Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth of health literacy research activity in three Middle Eastern countries

Background Health literacy is defined as the capacity to obtain, interpret and understand basic health information. In each country, the count of published literature is a good indicator for scientific activity. This study aimed to assess the growth rate of scientific production in the field of health literacy in Middle Eastern countries during 2005–2014. Methods We used the PubMed database and retrieved 839 papers in the field of health literacy from three productive countries in the Middle East: Iran, Saudi Arabia and Turkey. We applied the bibliometric indicator of Price’s Law to assess the increase of scientific literature. The correlation between bibliometric data and some health indicators such as gross domestic product and population was calculated. Results Worldwide research productivity in health literacy field was 56 653 documents while that from Middle Eastern countries were 839 papers. Iran, Turkey and Saudi Arabia were three productive countries in Middle East. Iran and Saudi Arabia have undergone exponential growth, but Turkey has undergone linear growth over the studied period. Conclusions In conclusion, although the present data show promising increase and good start in research productivity from countries in Middle East, they have a trivial sharing in publishing scientific papers in the field of health literacy through 2005–2014.
Cluster randomised controlled trial of an online intervention to improve healthy food purchases from primary school canteens: a study protocol of the ‘click & crunch’ trial

Introduction School canteens are the most frequently accessed take-away food outlet by Australian children. The rapid development of online lunch ordering systems for school canteens presents new opportunities to deliver novel public health nutrition interventions to school-aged children. This study aims to assess the effectiveness and cost-effectiveness of a behavioural intervention in reducing the energy, saturated fat, sugar and sodium content of online canteen lunch orders for primary school children. Methods and analysis The study will employ a cluster randomised controlled trial design. Twenty-six primary schools in New South Wales, Australia, that have an existing online canteen ordering system will be randomised to receive either a multi-strategy behavioural intervention or a control (the standard online canteen ordering system). The intervention will be integrated into the existing online canteen system and will seek to encourage the purchase of healthier food and drinks for school lunch orders (ie, items lower in energy, saturated fat, sugar and sodium). The behavioural intervention will use evidence-based choice architecture strategies to redesign the online menu and ordering system including: menu labelling, placement, prompting and provision of feedback and incentives. The primary trial outcomes will be the mean energy (kilojoules), saturated fat (grams), sugar (grams) and sodium (milligrams) content of lunch orders placed via the online system, and will be assessed 12 months after baseline data collection. Ethics and dissemination The study was approved by the ethics committees of the University of Newcastle (H-2017–0402) and the New South Wales Department of Education and Communities (SERAP 2018065), and the Catholic Education Office Dioceses of Sydney, Parramatta, Lismore, Maitland-Newcastle, Bathurst, Canberra-Goulburn, Wollongong, Wagga Wagga and Wilcannia-Forbes. Study results will be disseminated through peer-reviewed publications, reports, presentations at relevant national and international conferences and via briefings to key stakeholders. Results will be used to inform future implementation of public health nutrition interventions through school canteens, and may be transferable to other food settings or online systems for ordering food. Trial registration number ACTRN12618000855224.
A Toolbox to Characterize Human Induced Pluripotent Stem Cell-Derived Kidney Cell Types and Organoids.

BACKGROUND The generation of reporter lines for cell identity, lineage, and physiologic state has provided a powerful tool in advancing the dissection of mouse kidney morphogenesis at a molecular level. Although use of this approach is not an option for studying human development in vivo, its application in human induced pluripotent stem cells (iPSCs) is now feasible. METHODS We used CRISPR/Cas9 gene editing to generate ten fluorescence reporter iPSC lines designed to identify nephron progenitors, podocytes, proximal and distal nephron, and ureteric epithelium. Directed differentiation to kidney organoids was performed according to published protocols. Using immunofluorescence and live confocal microscopy, flow cytometry, and cell sorting techniques, we investigated organoid patterning and reporter expression characteristics. RESULTS Each iPSC reporter line formed well patterned kidney organoids. All reporter lines showed congruence of endogenous gene and protein expression, enabling isolation and characterization of kidney cell types of interest. We also demonstrated successful application of reporter lines for time-lapse imaging and mouse transplantation experiments. CONCLUSIONS We generated, validated, and applied a suite of fluorescence iPSC reporter lines for the study of morphogenesis within human kidney organoids. This fluorescent iPSC reporter toolbox enables the visualization and isolation of key populations in forming kidney organoids, facilitating a range of applications, including cellular isolation, time-lapse imaging, protocol optimization, and lineage-tracing approaches. These tools offer promise for enhancing our understanding of this model system and its correspondence with human kidney morphogenesis.
Costs of clinical events in type 2 diabetes mellitus patients in the Netherlands: A systematic review

Background Type 2 diabetes mellitus (T2DM) is an established risk factor for cardiovascular and nephropathic events. In the Netherlands, prevalence of T2DM is expected to be as high as 8% by 2025. This will result in significant clinical and economic impact, highlighting the need for well-informed reimbursement decisions for new treatments. However, availability and consistent use of costing methodologies is limited. Objective We aimed to systematically review recent costing data for T2DM-related cardiovascular and nephropathic events in the Netherlands. Methods A systematic literature review in PubMed and Embase was conducted to identify available Dutch cost data for T2DM-related events, published in the last decade. Information extracted included costs, source, study population, and costing perspective. Finally, papers were evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Results Out of initially 570 papers, 36 agreed with the inclusion criteria. From these studies, 150 cost estimates for T2DM-related clinical events were identified. In total, 29 cost estimates were reported for myocardial infarction (range: €196-€27,038), 61 for stroke (€495-€54,678), fifteen for heart failure (€325-€16,561), 24 for renal failure (€2,438-€91,503), and seventeen for revascularisation (€3,000-€37,071). Only four estimates for transient ischaemic attack were available, ranging from €587 to €2,470. Adherence to CHEERS was generally high. Conclusions The most expensive clinical events were related to renal failure, while TIA was the least expensive event. Generally, there was substantial variation in reported cost estimates for T2DM-related events. Costing of clinical events should be improved and preferably standardised, as accurate and consistent results in economic models are desired.
The Multifaceted Roles of Pyroptotic Cell Death Pathways in Cancer

Cancer is a category of diseases involving abnormal cell growth with the potential to invade other parts of the body. Chemotherapy is the most widely used first-line treatment for multiple forms of cancer. Chemotherapeutic agents act via targeting the cellular apoptotic pathway. However, cancer cells usually acquire chemoresistance, leading to poor outcomes in cancer patients. For that reason, it is imperative to discover other cell death pathways for improved cancer intervention. Pyroptosis is a new form of programmed cell death that commonly occurs upon pathogen invasion. Pyroptosis is marked by cell swelling and plasma membrane rupture, which results in the release of cytosolic contents into the extracellular space. Currently, pyroptosis is proposed to be an alternative mode of cell death in cancer treatment. Accumulating evidence shows that the key components of pyroptotic cell death pathways, including inflammasomes, gasdermins and pro-inflammatory cytokines, are involved in the initiation and progression of cancer. Interfering with pyroptotic cell death pathways may represent a promising therapeutic option for cancer management. In this review, we describe the current knowledge regarding the biological significance of pyroptotic cell death pathways in cancer pathogenesis and also discuss their potential therapeutic utility.
Investigating the Impact of Albumin on the Liver Uptake of Pitavastatin and Warfarin in Nagase Analbuminemic Rats

Albumin has been suggested to enhance the hepatic uptake of organic anion-transporting polypeptide (Oatp) substrates in various in vitro as well as liver perfusion models. However, it is not known whether the interplay between albumin and Oatp substrates is an experimental artifact or if this interaction occurs in vivo. The objective of this work was to investigate the hepatic uptake of warfarin and pitavastatin, which are both extensively bound to albumin but only pitavastatin being an Oatp substrate. Experiments were conducted in Nagase analbuminemic rats (NAR) which exhibit reduced albumin levels compared with F344 (wild type, WT). The fraction unbound (fu) was 140- and 10-fold greater in NAR plasma for warfarin and pitavastatin, respectively, whereas no meaningful differences were observed with tissue binding. In vitro, pitavastatin uptake into hepatocytes reconstituted in WT plasma was 17- and 3-fold greater than when reconstituted in buffer or NAR plasma, respectively. In vivo, the free tissue-to-free plasma ratios (Kp,u,u) from brain and liver in intact WT and NAR were not significantly different for warfarin. Contrarily, liver Kp,u,u of pitavastatin was 6-fold higher in WT animals, which corresponded to a 2.3-fold reduction in free plasma and 2.6-fold increase in free liver exposure. These results suggest that the enhanced hepatic uptake by albumin is not necessarily an experimental artifact but is also a relevant phenomenon in vivo. This work raises the possibility that other plasma proteins may also effect the function of additional drug transporters, and that modulating plasma protein binding may exhibit meaningful clinical relevance in the disposition of drugs. SIGNIFICANCE STATEMENT The interplay between albumin and Oatp substrates has been reported in hepatocytes and in liver perfusion studies, but the in vivo relevance of this interaction has yet to be elucidated. Using NAR and its corresponding WT animal, this study demonstrates that albumin may indeed enhance the hepatic uptake of pitavastatin in intact animals. In vivo demonstration of this interplay not only provides further justification for continued investigation into this particular mechanism but also raises the possibility that other plasma proteins may affect additional drug transporters and that modulating plasma protein binding may exhibit meaningful clinical relevance in the disposition of drugs.
Thermophoresis of biological and biocompatible compounds in aqueous solution

With rising popularity of microscale thermophoresis for the characterisation of protein-ligand binding reactions and possible applications in microfluidic devices, there is a growing interest in considering thermodiffusion in the context of life sciences. But although the understanding of thermodiffusion in non-polar mixtures has grown rapidly in recent years, predictions for associated mixtures like aqueous solutions remain challenging. This review aims to give an overview of the literature on thermodiffusion in aqueous systems, show the difficulties in theoretical description that arise from the non-ideal behaviour of water-mixtures, and highlight the relevance of thermodiffusion in a biological context. We find that the thermodiffusion in aqueous systems is dominated by contributions from heat of transfer, hydrogen bond interactions and charge effects. However, the separation of these effects is often difficult, especially in case of biological systems where a systematic exclusion of contributions may not be feasible.
Dapagliflozin Prevents NOX- and SGLT2-Dependent Oxidative Stress in Lens Cells Exposed to Fructose-Induced Diabetes Mellitus

Purpose: Cataracts in patients with diabetes mellitus (DM) are a major cause of blindness in developed and developing countries. This study aims to examine whether the generation of reactive oxygen species (ROS) via the increased expression of glucose transporters (GLUTs) and the receptor for advanced glycation end products (RAGE) influences the cataract development in DM. Methods: Lens epithelial cells (LECs) were isolated during cataract surgery from patients without DM or with DM, but without diabetic retinopathy. In a rat model, fructose (10% fructose, 8 or 12 weeks) with or without dapagliflozin (1.2 mg/day, 2 weeks) treatment did induce DM, as verified by blood pressure and serum parameter measurements. Immunofluorescence stainings and immunoblottings were used to quantify the protein levels. Endogenous O2˙¯ production in the LECs was determined in vivo with dihydroethidium stainings. Results: We investigated that GLUT levels in LECs differed significantly, thus leading to the direct enhancement of RAGE-associated superoxide generation in DM patients with cataracts. Superoxide production was significantly higher in LECs from rats with fructose-induced type 2 DM, whereas treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin prevented this effect in fructose-fed rats. Protein expression levels of the sodium/glucose cotransporter 2 (SGLT2), GLUT1, GLUT5, the nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase subunit p67-phox, NOX2/4 and RAGE were upregulated in fructose-fed animals, whereas dapagliflozin treatment reversed these effects. Conclusions: In rats with fructose-induced DM, dapagliflozin downregulates RAGE-induced NADPH oxidase expression in LECs via the inactivation of GLUTs and a reduction in ROS generation. These novel findings suggest that the SGLT2 inhibitor dapagliflozin may be a candidate for the pharmacological prevention of cataracts in patients with DM.
Simultaneous presentation of parathyroid carcinoma, papillary thyroid cancer and ACTH-independent hypercortisolism due to benign cortical adenoma

A 46-year-old woman presented with hypertension and renal disease. Investigations showed severe hypercalcaemia due to primary hyperparathyroidism. Imaging demonstrated renal calculi and an incidental left adrenal lesion. Additional biochemistry confirmed adrenocorticotropic hormone-independent hypercortisolism. Ultrasound and sestamibi scan found an enlarged right-sided parathyroid gland and a suspicious right thyroid nodule, biopsy of which suggested papillary carcinoma. The right parathyroid mass, right thyroid lobe and right central compartment tissue along with a segment of the right recurrent laryngeal nerve was resected en-bloc. Completion thyroidectomy and left adrenalectomy were performed 6 months later. Histology showed parathyroid cancer, multifocal papillary thyroid cancer and adrenal clear cell cortical adenoma. Genetic tests were normal. There was no evidence of recurrence at 12 months follow-up. Parathyroid cancer should be suspected in the presence of significant hypercalcaemia, very high parathyroid hormone and end organ damage. Suspicious thyroid nodules on imaging should be appropriately investigated.
Low-dose ladostigil for mild cognitive impairment

Objective Ladostigil reduces oxidative stress and microglial activation in aging rats. We assessed its safety and potential efficacy in a 3-year, randomized, double-blind, placebo-controlled phase 2 clinical trial in patients with mild cognitive impairment (MCI) and medial temporal lobe atrophy. Methods Patients 55 to 85 years of age with MCI, Clinical Dementia Rating (CDR) score of 0.5, Mini-Mental State Examination (MMSE) score >24, Wechsler Memory Scale–Revised Verbal Paired Associates I score ≤18, and Medial Temporal Lobe Atrophy Scale score >1 were stratified by APOE ε4 genotype and randomly assigned (1:1) to ladostigil 10 mg/d or placebo. Primary outcomes were safety and onset of Alzheimer disease dementia. Secondary endpoints were Neuropsychological Test Battery (NTB) composite, Disability Assessment in Dementia (DAD), and Geriatric Depression Scale (GDS) scores. Exploratory outcomes were NTB component, CDR, and MMSE scores. Biomarkers included MRI-derived whole-brain, hippocampus, and entorhinal cortex volumes. Results Two hundred ten patients from 15 sites in Austria, Germany, and Israel were randomly allocated to placebo (107 patients) or ladostigil (103 patients). After 36 months, 21 of 103 patients on placebo and 14 of 99 patients receiving ladostigil progressed to Alzheimer disease (log-rank test p = 0.162). There were no significant effects on the NTB composite, DAD, or GDS score. Whole-brain and hippocampus volumes decreased more in the placebo than in the ladostigil group (whole brain, p = 0.025, Cohen d = 0.43; hippocampus, p = 0.043, d = 0.43). Serious adverse events were reported by 28 of 107 patients treated with placebo and 26 of 103 with ladostigil. Conclusion Ladostigil was safe and well tolerated but did not delay progression to dementia. Its association with reduced brain and hippocampus volume loss suggests a potential effect on atrophy. ClinicalTrials.gov identifier NCT 01429623. Classification of evidence This study provides Class II evidence that for patients with MCI and medial temporal lobe atrophy, ladostigil did not significantly decrease the risk of the development of Alzheimer disease.
Optical Diagnostic Based on Functionalized Gold Nanoparticles

Au nanoparticles (NPs) possess unique physicochemical and optical properties, showing great potential in biomedical applications. Diagnostic spectroscopy utilizing varied Au NPs has become a precision tool of in vitro and in vivo diagnostic for cancer and other specific diseases. In this review, we tried to comprehensively introduce the remarkable optical properties of Au NPs, including localized surfaces plasmon resonance (LSPR), surface-enhanced Raman scattering (SERS), and metal-enhanced fluorescence (MEF). Then, we highlighted the excellent works using Au NPs for optical diagnostic applications. Ultimately, the challenges and future perspective of using Au NPs for optical diagnostic were discussed.
Comparative Characteristics of Ductile Iron and Austempered Ductile Iron Modeled by Neural Network

Experimental research of cutting force components during dry face milling operations are presented in the paper. The study was provided when milling of ductile cast iron alloyed with copper and its austempered ductile iron after the proper austempering process. In the study, virtual instrumentation designed for cutting forces components monitoring was used. During the research, orthogonal cutting forces components versus time were monitored and relationship of cutting forces components versus speed, feed and depth of cut were determined by artificial neural network and response surface methodology. An analysis was made regarding the consistency of the measured cutting forces and the values obtained from the model supported by an artificial neural network for the investigated interval of the cutting regime. Based on the results, an analysis of the feasibility of the application of austempered ductile iron in the industrial sector with the aspect of machinability as well as the application of the models based on artificial intelligence, was given. At the end of the presentation, the influence of the aforementioned cutting regimes on cutting force components is presented as well.
Cooperative Localization Approach for Multi-Robot Systems Based on State Estimation Error Compensation

In order to improve the localization accuracy of multi-robot systems, a cooperative localization approach with communication delays was proposed in this paper. In the proposed method, the reason for the time delay of the robots’ cooperative localization approach was analyzed first, and then the state equation and measure equation were reconstructed by introducing the communication delays into the states and measurements. Furthermore, the cooperative localization algorithm using the extended Kalman filtering technique based on state estimation error compensation was proposed to reduce the state estimation error of delay filtering. Finally, the simulation and experiment results demonstrated that the proposed algorithm can achieve good performance in location in the presence of communication delay while having reduced computational and communicative cost.
Strength training as a supplemental therapy for androgen deficiency of the aging male (ADAM): study protocol for a three-arm clinical trial

Introduction Androgen deficiency of the ageing male is a clinical syndrome resulting from the low production of androgens (testosterone levels <6.9 nmol/L) with symptoms including decline in lean mass, muscle strength, increases in body mass and overall fat mass. The aim of the study is to examine the effect of a 12 week strength training intervention on body composition, physical function, muscle cellular and molecular and selected biochemical markers of metabolic health in hypogonadal patients. Methods and analysis The study is three-group controlled 12-week experiment to assess the effect of strength training on hypogonadal patients with testosterone replacement therapy and newly diagnosed males without testosterone replacement therapy. Age matched healthy eugonadal males are also engaged in strength training. Lean mass is used to determine sample size indicating, that 22 subjects per group will be sufficient to detect intervention related changes at the power of 0.90. All outcomes are collected before the intervention (pre-intervention assessments) and after the intervention (post-intervention assessments). Clinical outcomes are body composition (lean mass, fat mass and total body mass) measured by dual-energy X-ray absorptiometry, physical functioning assessed by physical tests and psychosocial functioning. The most important haematological and biochemical parameters included are glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, testosterone, luteinizing hormone, follicle-stimulating hormone, sexhormone-binding globulin, insulin and prostate-specific antigen. Muscle cellular and molecular outcomes are muscle fibre size and regulators of muscle fibre size. Muscle cellular outcomes are measured from muscle biopsies obtained from musculus vastus lateralis. Ethics and dissemination This trial is approved by Ethics Committee of the University Hospital in Bratislava, Slovakia, (ref. trial number: 127/2017) and all subjects will be fully informed on the rationale, risks and benefits of the study and sign the written informed consent prior to entering the study. Results will be published in peer-reviewed journals and presented in scientific conferences. Trial registration number NCT03282682