Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China

Background: The optimal timing for initiation of antiretroviral therapy (ART) in HIV-positive patients with cryptococcal meningitis (CM) has not, as yet, been compellingly elucidated, as research data concerning mortality risk and the occurrence of immune reconstitution inflammatory syndrome (IRIS) in this population remains inconsistent and controversial. Method: The present multicenter randomized clinical trial was conducted in China in patients who presented with confirmed HIV/CM, and who were ART-naïve. Subjects were randomized and stratified into either an early-ART group (ART initiated 2–5 weeks after initiation of antifungal therapy), or a deferred-ART group (ART initiated 5 weeks after initiation of antifungal therapy). Intention-to-treat, and per-protocol analyses of data for these groups were conducted for this study. Result: The probability of survival was found to not be statistically different between patients who started ART between 2–5 weeks of CM therapy initiation (14/47, 29.8%) vs. those initiating ART until 5 weeks after CM therapy initiation (10/55, 18.2%) (p = 0.144). However, initiating ART within 4 weeks after the diagnosis and antifungal treatment of CM resulted in a higher mortality compared with deferring ART initiation until 6 weeks (p = 0.042). The incidence of IRIS did not differ significantly between the early-ART group and the deferred-ART group (6.4 and 7.3%, respectively; p = 0.872). The percentage of patients with severe (grade 3 or 4) adverse events was high in both treatment arms (55.3% in the early-ART group and 41.8% in the deferred-ART group; p=0.183), and there were significantly more grade 4 adverse events in the early-ART group (20 vs. 13; p = 0.042). Conclusion: Although ART initiation from 2 to 5 weeks after initiation of antifungal therapy was not significantly associated with high cumulative mortality or IRIS event rates in HIV/CM patients compared with ART initiation 5 weeks after initiation of antifungal therapy, we found that initiating ART within 4 weeks after CM antifungal treatment resulted in a higher mortality compared with deferring ART initiation until 6 weeks. In addition, we observed that there were significantly more grade 4 adverse events in the early-ART group. Our results support the deferred initiation of ART in HIV-associated CM. Clinical Trials Registration: www.ClinicalTrials. gov, identifier: ChiCTR1900021195.
Use of the Thrombolysis in Myocardial Infarction Risk Index for Elderly Patients With ST-Segment Elevation Myocardial Infarction

Background: Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI) is a simple risk assessment tool for patients with ST-segment elevation myocardial infarction (STEMI). However, its applicability to elderly patients with STEMI undergoing percutaneous coronary intervention (PCI) is uncertain. Methods: This was a retrospective analysis of elderly (≥60 years) patients who underwent PCI for STEMI from January 2010 to April 2016. TRI was calculated on admission using the following formula: heart rate × (age/10)2/systolic blood pressure. Discrimination and calibration of TRI for in-hospital events and 1 year mortality were analyzed. Results: Totally 1,054 patients were divided into three groups according to the tertiles of the TRI: <27 (n = 348), 27–36 (n = 360) and >36 (n = 346). The incidence of acute kidney injury (AKI; 7.8 vs. 8.6 vs. 24.0%, p < 0.001), AHF (3.5 vs. 6.6 vs. 16.2%, p < 0.001), in-hospital death (0.6 vs. 3.3 vs. 11.6%, p < 0.001) and MACEs (5.2 vs. 5.8 vs. 15.9%, p < 0.001) was significantly higher in the third tertile. TRI showed good discrimination for in-hospital death [area under the curve (AUC) = 0.804, p < 0.001; Hosmer-Lemeshow p = 0.302], which was superior to its prediction for AKI (AUC = 0.678, p < 0.001; Hosmer-Lemeshow p = 0.121), and in-hospital MACEs (AUC = 0.669, p < 0.001; Hosmer-Lemeshow p = 0.077). Receiver-operation characteristics curve showed that TRI > 42.0 had a sensitivity of 64.8% and specificity of 82.2% for predicting in-hospital death. Kaplan-Meier analysis showed that patients with TRI > 42.0 had higher 1 year mortality (Log-rank = 79.2, p < 0.001). Conclusion: TRI is suitable for risk stratification in elderly patients with STEMI undergoing PCI, and is thus of continuing value for an aging population.
Estimation of Mycophenolic Acid Exposure in Heart Transplant Recipients by Population Pharmacokinetic and Limited Sampling Strategies

Purpose: The aim of this study is i) to establish a strategy to estimate the area under the curve of the dosing interval (AUC0–12h) of mycophenolic acid (MPA) in the heart transplant recipients and ii) to find the covariates that significantly affect the pharmacokinetics of MPA exposure. Methods: This single-center, prospective, open-label, observational study was conducted in 91 adult heart transplant recipients orally taking mycophenolate mofetil dispersible tablets. Samples collected intensively and sparsely were analyzed by the enzyme-multiplied immunoassay technique, and all the data were used in PPK modeling. Potential covariates were tested stepwise. The goodness-of-fit plots, the normalized prediction distribution error, and prediction-corrected visual predictive check were used for model evaluation. Optimal sampling times by ED-optimal strategy and multilinear regression (MLR) were analyzed based on the simulated data by the final PPK model. Moreover, using intensive data from 14 patients, the accuracy of AUC0–12h estimation was evaluated by Passing–Bablok regression analysis and Bland–Alman plots for both the PPK model and MLR equation. Results: A two-compartment model with first-order absorption and elimination with a lag time was chosen as the structure model. Co-medication of proton pump inhibitors (PPIs), estimated glomerular filtration rate (eGFR), and albumin (ALB) were found to significantly affect bioavailability (F), clearance of central compartment (CL/F), and the distribution volume of the central compartment (V2/F), respectively. Co-medication of PPIs decreased F by 27.6%. When eGFR decreased by 30 ml/min/1.73 m2, CL/F decreased by 23.7%. However, the impact of ALB on V2/F was limited to MPA exposure. The final model showed an adequate fitness of the data. The optimal sampling design was pre-dose and 1 and 4 h post-dose for pharmacokinetic estimation. The best-fit linear equation was finally established as follows: AUC0–12h = 3.539 × C0 + 0.288 × C0.5 + 1.349 × C1 + 6.773 × C4.5. Conclusion: A PPK model was established with three covariates in heart transplant patients. Co-medication of PPIs and eGFR had a remarkable impact on AUC0–12h of MPA. A linear equation was also concluded with four time points as an alternative way to estimate AUC0–12h for MPA.
Impact of Role Conflict on Intention to Leave Job With the Moderating Role of Job Embeddedness in Banking Sector Employees

This study investigates why some employees intend to leave their jobs when facing conflict between family responsibilities and job routines. The present study also reveals the moderating role of on-the-job embeddedness between role conflict and intention to leave the job. Drawing on conservation of resources theory, the paper investigates the buffering effect of the three on-the-job embeddedness components (fit, links, and sacrifice). Data were collected from banking officers because most of the employees have to face role conflict between family and job responsibilities, as banking is considered among the most stressful jobs. Collected data were analyzed by applying structural equation modeling. Results indicate that the role conflict significantly influences intention to leave the job. Furthermore, the study shows that on-the-job embeddedness moderates the relationship between role conflict and intention to leave. The results suggest that organizations can reduce turnover intention during times of work and life conflict by developing employee on-the-job embeddedness. This study provides some insights to managers on why many employees leave their jobs and how to overcome this problem. Management should also offer extra and available resources in periods of greater tension to minimize early thinking regarding quitting.
High-Quality Genomes and High-Density Genetic Map Facilitate the Identification of Genes From a Weedy Rice

Genes have been lost or weakened from cultivated rice during rice domestication and breeding. Weedy rice (Oryza sativa f. spontanea) is usually recognized as the progeny between cultivated rice and wild rice and is also known to harbor an gene pool for rice breeding. Therefore, identifying genes from weedy rice germplasms is an important way to break the bottleneck of rice breeding. To discover genes from weedy rice germplasms, we constructed a genetic map based on w-hole-genome sequencing of a F2 population derived from the cross between LM8 and a cultivated rice variety. We further identified 31 QTLs associated with 12 important agronomic traits and revealed that ORUFILM03g000095 gene may play an important role in grain length regulation and participate in grain formation. To clarify the genomic characteristics from weedy rice germplasms of LM8, we generated a high-quality genome assembly using single-molecule sequencing, Bionano optical mapping, and Hi-C technologies. The genome harbored a total size of 375.8 Mb, a scaffold N50 of 24.1 Mb, and originated approximately 0.32 million years ago (Mya) and was more closely related to Oryza sativa ssp. japonica. and contained 672 unique genes. It is related to the formation of grain shape, heading date and tillering. This study generated a high-quality reference genome of weedy rice and high-density genetic map that would benefit the analysis of genome evolution for related species and suggested an effective way to identify genes related to important agronomic traits for further rice breeding.
Identification and Characterization of a Novel Chromosomal Aminoglycoside 2′-N-Acetyltransferase, AAC(2′)-If, From an Isolate of a Novel Providencia Species, Providencia wenzhouensis R33

Multidrug-resistant bacteria from different sources have been steadily emerging, and an increasing number of resistance mechanisms are being uncovered. In this work, we characterized a novel resistance gene named aac(2′)-If from an isolate of a novel Providencia species, Providencia wenzhouensis R33 (CCTCC AB 2021339). Susceptibility testing and enzyme kinetic parameter analysis were conducted to determine the function of the aminoglycoside 2′-N-acetyltransferase. Whole-genome sequencing and comparative genomic analysis were performed to elucidate the molecular characteristics of the genome and the genetic context of the resistance gene-related sequences. Among the functionally characterized resistance genes, AAC(2′)-If shares the highest amino acid sequence identity of 70.79% with AAC(2′)-Ia. AAC(2′)-If confers resistance to several aminoglycoside antibiotics, showing the highest resistance activity against ribostamycin and neomycin. The recombinant strain harboring aac(2′)-If (pUCP20-aac(2′)-If/DH5α) showed 256- and 128-fold increases in the minimum inhibitory concentration (MIC) levels to ribostamycin and neomycin, respectively, compared with those of the control strains (DH5α and pUCP20/DH5α). The results of the kinetic analysis of AAC(2′)-If were consistent with the MIC results of the cloned aac(2′)-If with the highest catalytic efficiency for ribostamycin (kcat/Km ratio = [3.72 ± 0.52] × 104 M–1⋅s–1). Whole-genome sequencing demonstrated that the aac(2′)-If gene was located on the chromosome with a relatively unique genetic environment. Identification of a novel aminoglycoside resistance gene in a strain of a novel Providencia species will help us find ways to elucidate the complexity of resistance mechanisms in the microbial population.
Two Sides of the Same Coin: Fluid Intelligence and Crystallized Intelligence as Cognitive Reserve Predictors of Social Cognition and Executive Functions Among Vulnerable Elderly People

The concept of cognitive reserve –CR– postulates two forms that prevent cognitive impairment: neural reserve and neural compensation. Both have been primarily linked to the protective role played by genetic factors, educational level, occupation or socioeconomic status. Though it is true that it has been related to executive functions, so far very little attention has been paid to its predictive capacity with other variables more related to social cognition and psychosocial adaptation. Considering socially vulnerable contexts with reduced cultural capital and educational levels, the neural reserve function would be the most relevant and best predictor of aspects related to social cognition and executive functions. We suggest that variables such as fluid and crystallized intelligence influence social cognition and executive functions. This study included a sample of 27 participants over 60 years old from varied contexts of social vulnerability. The procedure included data collection using various cognitive measures. Results show that elderly people with high intelligence—mainly fluid intelligence—have better executive functions, emotional recognition and theory of mind. These results focus on cognitive reserve and its importance because they show that elderly people in vulnerable contexts who strengthen these aspects protect themselves against the deterioration of cognitive skills. This study is the first preliminary research to present a relationship between cognitive reserve and social cognition factors in elderly subjects. Fluid intelligence functions as a highly related factor to protect the performance of executive functions, along with other social-cognitive factors relevant to facilitating the conditions of social adaptation.
Effect of Cavity Cleanser With Long-Term Antibacterial and Anti-Proteolytic Activities on Resin–Dentin Bond Stability

Objective Secondary caries caused by oral microbiome dysbiosis and hybrid layer degradation are two important contributors to the poor resin–dentin bond durability. Cavity cleansers with long-term antimicrobial and anti-proteolytic activities are in demand for eliminating bacteria-induced secondary caries and preventing hybrid layers from degradation. The objectives of the present study were to examine the long-term antimicrobial effect and anti-proteolytic potential of poly(amidoamine) dendrimers with amino terminal groups (PAMAM-NH2) cavity cleanser. Methods Adsorption tests by attenuated total reflectance–infrared (ATR-IR) spectroscopy and confocal laser scanning microscopy (CLSM) were first performed to evaluate whether the PAMAM-NH2 cavity cleanser had binding capacity to dentin surface to fulfill its relatively long-term antimicrobial and anti-proteolytic effects. For antibacterial testing, Streptococcus mutans, Actinomyces naeslundii, and Enterococcus faecalis were grown on dentin surfaces, prior to the application of cavity cleanser. Colony-forming unit (CFU) counts and live/dead bacterial staining were performed to assess antibacterial effects. Gelatinolytic activity within the hybrid layers was directly detected by in situ zymography. Adhesive permeability of bonded interface and microtensile bond strength were employed to assess whether the PAMAM-NH2 cavity cleanser adversely affected resin–dentin bonding. Finally, the cytotoxicity of PAMAM-NH2 was evaluated by the Cell Counting Kit-8 (CCK-8) assay. Results Adsorption tests demonstrated that the binding capacity of PAMAM-NH2 on dentin surface was much stronger than that of 2% chlorhexidine (CHX) because its binding was strong enough to resist phosphate-buffered saline (PBS) washing. Antibacterial testing indicated that PAMAM-NH2 significantly inhibited bacteria grown on the dentin discs as compared with the control group (p < 0.05), which was comparable with the antibacterial activity of 2% CHX (p > 0.05). Hybrid layers conditioned with PAMAM-NH2 showed significant decrease in gelatin activity as compared with the control group. Furthermore, PAMAM-NH2 pretreatment did not adversely affect resin–dentin bonding because it did not decrease adhesive permeability and microtensile strength. CCK-8 assay showed that PAMAM-NH2 had low cytotoxicity on human dental pulp cells (HDPCs) and L929. Conclusions PAMAM-NH2 cavity cleanser developed in this study could provide simultaneous long-term antimicrobial and anti-proteolytic activities for eliminating secondary caries that result from a dysbiosis in the oral microbiome and for preventing hybrid layers from degradation due to its good binding capacity to dentin collagen matrix, which are crucial for the maintenance of resin–dentin bond durability.
Producing reusable engineered systems through ontology: implementing an information sciences approach to architecture-driven, model-based, concurrent engineering

The engineering community faces multiple challenges as it moves toward a future that will consist of virtual reality, model-based enterprises, and a heavy reliance on simulation for requirements development, design, manufacturing, assembly, and training for future products. The focus on model-based activities (e.g. design, systems engineering, manufacturing) is seen as a way to better reuse knowledge, ensure higher quality, and reduce costs through virtual design and testing. However, the combination of discipline-focused decomposition, the functional to physical progression, proprietary data formats, and poor communication between disciplines due to different language and contexts leads to longer development times, increased rework, and a failure in product realization. Raytheon has been researching aspects of this future, targeted at shortening the product development lifecycle by an order of magnitude. One such recent Raytheon-funded study has indicated that a potentially more complete approach might be to address the problem from an information sciences perspective and the adoption of “product” models as the primary representation. In particular, the development of a workable rapid engineering environment will require an information architecture-leveraging product ontology designed specifically for this type of approach.
Evolution of Rosaceae Plastomes Highlights Unique Cerasus Diversification and Independent Origins of Fruiting Cherry

Rosaceae comprises numerous types of economically important fruits, ornamentals, and timber. The lack of plastome characteristics has blocked our understanding of the evolution of plastome and plastid genes of Rosaceae crops. Using comparative genomics and phylogenomics, we analyzed 121 Rosaceae plastomes of 54 taxa from 13 genera, predominantly including Cerasus (true cherry) and its relatives. To our knowledge, we generated the first comprehensive map of genomic variation across Rosaceae plastomes. Contraction/expansion of inverted repeat regions and sequence losses of the two single-copy regions underlie large genomic variations in size among Rosaceae plastomes. Plastid protein-coding genes were characterized with a high proportion (over 50%) of synonymous variants and insertion-deletions with multiple triplets. Five photosynthesis-related genes were specially selected in perennial woody trees. Comparative genomic analyses implied divergent evolutionary patterns between pomaceous and drupaceous trees. Across all examined plastomes, unique and divergent evolution was detected in Cerasus plastomes. Phylogenomic analyses and molecular dating highlighted the relatively distant phylogenetic relationship between Cerasus and relatives (Microcerasus, Amygdalus, Prunus, and Armeniaca), which strongly supported treating the monophyletic true cherry group as a separate genus excluding dwarf cherry. High genetic differentiation and distinct phylogenetic relationships implied independent origins and domestication between fruiting cherries, particularly between Prunus pseudocerasus (Cerasus pseudocerasus) and P. avium (C. avium). Well-resolved maternal phylogeny suggested that cultivated P. pseudocerasus originated from Longmenshan Fault zone, the eastern edge of Himalaya-Hengduan Mountains, where it was subjected to frequent genomic introgression between its presumed wild ancestors and relatives.
Lactobacillus fermentum ZS40 Ameliorates Inflammation in Mice With Ulcerative Colitis Induced by Dextran Sulfate Sodium

Ulcerative colitis is an inflammatory disease of the intestine caused by many reasons, and it may even develop into colon cancer. Probiotics are normal bacteria that exist in the human body and have been proven to regulate the balance of intestinal flora and alleviate inflammation. The current study aimed to study the effect of Lactobacillus fermentum ZS40 (ZS40) on dextran sulfate sodium (DSS)-induced ulcerative colitis mice. The length and weight of the colon were measured, and the histopathological morphological changes of colon tissue were observed to evaluate the effects of ZS40 on colitis. Biochemical kits, ELISA kits, real-time quantitative PCR (RT-qPCR), and western blot were also used to detect the effects of ZS40 on serum and colon tissue related oxidative indicators and pro-inflammatory and anti-inflammatory cytokines. We found that ZS40 could reduce colonic inflammatory cell infiltration and goblet cell necrosis, increase total superoxide dismutase and catalase in mouse serum, and reduce myeloperoxidase and malondialdehyde levels. ZS40 could down-regulate the level of proinflammatory cytokines and up-regulate the level of anti-inflammatory cytokines. More importantly, ZS40 down-regulated the relative expression of nuclear factor-κB p65 (NF-κBp65), IL-6, and TNF-α mRNA and protein, up-regulated the relative expression of inhibitor kapa B alpha (IκB-α). By regulating the NF-κB and MAPK pathways to down-regulated the relative expression of p38 and JNK1/2 mRNA and p38, p-p38, JNK1/2, and p-JNK1/2 proteins. Our study suggested that ZS40 may serve as a potential therapeutical strategy for ulcerative colitis.
Strong motion displacement waveforms using 10‐Hz precise point positioning GPS: an assessment based on free oscillation experiments

The recently developed precise point positioning (PPP) technique permits to compute instantaneous coordinates of a GPS station relatively to distant reference stations and waveforms of ground displacements during strong motions at the 1 Hz level. This is another application of GPS, different from the computation of static coseismic movements or of accurate monitoring of dynamic displacements of structures using a static receiver and a nearby moving receiver (DGPS). Recently, earthquake ground displacement waveforms using 10‐Hz GPS data have also been calculated, but no independent evidence to assess their quality exists. To overcome this problem, we evaluated the output of 10‐Hz PPP results on the basis of supervised learning experiments. Semistatic and dynamic displacements (damped harmonic oscillations) of known characteristics of the order of a few centimeter were produced and were recorded by GPS, an accelerometer, and a robotic total station. Time series of instantaneous displacements were analyzed using different PPP techniques and were compared with reference (true) values derived from DGPS and the other sensors. Our analysis revealed that the PPP‐derived coordinates are contaminated by long‐period noise but they can display the details of semistatic displacements, while their short‐period component describes well the pattern of waveforms and spectra (at least up to 4 Hz) of dynamic displacements, with up to 20 mm accuracy for isolated points. These results indicate that 10‐Hz PPP‐GPS is useful for earthquake engineering and can safely be used to reconstruct waveforms of deflections of the ground and of various points on structures during strong motions. Copyright © 2014 John Wiley & Sons, Ltd.