Miracle-dz/UniFAR-FTUs huggingface dataset:
tau4/tau c/AF-2 of the thyroid hormone receptor relieves silencing of the retinoic acid receptor silencer core independent of both tau4 activation function and full dissociation of corepressors

Members of the thyroid hormone (TR)-retinoic acid receptor (RAR) subfamily of nuclear hormone receptors silence gene expression in the absence of hormone. Addition of cognate ligands leads to dissociation of corepressors, association of coactivators, and transcriptional activation. Here, we used the hRAR alpha silencer core, which encompasses the ligand binding domain, including receptor regions D and E of RAR alpha without the activation function called tau4/tau c/AF-2 and without the F region, to analyze the mechanisms by which transcriptional silencing is relieved. Although the RAR silencer core is able to bind ligand, it acts as a constitutive transcriptional silencer. We have fused various small activation domains to the C terminus of the silencer core and analyzed hormone-dependent changes in receptor function. We show that nine amino acids derived from the hTRbeta are sufficient to transform the RAR silencer core into a hormone-dependent activator. Lengthening the linker between the silencer core and these nine amino acids is not critical for mediating ligand-induced relief of silencing and activation. In addition, we show that a transactivation function at the C terminus is not required for relief of silencing by the hormone, but it is required for transcriptional activation. Furthermore, we created functional silencer fusions which lose their repressive function upon addition of hormone, although the corepressors SMRT and N-CoR remain attached to the receptor.
Carbon dioxide assimilation in urea‐treated wheat leaves

Abstract Application of 10 mM urea to the flag leaf of wheat plants enhanced in vivo urease activity several fold. Photosynthetic rate was also increased considerably. There were significant differences in the leaf internal carbon dioxide (CO2) concentrations between the urea‐treated and untreated leaves. The finding that carbon (14C) was detected in the ethanol extract of the leaves fed with 14C‐urea suggests that CO2 released from urea is re‐fixed by the leaves.
Using borderline methods to compare passing standards for OSCEs at graduation across three medical schools

Context Medical schools in the UK set their own graduating examinations and pass marks. In a previous study we examined the equivalence of passing standards using the Angoff standard‐setting method. To address the limitation this imposed on that work, we undertook further research using a standard‐setting method specifically designed for objective structured clinical examinations (OSCEs).
State-of-the-Art Review : The Effect of Antiplatelet Drugs, Heparin, and Preanalytical Variables on Platelet Function Detected by the Platelet Function Analyzer (PFA-100®)

The platelet function analyzer (PFA)-100® is a newly developed instrument that provides a rapid, in vitro, quantitative measurement of platelet adhesion and aggregation in whole blood flowing through a small aperture under high shear conditions. Thirty patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and ten normal in dividuals were included in this study. In vitro and in vivo studies were conducted to discern the effect of combinations of antiplatelet drugs (aspirin, ticlopidine, abciximab) and heparin on the performance of the device as well as the effects of preanalytical variables, such as method of sample collection and ex vivo anticoagulants. Studies were also conducted ex amining the effect of aperture size (standard 150 μm vs. smaller 120 μm) on the ability of the device to detect the effect of antiplatelet drugs. There was no difference in mean PFA- 100® closure time with citrate versus PPACK anticoagulants or with venipuncture vs. sheath sampling. Closure times did not vary with heparin administration. Closure times were slightly longer for patients taking aspirin plus ticlopidine compared to aspirin alone (p = NS). In contrast adenosine disphosphate (ADP) induced platelet aggregation was significantly less in patients that took aspirin plus ticlopidine vs. aspirin alone (p = .0005). In vitro, there was a dose-dependent increase in closure time for both aperture sizes with increasing abciximab concen tration. Although both cartridges showed infinite closure times at an abciximab concentration of 2.25 μg/mL, there was a slight benefit to using the 120 μm aperture cartridges at abcix imab concentrations of 1.75 to 2.0 μg/mL. In ten patients who were followed during abciximab therapy to assess the effect of aperture size, the PFA-100® was able to detect in vivo platelet inhibition by abciximab, but detection of recovery from abcix imab-induced platelet dysfunction was slightly better for the PFA-100® with the 120 μm aperture compared to the standard 150 μm aperture collagen/ADP cartridge.
Secretory leukocyte protease inhibitor, but not alpha-1 protease inhibitor, blocks tryptase-induced bronchoconstriction.

Alpha-1-protease inhibitor (alpha(1)-PI) and secretory leukocyte protease inhibitor (SLPI) are two natural airway serine protease inhibitors. While inhibition of neutrophil elastase is a function common to both alpha(1)-PI and SLPI, we showed previously that they exhibit different patterns of protection against antigen-induced changes in airway function in allergic sheep. Specifically, the protective effect seen with SLPI was similar to the profile of action of synthetic tryptase inhibitors in the model. Based on these data, and the fact that tryptase is a serine protease, we hypothesized that SLPI, but not alpha(1)-PI, would block tryptase-induced bronchoconstriction. To test this, we compared the responses to inhaled tryptase in five sheep without treatment or after treatment with either aerosol alpha(1)-PI (10 mg) or aerosol SLPI (50 mg). The doses of alpha(1)-PI and SLPI selected had been shown to be effective in previous antigen-provocation studies. Treatments were given 30 min before aerosol challenge with tryptase (500 ng). Tryptase alone increased (mean+/-SEM) pulmonary resistance (R(L)) 142 +/- 24% over baseline. Pretreatment with alpha(1)-PI had no effect on the tryptase response (R(L)increased 122 +/- 20%). Pretreatment with SLPI, however, blocked the tryptase-induced response (R(L) increased only 40 +/- 4% P<0.05 vs. tryptase). These are the first studies comparing the inhibitory activity of SLPI and alpha(1)-PI on inhaled tryptase-induced bronchoconstriction. We conclude that, in vivo, SLPI, but not alpha(1)-PI, can block tryptase-induced bronchoconstriction and that this activity may explain the differential effects of these two serine protease inhibitors on antigen-induced airway responses in allergic sheep.
Annotated regions of significance of SELDI‐TOF‐MS spectra for detecting protein biomarkers

Peak detection is a key step in the analysis of SELDI‐TOF‐MS spectra, but the current default method has low specificity and poor peak annotation. To improve data quality, scientists still have to validate the identified peaks visually, a tedious and time‐consuming process, especially for large data sets. Hence, there is a genuine need for methods that minimize manual validation.
Missing values in longitudinal dietary data: A multiple imputation approach based on a fully conditional specification

Multiple imputation (MI) has increasingly received attention as a flexible tool to resolve missing data problems both in observational and controlled studies. Our goal has been to develop a valid and efficient MI procedure for the Diabetes Prediction and Prevention Nutrition Study, in which the diet of a cohort of newborn children with HLA‐DQB1‐conferred susceptibility to type 1 diabetes is repeatedly measured by 3‐day food records over early childhood. The estimation of risk is based on a nested case‐control design setup within the cohort. We have used an iterative procedure known as the fully conditional specification (FCS) to generate appropriate values for the missing dietary data, here playing the role of time‐dependent covariates. Our method extends the standard FCS to repeated measurements settings with the possibility of non‐monotone missingness patterns by being doubly iterative over the follow‐up time of the individuals. In addition, our proposed procedure is nonparametric in the sense that the variables can have distributions deviating strongly from normality: it makes use of quantile normal scores to transform to normality, performs imputations, and transforms back to the original scale. By the use of a moving time window and stepwise regression procedures, the two‐fold FCS method operates well with a great number of variables each measured repeatedly over time. Extensive simulation studies demonstrate that the procedure together with the proposed transformations and variable selection methods provides tools for valid and efficient statistical inference in the nested case‐control setting, and its applications extend beyond that. Copyright © 2009 John Wiley & Sons, Ltd.
Predicting microRNA-disease associations by integrating multiple biological information

MicroRNAs (miRNAs) are a set of small non-coding RNAs that play critical roles in many human diseases. Identifying potential miRNA-disease association is helpful to explore the underlying molecular mechanisms of disease. Currently, it is expensive and time-consuming to detect miRNA-disease associations with experimental methods. On the other hand, many known associations between miRNAs and diseases provide useful information for new miRNA-disease interaction discovery. In this study, we propose a computational framework to infer the relationship between miRNA and disease by integrating multiple data resources. We use sequence and function information of miRNA and semantic and function information of disease to measure similarity of miRNA and disease, respectively. In addition, kernelized Bayesian matrix factorization method is employed to infer potential miRNA-disease association by integrating these data resources. The experimental results demonstrate that our method can effectively predict unknown miRNA-disease association.
Ginsenoside Rb1 ameliorates Glycemic Disorder in Mice With High Fat Diet-Induced Obesity via Regulating Gut Microbiota and Amino Acid Metabolism

Accumulating evidences suggested an association between gut microbiome dysbiosis and impaired glycemic control. Ginsenoside Rb1 (Rb1) is a biologically active substance of ginseng, which serves anti-diabetic effects. However, its working mechanism especially interaction with gut microbes remains elusive in detail. In this study, we investigated the impact of Rb1 oral supplementation on high fat diet (HFD) induced obesity mice, and explored its mechanism in regulating blood glucose. The results showed that higher liver weight and lower cecum weight were observed in HFD fed mice, which was maintained by Rb1 administration. In addition, Rb1 ameliorated HFD induced blood lipid abnormality and improved insulin sensitivity. Several mRNA expressions in the liver were measured by quantitative real-time PCR, of which UCP2, Nr1H4, and Fiaf were reversed by Rb1 treatment. 16S rRNA sequencing analysis indicated that Rb1 significantly altered gut microbiota composition and increased the abundance of mucin-degrading bacterium Akkermansia spp. compared to HFD mice. As suggested via functional prediction, amino acid metabolism was modulated by Rb1 supplementation. Subsequent serum amino acids investigation indicated that several diabetes associated amino acids, like branched-chain amino acids, tryptophan and alanine, were altered in company with Rb1 supplementation. Moreover, correlation analysis firstly implied that the circulation level of alanine was related to Akkermansia spp. In summary, Rb1 supplementation improved HFD induced insulin resistance in mice, and was associated with profound changes in microbial composition and amino acid metabolism.
Alterations in the Composition of Intestinal DNA Virome in Patients With COVID-19

Patients with Coronavirus Disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly present with respiratory issues and related symptoms, in addition to significantly affected digestive system, especially the intestinal tract. While several studies have shown changes in the intestinal flora of patients with COVID-19, not much information is available on the gut virome of such patients. In this study, we used the viromescan software on the latest gut virome database to analyze the intestinal DNA virome composition of 15 patients with COVID-19 and investigated the characteristic alternations, particularly of the intestinal DNA virome to further explore the influence of COVID-19 on the human gut. The DNA viruses in the gut of patients with COVID-19 were mainly crAss-like phages (35.48%), Myoviridae (20.91%), and Siphoviridae (20.43%) family of viruses. Compared with healthy controls, the gut virome composition of patients with COVID-19 changed significantly, especially the crAss-like phages family, from the first time of hospital admission. A potential correlation is also indicated between the change in virome and bacteriome (like Tectiviridae and Bacteroidaceae). The abundance of the viral and bacterial population was also analyzed through continuous sample collection from the gut of patients hospitalized due to COVID-19. The gut virome is indeed affected by the SARS-CoV-2 infection, and along with gut bacteriome, it may play an important role in the disease progression of COVID-19. These conclusions would be helpful in understanding the gut-related response and contribute to the treatment and prevention strategies of COVID-19.
Day treatment for personality disorders: a review of research findings.

Day treatment, a form of partial hospitalization, may have unique advantages in the care of patients with personality disorders. It appears to offer a favorable level of intensiveness and containment, thus facilitating treatment of the chronic emotional and behavioral difficulties experienced by these individuals. Although several authors have written about the appropriateness of day treatment for personality disorder patients, empirical support has been slow to accumulate. More recently, greater research attention has been focused on this question. This review examines the current research. The findings suggest that day treatment is effective for this difficult patient population and that it is more effective than standard treatment (i.e., medication and support). Preliminary evidence indicates that day treatment may lead to a reduction in future health-services costs. Some findings also show that day treatment may be particularly beneficial for certain patients-for example, those who are more psychologically minded. Implications of these findings for clinical practice are considered. Limitations in our current approach to research in this area are highlighted, and recommendations for future study are provided.
Techniques used for the screening of hemoglobin levels in blood donors: current insights and future directions

Blood donor hemoglobin (Hb) estimation is an important donation test that is performed prior to blood donation. It serves the dual purpose of protecting the donors’ health against anemia and ensuring good quality of blood components, which has an implication on recipients’ health. Diverse cutoff criteria have been defined world over depending on population characteristics; however, no testing methodology and sample requirement have been specified for Hb screening. Besides the technique, there are several physiological and methodological factors that affect accuracy and reliability of Hb estimation. These include the anatomical source of blood sample, posture of the donor, timing of sample and several other biological factors. Qualitative copper sulfate gravimetric method has been the archaic time-tested method that is still used in resource-constrained settings. Portable hemoglobinometers are modern quantitative devices that have been further modified to reagent-free cuvettes. Furthermore, noninvasive spectrophotometry was introduced, mitigating pain to blood donor and eliminating risk of infection. Notwithstanding a tremendous evolution in terms of ease of operation, accuracy, mobility, rapidity and cost, a component of inherent variability persists, which may partly be attributed to pre-analytical variables. Hence, blood centers should pay due attention to validation of test methodology, competency of operating staff and regular proficiency testing of the outputs. In this article, we have reviewed various regulatory guidelines, described the variables that affect the measurements and compared the validated technologies for Hb screening of blood donors along with enumeration of their merits and limitations.
Ribosome Profiling and RNA Sequencing Reveal Genome-Wide Cellular Translation and Transcription Regulation Under Osmotic Stress in Lactobacillus rhamnosus ATCC 53103

To determine whether osmotic pressure affects the translation efficiency of Lactobacillus rhamnosus, the ribosome profiling assay was performed to analyze the changes in translation efficiency in L. rhamnosus ATCC 53103. Under osmotic stress, differentially expressed genes (DEGs) involved in fatty acid biosynthesis and metabolism, ribosome, and purine metabolism pathways were co-regulated with consistent expression direction at translation and transcription levels. DEGs involved in the biosynthesis of phenylalanine, tyrosine, and tryptophan, and the phosphotransferase system pathways also were co-regulated at translation and transcription levels, while they showed opposite expression direction at two levels. Moreover, DEGs involved in the two-component system, amino acid metabolism, and pyruvate metabolism pathways were only regulated at the transcription level. And DEGs involved in fructose and mannose metabolism were only regulated at the translation level. The translation efficiency of DEGs involved in the biosynthesis of amino acids was downregulated while in quorum sensing and PTS pathways was upregulated. In addition, the ribosome footprints accumulated in open reading frame regions resulted in impaired translation initiation and elongation under osmotic stress. In summary, L. rhamnosus ATCC 53103 could respond to osmotic stress by translation regulation and control the balance between survival and growth of cells by transcription and translation.
Unique vaginal microbiota that includes an unknown Mycoplasma-like organism is associated with Trichomonas vaginalis infection.

BACKGROUND The prevalence of Trichomonas vaginalis infection is highest in women with intermediate Nugent scores. We hypothesized that the vaginal microbiota in T. vaginalis-infected women differs from that in T. vaginalis-uninfected women. METHODS Vaginal samples from 30 T. vaginalis-infected women were matched by Nugent score to those from 30 T. vaginalis-uninfected women. Equal numbers of women with Nugent scores categorized as normal, intermediate, and bacterial vaginosis were included. The vaginal microbiota was assessed using 454 pyrosequencing analysis of polymerase chain reaction-amplified 16S ribosomal RNA gene sequences. The 16S ribosomal RNA gene sequence of an unknown organism was obtained by universal bacterial polymerase chain reaction amplification, cloning, and sequencing. RESULTS Principal coordinates analysis of the pyrosequencing data showed divergence of the vaginal microbiota in T. vaginalis-infected and T. vaginalis-uninfected patients among women with normal and those with intermediate Nugent scores but not among women with bacterial vaginosis. Cluster analysis revealed 2 unique groups of T. vaginalis-infected women. One had high abundance of Mycoplasma hominis and other had high abundance of an unknown Mycoplasma species. Women in the former group had clinical evidence of enhanced vaginal inflammation. CONCLUSIONS T. vaginalis may alter the vaginal microbiota in a manner that is favorable to its survival and/or transmissibility. An unknown Mycoplasma species plays a role in some of these transformations. In other cases, these changes may result in a heightened host inflammatory response.
Sirolimus Use and Cancer Incidence Among US Kidney Transplant Recipients

Sirolimus has anti‐carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population‐based cancer registries and national pharmacy claims. Recipients contributed sirolimus‐exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32 604 kidney transplants (5687 sirolimus‐exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70–1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15–3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57–0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.
Building an Automated Problem List Based on Natural Language Processing: Lessons Learned in the Early Phase of Development

Detailed problem lists that comply with JCAHO requirements are important components of electronic health records. Besides improving continuity of care electronic problem lists could serve as foundation infrastructure for clinical trial recruitment, research, biosurveillance and billing informatics modules. However, physicians rarely maintain problem lists. Our team is building a system using MetaMap and UMLS to automatically populate the problem list. We report our early results evaluating the application. Three physicians generated gold standard problem lists for 100 cardiology ambulatory progress notes. Our application had 88% sensitivity and 66% precision using a non-modified UMLS dataset. The systemâs misses concentrated in the group of ambiguous problem list entries (Chi-square=27.12 p<0.0001). In addition to the explicit entries, the notes included 10% implicit entry candidates. MetaMap and UMLS are readily applicable to automate the problem list. Ambiguity in medical documents has consequences for performance evaluation of automated systems.
Wavefront Sensing and the Dynamics of Tear Film

Purpose: To summarize our previous studies regarding the influence of tear-film dynamics on optical quality after blinking. Methods: Sequential higher-order aberration (HOA) measurements were performed by using a wavefront sensor. During the measurements, subjects were asked to blink every 10 seconds. The obtained aberration data were analyzed in the central 4-mm diameter for coma-like, spherical-like, and total HOAs up to the sixth-order Zernike polynomials. Results: Serial measurements of HOAs in healthy eyes showed variations even in clinically normal subjects and were classified into 4 groups by pattern: stable, small-fluctuation, sawtooth, and others. The sequential postblink change in HOAs after punctal plug insertion was quantitatively evaluated in a patient with dry eye who complained of paradoxical visual impairment with epiphora despite improvement of dry eye. Conclusions: Wavefront sensing is a useful objective method to evaluate sequential changes of visual performance related to tear-film dynamics. Serial measurement of HOAs might show a relationship between tear dynamics and quality of vision clinically.