Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Host Immunity on Predicting the Mortality of Carbapenem-Resistant Organism Infection

Carbapenem-resistant organisms (CROs) are associated with considerable mortality clinically. There is a lack of effective tool to predict individual prognosis. We aim to determine if host immunity can be utilized to predict the prognosis of patients infected with CRO. From December 2018 to August 2019, we recruited CRO-infected patients to evaluate risk factors for 30-day mortality. Clinical, routine laboratory, immune and microbiological features were investigated and subjected to univariate and multivariate analyses. The final predictive models were established based on the regression coefficients of multivariate logistic regression. A total of 127 CRO-infected patients were enrolled in our study, including 85 survivors and 42 non-survivors. The number and IFN-γ producing ability of lymphocytes were remarkably decreased in non-survivors. The number of IFN-γ+CD4+ T cells could effectively predict 30-day mortality of CRO infection. Its area under the receiver operating characteristic (ROC) curve, sensitivity, specificity and accuracy, were 0.889 (95% confidence interval [CI], 0.834–0.945), 81.0, 80.0, and 80.3%, respectively. In multivariate analysis of laboratory parameters, IFN-γ+CD4+ T cell number and creatinine concentration were selected for the 2-marker model to predict prognosis fleetly. Its area under the ROC curve, sensitivity, specificity and accuracy were 0.894 (95% CI, 0.841–0.947), 83.3, 82.4, and 82.7%, respectively. Impaired lymphocyte function was an important factor to affect the outcome of CRO-infected patients. A 2-marker model based on the combination of IFN-γ+CD4+ T cell number and creatinine showed good performance in predicting the prognosis of CRO infection.
Comparative Effect of Grain Moisture on the Biological Activity of Protect ants on Stored Corn

Increasing moisture content of corn had the same adverse effect on biological activity of fenitrothion formulated as an emulsifiable concentrate (EC), wettable powder, or dust against Tribolium castaneum (Herbst). The proportion of residues of the three formulations extracted by a surface wash with methanol was also reduced in similar proportions as moisture content increased. Among five organophosphorus compounds (all EC) tested against T. castaneum , fenitrothion was the most adversely affected by moisture content (14 and 18%) and chlorpyrifos-methyl the least, and all were more affected than the pyrethroid deltamethrin (EC). Against Rhyzopertha dominica (F.), biological activities of methacrifos and carbaryl (water-dispersed colloid) were much reduced at higher moisture content, while the activities of five pyrethroids (EC or miscible oil) were slightly reduced. Over a greater range of moisture contents, activities of fenitrothion, chlorpyrifos-methyl, and pirimiphosmethyl against T. castaneum were substantially reduced only above a corresponding equilibrium relative humidity of 70-80%. No such threshold was measured for carbaryl, an increase in moisture having considerable effect on activity even when grain was quite dry. Effect of moisture on activity of deltamethrin was significant but relatively small, particularly against T. castaneum .
The Long-run Economic Effects of School Desegregation∗

I estimate the effect of school desegregation on long-run economic outcomes by studying a natural experiment in Jefferson County, KY. In 1975, the district, under a court order, developed a unique busing assignment plan to merge the majority-white County district and the majority-black City district. Under this plan, students were assigned to be bused to new schools (versus stay at their home school and have new students bused in) based on their race and the first letter of their last name. Using this plausibly conditional random assignment and confidential data from the US Census Bureau, I find black students assigned busing to former County schools live in better neighborhoods (e.g. neighborhoods with higher tract-level income) at adulthood than black students assigned to remain in former City schools. This effect is strongest for students bused in earlier grades and is increasing in the total number of years a student is assigned busing. Busing assignment has small to zero effect on white students. I explore the implications of white disenrollment from the district (i.e. “white flight”) by using a novel dataset of archival yearbook records. I find the effect for white students remains small even after preliminary accounting for disenrollment. These results suggest that school desegregation in this setting had positive long-run effects for black students by giving them access to better schools (e.g. schools with more capital investment, more credentialed teachers, lower drop-out rates, etc.). JEL Classification: I20, I24
Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study

Combination therapy with inhibitors of cytotoxic T lymphocyte-associated protein (CTLA)4 and programmed death (PD)-1 has demonstrated efficacy in cancer patients. However, there is little information on CTLA4 and PD-1 expression levels and their clinical significance across diverse cancers. In this study, we addressed this question by analyzing PD-1 and CTLA4 levels in 33 different types of cancer along with their prognostic significance using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia datasets. Liver hepatocellular carcinoma (LIHC) patients receiving cytokine-induced killer cell (CIK) immunotherapy at Sun Yat-sen University cancer center were enrolled for survival analysis. The correlation between PD-1/CTLA4 expression and cancer immunity was also analyzed. The results showed that PD-1 and CTLA4 transcript levels varied across cancer cell lines, with aberrant expression detected in certain cancer types; Kaplan–Meier analysis with the Cox proportional hazards model showed that this was closely related to overall survival in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, acute myeloid leukemialymphoma, uterine corpus endometrial carcinoma, and uveal melanoma in TCGA. High serum PD-1 and CTLA4 levels predicted better survival in LIHC patients receiving CIK therapy. PD-1 and CTLA4 levels were found to be significantly correlated with the degree of tumor cell infiltration using Tumor Immune Estimation Resource, Estimating Relative Subsets of RNA Transcripts, and Estimation of Stromal and immune Cells in Malignant Tumor Tissues Using Expression Data as well as with tumor-infiltrating lymphocyte marker expression; they were also related to tumor mutation burden, microsatellite instability, mismatch repair, and the expression of DNA methyltransferases in some cancer types. Gene set enrichment analysis of 33 cancer types provided further evidence for associations between PD-1/CTLA4 levels and cancer development and immunocyte infiltration. Thus, PD-1 and CTLA4 play important roles in tumorigenesis and tumor immunity and can serve as prognostic biomarkers in different cancer types.
Neural Representation Enhanced for Speech and Reduced for Background Noise With a Hearing Aid Noise Reduction Scheme During a Selective Attention Task

Objectives Selectively attending to a target talker while ignoring multiple interferers (competing talkers and background noise) is more difficult for hearing-impaired (HI) individuals compared to normal-hearing (NH) listeners. Such tasks also become more difficult as background noise levels increase. To overcome these difficulties, hearing aids (HAs) offer noise reduction (NR) schemes. The objective of this study was to investigate the effect of NR processing (inactive, where the NR feature was switched off, vs. active, where the NR feature was switched on) on the neural representation of speech envelopes across two different background noise levels [+3 dB signal-to-noise ratio (SNR) and +8 dB SNR] by using a stimulus reconstruction (SR) method. Design To explore how NR processing supports the listeners’ selective auditory attention, we recruited 22 HI participants fitted with HAs. To investigate the interplay between NR schemes, background noise, and neural representation of the speech envelopes, we used electroencephalography (EEG). The participants were instructed to listen to a target talker in front while ignoring a competing talker in front in the presence of multi-talker background babble noise. Results The results show that the neural representation of the attended speech envelope was enhanced by the active NR scheme for both background noise levels. The neural representation of the attended speech envelope at lower (+3 dB) SNR was shifted, approximately by 5 dB, toward the higher (+8 dB) SNR when the NR scheme was turned on. The neural representation of the ignored speech envelope was modulated by the NR scheme and was mostly enhanced in the conditions with more background noise. The neural representation of the background noise was modulated (i.e., reduced) by the NR scheme and was significantly reduced in the conditions with more background noise. The neural representation of the net sum of the ignored acoustic scene (ignored talker and background babble) was not modulated by the NR scheme but was significantly reduced in the conditions with a reduced level of background noise. Taken together, we showed that the active NR scheme enhanced the neural representation of both the attended and the ignored speakers and reduced the neural representation of background noise, while the net sum of the ignored acoustic scene was not enhanced. Conclusion Altogether our results support the hypothesis that the NR schemes in HAs serve to enhance the neural representation of speech and reduce the neural representation of background noise during a selective attention task. We contend that these results provide a neural index that could be useful for assessing the effects of HAs on auditory and cognitive processing in HI populations.
Overexpression of GSK-3β in Adult Tet-OFF GSK-3β Transgenic Mice, and Not During Embryonic or Postnatal Development, Induces Tau Phosphorylation, Neurodegeneration and Learning Deficits

GSK-3β or tau-kinase I is particularly abundant in the central nervous system (CNS), playing a key role in the pathogenesis of Alzheimer’s disease (AD). Accordingly, transgenic mouse models overexpressing this kinase recapitulate some aspects of this disease, such as tau hyperphosphorylation, neuronal death, and microgliosis. These alterations have been studied in mouse models showing GSK-3β overexpression from birth. In this case, some of these alterations may be due to adaptations that occur during development. Here we explored the potential of the Tet-OFF conditional system in the murine CamKIIα-tTA/GSK-3β model to increase the activity of GSK-3β only during adulthood. To this end, the overexpression of GSK-3β remained OFF during embryonic and postnatal development by administration of doxycycline in drinking water for 6 months, while it was turned ON in adult animals by removal of the treatment for 6 months. In these conditions, the CamKIIα-tTA/GSK-3β mouse is characterized by an increase in phosphorylated tau, cell death, and microgliosis. Furthermore, the increase in GSK-3β expression in the adult animals triggered a cognitive deficit, as determined through the hippocampus-dependent object recognition test (OR). These results demonstrate that the GSK-3β plays a key role in AD and that previously published data with other transgenic models are neither caused by or a consequence of adaptations to high levels of the enzyme during development.
Efficacy and Safety of Corticosteroid Treatment in Patients With COVID-19: A Systematic Review and Meta-Analysis

Background COVID-19 is a type of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that was identified in December 2019. Corticosteroid therapy was empirically used for clinical treatment in the early stage of the disease outbreak; however, data regarding its efficacy and safety are controversial. The aim of this study was to evaluate the efficacy and safety of corticosteroid therapy in patients with COVID-19. Methods The PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal (VIP) databases were searched for studies. Data on clinical improvement, mortality, virus clearance time, adverse events (AEs), utilization of mechanical ventilation, length of intensive care unit (ICU) hospitalization, and hospital stay were extracted by two authors independently. Study quality was assessed by the Newcastle Ottawa Scale (cohort studies). The pooled data were meta-analyzed using a random effects model, and the quality of evidence was rated using the GRADE approach. Results Eleven cohort studies (corticosteroid group vs control group), two retrospective cohort studies (without control group), and seven case studies were identified. A total of 2840 patients were included. Compared with the control treatments, corticosteroid therapy was associated with clinical recovery (RR = 1.30, 95% CI [0.98, 1.72]) and a significantly shortened length of ICU hospitalization (RR = −6.50; 95% CI [−7.63 to −5.37]), but it did not affect the mortality ((RR = 1.59; 95% CI [0.69–3.66], I2 = 93.5%), utilization of mechanical ventilation (RR = 0.35; 95% CI [0.10, 1.18]), duration of symptoms (WMD = 1.69; 95% CI [−0.24 to 3.62]) or virus clearance time (RR = 1.01; 95% CI [−0.91 to 2.92], I2 = 57%) in COVID-19 patients. Treatment with corticosteroids in patients with COVID-19 may cause mild adverse outcomes. The quality of evidence was low or very low for all outcomes. Conclusion The findings of our study indicate that corticosteroid therapy is not highly effective, but it appears to improve prognosis and promote clinical recovery in patients with severe COVID-19.
The Potential of Clinical Decision Support Systems for Prevention, Diagnosis, and Monitoring of Allergic Diseases

Clinical decision support systems (CDSS) aid health care professionals (HCP) in evaluating large sets of information and taking informed decisions during their clinical routine. CDSS are becoming particularly important in the perspective of precision medicine, when HCP need to consider growing amounts of data to create precise patient profiles for personalized diagnosis, treatment and outcome monitoring. In allergy care, several CDSS are being developed and investigated, mainly for respiratory allergic diseases. Although the proposed solutions address different stakeholders, the majority aims at facilitating evidence-based and shared decision-making, incorporating guidelines, and real-time clinical data. We offer here an overview on existing tools, new developments and novel concepts and discuss the potential of digital CDSS in improving prevention, diagnosis and monitoring of allergic diseases.
A Semi-supervised Learning Method for Q-Matrix Specification Under the DINA and DINO Model With Independent Structure

Cognitive diagnosis assessment (CDA) can be regarded as a kind of formative assessments because it is intended to promote assessment for learning and modify instruction and learning in classrooms by providing the formative diagnostic information about students' cognitive strengths and weaknesses. CDA has two phases, like a statistical pattern recognition. The first phase is feature generation, followed by classification stage. A Q-matrix, which describes the relationship between items and latent skills, corresponds to the feature generation phase in statistical pattern recognition. Feature generation is of paramount importance in any pattern recognition task. In practice, the Q-matrix is difficult to specify correctly in cognitive diagnosis and misspecification of the Q-matrix can seriously affect the accuracy of the classification of examinees. Based on the fact that any columns of a reduced Q-matrix can be expressed by the columns of a reachability R matrix under the logical OR operation, a semi-supervised learning approach and an optimal design for examinee sampling were proposed for Q-matrix specification under the conjunctive and disjunctive model with independent structure. This method only required subject matter experts specifying a R matrix corresponding to a small part of test items for the independent structure in which the R matrix is an identity matrix. Simulation and real data analysis showed that the new method with the optimal design is promising in terms of correct recovery rates of q-entries.
Root Exudates Metabolic Profiling Suggests Distinct Defense Mechanisms Between Resistant and Susceptible Tobacco Cultivars Against Black Shank Disease

There is increasing evidence that root exudates play important roles in plant disease resistance. Black shank, caused by Phytophthora nicotianae, is a destructive soil-borne disease in tobacco (Nicotiana tabacum L.). The aim of the present study was to investigate the activity and composition of the root exudates from resistant and susceptible tobacco cultivars. The root exudates of the resistant cultivar Gexin 3 showed inhibitory activity against P. nicotianae, while the exudates of susceptible cultivar Xiaohuangjin 1025 stimulated the colony growth but had no effect on spore germination. Metabolic profiling using liquid chromatography/electrospray ionization-quadrupole-time-of-flight mass spectrometry depicted differing metabolic patterns of root exudates between Gexin 3 and Xiaohuangjin 1025. The activity and composition of root exudates was altered by P. nicotianae inoculation. Multivariate analysis showed that root exudates (including organic acids, alkaloids, fatty acids, and esters) were different between the two varieties. The defense substances in root exudates, such as tartaric acid, ferulic acid, and lauric acid, may represent a pre-infection prevention strategy for tobacco. Phenylpropanoids as well as inducers of salicylic acid, fatty acids, 6-hydroxyhexanoic acid, and hydrojasmonate may be involved in tobacco defense responses. Compared to the susceptible cultivar, the roots of the resistant cultivar exhibited high enzyme activities of phenylalanine ammonia-lyase, cinnamate-4-hydroxylase and 4-coumarate-CoA ligase, which may prompt the synthesis and secretion of phenylpropanoids. Our results indicated that the root exudates not only provide a pre-infection prevention strategy by exuding antimicrobial substances, but also increase tobacco disease resistance by eliciting plant defense responses. In addition, some defense compounds as well as compounds that play a role in inducing plant defense responses, showed potential for disease control application. This study provides an insight into possible disease resistance mechanisms of root exudates, and attempts the beneficial utilization of these secondary metabolites of plants.
Genome-Wide Characterization of Host Transcriptional and Epigenetic Alterations During HIV Infection of T Lymphocytes

Background and methods: Host genomic alterations are closely related to dysfunction of CD4+ T lymphocytes in the HIV–host interplay. However, the roles of aberrant DNA methylation and gene expression in the response to HIV infection are not fully understood. We investigated the genome-wide DNA methylation and transcriptomic profiles in two HIV-infected T lymphocyte cell lines using high-throughput sequencing. Results: Based on DNA methylation data, we identified 3,060 hypomethylated differentially methylated regions (DMRs) and 2,659 hypermethylated DMRs in HIV-infected cells. Transcription-factor-binding motifs were significantly associated with methylation alterations, suggesting that DNA methylation modulates gene expression by affecting the binding to transcription factors during HIV infection. In support of this hypothesis, genes with promoters overlapping with DMRs were enriched in the biological function related to transcription factor activities. Furthermore, the analysis of gene expression data identified 1,633 upregulated genes and 2,142 downregulated genes on average in HIV-infected cells. These differentially expressed genes (DEGs) were significantly enriched in apoptosis-related pathways. Our results suggest alternative splicing as an additional mechanism that may contribute to T-cell apoptosis during HIV infection. We also demonstrated a genome-scale correlation between DNA methylation and gene expression in HIV-infected cells. We identified 831 genes with alterations in both DNA methylation and gene expression, which were enriched in apoptosis. Our results were validated using various experimental methods. In addition, consistent with our in silico results, a luciferase assay showed that the activity of the PDX1 and SMAD3 promoters was significantly decreased in the presence of HIV proteins, indicating the potential of these genes as genetic markers of HIV infection. Conclusions: Our results suggest important roles for DNA methylation and gene expression regulation in T-cell apoptosis during HIV infection. We propose a list of novel genes related to these processes for further investigation. This study also provides a comprehensive characterization of changes occurring at the transcriptional and epigenetic levels in T cells in response to HIV infection.
Full Genomic Analysis of New Variants of Porcine Reproductive and Respiratory Syndrome Virus Revealed Multiple Recombination Events Between Different Lineages and Sublineages

Porcine reproductive and respiratory syndrome virus (PRRSV) has had a devastating impact on the pig industry in China, and monitoring its genetic diversity is important for epidemiological surveillance and understanding its evolution. Here, we determine the complete genome sequences of two PRRSV strains, GXYL1403 and GXNN1839. Comparative, phylogenetic, and recombination detection program analyses show that the two isolates are recombinant strains with large-fragment amino acid deletions in nsp2. GXYL1403 possesses a unique deletion region of 124 amino acids in nsp2, and GXNN1839 contains a deletion of 131 amino acids in nsp2 as compared with VR2332. Further analysis of the full-length sequence suggests that GXYL1403 is a natural recombinant between sublineages 8.1 (CH-1a like) and 8.3 (JXA1-like). The recombination site of GXYL1403 is located in nsp9–nsp12 (8961nt−11181nt). GXNN1839 is a natural recombinant between the lineage 5 (VR-2332-like) and lineage 1 (NADC30-like) strains. The recombination events occurred in nsp9 (7872nt-8162nt) and in ORF2 (12587nt−13282nt) in the genome of GXNN1839. These results provide new evidence that PRRSV strains circulating in the environment have undergone recombination among the different lineages or sublineages of field strains, and these add to our understanding of RNA combination events that occur in PRRSV.