-specific survival, partly reflecting careful candidate selection. Impact: These results do not demonstrate a detrimental effect of immunosuppression on cancer-specific survival and support current management strategies for transplant candidates with previous cancer diagnoses.
Effect of Fibre Orientation on the Quasi-Static Axial Crushing Behaviour of Glass Fibre Reinforced Polyvinyl Chloride Composite Tubes

In this study, glass fibre reinforced (GFRP) polyvinyl chloride (PVC) tubes were subjected to quasi-static axial compression tests to determine their crashworthiness performance. To this end, this study employed GFRP/PVC tubes with four different fibre orientations, 45°, 55°, 65° and 90°. A five-axis filament winding machine was used to fabricate the tubes. The results show that there was a considerable increase in all crashworthiness characteristics due to GFRP reinforcement. For the GFRP/PVC composite tubes of different fibre orientations, the load-bearing capacity, crush force efficiency and energy absorption capability generally improve with increasing fibre orientation. The GFRP/PVC 45° specimen was a notable exception as it exhibited the best specific energy absorption capacity and a crushing force efficiency that was only slightly less than for the GFRP/PVC 90° specimen.
Association between Chronic Obstructive Pulmonary Disease and Ménière’s Disease: A Nested Case—Control Study Using a National Health Screening Cohort

This study explored the relation between Ménière’s disease and chronic obstructive pulmonary disease (COPD). The ≥40-year-old population of the Korean National Health Insurance Service-Health Screening Cohort was included. In total, 7734 Ménière’s disease patients and 30,936 control participants were enrolled. Control participants were matched for age, sex, income, and region of residence with Ménière’s disease participants. The odds of having Ménière’s disease given a history of COPD were analyzed using conditional logistic regression. Subgroup analyses were conducted according to age, sex, income, and region of residence. The odds of having Ménière’s disease were found to be 1.18-fold higher with a history of COPD than with no history of COPD (95% confidence intervals (CI) = 1.06–1.32, E-value (CI) = 1.64 (1.31)). The ≥60 years old, male, low-income, and rural subgroups showed increased odds of developing Ménière’s disease when a history of COPD was reported. A history of COPD was associated with an increased risk of Ménière’s disease in the adult population.
Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes™, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p < 0.005) and 12 (85.0 [80.0, 90.0] cm, p < 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm; 4 weeks: 102.0 [95.7, 108.3] cm; 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.
Use of Visual Dashboards to Enhance Pharmacy Teaching

Teaching large cohorts of pharmacy students with a team of multiple tutors in a feedback intensive course poses challenges in relation the amount of data generated, data integrity, interpretation of the data and importantly application of the insights gained from the data. The dispensing and counselling course in the third year BPharm at the University of Sydney has implemented the USyd Pharmacy Dashboard, developed to address these challenges following the Technological Pedagogical Content Knowledge Framework (TPACK) to integrate technology into teaching. The dashboard was designed to improve the student experience through more consistent feedback, gain insights to improve teaching delivery and provide efficiencies in maintaining data integrity. The tool has been developed using an action-based research approach whereby ideas are put into practice as the means to further develop the idea and improve practice. Refinement of the USyd Pharmacy Dashboard over three years has shown improvements in teaching delivery as teachers can respond to emerging trends. Student performance and satisfaction scores have increased, mainly due to improved consistency between tutors and improved delivery of feedback. Time involved with administrative tasks such as data maintenance is reduced. Opportunities for further refinements such as real time benchmarking and developing an open learner model have become apparent.
High Choline Intake during Pregnancy Reduces Characteristics of the Metabolic Syndrome in Male Wistar Rat Offspring Fed a High Fat But Not a Normal Fat Post-Weaning Diet

Maternal choline intakes are below recommendations, potentially impairing the child’s later-life metabolic health. This study aims to elucidate the interaction between the choline content of the gestational diet (GD) and fat content of the post-weaning diet (PWD) on metabolic phenotype of male Wistar rats. Pregnant Wistar rats were fed a standard rodent diet (AIN-93G) with either recommended choline (RC, 1 g/kg diet choline bitartrate) or high choline (HC, 2.5-fold). Male pups were weaned to either a normal (16%) fat (NF) or a high (45%) fat (HF) diet for 17 weeks. Body weight, visceral adiposity, food intake, energy expenditure, plasma hormones, triglycerides, and hepatic fatty acids were measured. HC-HF offspring had 7% lower body weight but not food intake, and lower adiposity, plasma triglycerides, and insulin resistance compared to RC-HF. They also had increased hepatic n-3 fatty acids and a reduced n-6/n-3 and C 18:1 n-9/C18:0 ratios. In contrast, HC-NF offspring had 6–8% higher cumulative food intake and body weight, as well as increased leptin and elevated hepatic C16:1 n-7/C16:0 ratio compared to RC-NF. Therefore, gestational choline supplementation associated with improved long-term regulation of several biomarkers of the metabolic syndrome in male Wistar rat offspring fed a HF, but not a NF, PWD.