Miracle-dz/UniFAR-FTUs huggingface dataset:
Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro

Initially, patients that respond to cisplatin (DDP) treatment later relapse and develop chemoresistance. Agents that enhance DDP effectiveness will have a significant impact on cancer treatment. We have shown pronounced inhibitory effects of the progesterone-calcitriol combination on endometrial and ovarian cancer cell growth. Here, we examined whether and how progesterone-calcitriol combination potentiates DDP anti-tumor effects in cancer cells. Ovarian and endometrial cancer cells treated with various concentrations of DDP showed a concentration-dependent decrease in cell proliferation. Concurrent treatment of cells with DDP and progesterone-calcitriol ombination potentiated anticancer effects of DDP compared to DDP-calcitriol, or DDP-progesterone treated groups. The anticancer effects were mediated by increased caspase-3, BAX, and decreased BCL2 and PARP-1 expression in DDP and progesterone-calcitriol combination-treated cells. Stimulation of the PI3K/AKT and MAPK/ERK pathways seen in cancer cells was reduced in DDP-progesterone-calcitriol treated cells. Pretreatment of cells with specific inhibitors further diminished AKT and ERK expression. Furthermore, progesterone-calcitriol potentiated the anti-growth effects of DDP on cancer cells by attenuating the expression of SMAD2/3, multidrug resistance protein- 1 (MDR-1), and ABC transporters (ABCG1, and ABCG2), thereby impeding the efflux of chemo drugs from cancer cells. These results suggest a potential clinical benefit of progesterone-calcitriol combination therapy when used in combination with DDP.
The Role of Reactive Oxygen Species in the Life Cycle of the Mitochondrion

Currently, it is known that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. It is also known that mitochondria, because of their capacity to produce free radicals, play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including the stimulation of permeability transition pore opening. This process leads to mitoptosis and mitophagy, two sequential processes that are a universal route of elimination of dysfunctional mitochondria and is essential to protect cells from the harm due to mitochondrial disordered metabolism. To date, there is significant evidence not only that the above processes are induced by enhanced reactive oxygen species (ROS) production, but also that such production is involved in the other phases of the mitochondrial life cycle. Accumulating evidence also suggests that these effects are mediated through the regulation of the expression and the activity of proteins that are engaged in processes such as genesis, fission, fusion, and removal of mitochondria. This review provides an account of the developments of the knowledge on the dynamics of the mitochondrial population, examining the mechanisms governing their genesis, life, and death, and elucidating the role played by free radicals in such processes.
Analysis of Hygrothermal Microclimatic (HTM) Parameters in Specific Food Storage Environments in Slovakia

The quality of work environment, temperature changes and humidity must be controlled in every production process and in the locations where employees are present. The aim of this paper is to objectively assess the exposure of employees to microclimatic factors of the workplace environment: the warehouse, changing rooms, office and cold room refrigerator. Data were obtained in real working conditions. The heat stress due to cold and heat exposure in the individual locations was evaluated using the WBGT (wet bulb globe temperature) indicator. The parameters of the hygrothermal microclimate (HTM) were objectified by a QUES Temp 44/46 T spherical thermometer. The measurements were performed both in cold and hot periods of the year. The measurements confirmed standard temperatures for individual types of interiors in the winter period, but in the summer period there was a variability of results, leading to the thermal discomfort of employees. The assessment of the WBGT index revealed that nearly 80% of employees are susceptible to hypothermia as a result of thermal stress conditions. It was proven that the temperatures measured by a spherical thermometer in the hottest room were 8.62% higher than the calculated operating temperature, while the difference in the cold room refrigerator was only 1.28% higher.
SynergyFinder 2.0: visual analytics of multi-drug combination synergies

Abstract SynergyFinder (https://synergyfinder.fimm.fi) is a stand-alone web-application for interactive analysis and visualization of drug combination screening data. Since its first release in 2017, SynergyFinder has become a widely used web-tool both for the discovery of novel synergistic drug combinations in pre-clinical model systems (e.g. cell lines or primary patient-derived cells), and for better understanding of mechanisms of combination treatment efficacy or resistance. Here, we describe the latest version of SynergyFinder (release 2.0), which has extensively been upgraded through the addition of novel features supporting especially higher-order combination data analytics and exploratory visualization of multi-drug synergy patterns, along with automated outlier detection procedure, extended curve-fitting functionality and statistical analysis of replicate measurements. A number of additional improvements were also implemented based on the user requests, including new visualization and export options, updated user interface, as well as enhanced stability and performance of the web-tool. With these improvements, SynergyFinder 2.0 is expected to greatly extend its potential applications in various areas of multi-drug combinatorial screening and precision medicine.
Skeletal deformities in wild and farmed cleaner fish species used in Atlantic salmon Salmo salar aquaculture.

As a first attempt to assess bone health in cleaner fish production, wild and cultured ballan wrasse Labrus bergylta and lumpfish Cyclopterus lumpus were examined by radiology. In C. lumpus, wild fish (57%) had more vertebra deformities (≥1 deformed vertebrae) than cultured fish (2-16%). One wild C. lumpus had lordosis and another was missing the tail fin. In L. bergylta, wild fish (11%) had less vertebra deformities than cultured individuals (78-91%). Among the cultured L. bergylta, 17-53% of the fish had severe vertebra deformities (≥6 deformed vertebrae) with two predominate sites of location, one between vertebra 4 and 10 (S1) in the trunk, and one between 19 and 26 (S2) in the tail. Fusions dominated S1, while compressions dominated S2. Although wild L. bergylta had a low vertebra deformity level, 83% had calluses and 14% had fractures in haemal/neural spines and/or ribs. The site-specific appearance and pathology of fracture and callus in wild L. bergylta suggests these are induced by chronic mechanical stress, and a possible pathogenesis for fish hyperostosis is presented based on this notion. In conclusion, good bone health was documented in cultured C. lumpus, however, cultured L. bergylta suffered poor bone health. How this affects survival, growth, swimming abilities and welfare in cultured wrasse should be further investigated. This article is protected by copyright. All rights reserved.
Detection of the Amphibian Pathogens Chytrid Fungus (Batrachochytrium dendrobatidis) and Ranavirus in West Texas, USA, Using Environmental DNA

Abstract: Environmental DNA (eDNA) methods provide novel options for the detection of pathogens. The amphibian pathogens Batrachochytrium dendrobatidis (Bd) and Ranavirus have been relatively understudied in Texas, US, so we applied eDNA assays for the surveillance of these pathogens in the upper Brazos River basin near the Texas panhandle. We collected water samples from five urban playa lakes and one reservoir in and around Lubbock, Texas. Quantitative PCR detected both Bd and Ranavirus at one playa lake, representing novel detection of both pathogens in the region. Based on these results, we recommend increased monitoring for the pathogens and symptoms of amphibian disease throughout the region.
Plastics in Cyanobacterial Blooms—Genotoxic Effects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells

Ever-expanding environmental pollution is causing a rise in cyanobacterial blooms and the accumulation of plastics in water bodies. Consequently, exposure to mixtures of cyanotoxins and plastic-related contaminants such as bisphenols (BPs) is of increasing concern. The present study describes genotoxic effects induced by co-exposure to one of the emerging cyanotoxins—cylindrospermopsin (CYN)—(0.5 µg/mL) and BPs (bisphenol A (BPA), S (BPS), and F (BPF); (10 µg/mL)) in HepG2 cells after 24 and 72 h of exposure. The cytotoxicity was evaluated with an MTS assay and genotoxicity was assessed through the measurement of the induction of DNA double strand breaks (DSB) with the γH2AX assay. The deregulation of selected genes (xenobiotic metabolic enzyme genes, DNA damage, and oxidative response genes) was assessed using qPCR. The results showed a moderate reduction of cell viability and induction of DSBs after 72 h of exposure to the CYN/BPs mixtures and CYN alone. None of the BPs alone reduced cell viability or induced DSBs. No significant difference was observed between CYN and CYN/BPs exposed cells, except with CYN/BPA, where the antagonistic activity of BPA against CYN was indicated. The deregulation of some of the tested genes (CYP1A1, CDKN1A, GADD45A, and GCLC) was more pronounced after exposure to the CYN/BPs mixtures compared to single compounds, suggesting additive or synergistic action. The present study confirms the importance of co-exposure studies, as our results show pollutant mixtures to induce effects different from those confirmed for single compounds.
Gastrointestinal Stromal Tumours (GIST) in Young Adult (18–40 Years) Patients: A Report from the Dutch GIST Registry

Gastrointestinal stromal tumour (GIST) is a disease of older adults and is dominated by KIT/PDGFR mutations. In children, GIST is rare, predominantly occurs in girls, has a stomach location and generally lacks KIT/PDGFR mutations. For young adults (YA), aged 18 to 40 years, the typical phenotypic and genotypic patterns are unknown. We therefore aimed to describe the clinical, pathological and molecular characteristics of GIST in in YA. YA GIST patients registered in the Dutch GIST Registry (DGR) were included, and data were compared to those of older adults (OA). From 1010 patients in the DGR, 52 patients were YA (54% male). Main tumour locations were stomach (46%) and small intestine (46%). GIST genetic profiles were mutations in KIT (69%), PDGFRA (6%), SDH deficient (8%), NF1 associated (4%), ETV6-NTRK3 gene fusion (2%) or wildtype (10%). Statistically significant differences were found between the OA and YA patients (localisation, syndromic and mutational status). YA presented more often than OA in an emergency setting (18% vs. 9%). The overall five-year survival rate was 85%. In conclusion, YA GISTs are not similar to typical adult GISTs and also differ from paediatric GISTs, as described in the literature. In this series, we found a relatively high percentage of small intestine GIST, emergency presentation, 25% non-KIT/PDGFRA mutations and a relatively good survival.
Pharmacy Services beyond the Basics: A Qualitative Study to Explore Perspectives of Pharmacists towards Basic and Enhanced Pharmacy Services in Pakistan

Enhanced pharmacy services have been identified as a mechanism to address medicines and drug-related problems. The aim of the study was to explore the perspectives of practicing pharmacists on the scope of pharmacy service provision in Pakistan. This qualitative study was conducted at the Department of Pharmacy, the Islamia University of Bahawalpur (IUB). Face-to-face, in-depth interviews were conducted with practicing pharmacists at the university who were undertaking postgraduate studies. All interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. A total of 13 pharmacists were interviewed. The analysis of data yielded four themes and 12 subthemes. The themes included the current scenario of pharmacy services, the benefits of pharmacy services, barriers to implementation of pharmacy services, and strategies to improve their delivery. Pharmacist participants reported that patient-oriented pharmacy services have not been properly implemented in Pakistan. Pharmacists appear to be undertaking only conventional roles at various levels within the healthcare system. The participants indicated multiple benefits of patient-oriented pharmacy services, including safe and effective use of medicines, minimization of drug-related problems, and financial benefits to the healthcare system. Based on the findings, policy-makers are required to take the necessary steps to overcome pharmacist-related and policy-related barriers associated with the implementation of patient-oriented pharmacy services in Pakistan.
Student Perceptions of Non-traditional Level I Fieldwork

Academic programs commonly face challenges in developing Level I fieldwork where students have ample opportunity to practice and understand occupation. In response to this challenge, our academic program developed a non-traditional Level I fieldwork. The purpose of this study was to understand the student perceptions of this learning experience. Focus group methodology was employed. Fifty-nine students participated in one of six focus groups. Six themes were identified through the data analysis process. These included challenges and rewards of effective communication, learning to think like an OT, a greater understanding and focus on occupations, developing skills in cultural understanding and advocacy, gaining confidence through doing, and the logistical challenges of getting everyone on the same page. These themes supported that students viewed non-traditional Level I fieldwork paired with structured classroom learning activities positively. A pattern across all themes was that students learned because they were able to make mistakes, reflect on them, and change their action. Limitations include that student perceptions are only one aspect of understanding the impact of learning experiences; therefore further study is needed.
A Sec14 domain protein is required for photoautotrophic growth and chloroplast vesicle formation in Arabidopsis thaliana

Significance The light reactions of photosynthesis in algae and plants occur in thylakoid membranes within the chloroplast. Previous studies have implicated membrane contact sites, vesicle trafficking, and lipid-binding proteins in the formation of thylakoids at the chloroplast inner envelope, but the molecular basis of thylakoid biogenesis and maintenance remains enigmatic. Here we show that CPSFL1 is a chloroplast Sec14 domain protein that binds lipids and can transfer phosphoinositides between membranes in vitro. In the model plant Arabidopsis, CPSFL1 is necessary for the appearance of vesicles in chloroplasts. Our results provide molecular evidence supporting an essential role of chloroplast lipid and vesicle trafficking for photoautotrophic growth. In eukaryotic photosynthetic organisms, the conversion of solar into chemical energy occurs in thylakoid membranes in the chloroplast. How thylakoid membranes are formed and maintained is poorly understood. However, previous observations of vesicles adjacent to the stromal side of the inner envelope membrane of the chloroplast suggest a possible role of membrane transport via vesicle trafficking from the inner envelope to the thylakoids. Here we show that the model plant Arabidopsis thaliana has a chloroplast-localized Sec14-like protein (CPSFL1) that is necessary for photoautotrophic growth and vesicle formation at the inner envelope membrane of the chloroplast. The cpsfl1 mutants are seedling lethal, show a defect in thylakoid structure, and lack chloroplast vesicles. Sec14 domain proteins are found only in eukaryotes and have been well characterized in yeast, where they regulate vesicle budding at the trans-Golgi network. Like the yeast Sec14p, CPSFL1 binds phosphatidylinositol phosphates (PIPs) and phosphatidic acid (PA) and acts as a phosphatidylinositol transfer protein in vitro, and expression of Arabidopsis CPSFL1 can complement the yeast sec14 mutation. CPSFL1 can transfer PIP into PA-rich membrane bilayers in vitro, suggesting that CPSFL1 potentially facilitates vesicle formation by trafficking PA and/or PIP, known regulators of membrane trafficking between organellar subcompartments. These results underscore the role of vesicles in thylakoid biogenesis and/or maintenance. CPSFL1 appears to be an example of a eukaryotic cytosolic protein that has been coopted for a function in the chloroplast, an organelle derived from endosymbiosis of a cyanobacterium.
Hydrophobin-Protein A Fusion Protein Produced in Plants Efficiently Purified an Anti-West Nile Virus Monoclonal Antibody from Plant Extracts via Aqueous Two-Phase Separation

The development of monoclonal antibodies (mAbs) has provided vast opportunities to treat a wide range of diseases from cancer to viral infections. While plant-based production of mAbs has effectively lowered the upstream cost of mAb production compared to mammalian cell cultures, further optimization of downstream processing, especially in extending the longevity of Protein A resin by an effective bulk separation step, will further reduce the overall prohibitive cost of mAb production. In this study, we explored the feasibility of using aqueous two-phase separation (ATPS) in capturing and separating plant-made mAbs from host proteins. Our results demonstrated that an anti-West Nile virus mAb (E16) was efficiently separated from most plant host proteins by a single ATPS step, comprising the mixing of plant extracts containing Hydrophobin-Protein A fusion protein (HPA) and E16 and the subsequent incubation with an inexpensive detergent. This simple ATPS step yielded a highly enriched E16 mAb preparation with a recovery rate comparable to that of Protein A chromatography. The ATPS-enriched E16 retained its structural integrity and was fully functional in binding its target antigen. Notably, HPA-based ATPS was also effective in enriching E16 from plant host proteins when both HPA and E16 were produced in the same leaves, supporting the potential of further streamlining the downstream purification process. Thus, ATPS based on plant-produced HPA in unpurified extract is a cost-effective yet efficient initial capture step for purifying plant-made mAbs, which may significantly impact the approach of mAb purification.
Usefulness of O2-O3 intradiscal versus steroid intraforaminal injection in back pain control: a prospective double-blind trial in patients with different discovertebral pathologies

Poster: "ECR 2016 / B-0326 / Usefulness of O2-O3 intradiscal versus steroid intraforaminal injection in back pain control: a prospective double-blind trial in patients with different discovertebral pathologies" by: "M. Perri1, T. Popolizio1, C. Marsecano2, M. Varrassi2, A. Splendiani2, C. Masciocchi2; 1San Giovanni Rotondo/IT, 2L'Aquila/IT"
Temporal recalibration for improving prognostic model development and risk predictions in settings where survival is improving over time

Abstract Background Prognostic models are typically developed in studies covering long time periods. However, if more recent years have seen improvements in survival, then using the full dataset may lead to out-of-date survival predictions. Period analysis addresses this by developing the model in a subset of the data from a recent time window, but results in a reduction of sample size. Methods We propose a new approach, called temporal recalibration, to combine the advantages of period analysis and full cohort analysis. This approach develops a model in the entire dataset and then recalibrates the baseline survival using a period analysis sample. The approaches are demonstrated utilizing a prognostic model in colon cancer built using both Cox proportional hazards and flexible parametric survival models with data from 1996–2005 from the Surveillance, Epidemiology, and End Results (SEER) Program database. Comparison of model predictions with observed survival estimates were made for new patients subsequently diagnosed in 2006 and followed-up until 2015. Results Period analysis and temporal recalibration provided more up-to-date survival predictions that more closely matched observed survival in subsequent data than the standard full cohort models. In addition, temporal recalibration provided more precise estimates of predictor effects. Conclusion Prognostic models are typically developed using a full cohort analysis that can result in out-of-date long-term survival estimates when survival has improved in recent years. Temporal recalibration is a simple method to address this, which can be used when developing and updating prognostic models to ensure survival predictions are more closely calibrated with the observed survival of individuals diagnosed subsequently.
Alpha-Smooth Muscle Actin-Positive Perivascular Cells in Diabetic Retina and Choroid

Structural alterations of pericytes in microvessels are important features of diabetic retinopathy. Although capillary pericytes had been known not to have α-smooth muscle actin (αSMA), a recent study revealed that a specific fixation method enabled the visualization of αSMA along retinal capillaries. In this study, we applied snap-fixation in wild type and streptozotocin-induced diabetic mice to evaluate the differences in vascular smooth muscle cells of the retina and the choroid. Mice eyeballs were fixed in ice-cold methanol to prevent the depolymerization of filamentous actin. Snap-fixated retina showed αSMA expression in higher-order branches along the capillaries as well as the arterioles and venules, which were not detected by paraformaldehyde fixation. In contrast, most choriocapillaris, except those close to the arterioles, were not covered with αSMA-positive perivascular mural cells. Large choroidal vessels were covered with more αSMA-positive cells in the snap-fixated eyes. Diabetes induced less coverage of αSMA-positive perivascular mural cells overall, but they reached higher-order branches of the retinal capillaries, which was prominent in the aged mice. More αSMA-positive pericytes were observed in the choroid of diabetic mice, but the αSMA-positive expression reduced with aging. This study suggests the potential role of smooth muscle cells in the pathogenesis of age-related diabetic retinopathy and choroidopathy.