Miracle-dz/UniFAR-FTUs huggingface dataset:
Study on In Vitro Metabolism and In Vivo Pharmacokinetics of Beauvericin

Beauvericin (BEA) is a well-known mycotoxin produced by many fungi, including Beaveria bassiana. The purpose of this study was to evaluate the in vitro distribution and metabolism characteristics as well as the in vivo pharmacokinetic (PK) profile of BEA. The in vitro metabolism studies of BEA were performed using rat, dog, mouse, monkey and human liver microsomes, cryopreserved hepatocytes and plasma under conditions of linear kinetics to estimate the respective elimination rates. Additionally, LC-UV-MSn (n = 1~2) was used to identify metabolites in human, rat, mouse, dog and monkey liver microsomes. Furthermore, cytochrome P450 (CYP) reaction phenotyping was carried out. Finally, the absolute bioavailability of BEA was evaluated by intravenous and oral administration in rats. BEA was metabolically stable in the liver microsomes and hepatocytes of humans and rats; however, it was a strong inhibitor of midazolam 1′-hydroxylase (CYP3A4) and mephenytoin 4′-hydroxylase (CYP2C19) activities in human liver microsomes. The protein binding fraction values of BEA were >90% and the half-life (T1/2) values of BEA were approximately 5 h in the plasma of the five species. The absolute bioavailability was calculated to be 29.5%. Altogether, these data indicate that BEA has great potential for further development as a drug candidate. Metabolic studies of different species can provide important reference values for further safety evaluation.
Imaging Inflammation in Atherosclerosis with CXCR4-Directed [68Ga]PentixaFor PET/MRI—Compared with [18F]FDG PET/MRI

(1) This study compared [68Ga]PentixaFor uptake in active arterial segments with corresponding [18F]FDG arterial uptake as well as the relationship with cardiac [68Ga]PentixaFor uptake. (2) Method: Tracer uptake on atherosclerotic lesions in the large arteries was measured and target-to-background ratios (TBR) were calculated to adjust background signals with two investigators blinded to the other PET scan. On a patient-based and lesion-to-lesion analysis, TBR values of two tracers were compared and the relationship with cardiac inflammation was further explored. Furthermore, two cardiovascular risk-related groups were divided to explore the value of risk stratification of the two tracers in atherosclerosis. (3) Results: [68Ga]PentixaFor PET/MRI identified more lesions (88% vs. 48%; p < 0.001) and showed higher uptake than [18F]FDG PET/MRI (TBR, 1.90 ± 0.36 vs. 1.63 ± 0.29; p < 0.001). In the patient-based analysis, the TBR of [68Ga]PentixaFor uptake was also significantly higher than [18F]FDG uptake (1.85 ± 0.20 vs. 1.42 ± 0.19; p < 0.001). The TBR of active lesions for [68Ga]PentixaFor was significantly increased in the high-risk group (n = 9), as compared to the low-risk group (n = 10) (2.02 ± 0.15 vs. 1.86 ± 0.10, p = 0.015), but not for [18F]FDG (1.85 ± 0.10 vs. 1.80 ± 0.07, p = 0.149). (4) Conclusion: [68Ga]PentixaFor PET/MRI identified many more lesions than [18F]FDG PET/MRI. Patients with high-risk cardiovascular factors illustrated an increased uptake of [68Ga]PentixaFor. There was a correlation between the elevated uptake of [68Ga]PentixaFor in the active arterial segments and heart.
Mono and Multiple Tumor-Targeting Ligand-Coated Ultrasmall Gadolinium Oxide Nanoparticles: Enhanced Tumor Imaging and Blood Circulation

Hydrophilic and biocompatible PAA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.7 nm) were synthesized and conjugated with tumor-targeting ligands, i.e., cyclic arginylglycylaspartic acid (cRGD) and/or folic acid (FA). FA-PAA-Gd2O3 and cRGD/FA-PAA-Gd2O3 nanoparticles were successfully applied in U87MG tumor-bearing mice for tumor imaging using T1 magnetic resonance imaging (MRI). cRGD/FA-PAA-Gd2O3 nanoparticles with multiple tumor-targeting ligands exhibited higher contrasts at the tumor site than FA-PAA-Gd2O3 nanoparticles with mono tumor-targeting ligands. In addition, the cRGD/FA-PAA-Gd2O3 nanoparticles exhibited higher contrasts in all organs, especially the aorta, compared with those of the FA-PAA-Gd2O3 nanoparticles, because of the blood cell hitchhiking effect of cRGD in the cRGD/FA-PAA-Gd2O3 nanoparticles, which prolonged their circulation in the blood.
Leadership style, Environmental Factors, and Job Satisfaction as Correlates to Headmaster Performance in Selected High Schools in Jakarta

The performance of educational institutions is closely linked to the effectiveness of the headmasters’ performance. Thus, this study aims to analyse the direct or indirect influence of leadership style, environmental factors and job satisfaction on the performance of the high school heads in Jakarta. With a research sample of 240 teachers, this study examined the teachers’ perception on the variables studied. The study used path analysis with partial smart software at the square minimum. All tested data can be considered with r > 0.70. The result of the analysis showed direct influence of leadership style and environmental factors on job satisfaction, style of leadership, environmental factors and job satisfaction in relation to the performance of school leaders, the influence of leadership style through job satisfaction on the performance of school leaders indirectly and the outcome of environmental factors through job satisfaction on the performance of school leaders indirectly. Environmental factors at the site of learning activities during the pandemic require improvements for teachers and students.
Brain Delivery of IGF1R5, a Single-Domain Antibody Targeting Insulin-like Growth Factor-1 Receptor

The ability of drugs and therapeutic antibodies to reach central nervous system (CNS) targets is greatly diminished by the blood–brain barrier (BBB). Receptor-mediated transcytosis (RMT), which is responsible for the transport of natural protein ligands across the BBB, was identified as a way to increase drug delivery to the brain. In this study, we characterized IGF1R5, which is a single-domain antibody (sdAb) that binds to insulin-like growth factor-1 receptor (IGF1R) at the BBB, as a ligand that triggers RMT and could deliver cargo molecules that otherwise do not cross the BBB. Surface plasmon resonance binding analyses demonstrated the species cross-reactivity of IGF1R5 toward IGF1R from multiple species. To overcome the short serum half-life of sdAbs, we fused IGF1R5 to the human (hFc) or mouse Fc domain (mFc). IGF1R5 in both N- and C-terminal mFc fusion showed enhanced transmigration across a rat BBB model (SV-ARBEC) in vitro. Increased levels of hFc-IGF1R5 in the cerebrospinal fluid and vessel-depleted brain parenchyma fractions further confirmed the ability of IGF1R5 to cross the BBB in vivo. We next tested whether this carrier was able to ferry a pharmacologically active payload across the BBB by measuring the hypothermic and analgesic properties of neurotensin and galanin, respectively. The fusion of IGF1R5-hFc to neurotensin induced a dose-dependent reduction in the core temperature. The reversal of hyperalgesia by galanin that was chemically linked to IGF1R5-mFc was demonstrated using the Hargreaves model of inflammatory pain. Taken together, our results provided a proof of concept that appropriate antibodies, such as IGF1R5 against IGF1R, are suitable as RMT carriers for the delivery of therapeutic cargos for CNS applications.
Multivariate Analysis of Compound Flood Hazard Across Canada's Atlantic, Pacific and Great Lakes Coastal Areas

Compound flooding, caused by the simultaneous or successive occurrence of two or more flood mechanisms, is mainly associated with extreme precipitation, river overflows, and storm tides across coastal areas. The interdependencies between these components can increase the risks of flood impacts, threatening coastal communities and infrastructure systems. This study quantifies the corresponding multivariate hazard over Canada's coastal areas by characterizing the dependencies between multiple drivers of flooding based on the C‐vine copula statistical approach. The joint return periods of compound flooding considering the AND, OR, and Kendall scenarios are estimated and the corresponding failure probabilities are assessed. Further, the compound hazard ratio (CHR) index is applied to quantify possible under‐ or overestimations of the flood hazards when individual drivers are assessed independently. Analyses are performed at 41 locations across the Atlantic, Pacific, and the Great Lakes coasts, and the uncertainties are quantified based on the Bayes theorem. Results show that at approximately 50% of locations (mostly at the Great Lakes), the flood hazard associated with the AND scenario increases considerably when the dependencies are characterized compared to the (unrealistic) independence scenario, indicating the potential for compound flooding in these regions. Besides, at more than half of the studied locations, the CHR index exceeds one highlighting the interrelationships between drivers of flooding. The results of this study provide a deeper understanding of the flood mechanisms and their interdependencies across Canada's coasts, which support the development of resilient structures and improved coastal flood management.
CytM decreases photosynthesis under photomixotrophy Cytochrome c M decreases photosynthesis under photomixotrophy in Synechocystis

23 Photomixotrophy is a metabolic state which enables photosynthetic microorganisms to 24 simultaneously perform photosynthesis and metabolism of imported organic carbon 25 substrates. This process is complicated in cyanobacteria, since many, including 26 Synechocystis ( Synechocystis sp. PCC 6803), conduct photosynthesis and respiration in an 27 interlinked thylakoid membrane electron transport chain. Under photomixotrophy, the cell 28 must therefore tightly regulate electron fluxes from photosynthetic and respiratory 29 complexes. In this study, we demonstrate, via characterization of photosynthetic apparatus 30 and the proteome, that photomixotrophic growth results in a gradual inhibition of Q A- re- 31 oxidation in wild-type Synechocystis, which largely decreases photosynthesis over three 32 days of growth. This process is circumvented by deleting the gene encoding cytochrome c M 33 (CytM), a cryptic c -type heme protein widespread in cyanobacteria. The ΔCytM strain 34 maintained active photosynthesis over the three-day period, demonstrated by high 35 photosynthetic O 2 and CO 2 fluxes and effective yields of photosystems I and II. Overall, this 36 resulted in a higher growth rate than wild type, which was maintained by accumulation of 37 proteins involved in phosphate and metal uptake, and cofactor biosynthetic enzymes. While 38 the exact role of CytM has not been determined, a mutant deficient in the thylakoid-localised 39 respiratory terminal oxidases and CytM (ΔCox/Cyd/CytM) displayed a similar phenotype 40 under photomixotrophy to ΔCytM. This, in combination with other physiological data, 41 suggests that CytM does not transfer electrons to these complexes, which had previously 42 been hypothesized. In summary, our data suggest that CytM may have a regulatory role in 43 photomixotrophy by modulating the photosynthetic capacity of cells. These results demonstrate that during photomixotrophic growth, the electron flow at PSII 292 acceptor site gradually becomes inhibited in WT leading to drastically slower electron 293 transfer from PSII to Cyt b 6 f on the third day. Deletion of CytM circumvents this inhibition, 294 maintains PSII reaction center protein D1 amounts and a steady electron flux from PSII to 295 Cyt f .
Global Extratropical Response to Diabatic Heating Variability of the Asian Summer Monsoon

Global teleconnections associated with the Asian summer monsoon convective activities are investigated basedonmonthlydataof 29NorthernHemisphere summersdeﬁnedas June–September (JJAS). Two distinct teleconnection patterns are identiﬁed that are associated respectively with variabilities of the Indian summer monsoonandthewesternNorthPaciﬁcsummermonsoon. TheIndiansummermonsoonconvectiveactivityis associated with a global pattern that has a far-reaching connection in both hemispheres, whereas the western North Paciﬁc summer monsoon convective activity is connected to a Southern Hemisphere wave train that inﬂuences the high-latitude South Paciﬁc and South America. A global primitive equation model is utilized to assess the cause of the global circulation anomalies. The model responses to anomalous heatings of both monsoon systems match the general features of the observed circulation anomalies well, and they are mainly controlled by linear processes. The response patterns are largely determined by the summertime large-scale background mean ﬂow and the location of the heating anomaly relative to the upper easterly jet in the monsoon region.
Deletion of the murine scavenger receptor CD68

important Abstract Scavenger receptors (ScRs) are a structurally un-related family of receptors with the ability to bind modiﬁ ed low density lipoprotein (LDL) as well as a broad range of polyanionic ligands. CD68, whose expression is restricted to mononuclear phagocytes, is a unique ScR family member, owing to its lysosome associated membrane protein (LAMP)-like domain and predominant endosomal distribution. Knockout (ko) mice were generated to directly evaluate the role murine CD68 may play in oxidized LDL (Ox-LDL) uptake. However, CD68 (cid:2) / (cid:2) macrophages took up Ox-LDL robustly. Likewise, no defects were observed in the ability of CD68 (cid:2) / (cid:2) mononuclear phagocytes to take up or mount an effective innate response against a number of microbes. Curiously, CD68 (cid:2) / (cid:2) mononuclear phagocytes exhibited a trend toward enhanced antigen presentation to CD4+ T-cells, raising the possibility that CD68 may function either to negatively regulate antigen uptake, loading, or major histocompatibility complex class II (MHC-II) trafﬁ cking. —Song, L. , C. Lee, and C. Schindler. Deletion of the murine scavenger receptor CD68. J. Lipid Res. 2011. 52: 1542–1550.
Development and Application of a Novel Technology for Evaluation of Personal Exposure and Online Monitoring of Environmental Aerosol Nanoparticles

In order to assess the health effects of airborne particulates, it is necessary to determine the particle concentration and their composition in the breathing zone with regards to aerodynamic particle size. This is particularly important for nanoparticles (<100 nm), since these particles in the ambient contain a large portion of hazardous chemicals and can penetrate deeply inside lungs, eventually reaching the alveolar region. A personal sampler based on the “inertial filter” technology has been developed (Furuuchi et al., 2010) with ~140 nm at a 6 L/min of sampling flow rate. However, it is not enough to be called as “nanoparticles”. Although an impactor type of personal sampler was recently devised with a cutoff size of 100 nm of (Tsai et al., 2012), its sampling flow rate (2 L/min) was not always sufficient for the chemical analysis of particles. In this study, PM 0.1 personal sampler has been developed based on a new idea of a layered mesh inertial filter to the evaluation of personal exposure to nanoparticles. The layered mesh inertial filter could be adjusted to 100 nm cutoff size. Through assembly of the layered mesh inertial filter for PM 0.1 separation and pre-cut impactors for removal of huge or coagulated particles (PM 1.4 -TSP) along with a pre-cut inertial filter for the removal of fine particles between PM 0.5 -PM 1.4 . The present PM 0.1 personal sampler can be applicable to practical purposes including chemical analysis of collected particles. The devised PM 0.1 personal sampler has been used to evaluate the exposure to nanoparticles in living and working environments. The exposure to nanoparticles was found to be important in the breathing zone of smoker, the breathing zone of workers in the rubber smoke sheet factory and the textile factory. Moreover, the PM 0.1 separation unit, which consists of PM 0.1 inertial filter for PM 0.1 separation, the pre-cut inertial filter and pre-cut-impactors for the removal of coarse particles has been successfully applied to the online monitoring of the PM 0.1 number concentration and associated black carbon by combining with condensation particle counter (CPC) and multi angle absorption photometer
DDDT_A_285488 423..440

1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea; 3Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Health Science and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, Korea Background: To date, outcome data with a large sample size and data regarding the clinical outcomes of pharmacokinetic-guided (PK) dosing of vancomycin are limited. Aim: We evaluated the pharmacokinetic and clinical outcomes of a PK-guided dosing advisory program, pharmacokinetic consultation service (PKCS), in vancomycin treatment. Methods: We investigated vancomycin therapeutic drug monitoring (TDM) and PKCS use through a retrospective review of patients who had serum vancomycin trough concentration data from October 2017 to November 2018. Among these patients, we selected non-critically ill adult patients satisfying our selection criteria to evaluate the effect of PKCS. Target trough attainment rate, time to target attainment, vancomycin-induced nephrotoxicity (VIN), vancomycin treatment failure rate, and duration of vancomycin therapy were compared between patients whose dosing was adjusted according to PKCS (PKCS group), and those whose dose was adjusted at the discretion of the attending physician (non-PKCS group). Results: A total of 280 patients met the selection criteria for the VIN analysis (PKCS, n=134; non-PKCS, n=146). The incidence of VIN was similar between the two groups (PKCS, n=5; non-PKCS, n=5); however, the target attainment rate was higher in the PKCS group (75% vs 60%, P = 0.012). The time to target attainment was similar between the two groups. Further exclusions yielded 112 patients for the clinical outcome evaluation (PKCS, n=51; non-PKCS, n=61). The treatment failure rate was similar, and the duration of vancomycin therapy was longer in the PKCS group (12 vs 8 days, P = 0.008). Conclusion: In non-critically ill patients, an increase in target trough achieved by PKCS did not lead to decreased vancomycin treatment failures, shorter vancomycin treatment, or decreased nephrotoxicity in vancomycin treatment. Considering the excessive amount of effort currently put into vancomycin dosing and monitoring, more selective criteria for individualized pharmacokinetic-guided dosing needs to be applied.
A Model for Accelerating Discharge of Lane Traffic to Facilitate Intersection Access by EVs

Intelligent Transportation System (ITS) is the synergy of information technology, real-time control, and communication networks. The system is expected to perform more complex traffic arrangements, in particular, traffic management of Emergency Vehicles (EV) such as fire trucks, ambulances, and so forth. Implementation of traffic management using only Traffic Signal Pre-emption does not give enough space for an EV to cross an intersection safely, especially on streets where there is only one lane. This paper proposes a model of accelerated emptying of traffic in front of EVs . Accelerated emptying model uses historical approach, based on current characteristics of traffic. For example, if the normal vehicle speed is equal to the EV speed before accelerated emptying, the system indicator will be 0%, thereby indicating no need for accelerated emptying. Similarly, a negative system indicator result means an accelerated emptying process is not necessary. However, if the system indicator is close to 100%, this result indicates accelerated emptying is necessary.
JOINT MPH PROGRAM ADDIS CONTINENTAL INSTITUTE OF PUBLIC HEALTH AND UNIVERSITY of among

Epidemiological information on the prevalence of various intestinal parasitic infections and identification of local risk factors in different regions/localities is a prerequisite to develop appropriate control strategies, particularly among high-risk groups. Objective: the aim of this study was to determine the prevalence of intestinal parasites and associated risk factors among school children in Delgi elementary and junior secondary school in North Gondar administrative zone. Methods : A cross sectional parasitological study involving 704 school children was conducted from Sept.27-oct.6, 2010. Structured questionnaire were used to identify the risk factors. Stool specimens were examined using direct smear and formal -ether concentration technique. Finally Data entry and analysis was done using Epi-info and SPSS statistical soft ware respectively. Results: Ten species of intestinal parasites were identified with an overall prevalence of 79.8% (562 of 704 children). The predominant parasites involved were A. lumbricoides 338 (48%), G.lambilia 295 (41.9%) and E.histolytica/dispar 192(27.3%). The prevalence of A . lumbricoides was the highest compared with other parasite species. Of the total positive individuals 96(13.6%) single infection and 466(66.2%) were mixed infection, from this mixed infection the majority of the students had double infection309 (43.9%). The highest prevalent parasitic species among single and mixed infections were G.lamblia (6.3%) and A.lumbricoids and G.lambilia (14.1%) respectively. In this study intestinal parasite infection was not statistically associated with Age, sex, residence, availability and usage of latrines (p>0.05). On the other hand ,a statistical significance association was found Between intestinal parasite infection and in those children who have low mother educational level , children who have habit of eating raw/ unwashed vegetables , children who drink unprotected well/spring and river water and children who do not have hand washing practice before meal (P< 0.05). Conclusion: Intestinal parasite infection is a health problem among Delgi school children.