Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes

Abstract Context Cepharanthine (CEP) extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), has a range of therapeutic potential in clinical conditions. Whether it affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods The effects of CEP (100 μM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific probe actions and probe substrates. In addition, the enzyme kinetic parameters were calculated. Results The results showed that the activity of CYP3A4, CYP2E1 and CYP2C9 was inhibited by CEP, with IC50 values of 16.29, 25.62 and 24.57 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that CEP was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2C9, with Ki values of 8.12, 11.78 and 13.06 μM, respectively. Additionally, CEP is a time-dependent inhibitor for CYP3A4 with KI /Kinact value of 10.84/0.058 min/μM. Discussion and conclusions The in vitro studies of CEP with CYP isoforms indicate that CEP has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2C9. Further clinical studies are needed to evaluate the significance of this interaction.
New insights into the cognitive effects of sleep deprivation by decomposition of a cognitive throughput task.

STUDY OBJECTIVES A cognitive throughput task known as the Digit Symbol Substitution Test (DSST) (or Symbol Digit Modalities Test) has been used as an assay of general cognitive slowing during sleep deprivation. Here, the effects of total sleep deprivation (TSD) on specific cognitive processes involved in DSST performance, including visual search, spatial memory, paired-associate learning, and motor response, were investigated through targeted task manipulations. METHODS A total of 12 DSST variants, designed to manipulate the use of specific cognitive processes, were implemented in two laboratory-based TSD studies with N = 59 and N = 26 subjects, respectively. In each study, the Psychomotor Vigilance Test (PVT) was administered alongside the DSST variants. RESULTS TSD reduced cognitive throughput on all DSST variants, with response time distributions exhibiting rightward skewing. All DSST variants showed practice effects, which were however minimized by inclusion of a pause between trials. Importantly, TSD-induced impairment on the DSST variants was not uniform, with a principal component analysis revealing three factors. Diffusion model decomposition of cognitive processes revealed that inter-individual differences during TSD on a two-alternative forced choice DSST variant were different from those on the PVT. CONCLUSIONS While reduced cognitive throughput has been interpreted to reflect general cognitive slowing, such TSD-induced impairment appears to reflect cognitive instability, like on the PVT, rather than general slowing. Further, comparisons between task variants revealed not one, but three distinct underlying processes impacted by sleep deprivation. Moreover, the practice effect on the task was found to be independent of the TSD effect and minimized by a task pacing manipulation.
Identification of human peripheral blood monocyte gene markers for early screening of solid tumors

As cancer mortality is high in most regions of the world, early screening of cancer has become increasingly important. Minimally invasive screening programs that use peripheral blood mononuclear cells (PBMCs) are a new and reliable strategy that can achieve early detection of tumors by identifying marker genes. From 797 datasets, four (GSE12771, GSE24536, GSE27562, and GSE42834) including 428 samples, 236 solid tumor cases, and 192 healthy controls were chosen according to the inclusion criteria. A total of 285 genes from among 440 reported genes were selected by meta-analysis. Among them, 4 of the top significantly differentially expressed genes (ANXA1, IFI44, IFI44L, and OAS1) were identified as marker genes of PBMCs. Pathway enrichment analysis identified, two significant pathways, the ‘primary immunodeficiency’ pathway and the ‘cytokine-cytokine receptor interaction’ pathway. Protein- protein interaction (PPI) network analysis revealed the top 27 hubs with a degree centrality greater than 23 to be hub genes. We also identified 3 modules in Molecular Complex Detection (MCODE) analysis: Cluster 1 (related to ANXA1), Cluster 2 (related to IFI44 and IFI44L) and Cluster 3 (related to OAS1). Among the 4 marker genes, IFI44, IFI44L, and OAS1 are potential diagnostic biomarkers, even though their results were not as remarkable as those for ANXA1 in our study. ANXA1 is involved in the immunosuppressive mechanism in tumor-bearing hosts and may be used in a new strategy involving the use of the host's own immunity to achieve tumor suppression.
DNA methylation and cis-regulation of gene expression by prostate cancer risk SNPs

Genome-wide association studies have identified more than 100 SNPs that increase the risk of prostate cancer (PrCa). We identify and compare expression quantitative trait loci (eQTLs) and CpG methylation quantitative trait loci (meQTLs) among 147 established PrCa risk SNPs in primary prostate tumors (n = 355 from a Seattle-based study and n = 495 from The Cancer Genome Atlas, TCGA) and tumor-adjacent, histologically benign samples (n = 471 from a Mayo Clinic study). The role of DNA methylation in eQTL regulation of gene expression was investigated by data triangulation using several causal inference approaches, including a proposed adaptation of the Causal Inference Test (CIT) for causal direction. Comparing eQTLs between tumors and benign samples, we show that 98 of the 147 risk SNPs were identified as eQTLs in the tumor-adjacent benign samples, and almost all 34 eQTL identified in tumor sets were also eQTLs in the benign samples. Three lines of results support the causal role of DNA methylation. First, nearly 100 of the 147 risk SNPs were identified as meQTLs in one tumor set, and almost all eQTLs in tumors were meQTLs. Second, the loss of eQTLs in tumors relative to benign samples was associated with altered DNA methylation. Third, among risk SNPs identified as both eQTLs and meQTLs, mediation analyses suggest that over two-thirds have evidence of a causal role for DNA methylation, mostly mediating genetic influence on gene expression. In summary, we provide a comprehensive catalog of eQTLs, meQTLs and putative cancer genes for known PrCa risk SNPs. We observe that a substantial portion of germline eQTL regulatory mechanisms are maintained in the tumor development, despite somatic alterations in tumor genome. Finally, our mediation analyses illuminate the likely intermediary role of CpG methylation in eQTL regulation of gene expression.
Human γδ TCR Repertoires in Health and Disease

The T cell receptor (TCR) repertoires of γδ T cells are very different to those of αβ T cells. While the theoretical TCR repertoire diversity of γδ T cells is estimated to exceed the diversity of αβ T cells by far, γδ T cells are still understood as more invariant T cells that only use a limited set of γδ TCRs. Most of our current knowledge of human γδ T cell receptor diversity builds on specific monoclonal antibodies that discriminate between the two major subsets, namely Vδ2+ and Vδ1+ T cells. Of those two subsets, Vδ2+ T cells seem to better fit into a role of innate T cells with semi-invariant TCR usage, as compared to an adaptive-like biology of some Vδ1+ subsets. Yet, this distinction into innate-like Vδ2+ and adaptive-like Vδ1+ γδ T cells does not quite recapitulate the full diversity of γδ T cell subsets, ligands and interaction modes. Here, we review how the recent introduction of high-throughput TCR repertoire sequencing has boosted our knowledge of γδ T cell repertoire diversity beyond Vδ2+ and Vδ1+ T cells. We discuss the current understanding of clonal composition and the dynamics of human γδ TCR repertoires in health and disease.
Verification of Adaptive Collection for Brain Computer Interface

 Abstract — To provide speech prostheses for individuals with severe communication impairments, brain computer interfaces (BCIs) using silent speech have been studied. I proposed adaptive collection, which divided brainwaves into smaller elements and verified them, for BCIs using silent. This paper verified the effect of adaptive collection in comparison to the conventional method. Brainwaves were obtained when four subjects imagined vocalization. In adaptive collection, shortening time length of brainwaves for common spatial patterns was effective because the state of brainwaves changes fast when a subject imagined vocalization. As a result, using the adaptive collection with 12 ms of the time length and 20 elements for classification, the classification accuracies were improved to 87–99% and the averaged classification accuracy was improved to 93% for the pairwise classification /a/ vs. /u/ in the case of 63 channels of EEG.
Virulence factors in coagulase-positive staphylococci of veterinary interest other than Staphylococcus aureus

Abstract Coagulase-positive Staphylococci (CoPS) can exist as commensals in humans, companion and food-producing animals, but can cause severe or even lethal diseases. Exchange of these bacteria between humans and animals has been described. Special attention has been focused on Methicillin-Resistant Staphylococcus aureus, but other CoPS can also represent an important threat. In addition to significant antimicrobial resistance, these bacteria may carry a plethora of virulence factors - molecules that allow bacteria to establish on or within a host and increase their ability to cause disease. These virulence factors have been widely described in S. aureus but information about other species of CoPS is scarce. The aim of this paper is to review the recent literature about the virulence factors of non-aureus CoPS of animal origin. Their possible effects on human health are also described. The role and prevalence of different virulence factors including leukocidins, hemolysins, adhesins, enterotoxins, exfoliative and toxic shock syndrome toxins as well as superantigen-like proteins are addressed. The effect of these virulence factors on human health is also described. The possibility of misdiagnosis of species of CoPS has been demonstrated in human clinical samples. Prevalence of zoonotic infections could be higher than thought and medical laboratories should be aware of these other staphylococcal species. In keeping with the ‘One Health’ approach to animal and human disease, medical professionals, veterinarians and health workers should be aware of the risks derived from exposure to these bacteria in people in close contact with animals, including pet owners, farmers and veterinarians themselves.
Feasibility of Attachment-Focused Self-Hypnosis to Change Insecure God Attachment

ABSTRACT Secure God attachment is related to less psychological distress and greater well-being, while insecure God attachment is associated with higher levels of psychological distress and various forms of maladaptive coping. Cognitive resistance may arise, however, when therapists directly address insecure attachment beliefs through overt cognitive-behavioral techniques. Based on principles of the dual process model of cognition, the authors hypothesized that self-hypnosis may be a theoretically sound and feasible treatment to alter insecure attachment, since hypnosis addresses the emotional, experiential cognitive system rather than the analytical, deliberative cognitive system. To test this hypothesis, 35 college students practiced a prerecorded, self-guided hypnotic script for 6 weeks. The treatment group’s scores indicated significant postintervention decreases in insecure attachment compared to a wait-list control. Qualitative responses also indicated that the majority of participants (62.8%) noticed these relationship changes and attributed them to the intervention.
Serum B12 Levels in Type II Diabetics on Metformin Therapy and its association with Clinical Neuropathy

Background: Metformin use in type II DM has also been known to cause B12 deficiency in as reported many studies. Iatrogenic neuropathy caused by Metformin induced B12 deficiency can add to burden of peripheral neuropathy that already exists in diabetic patients. Aims and Objectives: 1)To determine the serum vitamin B12 levels in patients of type II DM on metformin therapy and compare it with those not on metformin therapy; 2) To correlate serum vitamin B12 levels with dose and duration of metformin therapy; 3) To investigate association between peripheral neuropathy and serum vitamin B12 levels. Method: The present two year hospital based cross sectional study enrolled total 132 cases of type 2 diabetes mellitus and divided into two groups, (metformin group 70 and non-metformin group 62). Serum vitamin B12 levels were measured in all patients. Toronto clinical scoring system (TCSS) and nerve conduction velocity (NCV) tests were used to assess peripheral neuropathy. The correlations of vitamin B12 levels with Toronto clinical score, nerve conduction studies, cumulative dose and duration of metformin therapy was done. Results: The serum vitamin B12 levels were significantly lower in patients who consumed metformin (292.64 152.82 pg/ml) as compared to non-metformin, (406.91 126.59 pg/ml) group. There was a significant negative correlation of serum vitamin B12 levels with cumulative dose and duration of metformin therapy. The incidence of neuropathy by TCSS and NCV test was significantly higher in metformin group with a positive correlation with cumulative dose and duration of metformin and a negative correlation with serum vitamin B12 levels. Conclusion: Metformin use is significantly associated with decrease in vitamin B12 levels and increased incidence of neuropathy, this is dependent on dose and duration of metformin therapy.
Physical exercise at term for enhancing the spontaneous onset of labor: a randomized clinical trial

Abstract Introduction Physical exercise at term is empirically used as a method of enhancing the spontaneous labor onset. The objective of this study was to evaluate the effect of controlled maternal physical exercise at term as a method of enhancing the spontaneous labor onset. Materials and methods At 38 weeks low-risk pregnant women, with a singleton cephalic fetus and no previous cesarean deliveries were randomly allocated to one of two arms: the experimental group performed 30 min of walking 3 times a week at 4 km/h, and the control group maintained their usual work and household activities. The primary outcome measure was the rate of labor induction. A sample size of 60 per group was planned to detect a 10% difference in labor induction rate, at a significance level of 0.05 and a power of 0.80. Results The exercise group had a lower rate of labor induction (17.5 versus 33.3%, adjusted odds ratio [OR] = 0.28, 95% confidence interval [CI]; 0.14–0.87) and fewer operative vaginal deliveries (20.6 versus 38.1%, adjusted OR = 0.42, 95% CI; 0.17–0.92). No differences were found in gestational age at onset of spontaneous labor, duration of the active phase of labor, interval between induction and the active phase of labor, cesarean section rates, birth weight, and Apgar scores. No maternal or fetal heart rate abnormalities were recorded during the exercise sessions. Conclusions For low-risk women at term walking for 30 min 3 times a week at 4 km/h from 38-week onwards is safe, enhances the spontaneous onset of labor and reduces operative vaginal delivery rates. Key Message Physical exercise at term is empirically used as a method of enhancing the spontaneous labor onset. In finding that for low-risk women walking for 30 min 3 times a week at 4 km/h from 38-week onwards enhances spontaneous labor onset of and reduces operative vaginal delivery. Clinical Trial Registration ClinicalTrials.gov. www.clinicaltrials. gov NCT02460185
Role of Computed Tomography in Transcatheter Aortic Valve Replacement

ABSTRACT The rapid development of transcatheter aortic valve replacement (TAVR) and its widespread adoption has heavily relied on rapid innovations in interventional cardiology and cardiovascular imaging. With a furious pace of evolution of data in recent years, the field has moved dramatically forward to a point of widespread acceptance and routine performance in an outpatient setting or a non-urgent inpatient setting. From its earliest iteration, it was recognized that a “heart team,” which comprised of cardiologists (valve specialists, imaging specialists and interventionalists) and cardiac surgeons was crucial for successful execution of a TAVR procedure. Additionally, it was also recognized that careful pre-procedural planning was also imperative in its success. This has led to the burgeoning field of multimodality structural and interventional imaging, which coincided with the maturation of modern imaging techniques such as 3D echocardiography, ECG gated multi-detector computed tomography (MDCT) and cardiac magnetic resonance imaging (CMR). Of these, MDCT has gained particular importance in the context of preprocedural planning in the setting of TAVR and its integration has been critical for its success. The current article is a state-of-the-art review of the role of MDCT in the context of TAVR. With the emergence of valve-in-valve TAVR, there will be evolution of newer details to be reported on a preprocedural MDCT; however these are beyond the scope of this article.
Information Asymmetry in Private-Label Mortgage Securitization: Evidence from Allocations to Affiliated Funds∗

Did underwriters capitalize on the information asymmetry embedded in the securitization process by placing mortgage-backed securities with affiliated investors? We expand the debate on incentives embedded in the originate-to-distribute model by presenting novel evidence on the placement of mortgage-backed securities with investors who are affiliated with either the security underwriter or issuer. We do so by capitalizing on a unique testing platform encompassing institutional holdings of mortgage-backed securities (MBS). We find that affiliated funds are associated with deals comprised of loans with lower expected prepayment rates and higher expected default rates. Thus, in contrast to the IPO market where evidence indicates that underwriters give preference to affiliated investors, our results suggest that MBS underwriters used affiliated investors to offload riskier mortgages. JEL Classifications: R3, R31, R38
Variation of Egg Size of Walleye Pollock Theragra chalcogramma with a Preliminary Examination of the Effect of Egg Size on Larval Size *

Alaska Fisheries Science Center, National Marine Fisheries Service. NOAA 7600 Sand Point Way NE. Seattle, Washington 98115 Variation of Egg Size of Walleye Pollock Theragra chalcogramma with a Preliminary Examination of the Effect of Egg Size on Larval Size* Abstract.Egg size has been shown to relate to survival and growth in the early life stages of fish. Combined field and laboratory studies examined variation in the egg size of walleye pollock Theragra c.haloogram-ma, a commercially important North Pacific gadoid; and a preliminary assessment of the effect of egg size on larval size was made. Differences in egg size were found over parts of the geographical range, among years, and over the spawning season in Shelikof Strait. Egg size did not appear to correlate with female length, age, or condition. Individual female's egg size decreased significantly over the course of the spawning cycle. Preliminary studies in the laboratory showed that egg size is correlated with larval size and may therefore affect mortality in the early larval stages.
Race and Gender Differences in the Association Between Experiences of Everyday Discrimination and Arterial Stiffness Among Patients With Coronary Heart Disease.

BACKGROUND Self-reported experiences of discrimination have been linked to indices of cardiovascular disease. However, most studies have focused on healthy populations. Thus, we examined the association between experiences of everyday discrimination and arterial stiffness among patients with a history of myocardial infarction (MI). PURPOSE We hypothesized that higher reports of discrimination would be associated with greater arterial stiffness and that associations would be more pronounced among Black women, in particular, relative to other race-gender groups, using an "intersectionality" perspective. METHODS Data were from 313 participants (49.2% female, mean age: 50.8 years) who were 6 months post-MI in the Myocardial Infarction and Mental Stress 2 study. Data were collected via self-reported questionnaires, medical chart review, and a clinic visit during which arterial stiffness was measured noninvasively using pulse wave velocity. RESULTS Reports of discrimination were highest in Black men and women and arterial stiffness was greatest in Black and White women. After adjustment for demographics and relevant clinical variables, discrimination was not associated with arterial stiffness in the overall study sample. However, discrimination was associated with increased arterial stiffness among Black women but not White women, White men, or Black men. CONCLUSIONS Despite no apparent association between discrimination and arterial stiffness in the overall study sample, further stratification revealed an association among Black women but not other race-gender groups. These data not only support the utility of an intersectionality lens but also suggest the importance of implementing psychosocial interventions and coping strategies focused on discrimination into the care of clinically ill Black women.
Diagnostic Impact of CSF Biomarkers in a Local Hospital Memory Clinic Revisited

Background/Aims: Research guidelines on predicting and diagnosing Alzheimer’s disease (AD) acknowledge cerebrospinal fluid (CSF) levels as pivotal biomarkers. We studied the usefulness of CSF biomarkers in the diagnostic workup of patients in a geriatric outpatient memory clinic of a community-based hospital, attempted to determine a cutoff age for the use of CSF biomarkers in this group of patients, and compared the total τ/Aβ ratio as an alternative CSF diagnostic rule with the usual rules for interpreting CSF levels. Methods: This was a prospective study of consecutively referred patients. Inclusion criteria were described on the basis of previous study results in the same setting. The CSF tool was applied either to differentiate between AD and no AD or to increase certainty having made the diagnosis of AD. Clinicians were asked to judge whether the CSF results were helpful to them or not. Results: The reasons to use the CSF tool in the diagnostic workup were in 78/106 patients to decide between the diagnosis “AD” and “no AD” and in 28/106 patients to increase the certainty regarding the diagnosis. In 75% of cases the CSF levels were considered diagnostically helpful to the clinicians. Results in the present setting suggest 65 years as the cutoff age to use CSF as a diagnostic tool. The sensitivity and specificity of the total τ/Aβ ratio using the clinical diagnosis as the gold standard were at least as good as the usual categorization rule. Conclusions: Our study results corroborate earlier findings that the CSF tool is of added value to the diagnostic workup in daily clinical practice outside tertiary referral centers. CSF levels can best be used in patients under 66 years of age. Given the limited use of this tool in settings outside research facilities, we recommend that the usefulness of CSF biomarkers is studied in a multicenter study. When in the future CSF levels can be reliably measured in plasma, this may become even more relevant.