Miracle-dz/UniFAR-FTUs huggingface dataset:
Interspecies allometric analysis of the comparative pharmacokinetics of 44 drugs across veterinary and laboratory animal species.

The purpose of this study was to apply the method of allometric analysis to a study of the comparative disposition of veterinary drugs using the Food Animal Residue Avoidance Databank (FARAD) as a source of the comparative pharmacokinetic data. An initial filtration of the FARAD data was performed in order to exclude drugs for which no pharmacokinetic data were available, in at least four species the route of administration was other than intravenous, and the matrix was different from blood, plasma or serum. This process restricted the study to a total of 44 candidate drugs. The primary pharmacokinetic parameter selected for study was half-life (t1/2). As this parameter is a composite of clearance (Cl) and volume of distribution (Vd), it was considered to be the most robust for interspecies scaling. Volume of distribution at steady state (Vdss) and clearance showed weak allometric correlations with weight across species. The relationships between body weight and elimination half-life (51/2 beta) were determined for this selected group of drugs by using the empirically determined function Y = a Wb. The function Y represents the parameter of concern (half-life), a is a coefficient typical of every drug (intercept), W is the species average body weight, and b is the scaling exponent. A total of 11 drugs (tetracycline, oxytetracycline, chlortetracycline, erythromycin, diazepam, prednisolone, cephapirin, ampicillin, gentamicin, apramycin and carbenicillin) showed statistically significant correlations and consequently are excellent candidates for interspecies extrapolation of pharmacokinetic parameters (half-life) in species of relevance to veterinary medicine. The remaining 33 drugs were divided into two groups which showed various degrees of lack of correlation. Many of the drugs that showed no allometric correlation were low hepatic extraction drugs. However, some other drugs demonstrated equivocal results which could either be due to a true lack of allometric correlation, or be inconclusive due to the lack of quality data or excessive variability due to the multi-laboratory origin of the FARAD data. The results of this study show that interspecies scaling is applicable to certain veterinary drugs. The experimental determination of the coefficients of the allometric equation for relevant pharmacokinetic parameters (clearance and volume of distribution) could be an important tool in estimating dose in species where the drug has never been studied. This could have important consequences in terms of avoiding the use of dose-titration studies in Phase I of drug development, for drugs that are experimentally 'well behaved. '
Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial

Objectives Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year. Methods The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD-inexperienced patients with ERA were stratified into a high-risk or low-risk group based upon presence of erosions, disease activity, rheumatoid factor and anticitrullinated protein antibodies. High-risk patients were randomised to a COBRA Classic (MTX + sulfasalazine + prednisone step-down from 60 mg), COBRA Slim (MTX + prednisone step-down from 30 mg) or COBRA Avant Garde (MTX + leflunomide + prednisone step-down from 30 mg) scheme. Low-risk patients were randomised to MTX tight step-up (MTX-TSU) or COBRA Slim. Primary outcome was the proportion of patients in 28 joint disease activity score calculated with C-reactive protein remission at week 52 in an intention-to-treat analysis. Secondary outcomes were safety and effectiveness (ClinicalTrial.gov identifier NCT01172639). Results 98 COBRA Classic, 98 COBRA Slim (high risk), 93 COBRA Avant Garde, 47 MTX-TSU and 43 COBRA Slim (low risk) patients were evaluated. Remission was achieved in 64.3% (63/98) COBRA Classic, 60.2% (59/98) COBRA Slim (high risk) and 62.4% (58/93) COBRA Avant Garde patients at W52 (p=0.840); and in 57.4% (27/47) MTX-TSU and 67.4% (29/43) COBRA Slim (low risk) patients (p=0.329). Less adverse events occurred per patient with COBRA Slim (high risk) compared with COBRA Classic or COBRA Avant Garde (p=0.038). Adverse events were similar in MTX-TSU and COBRA Slim (low risk) patients (p=0.871). At W52, 76.0% patients were on DMARD monotherapy, 5.2% used GCs and 7.5% biologicals. Conclusions MTX with a moderate-dose GC remission induction scheme (COBRA Slim) seems an effective, safe, low-cost and feasible initial treatment strategy for patients with ERA regardless of their prognostic profile, provided a treat-to-target approach is followed. Trial registration numbers EudraCT-number 2008-007225-39 and NCT01172639; Results.
Development of radiation-resistant magnets for the JHF project

In connection with the Japan Hadron Facility (JHF) Project, R&D work on the radiation-resistant magnets has continued at KEK. JHF is the next-generation high-intensity accelerator project of Japan and aims to provide 1 MW 3 GeV/50 GeV proton beams for various fields of science.
A4NT: Author Attribute Anonymity by Adversarial Training of Neural Machine Translation

Text-based analysis methods allow to reveal privacy relevant author attributes such as gender, age and identify of the text's author. Such methods can compromise the privacy of an anonymous author even when the author tries to remove privacy sensitive content. In this paper, we propose an automatic method, called Adversarial Author Attribute Anonymity Neural Translation ($A^4NT$), to combat such text-based adversaries. We combine sequence-to-sequence language models used in machine translation and generative adversarial networks to obfuscate author attributes. Unlike machine translation techniques which need paired data, our method can be trained on unpaired corpora of text containing different authors. Importantly, we propose and evaluate techniques to impose constraints on our $A^4NT$ to preserve the semantics of the input text. $A^4NT$ learns to make minimal changes to the input text to successfully fool author attribute classifiers, while aiming to maintain the meaning of the input. We show through experiments on two different datasets and three settings that our proposed method is effective in fooling the author attribute classifiers and thereby improving the anonymity of authors.
Adjuvant high‐dose intravenous gammaglobulin in the treatment of pemphigus and bullous pemphigoid: experience in six patients

At present, initial high‐dose prednisone is the treatment of choice for patients with pemphigus and bullous pemphigoid. To reduce the risks associated with long‐term corticosteroid treatment, other immunosuppressants are often given as steroid‐sparing agents. Occasionally, the dose of steroids cannot be reduced. In this study, we report six patients with pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid, in whom the daily corticosteroid dose could only be tapered to acceptable, effective, maintenance levels following treatment with high‐dose intravenous gammaglobulin.
Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis

OBJECTIVE To determine the effect of intramuscular gold and oral hydroxychloroquine(HCQ) on the lipid profile of patients with rheumatoid arthritis (RA). METHOD A prospective randomised clinical trial of 12 months’ duration was performed in 100 RA patients. Data on clinical and laboratory parameters of disease activity, and fasting serum lipid samples was collected at baseline and at three monthly intervals over one year. RESULTS The expected second line response was seen with no significant difference in efficacy between the groups at 12 months. The HCQ group had a significant overall improvement in their lipid profile while there was a trend for lipid profiles in the gold group to worsen. CONCLUSIONS HCQ is an effective second line agent that has beneficial effects on serum lipids. This should be taken into account when choosing a disease modifying anti-rheumatic drug in patients who suffer from RA and who have significant cardiovascular risk factors.
Polyomavirus DNA replication in the pancreas and in a transformed pancreas cell line has distinct enhancer requirements

The regulatory DNA (enhancer) of polyomavirus (Py) is a major determinant of tissue-specific DNA replication during acute infection of newborn mice. Previously, we reported that the combination of one of the two Py enhancers (A enhancer) and the repeated Moloney murine leukemia virus (Mo-MuLV) enhancer gave a chimeric Py genome (Py-MuLV) that replicates predominantly in the acinar cells of the pancreas, a tissue not permissive for wild-type PyA2 replication (R. Rochford, B. A. Campbell, and L. P. Villareal. Proc. Nat. Acad. Sci. USA 84:449-453,1987). In this report, we further examine the combined enhancer requirements for acinar cell-specific Py replication. We also compare enhancer requirements for Py replication in the acinar cells of the pancreas with those of a transformed acinar cell line (266-6 cells). The deletion of sequences within the A enhancer of Py-MuLV (nucleotides 5098 to 5132) results in a virus with 10-fold-reduced levels of pancreas-specific replication. The deletion, however, of one of the 72-bp repeated Mo-MuLV enhancer sequences from Py-MuLV results in a complete loss of pancreas-specific DNA replication. Thus, the Py A enhancer is required for efficient replication of Py in the pancreas without otherwise altering organ specificity, but both of the repeated copies of the Mo-MuLV enhancer are essential for pancreas-specific Py replication. In contrast to the enhancer requirements for in vivo pancreas replication, in transformed acinar cells (266-6), PyA2 wild-type replicated efficiently and the Py-MuLV recombinant replicated inefficiently. These data suggest that the cell-specific control of DNA replication is different between normal pancreas cells and their transformed cell line counterparts and that this difference is apparent in the enhancer requirement of cell-specific Py DNA replication.
AKARI OBSERVATION OF THE NORTH ECLIPTIC POLE (NEP) SUPERCLUSTER AT z = 0.087: MID-INFRARED VIEW OF TRANSITION GALAXIES

We present the mid-infrared (MIR) properties of galaxies within a supercluster in the north ecliptic pole region at z ∼ 0.087 observed with the AKARI satellite. We use data from the AKARI NEP-Wide (5.4 deg2) IR survey and the CLusters of galaxies EVoLution studies (CLEVL) mission program. We show that near-IR (3 μm)–mid-IR (11 μm) color can be used as an indicator of the specific star formation rate and the presence of intermediate-age stellar populations. From the MIR observations, we find that red-sequence galaxies consist not only of passively evolving red early-type galaxies, but also of (1) “weak-SFGs” (disk-dominated star-forming galaxies that have star formation rates lower by ∼4 × than blue-cloud galaxies) and (2) “intermediate-MXGs” (bulge-dominated galaxies showing stronger MIR dust emission than normal red early-type galaxies). These two populations can be a set of transition galaxies from blue, star-forming, late-type galaxies evolving into red, quiescent, early-type ones. We find that the weak-SFGs are predominant at intermediate masses (1010 M☉ < M* < 1010.5 M☉) and are typically found in local densities similar to the outskirts of galaxy clusters. As much as 40% of the supercluster member galaxies in this mass range can be classified as weak-SFGs, but their proportion decreases to <10% at larger masses (M* > 1010.5 M☉) at any galaxy density. The fraction of the intermediate-MXG among red-sequence galaxies at 1010 M☉ < M* < 1011 M☉ also decreases as the density and mass increase. In particular, ∼42% of the red-sequence galaxies with early-type morphologies are classified as intermediate-MXGs at intermediate densities. These results suggest that the star formation activity is strongly dependent on the stellar mass, but that the morphological transformation is mainly controlled by the environment.
Human Bocavirus Infection in Young Children in the United States: Molecular Epidemiological Profile and Clinical Characteristics of a Newly Emerging Respiratory Virus

Abstract BackgroundHuman bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as “children”) for HBoV MethodsChildren for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1–3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004 ResultsTwenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in ⩾50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period ConclusionsHBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children
Association of Unilateral Renal Agenesis With Adverse Outcomes in Pregnancy: A Matched Cohort Study.

BACKGROUND Data regarding the effect of a solitary kidney during pregnancy have come from studies of living kidney donors. We evaluated the risk for adverse pregnancy outcomes in women with a single kidney from renal agenesis. STUDY DESIGN Matched cohort study. SETTING & PARTICIPANTS Using data from 7,079 childbirths from an integrated health care delivery system from 1996 through 2015, we identified births from women with renal agenesis. Only first pregnancies and singleton births were included. After excluding those with diabetes and kidney disease, 200 women with renal agenesis were matched 1:4 by age (within 2 years), race, and history of hypertension to women with 2 kidneys. PREDICTOR Renal agenesis defined by International Classification of Diseases, Ninth Revision (ICD-9) codes prior to pregnancy. OUTCOMES The primary outcome was adverse maternal outcomes, including preterm delivery, delivery by cesarean section, preeclampsia/eclampsia, and hospital length of stay. Adverse neonatal end points were considered as a secondary outcome and included low birth weight (<2,500g) and infant death/transfer to acute inpatient facility. RESULTS Mean gestational age at delivery was 37.9±2.1 weeks for women with renal agenesis compared to 38.6±1.8 weeks for women with 2 kidneys. Compared with women with 2 kidneys, those with renal agenesis had increased risk for preterm delivery (OR, 2.88; 95% CI, 1.86-4.45), delivery by cesarean section (OR, 2.11; 95% CI, 1.49-2.99), preeclampsia/eclampsia (OR, 2.41; 95% CI, 1.23-4.72), and length of stay longer than 3 days (OR, 1.81; 95% CI, 1.18-2.78). Renal agenesis was not significantly associated with increased risk for infant death/transfer to acute facility (OR, 2.60; 95% CI, 0.57-11.89) or low birth weight after accounting for preterm delivery (OR, 2.11; 95% CI, 0.76-5.88). LIMITATIONS Renal agenesis was identified by ICD-9 code, not by imaging of the abdomen. CONCLUSION Women with unilateral renal agenesis have a higher risk for adverse outcomes in pregnancy.
Changes in serum levels of apolipoprotein A‐1 as an indicator of protein metabolism after hepatectomy

The clinical significance of serum apolipoprotein A‐1 levels as an indicator of hepatic protein synthesis after hepatectomy was investigated. A total of 50 patients who had undergone hepatectomy at our department from 1997 to 1999 were selected for this study. The serum levels of apolipoprotein A‐1, indocyanine green dye retention at 15 minutes, lectin‐cholesterol acyltransferase, prealbumin, and high‐density lipoprotein cholesterol were measured in these patients preoperatively and on postoperative days 7 and 14. The type of hepatic resection conducted was partial resection in 13 cases, subsegmentectomy in 13 cases, segmentectomy in five cases, and bisegmentectomy in 19 cases. All the patients tolerated the operation, and none of the cases had any severe complications, such as liver failure. In most cases, the serum apolipoprotein A‐1 levels decreased on postoperative day 7 and recovered by day 14. There were no significant differences in the changes in apolipoprotein A‐1 levels between patients with the individual types of operative procedures. The serum apolipoprotein A‐1 levels showed significant correlations with the serum high‐density lipoprotein cholesterol, lectin‐cholesterol acyltransferase and prealbumin levels on postoperative days 7 and 14; however, there was no significant correlation with the indocyanine green retention test. When the cases were divided into three groups according to the serum level of apolipoprotein A‐1 on postoperative day 7 (group A: over 81 mg/dl, group B: 61–80 mg/dl, group C: under 60 mg/dl), the serum indocyanine green retention, prealbumin, lectin‐cholesterol acyltransferase and high‐density lipoprotein cholesterol levels in group C were significantly lower than those in group A on postoperative day 7. On the basis of these results, it is suggested that the pattern of changes in the serum apolipoprotein A‐1 levels may be a good indicator of the hepatic protein synthetic ability during the perioperative period after hepatectomy.
La distribución del ingreso en el Perú: 1980-2010

Siguiendo una tradicion sistematica institucional,a lo largo de los ocho capitulos, los autores analizan la desigualdad distributiva del Peru a traves del estudio de sus dimensiones histoticas, macroeconomicas y regionales, asi como aspectos especificos como la escasez del agua, la influencia del status social y el genero del mercado laboral y los servicios micro-crediticios.
A Rapid, High-Quality, Cost-Effective, Comprehensive and Expandable Targeted Next-Generation Sequencing Assay for Inherited Heart Diseases.

RATIONALE Thousands of mutations across >50 genes have been implicated in inherited cardiomyopathies. However, options for sequencing this rapidly evolving gene set are limited because many sequencing services and off-the-shelf kits suffer from slow turnaround, inefficient capture of genomic DNA, and high cost. Furthermore, customization of these assays to cover emerging targets that suit individual needs is often expensive and time consuming. OBJECTIVE We sought to develop a custom high throughput, clinical-grade next-generation sequencing assay for detecting cardiac disease gene mutations with improved accuracy, flexibility, turnaround, and cost. METHODS AND RESULTS We used double-stranded probes (complementary long padlock probes), an inexpensive and customizable capture technology, to efficiently capture and amplify the entire coding region and flanking intronic and regulatory sequences of 88 genes and 40 microRNAs associated with inherited cardiomyopathies, congenital heart disease, and cardiac development. Multiplexing 11 samples per sequencing run resulted in a mean base pair coverage of 420, of which 97% had >20× coverage and >99% were concordant with known heterozygous single nucleotide polymorphisms. The assay correctly detected germline variants in 24 individuals and revealed several polymorphic regions in miR-499. Total run time was 3 days at an approximate cost of $100 per sample. CONCLUSIONS Accurate, high-throughput detection of mutations across numerous cardiac genes is achievable with complementary long padlock probe technology. Moreover, this format allows facile insertion of additional probes as more cardiomyopathy and congenital heart disease genes are discovered, giving researchers a powerful new tool for DNA mutation detection and discovery.
Effect of body posture on hand grip strength in adult Bengalee population

The present work was aimed to assess the variation of grip strength with the changes of posture and body joint angles and to establish an optimal body posture and joint angle for the maximum grip strength for adult Bengalee population. Methods: Adult male (n=156) and female (n=224) were involved in this study. The hand grip strength was measured by using Lafayette hand grip dynamometer. Results: The results revealed that male subjects had a significantly greater (p<0.001) grip strength compared to that of female subjects and the highest grip strength was found in standing posture with elbow angle of 900 in both adult male and female subjects. Conclusions: From the results it may be recommended that the grip strength of Bengalee population may be measured in standing posture with elbow angle of 90degrees, shoulder angle of 1800, and the trunk and wrist in neutral positions to provide maximum force.
Regulatory T Cells Modulate Postischemic Neovascularization

Background— CD4+ and CD8+ T lymphocytes are key regulators of postischemic neovascularization. T-cell activation is promoted by 2 major costimulatory signalings, the B7/CD28 and CD40–CD40 ligand pathways. Interestingly, CD28 interactions with the structurally related ligands B7-1 and B7-2 are also required for the generation and homeostasis of CD4+CD25+ regulatory T cells (Treg cells), which play a critical role in the suppression of immune responses and the control of T-cell homeostasis. We hypothesized that Treg cell activation may modulate the immunoinflammatory response to ischemic injury, leading to alteration of postischemic vessel growth. Methods and Results— Ischemia was induced by right femoral artery ligation in CD28-, B7-1/2–, or CD40-deficient mice (n=10 per group). CD40 deficiency led to a significant reduction in the postischemic inflammatory response and vessel growth. In contrast, at day 21 after ischemia, angiographic score, foot perfusion, and capillary density were increased by 2.0-, 1.2-, and 1.8-fold, respectively, in CD28-deficient mice, which showed a profound reduction in the number of Treg cells compared with controls. Similarly, disruption of B7-1/2 signaling or anti-CD25 treatment and subsequent Treg deletion significantly enhanced postischemic neovascularization. These effects were associated with enhanced accumulation of CD3-positive T cells and Mac-3–positive macrophages in the ischemic leg. Conversely, treatment of CD28−/− mice with the nonmitogenic anti-CD3 monoclonal antibody enhanced the number of endogenous Treg cells and led to a significant reduction of the postischemic inflammatory response and neovascularization. Finally, coadministration of Treg cells and CD28−/− splenocytes in Rag1−/− mice with hindlimb ischemia abrogated the CD28−/− splenocyte-induced activation of the inflammatory response and neovascularization. Conclusion— Treg cell response modulates postischemic neovascularization.