Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta-Analysis

Background: Vancomycin is used to treat serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). It is unclear whether MRSA isolates with minimum inhibitory concentration (MIC) 1.5 to 2 µg/mL are successfully treated with vancomycin. Objective: Evaluate vancomycin failure rates in MRSA bacteremia with an MIC <1.5 versus ≥1.5 µg/mL, and MIC ≤1 versus ≥2 µg/mL. Methods: A literature search was conducted using MESH terms vancomycin, MRSA, bacteremia, MIC, treatment and vancomycin failure to identify human studies published in English. All studies of patients with MRSA bacteremia treated with vancomycin were included if they evaluated vancomycin failures, defined as mortality, and reported associated MICs determined by E-test. Study sample size, vancomycin failure rates, and corresponding MIC values were extracted and analyzed using RevMan 5.2. 5. Results: Thirteen studies including 2955 patients met all criteria. Twelve studies including 2861 patients evaluated outcomes using an MIC cutoff of 1.5 µg/mL. A total of 413 of 1186 (34.8%) patients with an MIC <1.5 and 531 of 1675 (31.7%) patients with an MIC of ≥1.5 µg/mL experienced treatment failure (odds ratio = 0.72, 95% confidence interval = 0.49-1.04, P = .08). Six studies evaluated 728 patients using the cutoffs of ≤1 and ≥2 µg/mL. A total of 384 patients had isolates with MIC ≤1 µg/mL, 344 had an MIC ≥2 µg/mL. Therapeutic failure occurred in 87 and 102 patients, respectively (odds ratio = 0.61, 95% confidence interval = 0.34-1.10, P = .10). As heterogeneity between the studies was high, a random-effects model was used. Conclusion: Vancomycin MIC may not be an optimal sole indicator of vancomycin treatment failure in MRSA bacteremia.
Evaluation of Risks and Benefits of Physical Activity of Hypertensives and Normotensives: Fighting a Societal Burden

Physical Activity (PA) is considered a coadjutant factor in the control of hypertension, helping to control this societal burden. This study investigates the factors that may influence the adoption of PA recommendations by hypertensive individuals by comparing physical activity patterns among hypertensives and normotensives and the importance placed on PA by both groups. Data from 966 Portuguese participants aged between 18 to 90 years old, representing hypertensives (n=144) and normotensives (n=822) were collected using a face-to-face questionnaire. The results show significant differences between the two groups in terms of causes of non-participation and dropping out, preferred PA activities, perceived knowledge, and information-seeking behaviour. The main barriers to exercise reported by hypertensives were the perception that PA is not adequate or even dangerous to their health. Doctors must be considered a key factor in promoting exercise. When compared to normotensives, hypertensives feel that PA information available is not appropriate (p=.0006). Hypertensives consider that existing programmes will not meet their needs and do not like traditional fitness classes, such as those in gyms. The fear of risks associated with exercise seems to be a significant barrier that impairs PA participation.
When Sensor-Cloud Meets Mobile Edge Computing

Sensor-clouds are a combination of wireless sensor networks (WSNs) and cloud computing. The emergence of sensor-clouds has greatly enhanced the computing power and storage capacity of traditional WSNs via exploiting the advantages of cloud computing in resource utilization. However, there are still many problems to be solved in sensor-clouds, such as the limitations of WSNs in terms of communication and energy, the high latency, and the security and privacy issues due to applying a cloud platform as the data processing and control center. In recent years, mobile edge computing has received increasing attention from industry and academia. The core of mobile edge computing is to migrate some or all of the computing tasks of the original cloud computing center to the vicinity of the data source, which gives mobile edge computing great potential in solving the shortcomings of sensor-clouds. In this paper, the latest research status of sensor-clouds is briefly analyzed and the characteristics of the existing sensor-clouds are summarized. After that we discuss the issues of sensor-clouds and propose some applications, especially a trust evaluation mechanism and trustworthy data collection which use mobile edge computing to solve the problems in sensor-clouds. Finally, we discuss research challenges and future research directions in leveraging mobile edge computing for sensor-clouds.
Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats

The aim of this work was to develop ezetimibe self-micellizing solid dispersions using Kolliphor® RH40 (MS-K) as a surfactant incorporating ezetimibe (EZ) into the croscarmellose hydrophilic carrier. Different ezetimibe:Kolliphor® ratios were studied to select micellar systems that improve the dissolution properties of ezetimibe. The different formulations were characterized by means of solid state analysis by SEM, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and dissolution studies. These physicochemical studies showed a decrease from the crystalline structure of ezetimibe (EZ) to its amorphous state in the micellar systems (MS-K). A rapid dissolution profile was observed in these micellar systems compared to the drug raw material and physical mixture. Efficacy studies were conducted using a high-fat diet that induced hyperlipidemic rats. The micellar system selected (MS-K 1:0.75) revealed a significant improvement in serum levels of total cholesterol (TC), low-density lipoproteins (LDL), and triglycerides (TG) compared to ezetimibe raw material. The histopathological examination of liver tissue also showed that this micellar system exhibited more beneficial effects on liver steatosis compared to ezetimibe raw material (EZ-RM) and the high-fat diet group (HFD). This study suggests that EZ micellar systems using Kolliphor® RH40 could enhance the antihyperlipidemic effect of ezetimibe and reduce liver steatosis.
Recombinant Human Dentin Matrix Protein 1 (hDMP1) Expressed in Nicotiana benthamiana Potentially Induces Osteogenic Differentiation

Inductive molecules are critical components for successful bone tissue engineering. Dentin matrix protein-1 (DMP1), a non-collagenous protein in the bone matrix, has been shown to play roles in osteogenic differentiation and phosphate homeostasis. This study aimed to produce recombinant human dentin matrix protein-1 (hDMP1) in Nicotiana benthamiana and investigated the ability of this plant-produced DMP1 to induce osteogenesis in human periodontal ligament stem cells (hPDLSCs). The hDMP1 gene was cloned into the geminiviral vector for transient expression in N. benthamiana. We found that hDMP1 was transiently expressed in N. benthamiana leaves and could be purified by ammonium sulphate precipitation followed by nickel affinity chromatography. The effects of hDMP1 on the induction of cell proliferation and osteogenic differentiation were investigated. The results indicated that plant-produced hDMP1 could induce the cell proliferation of hPDLSCs and increase the expression levels of osteogenic genes, including osterix (OSX), type I collagen (COL1), bone morphogenetic protein-2 (BMP2), and Wnt3a. Moreover, the plant-produced hDMP1 promoted calcium deposition in hPDLSCs as determined by alizarin red S staining. In conclusion, our results indicated that plant-produced hDMP1 could induce osteogenic differentiation in hPDLSCs and could potentially be used as a bone inducer in bone tissue engineering.
Adenotonsillectomy for the Treatment of Obstructive Sleep Apnea in Children with Prader-Willi Syndrome: A Meta-analysis

Objective Adenotonsillectomy outcomes in obstructive sleep apnea (OSA) treatment among children with Prader-Willi syndrome (PWS) remain unclear. This study aimed to elucidate the effectiveness of adenotonsillectomy in OSA treatment among children with PWS. Data Source PubMed, MEDLINE, Embase, and Cochrane Review up to February 2019. Review Methods The registry number of the protocol published on PROSPERO was CRD42015027053. Two authors independently searched the relevant database. Polysomnography outcomes in these children were examined, including net postoperative changes in the apnea-hypopnea index (AHI), net postoperative changes in the minimum and mean oxygen saturation, the overall success rate for a postoperative AHI <1, and the overall success rate for a postoperative AHI <5. Results Six studies with 41 patients were analyzed (mean age, 5.0 years; 55% boys; mean sample size, 6.8 patients). All children had PWS and received adenotonsillectomy for the treatment of OSA. The AHI was 13.1 events per hour (95% CI, 11.0-15.1) before surgery and 4.6 events per hour (95% CI, 4.1-5.1) after surgery. The mean change in the AHI was a significant reduction of 8.0 events per hour (95% CI, −10.8 to −5.1). The overall success rate was 21% (95% CI, 11%-38%) for a postoperative AHI <1 and 71% (95% CI, 54%-83%) for a postoperative AHI <5. Some patients developed velopharyngeal insufficiency postoperatively. Conclusion Adenotonsillectomy was associated with OSA improvement among children with PWS. However, residual OSA was frequently observed postoperatively in these patients.
Rates Of Suicide And Non-Fatal Suicide Attempts Among Persons Undergoing Organ Transplantation In Denmark From 1995 Through 2015

Complications following organ transplant – such as complex medical regimens involving adherence to lifelong immunosuppressant medications, adverse effects, infection, and rejection of the transplanted organ – may increase the risk of stress and mental disorders.1 Only one population-based study has examined the association between organ transplant and suicide, and found that the suicide rate among liver transplant recipients was five times that of the Nordic general population between the years 2000 and 2010.2 In this study, we examined associations between heart, lung, kidney, and liver transplants and suicide and non-fatal suicide attempts in the population of Denmark.
A Novel Site-Specific Integration System for Genetic Modification of Aspergillus flavus

Aspergillus flavus is a fungus that produces aflatoxin B1, one of the most carcinogenic secondary metabolites. Understanding the regulation mechanism of aflatoxin biosynthesis in this fungus requires precise methods for genomic integration of mutant alleles. To avoid the disadvantage of DNA integration into the genome by non-homologous or ectopic recombination, we developed a novel strategy for site-specific integration of foreign DNA by using a carboxin-resistant sdh2R allele (His 249 Leu). Our results demonstrated that the transformants were generated with a high efficiency (>96%) of correct integration into the sdh2-lcus of the genome of A. flavus NRRL 3357. The advantage of this method is that introduction of the eGFP expression cassette into the sdh2-locus had little effect on fungal growth and virulence while also being rapid and efficient. This system will be a valuable tool for genetic manipulation in A. flavus. To the best of our knowledge, this is the first report on the efficient site-specific integration at the sdh2-locus in the genome of Aspergillus.
Choroideremia: Update On Clinical Features And Emerging Treatments

Abstract Choroideremia (CHM) is an X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium and retina. This disease is caused by mutations in the X-linked CHM gene encoding a Ras-related GTPase Rab escort protein (REP)-1, which is extremely important for the retinal function. Clinically, male-affected patients have a progressive reduction in visual acuity. This disease is formally considered incurable, although new promising treatments have been recently introduced. In this article, a review of the salient pathogenetic features of choroideremia, essential for the proper interpretation of therapeutic approaches, is followed by a discussion of the fundamental clinical features of this hereditary disease. Finally, relevant new therapeutic approaches in this disease will be discussed, including gene therapy, stem cells, small molecules, and retinal prosthesis.
The role of lyases, NblA and NblB proteins and bilin chromophore transfer in restructuring the cyanobacterial light harvesting complex.

Phycobilisomes are large light-harvesting complexes attached on the stromal side of thylakoids of cyanobacteria and red algae. They can be remodeled or degraded in response to changing light and nutritional status. Both the core and the peripheral rods of the phycobilisome contain biliproteins. During biliprotein biosynthesis, open-chain tetrapyrrole chromophores are attached covalently to the apoproteins by dedicated lyases. Another set of non-bleaching proteins has been implicated in phycobilisome degradation, among them NblA and NblB. We report in vitro experiments with lyases, biliproteins and NblA/B implying more involved functions than currently discussed: lyases can also detach the chromophores and NblA and NblB can modulate lyase-catalyzed binding and detachment of chromophores in a complex fashion. We show: 1) NblA and NblB can interfere with chromophorylation as well as chromophore-detachment of phycobiliprotein, they are generally inhibitors but in some cases enhance the reaction. 2) NblA and NblB promote dissociation of whole phycobilisomes, cores and, in particular, allophycocyanin trimers. 3) While NblA and NblB do not interact with each other, both interact with lyases, apo- and holo-biliproteins. 4) They promote synergistically the lyase-catalyzed chromophorylation of the β-subunit of the major rod component, CPC. 5) They modulate lyase-catalyzed and lyase-independent chromophore transfers among biliproteins, with the core protein, ApcF, the rod protein, CpcA, and sensory biliproteins (phytochromes, cyanobacteriochromes) acting as potential traps. The results indicate that NblA/B can cooperate with the lyases in remodeling the phycobilisomes, for balancing the metabolic requirements of acclimating their light-harvesting capacity without straining the overall metabolic economy of the cell.
A Probabilistic Approach to Assessing and Predicting the Failure of Notched Components

This work presents a probabilistic model to evaluate the strength results obtained from an experimental characterisation program on notched components. The generalised local method (GLM) is applied to the derivation of the primary failure cumulative distribution function (PFCDF) as a material property (i.e., independent of the test type, load conditions and specimen geometry selected for the experimental campaign), which guarantees transferability in component design. To illustrate the applicability of the GLM methodology, an experimental program is performed using specimens of EPOLAM 2025 epoxy resin. Three different samples, each with a specific notch geometry, are tested. As a first scenario, a single assessment of each sample is obtained and the PFCDFs are used to perform cross predictions of failure. Some discrepancies are noticeable among the experimental results and cross-failure predictions, although they are within the expected margins. A possible reason for the disagreement can be assigned to the inherent statistical variability of the results and the limited number of tests per each sample. As a second scenario, a joint assessment of the three samples is performed, from which a unique PFCDF is provided, according to the GLM. In the latter case, a more reliable assessment of the experimental results from the geometry conditions is achieved, the suitability of the selected driving force is verified, and the transferability of the present material characterisation is confirmed.
CNS Penetration of Cyclophosphamide and Metabolites in Mice Bearing Group 3 Medulloblastoma and Non-Tumor Bearing Mice.

PURPOSE Cyclophosphamide is widely used to treat children with medulloblastoma; however, little is known about its brain penetration. We performed cerebral microdialysis to characterize the brain penetration of cyclophosphamide (130 mg/kg, IP) and its metabolites [4-hydroxy-cyclophosphamide (4OH-CTX) and carboxyethylphosphoramide mustard (CEPM)] in non-tumor bearing mice and mice bearing orthotopic Group 3 medulloblastoma. METHODS A plasma pharmacokinetic study was performed in non-tumor-bearing CD1- nude mice, and four cerebral microdialysis studies were performed in non-tumor-bearing (M1 and M3) and tumor- bearing mice (M2 and M4). Plasma samples were collected up to 6-hours post-dose, and extracellular fluid (ECF) samples were collected over 60-minute intervals for 24-hours post-dose. To stabilize and quantify 4OH-CTX, a derivatizing solution was added in blood after collection, and either directly in the microdialysis perfusate (M1 and M2) or in ECF collection tubes (M3 and M4). Plasma/ECF cyclophosphamide and CEPM, and 4OH-CTX concentrations were separately measured using different LC-MS/MS methods. RESULTS All plasma/ECF concentrations were described using a population-based pharmacokinetic model. Plasma exposures of cyclophosphamide, 4OH-CTX, and CEPM were similar across studies (mean AUC=112.6, 45.6, and 80.8 µmol∙hr/L). Hemorrhage was observed in brain tissue when the derivatizing solution was in perfusate compared with none when in collection tubes, which suggested potential sample contamination in studies M1 and M2. Model-derived unbound ECF to plasma partition coefficients (Kp,uu) were calculated to reflect CNS penetration of the compounds. Lower cyclophosphamide Kp,uu was obtained in tumor-bearing mice versus non-tumor bearing mice (mean 0.15 versus 0.22, p=0.019). No differences in Kp,uu were observed between these groups for 4OH- CTX and CEPM (overall mean 0.10 and 0.07). CONCLUSIONS Future studies will explore potential mechanisms at the brain-tumor barrier to explain lower cyclophosphamide brain penetration in tumor-bearing mice. These results will be used to further investigate exposure-response relationships in medulloblastoma xenograft models.
Chrysoviruses Inhabited Symbiotic Fungi of Lichens

A lichen body is formed most often from green alga cells trapped in a net of ascomycetous fungi and accompanied by endolichenic or parasitic fungi, other algae, and symbiotic or free-living bacteria. The lichen’s microcosmos is inhabited by mites, insects, and other animals for which the lichen is a source of food or a place to live. Novel, four-segmented dsRNA viruses were detected in saxicolous Chrysothrix chlorina and Lepraria incana lichens. Comparison of encoded genome proteins revealed classification of the viruses to the genus Alphachrysovirus and a relationship to chrysoviruses from filamentous ascomycetous fungi. We propose the names Chrysothrix chrysovirus 1 (CcCV1) and Lepraria chrysovirus 1 (LiCV1) as acronyms for these viruses. Surprisingly, observation of Chrysothrix chlorina hybridization with fluorescent-labelled virus probe by confocal microscope revealed that the CcCV1 virus is not present in the lichen body-forming fungus but in accompanying endolichenic Penicillium citreosulfuratum fungus. These are the first descriptions of mycoviruses from a lichen environment.
Cortical Excitability Measures May Predict Clinical Response to Fampridine in Patients with Multiple Sclerosis and Gait Impairment

Background: Most multiple sclerosis (MS) patients will develop walking limitations during the disease. Sustained-release oral fampridine is the only approved drug that will improve gait in a subset of MS patients. Objectives: (1) Evaluate fampridine cortical excitability effect in MS patients with gait disability. (2) Investigate whether cortical excitability changes can predict the therapeutic response to fampridine. Method: This prospective observational study enrolled 20 adult patients with MS and gait impairment planned to receive fampridine 10 mg twice daily for two consecutive weeks. Exclusion criteria included: Recent relapse (<3 months), modification of disease modifying drugs (<6 months), or Expanded Disability Status Scale (EDSS) score >7. Neurological examination, timed 25-foot walk test (T25wt), EDSS, and cortical excitability studies were performed upon inclusion and 14 days after initiation of fampridine. Results: After treatment, the mean improvement of T25wt (ΔT25wt) was 4.9 s. Significant enhancement of intra-cortical facilitation was observed (139% versus 241%, p = 0.01) following treatment. A positive correlation was found between baseline resting motor threshold (rMT) and both EDSS (r = 0.57; p < 0.01) and ΔT25wt (r = 0.57, p = 0.01). rMT above 52% of the maximal stimulator output was found to be a good predictor of a favorable response to fampridine (accuracy: 75%). Discussion: Fampridine was found to have a significant modulatory effect on the cerebral cortex, demonstrated by an increase in excitatory intracortical processes as unveiled by paired-pulse transcranial magnetic stimulation. rMT could be useful in selecting patients likely to experience a favorable response to fampridine.
An Isocaloric Nordic Diet Modulates RELA and TNFRSF1A Gene Expression in Peripheral Blood Mononuclear Cells in Individuals with Metabolic Syndrome—A SYSDIET Sub-Study

A healthy dietary pattern is associated with a lower risk of metabolic syndrome (MetS) and reduced inflammation. To explore this at the molecular level, we investigated the effect of a Nordic diet (ND) on changes in the gene expression profiles of inflammatory and lipid-related genes in peripheral blood mononuclear cells (PBMCs) of individuals with MetS. We hypothesized that the intake of an ND compared to a control diet (CD) would alter the expression of inflammatory genes and genes involved in lipid metabolism. The individuals with MetS underwent an 18/24-week randomized intervention to compare a ND with a CD. Eighty-eight participants (66% women) were included in this sub-study of the larger SYSDIET study. Fasting PBMCs were collected before and after the intervention and changes in gene expression levels were measured using TaqMan Array Micro Fluidic Cards. Forty-eight pre-determined inflammatory and lipid related gene transcripts were analyzed. The expression level of the gene tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) was down-regulated (p = 0.004), whereas the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit, RELA proto-oncogene, was up-regulated (p = 0.016) in the ND group compared to the CD group. In conclusion, intake of an ND in individuals with the MetS may affect immune function.