Miracle-dz/UniFAR-FTUs huggingface dataset:
The process of adjustment over time following stroke: A longitudinal qualitative study

ABSTRACT Understanding how people adjust following stroke is essential to optimise recovery and ensure services are responsive to people’s needs. This study aimed to explore people’s experiences over the first three years post-stroke and identify what helped or hindered recovery. As part of a longitudinal, qualitative descriptive study, 55 people and 27 significant others purposefully selected from a population-based stroke incidence study were interviewed 6, 12, 24 and 36 months post-stroke. Interviews were audio taped and transcribed verbatim. Participants described an ongoing process of shock, disruption, and fear, making sense of what happened, needing to fit in with what’s offered, finding what works for them and evolving a new normal, whilst managing the ups and downs of life. This process needed to be re-negotiated over time, as people experienced changes in their recovery, comorbidities and/or wider circumstances. The adjustment process continued over the three years post-stroke, even for those who perceived that they were recovering well. Rehabilitation services need to support patients to make sense of their stroke, navigate the health system, address individual concerns and priorities and to know what, when and how much to challenge themselves. Rehabilitation plans need to be revised as circumstances change to facilitate adjustment following a stroke.
The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells

G protein-coupled receptor, regulates melanosome transport in pigment cells Ilaria Palmisano1,, Paola Bagnato1,2,, Angela Palmigiano1, Giulio Innamorati1, Giuseppe Rotondo1, Domenico Altimare1, Consuelo Venturi2, Elena V. Sviderskaya3, Rosanna Piccirillo1, Massimiliano Coppola4, Valeria Marigo5, Barbara Incerti4, Andrea Ballabio4, Enrico M. Surace4, Carlo Tacchetti2, Dorothy C. Bennett3 and Maria Vittoria Schiaffino1,
Molecular Adjuvants Based on Plasmids Encoding Protein Aggregation Domains Affect Bone Marrow Niche Homeostasis

Background: During last years, DNA vaccine immunogenicity has been optimized by the employment of co-stimulatory molecules and molecular adjuvants. It has been reported that plasmid (pATRex), encompassing the DNA sequence for the von Willebrand A (vWA/A) domain of the An-thrax Toxin Receptor-1 (ANTXR-1, alias TEM8, Tumor Endothelial Marker 8), acts as strong immune adjuvant by inducing formation of insoluble intracellular aggregates. Markedly, we faced with upsetting findings regarding the safety of pATRex as adjuvant since the aggregosome formation prompted to os-teopenia in mice. Objective: The present study provides additional evidences about the proteinaceous adjuvants action within bone marrow and questioned regarding the self-aggregation protein adjuvants immunotoxicity on marrow niches. Methods & Results: Using histological, biochemical and proteomic assays we shed light on pATRex effects within bone marrow niche and specifically we evidenced an aplastic-like bone marrow with dis-rupted cytokine/chemokine production. Conclusion: The above findings provide compelling support to the thesis that adjuvants based on plas-mids encoding protein aggregation domains disrupt the physiological features of the bone marrow ele-ments.
Factors determining dengue outbreak in Malaysia

A large scale study was conducted to elucidate the true relationship among entomological, epidemiological and environmental factors that contributed to dengue outbreak in Malaysia. Two large areas (Selayang and Bandar Baru Bangi) were selected in this study based on five consecutive years of high dengue cases. Entomological data were collected using ovitraps where the number of larvae was used to reflect Aedes mosquito population size; followed by RT-PCR screening to detect and serotype dengue virus in mosquitoes. Notified cases, date of disease onset, and number and type of the interventions were used as epidemiological endpoint, while rainfall, temperature, relative humidity and air pollution index (API) were indicators for environmental data. The field study was conducted during 81 weeks of data collection. Correlation and Autoregressive Distributed Lag Model were used to determine the relationship. The study showed that, notified cases were indirectly related with the environmental data, but shifted one week, i.e. last 3 weeks positive PCR; last 4 weeks rainfall; last 3 weeks maximum relative humidity; last 3 weeks minimum and maximum temperature; and last 4 weeks air pollution index (API), respectively. Notified cases were also related with next week intervention, while conventional intervention only happened 4 weeks after larvae were found, indicating ample time for dengue transmission. Based on a significant relationship among the three factors (epidemiological, entomological and environmental), estimated Autoregressive Distributed Lag (ADL) model for both locations produced high accuracy 84.9% for Selayang and 84.1% for Bandar Baru Bangi in predicting the actual notified cases. Hence, such model can be used in forestalling dengue outbreak and acts as an early warning system. The existence of relationships among the entomological, epidemiological and environmental factors can be used to build an early warning system for the prediction of dengue outbreak so that preventive interventions can be taken early to avert the outbreaks.
Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.
A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders

Today, tens of millions of elderly individuals worldwide suffer from dementia. While the pathogenesis of dementia is complex and incompletely understood, it may be, at least to a certain extent, the consequence of systemic vascular pathology. The metabolic syndrome and its individual components induce a proinflammatory state that damages blood vessels. This condition of chronic inflammation may damage the vasculature of the brain or be directly neurotoxic. Associations have been established between the metabolic syndrome, its constituents and dementia. A relationship has also been observed between certain dietary factors, such as constituents of the ‘Mediterranean diet’, and the metabolic syndrome; similar associations have been noted between these dietary factors and dementia. Fruit juices and extracts are under investigation as treatments for cognitive impairment. Blueberry, strawberry, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired rodents. Published trials of the benefits of grape and blueberry juice in the treatment of small numbers of cognitively impaired persons have recently appeared. The benefits of fruit products are thought to be a result of its polyphenol content. A grape polyphenol found in grapes, resveratrol, now being studied in humans, and one in grapes and blueberries, pterostilbene, have been found to improve cognition in rodents. In the design of future human trials, one ought to consider the poor bioavailability of these products, the possible need to initiate the experimental therapy long before the onset of symptoms, and currently limited knowledge about the appropriate form (e.g. juice, powder or individual polyphenol) of treatment.
The combination of MLN2238 (ixazomib) with interferon-alpha results in enhanced cell death in melanoma

The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed. Apoptosis induced by ixazomib was first observed at 12 hours and was maximal at 48 hours with similar levels of cell death compared to bortezomib. IFN-α alone had little effect on cell viability in vitro. However, the combination of ixazomib with IFN-α significantly enhanced ixazomib's ability to induce apoptotic cell death in BRAF V600E mutant and BRAF wild-type human melanoma tumor cells. The combination of ixazomib and IFN-α also enhanced inhibition of cell proliferation in BRAF V600E mutant melanoma tumor cells; however, this was not seen in BRAF wild-type cells. Ixazomib-induced apoptosis was associated with processing of the pro-apoptotic proteins procaspase-3, -7, -8, and -9, and cleavage of poly-ADP-ribose polymerase (PARP). In an in vivo xenograft model of human melanoma, combination treatment with IFN-α-2b and ixazomib demonstrated a significant reduction in tumor volume when compared to vehicle (p = 0.005) and single therapy ixazomib (p = 0.017) and IFN-α-2b (p = 0.036). These pre-clinical results support further evaluation of combination treatment with ixazomib and IFN-α for the treatment of advanced BRAF V600E mutant melanoma.
Aminoarabinosylation of Lipid A Is Critical for the Development of Colistin Resistance in Pseudomonas aeruginosa

ABSTRACT Lipid A aminoarabinosylation is invariably associated with colistin resistance in Pseudomonas aeruginosa; however, the existence of alternative aminoarabinosylation-independent colistin resistance mechanisms in this bacterium has remained elusive. By combining reverse genetics with experimental evolution assays, we demonstrate that a functional lipid A aminoarabinosylation pathway is critical for the acquisition of colistin resistance in reference and clinical P. aeruginosa isolates. This highlights lipid A aminoarabinosylation as a promising target for the design of colistin adjuvants against P. aeruginosa.
Spatial learning and memory impairments are associated with increased neuronal activity in 5XFAD mouse as measured by manganese-enhanced magnetic resonance imaging

Dysfunction of neuronal activity is a major and early contributor to cognitive impairment in Alzheimer's disease (AD). To investigate neuronal activity alterations at early stage of AD, we encompassed behavioral testing and in vivo manganese-enhanced magnetic resonance imaging (MEMRI) in 5XFAD mice at early ages (1-, 2-, 3- and 5-month). The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-β. In the Morris water maze, 5XFAD mice showed longer escape latency and poorer memory retention. In the MEMRI, 5XFAD mice showed increased signal intensity in the brain regions involved in spatial cognition, including the entorhinal cortex, the hippocampus, the retrosplenial cortex and the caudate putamen. Of note, the observed alterations in spatial cognition were associated with increased MEMRI signal intensity. These findings indicate that aberrant increased basal neuronal activity may contribute to the spatial cognitive function impairment at early stage of AD, and may further suggest the potential use of MEMRI to predict cognitive impairments. Early intervention that targets aberrant neuronal activity may be crucial to prevent cognitive impairment.
Design and Parametric Study of the Magnetic Sensor for Position Detection in Linear Motor Based on Nonlinear Parametric Model Order Reduction

This paper presents a design approach for a magnetic sensor module to detect mover position using the proper orthogonal decomposition-dynamic mode decomposition (POD-DMD)-based nonlinear parametric model order reduction (PMOR). The parameterization of the sensor module is achieved by using the multipolar moment matching method. Several geometric variables of the sensor module are considered while developing the parametric study. The operation of the sensor module is based on the principle of the airgap flux density distribution detection by the Hall Effect IC. Therefore, the design objective is to achieve a peak flux density (PFD) greater than 0.1 T and total harmonic distortion (THD) less than 3%. To fulfill the constraint conditions, the specifications for the sensor module is achieved by using POD-DMD based reduced model. The POD-DMD based reduced model provides a platform to analyze the high number of design models very fast, with less computational burden. Finally, with the final specifications, the experimental prototype is designed and tested. Two different modes, 90° and 120° modes respectively are used to obtain the position information of the linear motor mover. The position information thus obtained are compared with that of the linear scale data, used as a reference signal. The position information obtained using the 120° mode has a standard deviation of 0.10 mm from the reference linear scale signal, whereas the 90° mode position signal shows a deviation of 0.23 mm from the reference. The deviation in the output arises due to the mechanical tolerances introduced into the specification during the manufacturing process. This provides a scope for coupling the reliability based design optimization in the design process as a future extension.
Genomewide Analysis of the Antimicrobial Peptides in Python bivittatus and Characterization of Cathelicidins with Potent Antimicrobial Activity and Low Cytotoxicity

ABSTRACT In this study, we sought to identify novel antimicrobial peptides (AMPs) in Python bivittatus through bioinformatic analyses of publicly available genome information and experimental validation. In our analysis of the python genome, we identified 29 AMP-related candidate sequences. Of these, we selected five cathelicidin-like sequences and subjected them to further in silico analyses. The results showed that these sequences likely have antimicrobial activity. The sequences were named Pb-CATH1 to Pb-CATH5 according to their sequence similarity to previously reported snake cathelicidins. We predicted their molecular structure and then chemically synthesized the mature peptide for three putative cathelicidins and subjected them to biological activity tests. Interestingly, all three peptides showed potent antimicrobial effects against Gram-negative bacteria but very weak activity against Gram-positive bacteria. Remarkably, ΔPb-CATH4 showed potent activity against antibiotic-resistant clinical isolates and also was observed to possess very low hemolytic activity and cytotoxicity. ΔPb-CATH4 also showed considerable serum stability. Electron microscopic analysis indicated that ΔPb-CATH4 exerts its effects via toroidal pore preformation. Structural comparison of the cathelicidins identified in this study to previously reported ones revealed that these Pb-CATHs are representatives of a new group of reptilian cathelicidins lacking the acidic connecting domain. Furthermore, Pb-CATH4 possesses a completely different mature peptide sequence from those of previously described reptilian cathelicidins. These new AMPs may be candidates for the development of alternatives to or complements of antibiotics to control multidrug-resistant pathogens.
Effects of Lime, Wood Ash, Manure and Mineral P Fertilizer Rates on Acidity Related Chemical Properties and Growth and P Uptake of Wheat (Triticum aestivum L.) on Acid Soil of Farta District, Northwestern Highlands of Ethiopia

The effects of lime, wood ash, manure and mineral P fertilizers on the growth of wheat (Triticum aestivum L.) and selected soil chemical properties related to acidity were investigated in a pot experiment and an in incubation study on a kaolinite rich, high P fixing and strongly acidic soil (pH 4.9) of Farta District. Four rates of lime and wood ash (3.5, 7.0, 9.2 and 11.2 tons CaCO3 equivalents ha -1 ) were separately applied to obtain target soil pH values of 5.5, 6.0, 6.5 and a lower pH obtained with half of the lime requirement needed to bring the pH to 5.5. Three rates of mineral P fertilizer and manure P (32.5, 65 and 130 kg P ha -1 ) were uniformly applied separately into the whole soil volume. To mimic localized application, the mineral P rates were also applied into 2 and 5% of the soil volumes. The impact of P additions on solution P concentration was estimated with a quantity-intensity (Q/I) plot. Wood ash and lime (7 tons CaCO3 equivalents ha -1 ) were combined separately with each of the manure P and mineral P rates as additional treatments. Incubation of the soil with the different rates of lime, wood ash, manure and manure plus 7.0 tons of CaCO3 ha -1 lime or wood ash for 60 days before sowing significantly increased the available Olsen P and pH and decreased the exchangeable acidity and Al compared to the control treatment. The plant height, dry shoot biomass and P uptake of wheat increased significantly (P ≤ 0.001) by the application of the treatments except manure compared to the control. Application of mineral P plus wood ash (130 kg P ha -1
Supply chain simulation tools and techniques: a survey

The main contribution of this paper is twofold: • it surveys different types of simulation for supply chain management • it discusses several methodological issues. These different types of simulation are spreadsheet simulation, system dynamics, discrete-event simulation and business games. Which simulation type should be applied, depends on the type of managerial question to be answered by the model. The methodological issues concern validation and verification, sensitivity, optimisation, and robustness analyses. This sensitivity analysis yields a shortlist of the truly important factors in large simulation models with (say) a hundred factors. The robustness analysis optimises the important factors controllable by management, while accounting for the noise created by the important non-controllable, environmental factors. The various methodological issues are illustrated by a case study involving the simulation of a supply chain in the mobile communications industry in Sweden. In general, simulation is important because it may support the quantification of the benefits resulting from supply chain management.
MIPAS IMK/IAA Carbon Tetrachloride (CCl 4 ) Retrieval

MIPAS thermal limb emission measurements were used to derive vertically resolved profiles of carbon tetrachloride (CCl 4 ). Level-1b data versions MIPAS/5.02 to MIPAS/5.06 were converted into profiles using the level-2 processor developed at Karlsruhe Institute of Technology (KIT) Institute of Meteorology and Climate Research (IMK) and Consejo Superior de Investigaciones Cientificas (CSIC), Instituto de Astrofisica de Andalucia (IAA). Consideration of peroxyacetyl nitrate (PAN) as interfering species, which is jointly retrieved and CO 2 line mixing, was found to be crucial for reliable retrievals. Parts of the CO 2 Q-branch region that overlap with the CCl 4 signature were omitted, since large residuals were still found even though line mixing was considered in the forward model. However, the omitted spectral region could be narrowed considerably when line mixing was a 4 4 volume mixing ratios. In general, latitude-altitude cross-section show the expected CCl 4 features with highest values of around 90 pptv at altitudes at and below the tropical tropopause and values decreasing with altitude and latitude due to stratospheric decomposition. Other patterns, such as subsidence in the polar vortex during winter and early spring, are also visible in the distributions. The decline in CCl 4 abundance during the MIPAS Envisat measurement period (July 2002 to April 2012) is clearly reflected in the retrieved distributions.
High‐resolution mass spectrometry of skin mucus for monitoring physiological impacts and contaminant biotransformation products in fathead minnows exposed to wastewater effluent

High‐resolution mass spectrometry is advantageous for monitoring physiological impacts and contaminant biotransformation products in fish exposed to complex wastewater effluent. We evaluated this technique using skin mucus from male and female fathead minnows (Pimephales promelas) exposed to control water or treated wastewater effluent at 5, 20, and 100% levels for 21 d, using an on‐site, flow‐through system providing real‐time exposure. Both sex‐specific and non‐sex–specific responses were observed in the mucus metabolome, the latter suggesting the induction of general compensatory pathways for xenobiotic exposures. Altogether, 85 statistically significant treatment‐dependent metabolite changes were observed out of the 310 total endogenous metabolites that were detected (156 of the 310 were annotated). Partial least squares‐regression models revealed strong covariances between the mucus metabolomes and up‐regulated hepatic messenger ribonucleic acid (mRNA) transcripts reported previously for these same fish. These regression models suggest that mucus metabolomic changes reflected, in part, processes by which the fish biotransformed xenobiotics in the effluent. In keeping with this observation, we detected a phase II transformation product of bisphenol A in the skin mucus of male fish. Collectively, these findings demonstrate the utility of mucus as a minimally invasive matrix for simultaneously assessing exposures and effects of environmentally relevant mixtures of contaminants. Environ Toxicol Chem 2018;37:788–796. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.